Diabetes Mellitus A Medical History Journey (Public Health Practices, Methods and Policies) 1st Edition 2016 PDF

PUBLIC HEALTH: PRACTICES, METHODS AND POLICIES
DIABETES MELLITUS
A MEDICAL HISTORY JOURNEY
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PUBLIC HEALTH: PRACTICES, METHODS AND POLICIES
DIABETES MELLITUS
A MEDICAL HISTORY JOURNEY
DONALD E. GREYDANUS
AND
JOAV MERRICK
New York
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CONTENTS
Introduction 1
Chapter 1 Trends in child and youth diabetes 3
Section One: Diabetes mellitus history 9
Chapter 2 A historical journey of diabetes mellitus 11
Section Two: Acknowledgments 73
Chapter 3 About the authors 75
Chapter 4 About the Department of Pediatric and Adolescent
Medicine, Western Michigan University Homer
Stryker MD School of Medicine (WMED),
Kalamazoo, Michigan, USA 77
Chapter 5 About the National Institute of Child Health and
Human Development in Israel 81
Chapter 6 About the book series “Public health: Practices,
methods and policies” 85
Section Three: Index 87
Index 89
INTRODUCTION
Chapter 1
TRENDS IN CHILD AND YOUTH DIABETES
It is estimated that 86 million adult Americans have prediabetes and with

that, a risk of developing T2DM (type 2 diabetes) within one in ten
patients. About 29 million people have actual diabetes, most with T2DM.
It was estimated in 2012 that about 208,000 people under the age of 20
have diabetes in the United States, but there is little data available on the
prevalence of diabetes in the adolescent population. A recent study
looking at 12-19 year olds from 2005-2014 found the prevalence of
diabetes at 0.8%, with 28.5% undiagnosed and the prevalence of
prediabetes 17.7%, more common among boys (22%) than girls (13.2%).
With about 9% of the total US population having diabetes, this a public
health issue of considerable proportion.
INTRODUCTION
Physical activity is important for a healthy lifestyle and quality of life. For
example, parks can provide opportunities for physical activity for both
children and adults in their neighborhood (1). A study in 20 neighborhood
parks in Durham, North Carolina with 2,712 children and adolescents showed
that the type of activity area and presence of other active children were
positively associated with physical activity, while the presence of a parent was
negatively associated (1). Results showed that physical activity of girls was
more strongly affected by social effects (like other active children), whereas
physical activity of boys was more strongly influenced by the availability of
park facilities (1).
4 Donald E. Greydanus and Joav Merrick
A study from Finland of 37,699 adults looked at childhood adverse

psychosocial factors and adult neighborhood disadvantage to understand if
there was a link to increased cardiovascular disease (2). They found that
combined exposure to high childhood adversity and high adult disadvantage
was associated with cardiovascular disease risk factors (hypertension,
dyslipidemia, diabetes, obesity, smoking, heavy alcohol use and physical
inactivity), while exposure to high childhood adversity or high adult
neighborhood disadvantage alone was not significantly associated with
cardiovascular disease (2).
Another study with 1,842 adults from Brazil looked at the local retail food
environment and consumption of fruits and vegetables and sugar-sweetened
beverages (3). They found that availability in neighbourhoods was associated
with regular fruits and vegetables consumption, but regular fruits and
vegetables consumption prevalence was significantly lower among lower-
income individuals living in neighbourhoods with fewer supermarkets and
fresh produce markets. A greater variety of sugar-sweetened beverages was
associated with a 15 % increase in regular SSB consumption.
NEIGHBORHOODS
A recent (4) study used data from the Multi-Ethnic Study of Atherosclerosis
(MESA), which involved more than 6,000 men and women from six
communities in the United States (New York, Baltimore, Chicago, Los
Angeles, Twin Cities and Winston Salem) to look at how neighborhood
environments may influence the risk for developing type 2 diabetes mellitus
(T2DM). They wanted to investigate long-term exposures to neighborhood
physical and social environments, availability of healthy food and physical
activity resources and levels of social cohesion and safety in relationship to
T2DM. During a follow-up period of about ten years of adults aged 45-84
years at baseline 616 out of 5,124 participants (12.0%) developed T2DM and
the study found a lower risk for developing T2DM associated with greater
cumulative exposure to indicators of neighborhood healthy food and physical
activity resources (4).
The studies above are just examples of recent research interest into the
interrelation between neighborhood and the effects on health (5). This
relationship is complex and also very hard to research, since it is
multidisciplinary and multi agency with different community development
policies, urban planning, zoning and transportation policies involved. In order
Trends in child and youth diabetes 5
to better understand the role of these environments and identify the most
effective interventions in order to improve health will require partnerships
between researchers, the neighborhood communities and policy makers.
DIABETES, CHILDREN AND YOUTH

There has been an increase in both T1DM (type 1 diabetes) and T2DM in
children and youth (6, 7) and diabetes is no longer a rare disease in school-
aged children. T1DM is still the leading cause of diabetes in children and
accounts for about 5% of all diagnosed cases of diabetes (8). T2DM used to be
mainly diagnosed in adults, but now more often seen in children 10 years and
older (8) and apparently a result of more obesity and life style changes that has
occured also in the pediatric population (8).
The American Diabetes Association and the American Academy of
Pediatrics have therefore provided consensus statements and guidelines on
both T1 and T2DM (9-12).
TRENDS IN PEDIATRIC AND ADOLESCENT DIABETES

It is estimated in 2012 that about 208,000 persons under the age of 20 years
have diabetes (6, 8), but there is little data available on the prevalence of
diabetes in for example the adolescent population (13).
A recent research letter in JAMA (13) examined data from the National
Health and Nutrition Examination Survey (NHANES) from 2005 to 2014.
This survey is representative of the civilian, non-institutionalized United States
population, which both include in-person interviews and examinations in
mobile centers (13). The authors used data collected from adolescents aged 12-
19 years randomly selected to have blood glucose testing after fasting. In
2,606 adolescents they found that 62 had diabetes and 512 had prediabetes
with the finding that among those with the disease, 20 had not even been
diagnosed (13).
The prevalence of diabetes was therefore 0.8%, with 28.5% undiagnosed
and the prevalence of prediabetes was 17.7%, more common among the boys
(22%) than the girls (13.2%). These figures were much higher than previous
estimates of diabetes prevalence among teenagers (0.34%) (13). Diabetes and
pre-diabetes prevalences did not change over the time period in this study (13).
Black and Hispanic teenagers were more likely than white youth to have
prediabetes and minority teenagers with diabetes were also more likely to be
undiagnosed. Among black teenagers with diabetes, 49.9% did not know they
had diabetes and 21% have prediabetes. Among Hispanic teenagers, 39.5%
who had diabetes were unaware and 22.9% had prediabetes.
CONCLUSION
The United States CDC (Center for Disese Control and Prevention) estimated
that 86 million adult Americans have prediabetes and therefore risk of
developing T2DM (14), and 1 in 10 are unaware of their condition. About 29
million people have actual diabetes with most T2DM. With about 9% of the
population having diabetes, we are talking about a public health issue of
proportion.
REFERENCES
[1] Bocarro JN, Floyd MF, Smith WR, Edwards MB, Schultz CL, Baran P, et al. Social
and environmental factors related to boys' and girls' park-based physical activity.
Prev Chronic Dis 2015 Jun 18;12:E97. Doi: 10.5888/pcd12.140532.
[2] Halonen JI, Stenholm S, Pentti J, Kawachi I, Subramanian SV, Kivimäki M, et al.
Childhood psychosocial adversity and adult neighborhood disadvantage as predictors
of cardiovascular disease: A cohort study. Circulation 2015 Jun 11. pii:
CIRCULATIONAHA.115.015392. [Epub ahead of print].
[3] Duran AC, de Almeida SL, Latorre MD, Jaime PC. The role of the local retail food
environment in fruit, vegetable and sugar-sweetened beverage consumption in
Brazil. Public Health Nutr 2015 Jun 9:1-10. [Epub ahead of print].
[4] Christine PJ, Auchincloss AH, Bertoni AG, Carnethon MR, Sanchez BN, Moore K,
et al. Longitudinal associations between neighborhood physical and social
environments and incident type 2 diabetes mellitus: The Multi-Ethnic Study of
Atherosclerosis (MESA). JAMA Intern Med 2015 Jun 29. Doi:
10.1001/jamainternmed.2015.2691. [Epub ahead of print].
[5] Diez-Roux AV. Neighborhoods and health: Where are we and were do we go from
here? Rev Epidemiol Sante Publique 2007;55(1):13-21.
[6] Centers for Disease Control and Prevention. National diabetes statistics report:
Estimates of diabetes and its burden in the United States, 2014. Atlanta, GA: US
Department of Health and Human Services, 2014.
[7] Lipman TH, Chang Y, Murphy KM. The epidemiology of type 1 diabetes in children
in Philadelphia 1990-1994: evidence of an epidemic. Diabetes Care
2002;25(11):1969-75.
Trends in child and youth diabetes 7
[8] National Diabetes Education Program (NDEP). Oerview of diabetes in children and
adolescents. Bethesda, MD: NIH, CDC, 2014.
[9] Silverstein J, Klingensmith G, Copeland K, et al. Care of children and adolescents
with type 1 diabetes: a statement of the American Diabetes Association. Diabetes
Care 2005;28(1):186-212.
[10] American Diabetes Association. Type 2 diabetes in children and adolescents.
Diabetes Care 2000;23(3):381-9.
[11] Copeland KC, Silverstein J, Moore KR, Prazar GE, Raymer T, Shiffman RN, et al.
Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and
adolescents. Pediatrics 2013;131(2):364-82.
[12] American Diabetes Association. Standards of medical care in diabetes-2014.
Diabetes Care 2014;37(Suppl 1):S14-80.
[13] Menke A, Casagrande S, Cowie CC. Prevalence of diabetes in adolescents age 12 to
19 years in the United States, 2005-2014. JAMA 2016; 316(3):344.
[14] Center for Disease Control and Prevention. National diabetes month-November
2015. MMWR 2015;65(45):1261.
SECTION ONE:
DIABETES MELLITUS HISTORY
Chapter 2
A HISTORICAL JOURNEY
OF DIABETES MELLITUS
This chapter provides a medical history synopsis behind the 21st century
knowledge of diabetes mellitus, a disorder of terrifying tabescence known
to ancient as well as modern homo sapiens. The term, diabetes, come
from the Greek language and is attributed to Apollonius of Memphis in
the 2nd century BC and Areteus of Capadocia (81-138 AD). There are
many experts involved over thousands of years who helped unravel many
of the mysteries of this disorder and these include Byzantine writers such
as Greek physician Alexander Traillianus (Alexander of Tralles; 525-605
AD), Persian physician Rhazes (865-925), Islamic physician Avicenna
(980-1037 AD), Jewish physician-scholar Moses Maimonides (1138-
1204), British physician Thomas Willis (1621-1675), British
physiologist-physician Matthew Dobson (1732-1784), the great French
father of physiology Claude Bernard (1813-1878), French physician-
biochemist-pharmacist Apollinaire Bouchardat (1806-1886), Lithuanian
physician Oscar Minkowski (1858-1931), German physician Joseph
Freiherr von Mering (1849-1908), and many others. Many millennia of
wonder and research regarding diabetes mellitus was cyrstalized in the
20th century with the 1922 identification of insulin by the Toronto team
(Sir Frederick Grant Banting [891-1941], Charles Herbert Best [1899-
1978], John James Rickard (JJR) Macleod James [1876-1935] and James
Bertram Collip [1892-1965]). The 20th century continued to improve the
Toronto Group’s work with the purification of as well as identification of
the crystalline structure of insulin by biochemist John Jacob Abel (1857-
1938), identification of two types of diabetes mellitus by Sir Harold
Himsworth (1905-1993) in 1936, description of insulin’s molecular
structure by Frederick Sanger (1918-2013), development of NPH insulin
by Hans Christian Hagedorn (1888-1971), the discovery of proinsulin by
Donald Frederick Steiner (1930-2014), and so much more as the 20th

century faded into the 21st century. It is the story of the human mind
steadfastly seeking to understand its world—a story worth telling again
and again—a surrealistic story that has saved millions of lives from a
premature death of misery in the 20th and now 21st century.
INTRODUCTION
The study of life began with the emergence of Homo sapiens over 200,000
years ago (1-6). Prior to the emergence of writing by the Sumerians in 3200
BC that emerged from earlier Neolithic writing, we can only guess at what
ancient humans thought of a human disease with increased thirst and urination
along with wasting of the body until death that we now call diabetes mellitus.
Rudimentary knowledge of medical conditions is traced to the
Mesopotamia (3100 BC to 332 BC) that included Sumer and the Akkadian,
Babylonian, and Assyrian empires in modern-day Iraq. The word,
Mesopotamia, is Greek for “land between rivers” and indeed was between the
Tigris and Euphrates rivers—major waterways of antiguity. Scholars who have
looked at cuneiform clay tablets of this era identify references to descriptions
reflective of urinary problems such as obstruction, urethritis (and urethral
discharge), stones, and cysts (2-4).
Knowledge of ancient Egyptian medicine is known from such work
reflected in the 1875 discovery by the German Egyptologist Georg Ebers
(1837-1898) of what is called the Ebers Papyrus that dates to the reign of
Amenophis I (second King of the 18th Dynasty) in 1536 BC (7-9). This
document was over 20 meters in length and had 108 columns of text with a
series of prescriptions organized by different diseases (7). The oldest known
surgical document or text is the Edwin Smith Papyrus which was discovered in
1862 near Luxor, Egypt (8). Edwin Smith (1822-1906) was an American
dealer and collector whose name was given to this papyrus.
Babylonian physicians based diagnoses on the appearance of urine (i.e.,
beet juice, wine, beer, paint, others) and therapy of renal or genitourinary
conditions was with local remedies from local minerals or plants and blowing
chemicals into the urethra. Alcohol served as an anesthetic. In their
descriptions of urine these ancient physicians (1500 BC) commented on a
disorder with “too great emptying of the urine” which is probably one of the
earliest references to diabetes in the history of Western medicine; its treatment
included sweet beer, wheat grains, and fruit (10).
A historical journey of diabetes mellitus 13
Physicians were given considerable honor in ancient Israel and they were
often priests from the line of Aaron.
Honor the physician with the honor due him, [a] according to your
need of him, for the Lord created him;
for healing comes from the Most High, and he will receive a gift
from the king.
The skill of the physician lifts up his head, and in the presence of
great men he is admired.
The Lord created medicines from the earth, and a sensible man will
not despise them.
Was not water made sweet with a tree in order that his[b] power
might be known?
And he gave skill to men that he[c] might be glorified in his
marvelous works.
By them he heals and takes away pain;
the pharmacist makes of them a compound.
His works will never be finished; and from him health[d] is upon the
face of the earth.
(Old Testament Book, Ecclesiastes 38:1-8, 3rd century BC)
ANCIENT PHYSICIANS OF INDIA

This condition of excess urination was also identified by clinicians in India at
approximately the same time as these ancient Egyptian physicians (1500 BC).
These Hindus physicians in India described urine in the Ayur Veda that
attracted insects (i.e., flies, ants) and gave diabetes its earliest name---
madhumeha” (“honey urine”) (10). One of the oldest medical traditions is the
Indian Ayurvedic tradition---formed from the Vedic philosophies; two
important texts were the Susruta Samhita and the Charaka Samhita (11).
Susruta of the Hindus (450 BC-380 BC), the father of medicine in India,
recognized this condition in the 5th century BC (12, 13). In the spirit of 20th
century Jacques Cousteau, these clinicians passed their understanding of
science on to future clinicians to unravel the mysteries of this strange
urination-wasting malady. Charaka and Susruta of India called it “Madhu
Meha” in their Samhitas and the Susruta Samhita discusses increased urine
(that was sweet), loss of weight, and other features associated later in the West
with diabetes.
What is a scientist after all? It is a curious man looking through a

keyhole, the keyhole of nature, trying to know what's going on
(Jacques Cousteau: 1910-1997)
ANCIENT GREEK PHYSICIANS

Only by this historical route can many problems in medicine be
approached profitably
(Sir William Osler: 1849-1919).
Western civilization’s understanding of science is traced to the ancient

Greek scholars and the first known Greek medical school was in Cnidus in 700
B.C. One of its early medical scholars was Alcmaeon of Croton (born around
510 BC) who helped to establish the principle of observing patients to
understand disease (14). He was a student of the famous Ionian Greek
philosopher and mathematician, Pythagoras (570 BC-490 BC). Though
certainly influenced by ancient Egyptian medicine, these Greek physicians and
scholars sought to move the knowledge of medicine further and indeed they
did as they established the basis for modern Western medicine.
Table 1. Ancient physicians in the history of diabetes
Alcmaeon of Croton (born around 510 BC)

Susruta of the Hindus (450 BC-380 BC)
Thucydides (460 BC-400 BC)
Hippocrates of Kos (460-370 BCE),
Apollonius of Memphis (2nd century BCE)
Demetrius of Apamea (late first century BC)
One of the earlier movers in this direction was the Greek historian and
political philosopher, Thucydides (460 BC-400 BC) of Athens who wrote the
famous incunabulum, History of the Peloponnesian War, that detailed the 5th
century BC war between the ancient enemies, Athens and Sparta. Thucydides
is called the father of scientific history whose writings were based on
verifiable data that did not include the effects of the Greek gods in the lives of
human beings and rejected theories based on apotropaism. He noted that
prayers were not effective in the treatment of medical disorders such as the
plague. The age of scientific discovery was now born though based on the
classic theory of humorism or the balance of the four classic humours (i.e.,
black bile, yellow bile, phlegm, and blood)---this Zeitgeist of ancient Greece
persisted well after the Renaissance period into the 16th century!
Modern Western medicine traces its roots to the famous Greek physician,
Hippocrates of Kos (460-370 BCE), who taught all future people of medicine
to emphasize the patient and powers of observation, and not the disease itself
or only rely on the leading of experience; the Hippocratic school speciously
linked health and disease to four bodily humors (2,15). Its Corpus
Hippocraticum was the beginning of modern Western medicine and is a link
between ancient medicine and medicine of the 21st century. Hippocrates
provided descriptions of the urine though not specifically with regard to
diabetes:
Bubbles appearing on the surface of the urine indicate disease of the

kidneys and a prolonged illness…..colorless urine is bad…..the
sudden appearance of blood in the urine indicates that a small renal
vessel has burst… Corpus Hippocraticum (2)
However, the Hippocrates dictum of observing the patient encouraged

others to make progress in the understanding of diabetes in the ancient world.
An example is Apollonius of Memphis (Apollonius Memphites; Apollonius
Stratonicus) who used the term “diabetes” (Greek διαβαίνειν [diabainein]—dia
[through] + betes [to go]; Middle English diabete from the Medieval Latin
diabetes--siphon). This Greek physician who was born in Egypt used this term
to describe the condition “to pass through” in 230 BC (BCE) that was felt to
be a kidney disease or form of “dropsy” and was treated with bloodletting and
dehydration (10, 16). Caelius Aurelianus was a Greco-Roman physician and
medical writer in the 5th century AD who wrote De morbis acutis et chronicus
(Concerning Acute and Chronic Diseases) (17, 18). Caelius Aurelianus credits
Apollonius of Memphis with using the term “diabetes.”
Apollonius of Memphis was part of the school of anatomy in Alexandria,
Egypt founded by Greek physicians Erasistratus (304 B -250 BC) and
Herophilus (335 BC-280 BC). Herophilus of Chalcedon was the first
anatomist and he described the anatomy of heart valves while Erasistratus
further distinguished between veins and arteries in which one had a pulse
(artery) and one (vein) did not based on vivisection work on the necks of pigs.
Herophilus noted that arteries were thicker than veins and Erasistratus
demonstrated the presence of semilunar valves. Based on the conclusions of
the earlier philosophers (such as Plato and Aristotle) that the human body had
no role after death, these Greek scientists at Alexandria began to dissect

humans both dead and alive (i.e., vivisection).
Their work allowed physicians to conclude that the heart was not the
center of sensations but was a pump to keep one alive. Erasistratus showed
how blood was stopped from retrograde flow in normal conditions and that
arteries were filled with air carrying “pneuma” or the “animal spirit (19).” He
concluded that the blood flowed via vacuums. The removal of the anatomical
location of the soul from the heart in ancient thought to the whole body and
beyond was a process of many millennia that was stimulated by the knowledge
of the heart as a pump and to explore complex human diseases (20, 21).
One of the students of Herophilus of Chalcedon was a Hellenistic
physiologist in the late first century BC, Demetrius of Apamea (Asia minor).
Demetrius of Apamea noted that increased urination (i.e., polyuria) was
similar to a method called “racking” in which wine was siphoned between pots
to remove dead yeast and encourage proper wine aging; he may have referred
to this with the term, diabetes, or siphon (“passing-through”) (22). Thus,
history often credits Demetrius of Apamea, a Hellenistic physiologist of the
Herophilean school with the term, diabetes, and reflects the ancient view of
polyuria as being caused by having ingested fluid pass through the person
without changes as going through a tube.
THE FIRST AND SECOND CENTURIES AD

Scholars attribute the initial clinical description of diabetes to the writings of
the first century Roman encyclopaedist, Aulus Cornelius Celsus (25 BC-50
AD) (10). Still surviving is his eight volume work, De medicina, which alerted
his contemporaries and those to follow about this mysterious condition (23-
25). One of these persons was Galen of Pergamos (Aelius Galenus or Claudius
Galenus--AD 129 – c.200/c.216), father of modern and experimental Western
medicine; he was a physician, surgeon, and philosopher (26-29). Galen was
the son of a wealthy architect (Aelius Nicon) who shared a love of knowledge
with his son and inspired him to become a foudroyant polymath for the ages.
Galen’s views on medicine and surgery were influential well into the
Renaissance period in Europe. Galen felt that the strange disorder causing
increased thirst and urination was a rare condition and named it diarrhea of the
urine (diarrhea urinosa); the excessive thirst led to the term dipsakon (ardent
thirst) (30). Galen did not agree with a theory contemporary with his times that
this condition was a stomach ailment, but located it in the kidneys.
Table 2. Key physicians from the first two centures in the history of
diabetes
Aulus Cornelius Celsus (25 BC-50 AD)

Galen of Pergamos (Aelius Galenus or Claudius Galenus – AD 129 –
c. 200/c. 216)
Rufus of Ephesus (80-150 AD)
Areteus of Capadocia (81-138 AD)
Chang Chung Ching (150-219 AD)
Rufus of Ephesus (80-150 AD) was a Greek physician and anatomist who
wrote about diseases of the kidneys; he also developed the term, pancreas (pan
for all and kreas for flesh) but did not connect diarrhea urinosa with the
pancreas which he concluded was an organ in its place to guard posterior
abdominal wall blood vessels (31, 32). This scholarly physician stressed the
importance of precise nomenclature in anatomy and this influenced many of
his colleagues as well as others who followed including Galen, Oribasius (see
below), and many others. Parts of his treatises were preserved by medieval
Arabic medical writers—particularly Rhazes (see below) (31).
Areteus of Capadocia (81-138 AD)
An important physician in the early history of diabetes is Arateus of

Cappadocia (81-138 AD) from the late Hellenistic period; Cappadocia is in the
eastern Asia Minor. He studied medicine in Alexandria, practiced in Rome,
and provided important writings based on the Hippocratic Corpus and his own
brilliant observations on many conditions including heart murmur, asthma,
epilepsy, pneumonia, psychiatric conditions, diabetes and others (33-37). His
eight volume book was written in Greek and was called “On the causes,
symptoms, and cure of acute and chronic diseases (37).”
Arateus the Cappadocian provided further comprehensive descriptions of
this condition and was the person who first distinguished between two types of
diabetes—now called diabetes mellitus and diabetes insipidus (10, 35, 38-40).
His description of this condition characterized by “melting away of flesh into
urine” has resounded down the ages (35, 39). Diabetes was attributed to effects
of cold and moisture reflecting the “pneumatic school” of thought (35, 41). His
views were lost in later years until the first Latin version of his works were
published in 1552 by Junius Paulus Crassus (Giunio Paolo Grassi) who died in
1575 (35, 42).
Diabetes is a remarkable affliction, not very frequent among

men…the patients never stop making water, but the flow is
incessant, as if from the opening of aqueducts,,,the nature of the
disease, then, is chronic,,,the patient is short-lived,….the death
speedy….life is disgusting and painful….Hence the disease appears
to me to have got the name diabetes as if from the Greek
word…which signifies a siphon, because the fluid does not remain in
the body, but uses the man’s body as a ladder, whereby to leave
it,,,,many parts of the flesh pass out along with the urine. (Arateus of
Cappadocia (35))
Chang Chung Ching (150-219 AD)
In 200 AD Chang Chung Ching (Zhang Zhongjing [150 AD-219AD)]), a Han

dynasty (206 BC-221 AD) physician called the Chinese Hippocrates,
described the symptoms of diabetes mellitus and noted that the patient’s urine
was so sweet that dogs licked it (43-45). This urinary sweetness has been
recorded in ancient India, China, and Greece and he was the first to test for
diabetes with sweet urine (44). Chang Chung Ching is the best known of the
ancient Chinese herbal physicians and wrote a book on herbal medication with
two parts: Shang Han Lun and Chin Kuei Yao Lueh (Jin Gui Yao Lue). Many
of these herbal remedies are still used in China and other parts of the world.
We have come to understand that we are who we are is also who we

were. (John Quincy Adams [1767-1848])
BYZANTINE WRITERS (4TH TO 9TH CENTURY AD)

Oribasius (325-403 AD) was a Greek physician living in the Oriental Roman
Empire (Byzantium) who was born in Pergamum of Mysia (Western Turkey)
and studied medicine at Alexandria under Zeno of Cyprus. He became the
personal physician to the Roman emperor, Julian the Apostate (Flavius
Claudius Iulianus Augustus: 331-363 AD) and was the leading physician as
well as important medical historical of his time (46). Oribasius established
Byzantine nephrology and utilizing magnifying lenses, confirmed Erasistratus’

concept of a connection (anastomosis which he called capillaries) between
arteries and veins (47).
Table 3. Byzantine physicians/writers (4th to 9th Centuries AD) in the

history of diabetes
Oribasius (325-403 AD)

Stephanus Alexandriensis (550 AD-622 AD)
Alexander Traillianus (Alexander of Tralles; 525-605 AD)
Aetius Amidenus (Aëtius of Amida---5th century AD)
Paul of Aegina: 625-690 AD)
Theophilus Protospatharius (7th century AD)
Stepanus of Athens (7th Century AD)
Leon of Pella (9th century AD)
He also identified circulation in the kidneys that including blood flow

through the aorta’s renal artery branch with venous return via the inferior vena
cava’s renal vein branch (47). Orbasius also provided descriptions of patients
with diabetes as did other Byzantine writers from the fourth to the ninth
century AD under the Graeco-Roman influence in medicine (see Table 3) (48).
His writings included works of Galen and other medical writers of the ancient
world that was found in 70 books with only 25 having survived in what has
been called “Collectiones medicae” (49-52). Many of the ancient medical
writers’ works would have been lost to modern times except for the
encyclopaedic contributions of Oribasius.
Observations were occurring in medicine in other countries as well. For
example, Sushruta and Charaka were two Indian physicians from the 5th
century who noted that persons with a thin physique developed symptoms of
diabetes earlier than heavier individuals; these older patients lived longer than
the thin ones with their symptoms---thus, recognizing two different types of
disease later called type I diabetes mellitus and type 2 (10, 53).
Stephanus Alexandriensis (550 AD-622 AD)
Another Byzantine writer who commented on symptoms of diabetes was

Stephanus Alexandriensis (550 AD-622 AD) who wrote about ancient
physicians (i.e., Hippocrates as well as Galen) and taught at the University of
Constantinople that had been founded by the Byzantine Emperor Theodosius

II (401-450 AD) in 425 AD (54-56). In addition to medicine Stephanus
Alexandriensis also wrote about astronomy, philosophy and alchemy
(alchemical work).
Alexander Traillianus (525-605 AD)
Alexander Traillianus (Alexander of Tralles; 525-605 AD) was a Greek

physician born in Tralles in Lyia (now Turkey); his father (Stephen) was a
physician and he had a well-known mathematician brother (Anthemios) who
was the architect of the church Hagia Sophia in Constantinople (57-59).
Alexander practice in Rome, Italy and wrote a number of treatises on medicine
with the main one being the Therapeutics (Twelve Books on Medicine) while
others included On Fevers, On Intestinal Worms, and others (57-61).
I like to use every possible means in treating my patients.

(Alexander Traillianus) (57)
Alexander Traillianus wrote about symptoms of diabetes and epilepsy

while covering issues of craniofacial surgery as well (57, 62, 63). Persons with
polyuria, polydipsia, and weight loss were felt to have a kidney disease—
consistent with ideas of other Byzantine medical writers (48, 64). Some of his
medical writing was translated into Latin around 700 AD and later to Arabic
and Hebrew (57). A Greek text of some of his work was printed in Paris,
France in 1548 and in Venice in 1570. Such translations allowed seminal
Western concepts to be passed on to future generations despite the Dark Ages
that began with the Fall of Rome in 476 AD.
I have assembled from my rich experience of treatments of various

diseases…although I am an old man and no longer able to exert
myself greatly, I…wrote this book, after having collected my
experiences from my many contacts with human diseases. And I
know this will please many people who are not envious to look at the
good reasoning of my medical theories and at the same time the
brevity and clarity of the exposition. (Alexander of Trailles) (57)
Aetius Amidenus
An early to mid-6th century Byzantine physician who continued the Byzantine

reflection of diabetes and kidney disease was Aetius Amidenus (Atius of
Amida), though some scholars place him in the 5th century (48,64,65). He was
a Greek born in Amida (now Diyarbakir, Turkey) and as was noted with many
physicians of his era, studied medicine in Alexandria (66). Aetius Amidenus
wrote on a variety of medical and surgical topics that included apoplexy,
pelvic abscesses, pain relief (using opium), acne (one of earliest descriptions),
ophthalmology, cranio-maxillofacial surgery, and others (65,67-75).
Paulus Aegineta (625-690 AD)
Paulus Aegineta (Paul of Aegina: 625-690 AD) was a 7th century Byzantine
physician and writer who also wrote about symptoms of diabetes (48, 64). He
concluded that diabetes was due to a disease of the kidneys and suggested a
variety of treatments including blood removal (venesection), dark wine,
myrtle, dates, juice from knotgrass, and lettuce. He was a Greek born on the
island of Aegina, practiced surgery as well as gynecology in Alexandria and
was a traveling physician whose best known book was called Epitome
medicae libri septem (medical compendium in seven books), which was
largely based on the writings of Galen as well as Oribasius and provided a
summary of Western medicine at that time (48, 64, 76, 77). He was highly
regarded by the Arab physicians of his day and into future centuries. His work
set the stage for later development in surgery (including plastic surgery) with
the sixth book that was devoted to surgery (78-81).
Li-Hsuan and Chen Chuan
During the same 7th century a Chinese physician, Li-Hsuan, also described
diabetes noting that the patient with this condition had a tendency to develop
skin infections (boils) and pneumonia; treatment included the avoidance of
alcohol, starch and sex (10, 82). A Chinese colleague of Li-Hsuan, Chen
Chuan also noted the sweetness of urine and named this disease Hsiao kho
ping (for strong thirst, polydipsia, and polyuria with sweet tasting urine (46).
Such urinary sweetness was not appreciated in the West until the observations
of Oxford physician Thomas Willis (1621-1675) in 1674, as discussed later in
this article (10, 39, 83). Li-Hsuan also commented on the sweetness of urine in
these patents (84):
This disease is due to weakness of the renal and urogenital system. In

such cases the urine is always sweet. Many physicians do not
recognize this symptom. The cereal foods of the farmers are the
precursors of sweetness…the methods of making cakes and
sweetmeats…mean that they all very soon turn to sweetness…It is
the nature of the saline quality to be excreted. But since the renal and
urogenital system at the reins [i.e., kidneys] is weak, it cannot distill
the nutrient essentials, so that all is excreted as urine. Therefore the
sweetness in the urine comes forth, and the latter does not acquire its
normal color.
Theophilus Protospatharius
Another 7th century Byzantine physician and writer, though less known than
Paul of Aegina, was Byzantine writer Theophilus Protospatharius who also
commented on the symptoms of diabetes (48, 64). Byzantine management of
his patients with diabetes included nutritional counseling, bloodletting, use of
various herbs, herbal poultices for skin infections, and avoidance of diuretics
(48). Theophilus Protospatharius is often identified as the Byzantine founder
of urology with a written compiling of known information that was called De
Urinis (85-88).
Contemporaries of Theophilus Protospatharius and Paulus Aegineta
include Stepanus of Athens and Leon of Pella (9th century AD) who were
Byzantine writers that also reflected on these difficult patients with polyuria,
polydipsia, and weight loss before death (48, 66, 87, 89-94). Rhazea (865-925
AD) was an Arab writer who translated the Sanskrit into Arabic and discussed
patients with symptoms reflective of diabetes (see below) (95).
Stephanus’ aim is to imbue his pupils with proper method and he

contrasts the Hippocratic physician often with the ‘idiot’ physician,
who through ignorance of the proper method commits error after
error and who is led astray by a simplistic reliance on symptoms. But
there are limits to a doctor’s knowledge; only…a higher power
knows everything or disposes health to every patient, and the
workings of the heavens are not always revealed to the physician.
Sometimes the responsibility for a patient’s failure to recover can be
properly laid at the door of his doctor, but at other times chance and
the vagaries of the patient himself must take the blame (90)
GOLDEN AGES OF ISLAMIC ERA: 9TH TO 12TH CENTURIES

The Fall of Rome in 476 AD led to a loss of medical knowledge in Europe
though medicine was kept alive and advanced by brilliant Persian and Arab
physicians in the 9th century and beyond (see Table 1) (47,96,97). As the
Western world was hurled into the Dark Ages (476 BCE to 1000 BCE), they
continued to study cardiology, nephrology, and other aspects of human health
and disease (98-101). Persian-born physicians include Doctors Taberi, Magusi,
and Razi (102).
Table 4. Arab/Persian Clinicians of the Golden Age of the Islamic Era

(Partial List)
Ali at-Taberi (838-870 AD)

Ar-Razi (Rhazes:865-925 AD)
Ali ibn al-Abbas al-Magusi (Haly: died around 990 AD)
ibn al-Qasim al-Zahrawi (Abulcasis: 936-1013 AD)
ibn al-Haitam (Alhazen: 965-1040 AD)
ibn Sina (Avicenna: 980-1037 AD)
ibn Abi al-Ala Zuhr (Avenzor: 1091-1131 AD)
ibn Rushd (Averroes: 1126-1198 AD)
ibn al-Baitar (1197-1248 AD)
ibn al-Nafis (1213-1288 AD)
Rhazes
Rhazes (Abu Bakr Muhammad ibn Zakariyya al-Razi; 865-925), a musician

turned physician, perhaps is the best known of the Persian physicians who is
acclaimed as a father of pediatrics. Complications of diabetes were recognized
by physicians in the 8th century and beyond (as Rhazes) that included vision
damage, furuncles, and ulceration (46, 98).
Avicenna
Often acclaimed as the most influential Islamic physician/philosopher was Ibn

Sina (Avicenna; Abou Ali al-Housayn ibn-Abdoullah ibn-Sina; 980-1037 AD)
who wrote a medical encyclopedia called Cannon of Medicine (Qanun fil-tibb)
and a work on cardiac drugs (98-100,103-106). His encyclopedic work, The
Book of Healing, became well-known for eons (100,103). Avicenna was born
in Bukhara (present-day Uzbekistan) and died in Hamadan; he was a prolific
polymath in various fields including medicine, mathematics, physics, Islamic
theology, astronomy, geology, and poetry. His father was a respected scholar
and installed this love of scholarship in his son.
Avicenna refined Galen’s theory of pulses and provided details on a
number of drugs that effected the heart. He made mention of pericardial
disease and prevention of cardiac diseases including the importance of a
“healthy” diet for those with heart disease. In his book on drugs for heart
disease there is mention of various drug treatments that came from mineral,
vegetable, and animal sources (103, 104). He was the first to use a drug that
eventually (i.e., modern times) was classified as a calcium channel drug (105).
He described what was later called the Willis circle, capillary circulation,
cardiac tamponade, hypertension, palpitation, stroke, hypersensitivity and its
link with vasovagal syncope, and the connections of emotion with cardiac
action (98,104).
He provided descriptions of diabetes as well as its complications such as
sexual dysfunction (i.e., impotence), mental illness, furuncles, and gangrene
(10, 46). Avicenna called this condition a water wheel (aldulab) as well as
kidney diarrhea (zalkh el kuliah); he described diabetes with body wasting that
was different from other causes of excess urination (106).
He treated this disorder with substances inducing vomiting and sweating,
exercise (such as horseback riding), baths (lukewarm), “fragrant” wine, and
avoidance of agents causing diuresis (107). The concept of exercise was to
develop heat in the body to help with removal of bodily wastes and enhance
digestion to prevent accumulation of toxins (109). Horseback riding was
theorized to develop friction and improve polyuria. Some physicians in the
13th century treated diabetes with purgatives, astringents, and refrigerant
remedies (107). Avicenna’s work was influential for the next several centuries
and even to the 21st century (108, 109-119).
In 1914 the highly-respected Sir William Osler write about the need to
restore the tomb of Avicenna (111). Avicenna has been linked in medical
writing to the description of a physician found in “Canterbury tales” by
Geoffrey Chaucer (1340-1400) as translated by the English literary scholar

Nevill Josiah Aylmer Coghill (1852-1879):
A Doctor too emerged as we proceeded;

No one alive could talk as well as he did
On points of medicine and of surgery,
For, being grounded in astronomy,
He watched his patient’s favourable star….”
Ibn al-Nafis (1213-1288)
Ibn al-Nafis was an Arab physician who challenged the Galenic theory of
circulation and did not agree with the belief in a porous interventricular
septum (120,121). Ibn al-Nafis described the pulmonary circulation and wrote
about pores between the pulmonary artery and vein that four centuries later
were called pulmonary capillaries by Marcello Malpighi (120-123). Some
have incorrectly noted that the 16th century European scientists discovered the
pulmonary circulation but this distinction belongs to Ibn al-Nafis in the minds
of some scholars (123-125). He was a famous ophthalmologist who also
described the coronary circulation (124). Contributions of Inn al-Nafis
sometimes are confused in the English speaking world since his and other
works of physicians in the Islamic Golden Age of Medicine were published in
Persian and/or Arabic.
If I don’t know that my work will not last up to ten thousand years
after me, I would not write them. Ibn al-Nafis (123)
Moses Maimonides (1138-1204)
A physician should begin with simple treatments trying to cure by

diet before he administers drugs….Like unto a murderer is the
physician who refuses to tender his assistance in time of necessary or
who practices without due study of the ailment which he is treating.
(Moses Maimonides, Commentary on the Mishnah) (126)
The great Jewish scholar, Moses Maimonides (1138-1204) was a

prominent physician (as well as rabbi, philosopher, astronomer) born in
Cordova, Spain as the son of a noted Jewish rabbi (126-135). He lived in Spain
as well as North Africa and eventually became the court physician to the
sultan Saladin in Cairo, Egypt. He was called the Rambam based on his name
of Rabbi Moses Ben Maimon; in the Arabic literature his name was Abu
‘Imran Musa ben Maimun ibn’ Abd Allah (126). He was a highly regarded
scholar and physician as noted by this Arabic poem by Al-Sa’id ibn Surat al-
Mulk:
Galen’s art healed only the body,

But Abu “Imran’s (Maimonides), the body and soul.
With his wisdom he could heal all the sicknesses of ignorance.
If the moon would submit to his art,
He would deliver her of her spots at the time of full moon,
Cure her of her periodic defects,
And at the time of her conjunction save her from her waning (126)
Moses Maimonides provided much information on medicine such as

nephrology that included expanding the understanding of urinalysis. For
example, he gave descriptions of red urine (later identified by the eminent 19th
century English physician, Richard Bright MD (1789-1858) as
glomerulonephritis) and black urine (later identified as a sign of malaria) (98).
You must accept the truth from whatever source it comes

Maimonides
Moses Maimonides detailed various aspects of diabetes in patients

including symptoms of acidosis (46,83). He provided many aphorisms about
medicine that have sounded throughout the ages (133). As noted by Rodin,
many have noted: “From Moses the lawgiver until Moses ben Maimon, there
was none like Moses!” (126).
The more perfect a person becomes in one of the sciences, the more
cautious he grows, developing doubts, questions, and problems that
are only partially solved; whereas one deficient in science will find it
“easier to understand every difficulty. Moses Maimonides (1135-
1204) (131)
RENAISSANCE ERA AND THE PANCREAS

(1300/1400-1600 AD)
Abdel Latif el Baghdadi (Abd al-Latif al-Baghdadi; Muwaffaq al-Din
Muhammad; Abd al-Latif ibn Yusuf al-Baghdadi; 1162-1231 AD) was an
Arabic physician and historian who was also a prolific writer; he wrote a
disquisition on diabetes that is still in existence (106). Diabetes was seen as a
kidney disease and treatment included ways to ameliorate kidney strain with
purgatives; other therapeutic measures included astringents and refrigerant
modalities (107).
Table 5. Renaissance era physicians and the pancreas (1300/1400-1600)

in the history of diabetes
Abdel Latif el Baghdadi (Abd al-Latif al-Baghdadi; Muwaffaq al-Din

Muhammad) 1162-1231 AD)
Paracelsus (Theophrastus Bombastus von Hohenheim: 1493-1541)
Gerolamo (or Girolamo or Geronimo) Cardano (French: Jérôme
Cardan; Latin: Hieronymus Cardanus) (1501-1576)
Parcelsus (1494-1541)
Paracelsus (Theophrastus Bombastus von Hohenheim: 1493-1541), a famous

and colorful physician from Switzerland, wrote about proteinuria, hematuria,
gout, and edema; his work was the forerunner of using specific gravity in
urinalysis (2, 136).
Paracelsus (1494-1541) noted that a white residue was seen after the urine
of a patient with diabetes evaporated; he thought this residue was salt and felt
the etiology of diabetes was salt deposited in the kidneys (10, 136). History
has also negatively identified Paracelsus as publically burning the treatises of
Galen and Avicenna in 1527 in Basel, Switzerland that was part of the
complex religious fervor of the 16th century Reformation Period in Europe.
Gerolamo Cardano (1501-1576)
Gerolamo (or Girolamo or Geronimo) Cardano (French: Jérôme Cardan;

Latin: Hieronymus Cardanus) (1501-1576) was an Italian physician and
mathematician who gained considerable fame for writing the first Latin work
on algebra called Ars Magna (136). In his work as a physician, this brilliant
Italian polyglot also looked at patients with diabetes, noted great differences as
he measured their fluid intake/output, and concluded that these persons lose
more water than they consume for reasons that eluded him as well as others in
his century and beyond (137-141). He also became one of the infamous
gamblers of the Renaissance (Scarani) (142).
Table 6. 17th and 18th century giants in the history of diabetes
Morgagni (Giovanni Battista Morgagni: 1682-1771)

Thomas Sydenham (1624-1689)
Thomas Willis (1621-1675)
Johann Conrada Brunner (1653-1727)
William Cullen MD (1710-1790)
Matthew Dobson (1732-1784)
John Rollo (died 1809)
PROGRESS IN THE 17TH AND 18TH CENTURIES

Table 6 lists physicians who were 17th and 18th century giants in diabetes.
This includes the founder of pathological anatomy, Morgagni (Giovanni
Battista Morgagni: 1682-1771), who described various renal disorders via
autopsy (98,143). Diabetes in this era was felt to be a kidney diseases and
Morgagni felt that the sweet taste of diabetic’s urine was due to the fact that
water and nutrients went unchanged into the urine (83). Though he started out
with little fanfare, his acceptance by the great English philosopher, John
Locke, and others led to his great acceptance by his peers (143).
Thomas Sydenham (1624-1689)
Thomas Sydenham was one of the most influential Western physicians of the
19th century who is often called the English Hippocrates (144-148). His fame
was stimulated by his acceptance by the great English philosopher and
physician John Locke (1632-1704) that led to widespread acclaim by his peers
as his career unfolded (146). Sydenham theorized that diabetes was a systemic
illness due to incomplete chyle digestion which also causes polyuria seen in
these patients (147).
Thomas Willis was a British (Oxford) physician and anatomist who was one of
the greatest physicians of his time---he identified the circle of Willis, Willis’s
nerve and provided many other anatomical insights as the founder of modern
neurology (46, 149-151). This giant of medicine separated diabetes in 1670
from other causes of polyuria by the sweet taste of the diabetic patient’s urine
and concluded the sweetness first was seen in the blood. He added the word
“mellitus” for honey sweet and utilized this to differentiate diabetes mellitus
from other conditions causing polyuria (46, 83, 152-154). Willis concluded
that the sweetness was due to salts and acids (148, 155). He described diabetic
neuropathy and concluded diabetes was a blood disorder though many of his
peers viewed this condition as a kidney disorder; astringents were often used
in its treatment (46, 107). Many clinicians in his day believed that diabetes
was due to humoral changes and too much drinking of alcohol (107).
Willis’ description of the autonomic nervous system provided him with
insights in the contribution of emotion in disease. Thomas Willis insightfully
speculated on the importance of emotion in diabetes in 1678; in his book,
Pharmaceutice Rationalis, he theorized that prolonged sorrow (“sadness, long
grief”) was etiologically linked to diabetes along with strong wine (beer and
cider) and nervous system juice (148, 156). His reflections led to future
clinicians and researchers seeking to understand the impact of psychological
issues in human disease, such as diabetes mellitus (157).
Johann Conrada Brunner (1653-1727)
Johann Conrada Brunner was a Swiss physician and anatomist who was a
leading researcher of his era on the pancreas and duodenum (158). He
performed experiments in dogs that included a subtotal pancreatectomy with
reversible traumatic damage to the remaining pancreatic tissue (159, 160).
After the canine surgery, Brunner noted in 1682: “….the animal made water
very frequently and he was very thirsty, drinking largely of water in proportion
to the discharge of urine (160).” Despite his successful surgery on 8 dogs that
led to canine diabetes and his description of the induced symptoms (i.e.,
polydipsia, polyuria, polyphagia), Brunner did not associate this with diabetes
and thus, the link of the pancreas with diabetes waited for conclusions of
research in the late 19th century as discussed later (159-161). This is an
example of some “near-misses” in understanding diabetes mellitus seen
throughout medical history.
Matthew Dobson (1732-1784)
Matthew Dobson was a British (Liverpool) physiologist and physician who

revealed in his 1776 work, Experiments and Observations on the urine in
diabetics, that evaporation of urine of diabetic patients produced a residue that
was a crystalline material with the taste of brown sugar (46, 162, 163). He
noted that this material “was granulated and broke easily between the fingers;
it smelled sweet like brown sugar, neither could it be distinguished from sugar,
except that the sweetness left a slight sense of coolness on the palate” (162).
This process involved boiling the urine to dryness and he noted that the
urinary sugar concentration was increased (163). He concluded that the urinary
sugar first appeared in the blood and then in the urine; thus, he identified
hyperglycemia and suggested that diabetes was a systemic disease and not a
kidney disease that require special diets for treatment (10, 83, 136, 163, 164).
Matthew Dobson noted that: “….that this substance had previously existed in
the serum rather than being formed in the kidneys…..“this idea of the disease
explains its emaciating effects from so large a proportion of the alimentary
matter being drawn off by the kidneys, before it is perfectly assimilated and
applied to the purpose of nutrition (162).”
Before Matthew Dobson presented his results on a saccharine material in
the urine of diabetic patients in 1776, he consulted with William Cullen, MD
(1710-1790) who was a Scottish physician and chemist at the Edinburgh
Medical School. Professor Cullen was one of the most famous medical
scholars of his day who was the first to separate out diabetes mellitus and
diabetes insipidus (164, 165). Thousands of patients consulted with Dr. Cullen
in Edinburgh including the famous economist, Adam Smith (1723-1790)
(167). Cullen noted a type of diabetes with urine having “the smell, color, and
flavor of honey” versus diabetes with “limpid but not sweet urine” (167).
Cullen advised Dobson: “You have done something in putting it beyond all
doubt by your experiments... I have only to add that I wish you would examine
both by taste and evaporation what might be called the Urina Potus or that
copius limpid urine which runs in some people after their drinking largely of
water or watery liquors” (164, 167).
Shortly after Matthew Dobson’s work, Thomas Cawley noted that patients
with pancreatic trauma developed diabetes and thus proposed a cause and
effect in 1788; an example of injury to the pancreas was from stones as seen
during an autopsy of a person with diabetes (10, 168). This observation (“near-
miss”) was neither appreciated nor understood until late into the next century!
Matthew Baillie (1761-1823)
Matthew Baillie (1761-1823) was a well-known Scottish physician and

pathologist who came from a well-educated family and is noted by medical
history for identifying situs inversus and transposition of the great arteries
(169-172). The trio of Matthew Baille and is two famous uncles (William and
John Hunger) have been called the founders of Great Britian’s medicine.
Matthew Baille wrote the first classified book on pathology as its own
topic and, as a pathologist, wrote:”…upon examination of the kidneys…it
seemed probable that diabetes depends, in a considerable degree, upon a
deranged action of the kidneys, by which the blood there is disposed to new
combinations” the effect of which is the production of ‘a saccharine matter’….
the chyle may be so imperfectly formed, as to make the blood be more readily
changed into a saccharine matter, by the action of the kidneys” (172).
John Rollo (died 1809)
John Rollo was a Scottish military surgeon who became a consultant to

patients with diabetes. In 1789 He used the term “mellitus” (Greek for honey:
μέλι [meli]) to differentiate it from polyuria with no sugar and no taste
(“insipidus”) and felt that diabetes mellitus was a stomach disorder that
developed from “vegetable substances containing saccharine matter” and this
was promptly removed as a foreign body by the kidneys (10, 149, 173, 174).
He utilized a urine glucose test developed by Matthew Dobson.
John Rollo wrote about increased sugar in the blood, an acetone odor on
the breath of some diabetic patients and associated cataracts with diabetes
(107). He recommended a meat diet (protein-rich, low carbohydrate) for
management of diabetes mellitus that was used into the early 20th century
(173, 174). He described his diet as high in “animal food” that was fat with
meat (“plain blood puddings” with “rancid meat”) as well as low in “vegetable
matter (grains and breads)” (173, 174). Other therapeutic regimens included
antimony, digitalis, and opium (107).
Table 7. 19th century giants in the history of diabetes
John Elliotson (1791-1868)

Michel Eugène Chevreuil (1786-1889)
Hermann von Fehling (1812-1885)
Claude Bernard (1813-1878)
William Prout (1785-1850)
Richard Bright (1789-1858)
Apollinaire Bouchardat (1806-1886)
Étienne Lancereaux (1829-1910)
Friedrich Theodor von Frerichs (1819-1885)
Adolf Kussmaul (1822-1902 AD)
Henry Noyes (1832-1900)
Edward Nettelship (1845-1913)
Bernard Naunyn (1840-1914)
Paul Langerhans (1847-1888)
Edouard Laguesse (1861-1927 AD)
Oscar Minkowski (1858-1931)
Joseph Freiherr von Mering (1849-1908)
PROGRESS IN THE 19TH CENTURY

A number of individuals contributed to the explosion of knowledge about
diabetes in the 19th century (see Table 7). This includes Michel Eugène
Chevreuil (1786-1889)—a famous and long-living French chemist with much
fame for his work with fatty acids, creatine, and other scientific work (175-
177). In 1815 he published his work that identified the sweet substance of
Matthew Dobson’s studies as being the same as grape sugar (i.e., glucose) (10,
149, 176). In 1849 German chemist Hermann von Fehling (1812-1885)
developed a quantitative test (Fehling’s solution) for glycosuria and the 19th
century continued with an explosion of research on diabetes (10, 175, 176).
John Elliotson was a Scottish professor of medicine who was one of the early
physicians to use a stethoscope. In his observation of patients with diabetes
mellitus, which he concluded was a renal disorder, he noted possible etiologic
factors that included “grief, chills, and excessive use of venery (149, 178).” He
was an advocate for the use of phrenology and mesmerism in the treatment of
human disease (179-181).
A scientist whose works were translated into many languages and who is
acclaimed in his native country and beyond is Claude Bernard, the most
distinguished French physiologist of the 19th century (and beyond!) (98, 182).
Though born to a poor family in the Beaujolais region of France and starting
out to write theatre plays (la Rose du Rhône and Arthur de Bretagne), he rose
to become chair of experimental physiology at the College de France
(succeeding his mentor, François Magendie [1783-1855]) (46). Though
honored by the Emperor Napoleon, Bernard was abandoned by his family over
his experiments involving vivisection (46).
He accomplished many experiments in physiology that set the stage for
sound scientific methodology and is acclaimed as the father of modern
physiology and called by the eminent French microbiologist and chemist Louis
Pasteur (1822-1895) as “physiology itself” (10, 98, 183). Bernard was willing
to change his views based on science as illustrated by his initial idea that
diabetes was a “nervous affection of the lungs” and later linking this disorder
to the liver (46). He emphasized blind experiments to ensure scientific
objectivity and he performed now classic experiments on the pancreas’
function (i.e., discovered the lipolytic function of the exocrine pancreas) as
well as the glycogenic function of the liver (with improvement in knowledge
of diabetes mellitus) (98, 149, 155, 182-190).
Claude Bernard was the first to describe homeostasis or constancy of the
internal environment (le milieu intèrieur) and the vasomotor system. This
allowed future researchers to apply these principles to renal physiology. For
example, research in the first half of the 20th century lead to the definition of
electrolyte content of le milieu intérieur—the extracellular, intracellular, and
interstitial fluid compartments (98, 191-193).
Claude Bernard identified his “starch-like” material (glycogen) that was a

glucose precursor and alerted the medical community to the important role of
the liver in its production and in diabetes (164). It was a major discovery that
the sugar found in the diabetic patient’s urine was the stored in the liver and
Bernard concluded that glycogenolysis led to diabetes; he concluded that
sympathetic influence was important in this process as he was the discover of
vasomotor innervation (46, 107, 149). In his work on dogs he was able to
decrease their pancreatic masses but since they did not develop diabetes, he
did not associate diabetes with a pancreatic disorder (194). However, his
technique to ligate pancreatic ducts was utilized later by researchers to search
for the cause of diabetes (10).
Claude Bernard wrote about the development of temporary glycosuria in
animals after their fourth ventricle were punctured in a procedure he called
“piqûre diabétique;” this transient state set the stage for the influence of the
central nervous system and emotion on diabetes that was later identified (46,
155).
The living organism does not really exist in the milieu exterieur (the
atmosphere if it breathes, salt or fresh water if that is its element) but
in the liquid milieu interieur formed by circulating organic liquid,
which surrounds and bathes all tissue elements,…the stability of the
milieu interieur is the primary condition for freedom and
independence of existence; the mechanism which allows this is that
which ensures in the milieu interieur the maintenance of all
conditions necessary to the life of the elements.”
Claude Bernard (190)
William Prout (1785-1850)
William Prout (1785-1850) was an acclaimed English physician

(endocrinologist) and chemist known for the Prout’s hypothesis regarding the
internal arrangement of the atom and identified hydrochloric acid as the acid
of gastric secretion (195). He concluded that diabetes was a gastric disorder
(196). He is known in the medical field for being the first person to identify
diabetic coma (10,195-199). He hypothesized that etiologic factors in diabetes
included “drinking of cold fluids when heated,” as well as “mental anxiety and
distress” (195-202).
Richard Bright (1789-1858)
The 19th and 20th century brought forth brilliant scholars, who, standing on the
shoulders of previous giants, advanced the field of clinical nephrology to its
current level. Perhaps the beginning of modern nephrology can be traced to the
Richard Bright (1789-1858) who has been called the “greatest physician of his
day and one of five or six great physicians of all time” (98, 202). He was one
of the famous triumvirate of London’s Guy’s Hospital in the Victorian era—
along with Thomas Addison (1793-1860) and Thomas Hodgkin (1798-1866).
Each of these three medical giants had diseases named after them.
This father of modern renal diseases noted that the finding of albuminuria
with edema meant the patient had renal disease. The first clinical mention of
proteinuria was in 1697 but it was Richard Bright who, standing on the
shoulders of giants, moved this observation further in 1827(203,204). He
established the first medical research unit at his hospital and provided a series
of insightful descriptions of acute nephritis, nephrotic syndrome, uremia, small
and enlarged kidneys, and a link between renal disease and enlarged ventricles
of the heart (98, 205-210).
Acute and chronic nephritis was called Bright’s disease long after his
death that may have been caused by the very disease he described so well.
Richard Bright’s studies were often post-mortem on patients with advanced
renal disease and his written observations are preserved in the Gordon
Museum at London’s Guy’s Hospital (209). Analysis by late 20th century
nephrologists revealed two had mesangiocapillary (membranoproliferative)
glomerulonephritis; one had a five-year clinical history and died from chronic
renal failure with uremia while the other died after 3 to 4 months with severe
nephrotic syndrome (209). In his post-mortem observations of patients he
concluded that diabetes was not due to renal disease but that the kidneys were
affected by this condition—a concept affirmed in the 20th century (202).
Apollinaire Bouchardat (1806-1886)
Apollinaire Bouchardartis was a renowned French physician, biochemist,

pharmacist, and hygienist. As a food crisis unfolded and many persons were
starving during the Franco-Prussian war of 1870-1871, he noted that starvation
reduced the glycosuria and other features of diabetes in patients with diabetes
mellitus (107). His book, De la Glycosurie ou diabète sucré, son traitement
hygénigue, is the first text on diabetes and was published in 1883; his advice
to his diabetic patients was “mangez le moins possible” (“eat as little as

possible”) (211).
Bouchardartis is considered the founder of modern diabetology for his
work on diet control of diabetes (with regular fasting and the Bouchardat’s
treatment with a low-carbohydrate meals), identifying the need for patient
education as well as patient self-monitoring, development of a test for
glycosuria used by the patient, stressing the importance of exercise, and
correctly concluding that the etiology of diabetes was found in the pancreas
(211-216).
Étienne Lancereaux (1829-1910)
Étienne Lancereaux (1829-1910) was a remarkable French physician who

identified that diabetes was a condition of the pancreas and he used the term
pancreatic diabetes (diabète pancréatique) after comparing the histology of
pancreatic islet cells in those with and without diabetes (194, 217-219). He
divided diabetes into two types: diabetes maigre (lean diabetes) and diabetes
gras (fat diabetes) (217-219). The eponym Lancereaux's diabetes refers to
diabetes mellitus with severe cachexia or emanciation. Not only was his
pancreatic association of diabetes mellitus proven correct by later researchers
(as considered later), but one of his students, Nicolae Paulescu (1869-1931)
has been credited as one of the researchers who discovered insulin (220, 221).
Friedrich Theodor von Frerichs (1819-1885)
A large number of researchers and physicians attempted to further the

knowledge of diabetes. A classic example of this movement was Friedrich
Theodor von Frerichs (1819-1885); he was a German pathologist who
developed a clinic for experimental medicine and wrote a treatise on diabetes
mellitus (Über den Diabetes) in 1884 (202). In this work he noted that 20% of
persons with diabetes had severe pathological pancreatic abnormalities (202).
He had a number of students and assistants who made contributions to diabetes
including Bernhard Naunyn (1840-1914, Paul Langerhans (1847-1888), and
Paul Ehrlich (1854-1915). He provided a classic work on Bright’s disease and
provided information in hepatology, neurology (multiple sclerosis), and other
fields (222-226). Slowly, but surely, diabetes was revealing its secrets and
perplexities as the persistence of human curiosity and inquiry continued from

century to century and from one medical giant to another.
Adolf Kussmaul (1822-1902)
Adolf Kussmaul was a German physician and teacher who provided a number
of contributions to clinical medicine in his illustrious career that included
neurology (i.e., progressive bulbar paralysis), endocrinology, cardiology
(pulsus paradoxus), psychiatry, gastroenterology (developed gastric lavage;
experimented with esophagoscopy as well as gastroscopy), and rheumatology
(i.e., polyarteritis nodosa) (227-231). He is internationally known in diabetes
for his classic description of typical air hunger (acidotic breathing) of diabetic
ketoacidosis (232, 233). The puzzle of diabetes was being methodically
assembled in this century. For example, Wilhelm Petters had identified in
1857 that acetone was found in the urine of those with diabetes (10). Adolf
Kussmaul theorized that acetonemia caused the ketoacidotic coma in diabetes
(10).
Since I have seen three diabetics in the course of a year die, with
remarkably similar symptoms in which there was a peculiar
comatose condition preceded and accompanied by dyspnoea, I
believe that it is not merely chance, but am of the opinion that it has
to do with a form of death in diabetes which is rarely observed and
bears the closest relationship to the disturbances in the metabolism in
diabetes. (Adolf Kussmaul) (232)
Henry Noyes (1832-1900)
Henry Noyes was an American ophthalmologist who wrote two classic texts
on eye diseases: A treatice on diseases of the eye (New York, 1881) and A
textbook of diseases of the eye (New York, 1890, 2nd Edition: 1894). He
invented a number of eye instruments still used today----such as the Noyes
micro scissors, the Noyes iris scissors, and the Noyes fixation forcepts. Using
the newly developed opthalmoscope, Henry Noyes wrote a paper in 1869 that
noted patients with glycosuria develop retinitis and it was an early
identification of diabetic retinopathy (10, 202, 234, 235). Finally, the
Americans were chasing after the perplexities of diabetes!
A renowned British ophthalmologist, Edward Nettelship (1845-1913)

confirmed this link with a seminar paper in 1872 showing histopathological
evidence of “cystoid degeneration of the macula” in persons with diabetes; in
1877 he published a treatise on retinal pathology in these patients (235-239).
Slowly but surely the pathology and complications of diabetes mellitus were
being unravealed in the 19th century. Only some of these investigators are
discussed in this book’s edition, but addition heroes in this endeavor will be
covered in future editions.
The esteem and regard which Nettleship was universally held by his
pupils and colleagues found definite expression at the date of his
retirement from practice. The Fund then collected was, in accordance
with his own desire, devoted to the establishment of a metal ‘for the
encouragement of scientific ophthalmic work.’ This Prize is in the
custody of the Opthalmological Society and is awarded triennially. In
1909, to the great satisfaction of all, it was awarded to Nettleship
himself, in recognition of his researches upon the heredity of diseases
of the eye. (Lancet, Nov 8, 1913) (238)
Bernard Naunyn was a German pathologist who was born as well as trained in
Berlin and, as noted, was a junior official to the imminent German pathologist,
Friedrich Theodor von Frerichs (1819-1885) (222-226). He developed a clinic
for persons with diabetes and wrote a book on this disorder in 1898 (240).
Naunyn used the term “acidosis” in persons with diabetes mellitus and
recommended the use of bicarbonate to manage this issue (10, 202, 240). He
was part of the German Medical School of Strasbourg and worked with such
luminaries as Oscar Minkowski and Joseph Freiherr von Mering to induce
diabetes in dogs via pancreatectomy (155, 241). He also contributed to the link
of psychological factors and diabetes by identifying a case of diabetes mellitus
developing under the catastrophic circumstances of a city bombing (157). His
work on drug metabolism, pharmacology, and cholelithiasis was also
acclaimed (242).
Paul Langerhans (1847-1888)
Paul Langerhans was a German pathologist who studied under the famous
father of pathology and social medicine, Rudolf Virchow (1821-1902) (243-
251). As a medical student Paul Langerhans provided novel descriptions of
tiny clusters of cells (“zellhaufen”) from the pancreas not emptied by ducts of
the pancreas (247). This finding was presented in his doctoral dissertation at
the University of Berlin in 1869 that identified 9 types of cells in the pancreas
based on his studies of the rabbit (249-251). He noted one set of pancreatic
cells involved with normal pancreatic secretion and another set with unknown
function (s). In our book “Chronic illness and disability: The pediatric
pancreas,” we present results of another doctoral dissertation on diabetes
mellitus.
Description of what was later called Islets of Langerhans by

PaulLangerhans: “…kleine Zellen von meist ganz homogenem Inhalt
und polygonaler mit rundern Kern ohne Kernkörpechen meist zu
zweien oder zu kleinen Gruppen beisammen liegende.” (“….small
cells of almost perfect homogeneous content and of a polygonal
form, with round nuclei without nucleoli, mostly lying together in
pairs or small groups. (250)
Langerhans did not know the significance of these clusters though he

speculated they may be lymph node or nerve tissue. He died in 1888 age at age
41 years before knowing their connection to insulin production and that they
would be later be called islets of Langerhans by Edouard Laguesse (see below)
and others. Paul Langerhans is a classic example of posthumous fame and
honor. The inscription over his gravestone reads in Greek that is translated into
English as: “Nor did my heart wish any longer to be alive and see the light of
the sun.” (248)
Edouard Laguesse (1861-1927)
Edouard Laguesse (Gustave François Antoine dit Édouard Laguesse) was a

French physician, anatomist and histologist who identified the term,
“endocrine,” for the glands of internal secreation (252). In 1893 he theorized
in that the pancreatic islands that were described by Paul Langerhans in 1869
that he called “les ilots de Langerhans” may be the basis or determinant of
blood glucose control and were the endocrine glands or tissue of the pancreas
(253-257).
CLOSE OF THE 19TH CENTURY:

PSYCHOLOGICAL FACTORS
As the 19th century rushed to a close, the result of furious scientific
experiments began to come to fruition. After thousands of years of confusion
about the etiology, symptoms, and treatment for persons with diabetes
mellitus, science was merging into a clearer understanding of this disorder. It
was not a gastric nor renal disorder, but one of the pancreas. Psychological
factors also play a role, as first revealed by Thomas Willis and Claude Bernard
(157). William H Dickinson wrote in 1875 that diabetes was a disease of the
nervous system that involved secretion of saccharine in the urine (202,258).
Though departing from the growing sense in the later 19th century that
diabetes was a pancreatic condition, it continued the notion that the nervous
system and perhaps psychological factors were involved in this complex
disorder (157).
Oscar Minkowski (1858-1931) and Joseph Freiherr von Mering

(1849-1908)
Oscar Minkowski (1858-1931) was born in Alexoten (now in Lithuania) and

his family moved to Königsberg (Prussia) 14 years after his birth. He studied
medicine at the University of Königsberg and his interest in research as well as
his surgical prowess would serve the cause of diabetes knowledge well (241).
Joseph von Mering (Joseph Frieprich Freiherr von Mering; 1849-1908) was
born in Cologne, Germany who became a physician and was involved in the
discovery of the class of sedative drugs called barbiturates. His interest in the
pancreas and his teaming up with Minkowski lead to a seminar progress in the
field of diabetes.
Von Mering was visiting the library at the University of Strasbourgh and
met Minkowski. Von Mering had been publishing on temporary glycosuria
due to phloridzin which is a flavonoid found in apples, leaves, bark, and other
naturally occurring tissues (46, 241). Von Mering had been looking at lipid
digestion using an oil substance called Lipanin that contained free fatty acids
(46, 241). Their meeting with resultant communication led to their famous
work in which Oscar Minkowski and Joseph Mereing were able to perform a
pancreatectomy on a dog in 1889 and the dog lived but then developed fatal
diabetes (46, 83, 106, 107, 154, 155, 259-264).
This was discovered after Minkowski looked for and found glycosuria in
the urine left on the floor, because it had not been cleaned up after the dog
developed polyuria (46, 149, 265). Since they were not sure if this was caused
by this dog having been on phloridzin, these researchers performed
pancreatectomy in three more dogs who did not have presurgical glycosuria,
but who developed post-surgical glycosuria (46). Unlike the earlier
experiments by Johann Conrad Brunner (1653-1727) as noted earlier, the
Minkowski-Von Mering experiments on the canine pancreas stimulated others
to seek to find the pancreatic substance linked with glucose metabolism (155,
157, 266). Minkowski and others also noted that when pancreatic tissue was
added subcutaneously, glucose metabolism improved even if the pancreas was
removed until the tissue was removed or became non-functional (46).
Treatment of persons with diabetes mellitus was based on diet as championed
by Bouchardat and others in the 19th century such as Ludwig Traube (1816-
1876) advocating reduced carbohydrate intake (107, 266, 267).
A dead thing can go with the stream, but only a living thing can go
against it. Gilbert K Chesterton. (1874-1936)
REFULGANT DIABETES RESEARCH IN THE 20TH CENTURY

Standing on the shoulders of giants, medicine marches forward. Table 8 lists
giants of the 20th century who marched medicine toward more definitive
understanding of this disease that had perplexed homo sapiens for millennia.
As noted earlier, the French physician and anatomist, Edouard Laguesse
(1861-1927), in 1893 named the clusters of cells identified by Paul Langerhans
in 1869 the “les ilots de Langerhans” and theorizied that they were involved in
blood glucose control (248, 252-256). The Americans entered the study of
diabetes with the work of the great 20th century pathologist, Eugene Lindsay
Opie (1873-1971) (267-277). He was born in Virginia and grew up in Marland
where he graduated from medical school at Johns Hopkins in Baltimore,
Maryland.
Table 8. 20th century giants in the history of diabetes (Partial list)
Eugene Lindsay Opie (1873-1971)

Georg Ludwig Zuelzer (1870-1949)
Jean de Mayer (1878-1934)
Edward Albert Sharpey-Schafer (1850-1935)
Russell Lafayette Cecil MD (1881-1965)
Walter Bradford Cannon (1871-1945)
Sir Archibald E. Garrod (1857-1936)
Frederick Madison Allen (1878-1964)
Elliott Proctor Joslin (1869-1962)
Israel Kleiner (1885-1966)
Nicolae Constantine Paulescu (1869-1931)
Moses Barron (1884-1974)
Sir Frederick Grant Banting (1891-1941)
John James Rickard (JJR) Macleod (1876-1935),
Charles Herbert Best (1899-1978)
James Bertram Collip (1892-1965)
John Jacob Abel (1857-1938)
Sir Harold Himsworth (1905-1993),
Frederick Sanger (1918-2013
Hans Christian Hagedorn (1888-1971)
Donald Frederick Steiner (1930-2014)
Many others in the later part of the 20th century
Similar to the story of Paul Langerhans, Opie was a remarkable medical

student and studied these clusters of cells. He know from previous scientists
(i.e., von Mering, Merkowski, and Russian physician Leonid W. Ssobolew
[1876-1919] and others) that complete blockage of pancreatic secreting ducts
by pancreatic duct ligatiion did not lead to diabetes (271). It was also known
that some type of “internal secretions” of the pancreas was involved in glucose
metabolism.
In the very early 20th century Opie linked damage to the islets of
Langerhans to diabetes and distinguished two forms of chronic insterstitial
nephritis with islets that were damaged (272, 273). Eugene Opie went on to
link damage to the islets of Langerhans to diabetes in 1901. He was able to
distinguish two forms of chronic interstitial nephritis with damage islets. He
wrote the first edition of “Diseases of the pancreas” in 1903. He noted that
“Diabetes mellitus… is caused by destruction of the islands of Langerhans and
occurs only when these bodies are in part or wholly destroyed” (274). His
legacy in the field of diabetes lives on into the 21st century (149, 274-277).
Modern scientific medicine, with its deep insight into the nature of
disease, is capable of conferring immense benefit upon mankind.
[Indeed] medicine offers one of the greatest opportunities to serve
mankind. (Eugene Lindsay Opie (1873-1971) (268)
Early 20th century progress: 1900-1905
In addition to the work of Eugene Lindsay Opie (1873-1971), the first five
years of the 20th century also provided research by the Russian physician,
Leonid W Ssobolew (1876-1919), who ligated animal pancreatic ducts (i.e.,
rabbits, cats, and dogs) and noted this led to degeneration of enzyme-secreting
acini cells; the islet cells were viable for weeks and diabetes did not result
(278, 279). Other researchers were involved in such experiments, such as
Schulze, in 1900 who independently reached the same result (278, 279).
Other progress was seen in 1902 when English physiologists Sir William
Maddock Bayliss (1860-1924) and Ernest Henry Starling (1866-1927)
revealed the concept of gastrointestinal peristalsis and the presence of a
peptide bioactive substance called secretin in the gastrointestinal tract since it
was secreted in the intestinal tract and regulated secretions of the pancreas and
other organs; they introduced the term “hormone” for the first time in 1905
(280-284). They became well-known in the science community of the 20th and
now 21st century for these and other achievements in physiology research. The
role of secretin continued to be investigated to the present including potential
role in managing obesity (283, 284).
Between 1906 and 1908 Georg Ludwig Zuelzer (1870-1949) was involved in
early research on pancreatic extracts and diabetes. This physician in Berlin,
Germany performed pancreatectomy on dogs and then injected the animals
with pancreatic extracts which reduced glucose in their urines (10, 155, 202,
285-288). He developed a US patent on his alcoholic extract (called
Acomatol), but intolerable side effects resulted from the use of the pancreatic
digestive enzymes. The side effects included a convulsive reaction perhaps
due to hypoglycemia (10). Though his extract did have a hypoglycemic effect,
he did not continue with this research perhaps, as noted by some authorities,
Zuelzer was not encouraged to pursue it partially due to the emergence of
World War I.
However, Georg Ludwig Zuelzer was the first person in thousands of
years to have partial success with a pancreatic extact (155). The secrets of the
pancreas were slowly being understood. Scientists Michael Lane and RR
Bensley identified the pancreatic ilets A and B cells in 1907 and 1911
respectively using improved histological methods (290, 291). Eventually it is
found that the A (α) cells produce glucagon and the B (ß) cells produce insulin
(292-294).
In 1909 Beglian physician Jean de Mayer (1878-1934) uses the term
insulin (Latin for insulina or island) for the material in the ilets of Langerhans
that many have concluded is in the pancreas and in agreement with concepts of
previously mentioned, French anatomist/physician, Edouard Laguesse (1861-
1927 AD), controls glucose metabolism.
Another scientiest, Scottish endocrinologist and physiologist Sir (knighted
in 1913) Edward Albert Sharpey-Schafer (1850-1935) also independently
proposes the name insulin for this pancreatic substance calling it “pro-
insuline” in 1910 and theorized that diabetes is caused by a deficiency of this
material that he called an antidiabetic chemical (295, 296). He has been called
an important link in the development of endocrinology as a specialty of
medicine. He is also known for contributions to the methodology of artificial
respiration (297, 298).
One of the great American physicians and internists of the 20th century was
Russell Lafayette Cecil, MD (1881-1965) (299-303). Early in his career he
joined with other researchers and clinicians in 1911 who were linking damage
of the islets of Langerhans to diabetes mellitus (304). He became well-known
for his work on pneumonia, established concepts of controlled trials (clinical
trials), and then starting in 1927 he edited what became one of the best known
American textbooks of internal medicine (Cecils’s textbook of medicine) that
is now in its 25th edition despite his death in 1965 (303-311).
Table 9. Giants in the field of behavioral factors in diabetes mellitus

(partial list)

Walter Bradford Cannon (1871-1945)
Sir Archibald E. Garrod (1857-1936)
In 1911 Ernest L Scott at the University of Chicago reported that

glycosuria in pancreatectomized dogs was “slightly” lowered after providing
intravenous aqueous pancreatic extracts. In the same unfortunate milieu as
experienced by Georg Ludwig Zuelzer (1870-1949) a few years ea rlier,
Scott’s experiments of 1911 and 1912 were dismissed as being unimportant
and the discovery of insulin had to wait another ten years (287, 288). His
mentors suggested this mild reduction in urine glucose was “doubtless
explained by renal or other nonspecific changes (287, 288).” Ernest L Scott
was in the right direction but stopped short of the goal of finding insulin and
his work became another near-miss in the search for effective management of
diabetes mellitus (312).
EMOTIONAL GLYCOSURIA
As researchers were unfathoming the mysteries of diabetes in the second
decade of the 20th century, the influence of emotion and psychological factors
on diabetes was also being explored (see Table 9). As noted earlier in this
treatise, a link of emotion and diabetes was identified by the 17th century
British physician/anatomist, Thomas Willis (1632-1675) (149, 157). This
association was also explored by the great French physiologist of the 19th
century, Claude Bernard (1813-1878) (46, 157). Also, as noted earlier the
German pathologist Bernard Naunyn (1840-1914) wrote about diabetes
developing during the stressful milieu of war with bombing of a city in 1870
(157).
The German term, “Fesselungs diabetes” arose from the experiments of
German researchers Boehm and Hoffmann who published their work in 1878
about the appearance of glycosuria within 30 minutes in cats who were
fastened to a board and were tracheotomized without anesthesia (313). A
researcher who would receive the Nobel Prize in 1923 noted in 1907 that the
amount of sugar in the blood was controlled by afferent and efferent nerve
fibers (314).
In 1911 this link was further developed by the work of the great American
physiologist, Walter Bradford Cannon (1871-1945), who became of
considerable fame from various experiments and ideas including his
identification of the fight or flight response and furthered the concept of
Claude Bernard’s concepts of homeostatis in human beings (315-319). Cannon
agreed and confirmed the Fesselungs glycosuria found by Boehm and
Hoffmann but he did not feel that the glycosuria was due to pain or being
bound; instead, he felt that this physiologic effect was due to metabolic effects
induced by the fight or flight response and that this stress led to sympathetic
nervous system stimulation with an increase in epinephrine (157, 320, 321).
Cannon advanced the concept of “emotional” glycosuria and connected it
to the sympathetic nervous system. Some researches noted in 1911 that
emotional glycosuria can be due to stress-induced hypervention that leads to
acapnia (322). The English physician, Sir Archibald E Garrod (1857-1936),
father of the field of inborn errors of metabolism (323, 324), concluded in
1912 that “psychic strain or stress” was a contributing factor in emotional
glycosuria (157, 325). In 1914 researchers O Folin, W. Denis, and WG Smillie
published their observations in which medical and college students developed
transient glycosuria under the stress of examinations (326).
Frederick Madison Allen (1879-1964)
Frederick Madison Allen was an American physician best remembered for his
promotion of a carbohydrate-restricted/high fat diet in the second decade of
the 20th century for management of diabetes mellitus (327-331). It proved to
be a desperate measure that improved the glycosuria of some but this so-called
“starvation diet” (70% fat, 8% carbohydrate) led to the deaths of others (331-
333).
Elliott Proctor Joslin (1869-1962)
Elliott P Joslin became the leading specialist in diabetes mellitus in the 20th
century and was the first physician to fully specialize in one disease as
diabetes (334,335). His interest in metabolism began in the 19th century and,
before insulin was available, agreed with Frederick Madison Allen (1889-
1964) that a restricted diet was helpful to patients with diabetes mellitus (332,
336). In the second decade of the 20th century he began to write about
management of diabetes mellitus and in 1916 wrote a monograph “The
treatment of diabetes mellitus” followed by his 1918 “Diabetic manual”—for
the doctor and patient (337, 338). These works went into many editions as he
established the Joslin Diabetes Center in Boston as a major institute for the
study and treatment of diabetes mellitus (338). He was an advocate for patient
education and tight glucose control—an approach noted later in the 20th
century to be the correct one for maximal health and longevity of the person
with diabetes mellitus.
A patient needs a doctor, not a committee….Doctors treated

individuals, not statistical averages…If you don’t examine the trees,
you may get lost in the woods. The proper study of mankind is man.
(John P Peters, MD, 1887-1955) (98)
Israel Kleiner (1885-1966)
Between 1915 and 1919 researcher Israel Kleiner (1885-1966) was injecting
pancreatic extracts into depancreatized animals and measuring the reduction in
the blood sugar at the Rockefeller Institute in New York City (287, 288, 339-
342). His work confirmed that a substance in the pancreas was involved in
glucose control but his injections caused potential severe adverse effects and
he was not able to find this purified substance.
The result is regarded as further evidence for the internal secreation

theory of experimental diabetes. Israel Kleiner (339)
Nicolae Constantine Paulescu (1869-1931)
Nicholas Paulesco was a professor of physiology in the Romanian School of

Medicine (Bucharest, Romania) who performed research on dogs in the
middle of the second decade of the 20th century seeking to identify the
pancreatic extract substance that was involved in glucose metabolism (287,
288, 342-346). In August of 1921 he reported his results on a pancreatic
substance he called “pancrein” and noted it lowered blood sugar in dogs (347).
For a variety reasons involving controversy and the interruption of World

War I, Nicolae Paulescu was not given official recognition for his findings and
this was given to Frederick Banting and colleaues in Toronto, Canada as
discussed in the next section. Some scholars, including those in his home
country, feel that this professor did not receive the recognition he should have
and the readers of this book can research this issue and make up their own
minds in this regard (270, 287, 342, 344-352).
There is a tide in the affairs of men

Which taken at the flood, leads on to fortune;
Omitted, all the voyage of their life
Is bound in shallows and in miseries. —
Shakespeare, Julius Caesar, act iv, scene 3
Sir Frederick Grant Banting (1891-1941)
Frederick Grant Banting was a young Canadian orthopedic surgeon who had
served heroically in World War I, where he was wounded and given credit by
history as the discoverer of insulin though with some controversy as
previously noted (353-357). The typically story that is “told” is that before
giving a talk on diabetes in London (Ontario, Canada), he read an article by
Moses Barron published in 1920 that had an important, seminal reflection that
diabetes was not found in persons with pancreatic disease if the pancreatic
islets were not involved (149, 356, 357). Moses Barron (1884-1974) was a
physician and researcher born in Russia and grew up in Minnesota, USA. He
also served in World War I and received the 1964 Banting Award from the
American Diabetes Association (358,359).
In his classic 1920 article there was the discussion of a pancreas with
fibrosis with intact islet cells but absent acinar cells and absent diabetes
mellitus; the paper also provided citations of others’ research with similar
results from pancreatic duct ligation (267, 357, 358). Moses Barron discussed
his work in article in Minnesota Medicine (1966; 49:689). This work relates to
that of French physician and anatomist, Eugene Lindsay Opie (1873-1971)
(271-278), Russian physician Leonid W Ssobolew [1876-1919] (271,278), and
others as previous reviewed in this article.
The inspiration of reading this article led Sir Frederick Banting to talk to
one of the great carbohydrate experts of his time, Professor John James
Rickard (JJR) Macleod (1876-1935), an Aberdonian Scott who emigrated to
Canada; Banting asked for the use of a laboratory to carry out experiments he
had in mind that included ligation of canine pancreatic ducts (287,350).
Though described as skeptical JJR Macleod provided this young inexperienced
researcher (Banting) with a laboratory, some dogs (Scottish border collies),
and a laboratory assistant at the Toronto General Hospital. Banting went to
work that night and two lab assistants were available and so a coin toss picked
medical student Charles Herbert Best (1899-1978)—later elevating this
American-Canadian to the glory as a co-discoverer of insulin and the other lab
assistant to Shakespearean obscurity (288,357,360).
There is a tide in the affairs of men

Which taken at the flood, leads on to fortune;
Omitted, all the voyage of their life
Is bound in shallows and in miseries. —
Shakespeare, Julius Caesar, act iv, scene 3
Much has been written about the details of the Banting-Best experiments
(10, 107, 287, 288, 342). A classic description is by Banting himself, including
that given on September 15, 1925 as his Nobel lecture given in Stockholm
(288). The publications of Professor John JR Mccleod are also helpful in this
regard (361-363) as well other publications by Banting and Best (364, 365).
The key was finding an extract from the pancreas that would safely lower
blood sugar in human beings. Initial extracts would produce unacceptable
advere effects such as fever.
The breakthrough came when JJR Macleod, instead of giving up on the
experiments and joining in a long line of “near-misses” in diabetes research,
added a chemist to the Toronto group destined for medical glory--- James
Bertram Collip (1892-1965)---a biochemist who could purify a crude alcohol
pancreatic extract, keep it cool on ice, and added the seminal idea of using
beef pancreatic extracts as well as effects of the extracts in rabbits to help
meansure the glucose lowering potential to avoid an insulin overdose (164,
287, 364-366).
After working with pancreatectomized dogs the breakthrough patient was
14 year old Leonard Thompson (1908-1935) with type 1 diabetes mellitus who
developed an allergic reaction to the original Banting-Best pancreatic extract
given on January 11, 1922 but did well with the extract refined by biochemist
James Collip and given 12 days later; this patient lived to age 27 years and
died from pneumonia (149, 267, 342). Banting and Macloud received the 1923
Nobel Prize for their discovery of insulin and Banting provided public
recognition for Charles Best (sharing the Nobel Prize with him) and Macloud
did the same for James Collip (166, 362).
Macleod provided his thoughts on the action of this hypoglycemic
compound in his 1925 Nobel Lecture and wondered about its mechanism---a
question that would take many decades in the 20th century to answer (361).
Clashes of personalities led to the Toronto team dissolving and others taking
leadship in diabetes management advances in the 20th century—perhaps
accentuated by post-tramatic stress issues with Banting as a WWI veteran
(349). Frederick Banting died in 1941 in a plane crash. As noted, history has
clouded the Toronto group with considerable controvery and the reader can
decide what is valid and what is not (267, 287, 342, 344-352). Certainly their
success followed the work of others in the past (202).
However, the mantel of glory is generally given to this Toronto group
whose discovery that insulin is secreted in the beta cells of the pancreas went
on to save millions and millions of lives in the 20th and now 21st century
(107, 342). Frederick Banting was knighted in 1934. Certainly sharing in the
glory of insulin discovery and purification is the pharmaceutical industry (i.e.,
Connaught Laboratories, Eli Lilly and Company, and Nordisk Insulin
Laboratory) who made a safe insulin product available to the public within
months of this discovery (149, 164, 166).
Mine is the first step and therefore a small one, though worked out
with much thought and hard labor. You, my readers or hearers of my
lectures, if you think I have done as much as can fairly be expected
of an initial start. . . will acknowledge what I have achieved and will
pardon what I have left for others to accomplish. Aristotle.
(385 BC-322 BCE)
POST-BANTING/BEST ERA
Sir Henry Hallett Dale (1875-1968) was an English pharmacologist who was
involved in organizing scientific meetings in 1923 and 1925 to develop
international standards for insulin and other biological agents; he established
the National Institute for Medical Research to establish these critically
important standards (368). Henry H Dale received a Nobel Prize in 1936 for
his work on acetylcholine. John Jacob Abel (1857-1938) was a biochemist and
pharmacologist with an MD degree who chaired the first department of
pharmacology at the Univeristy of Michigan and then was chair of
pharmacology at Johns Hopkins University (369, 370). He purified insulin and

identified its crystalline structure in 1926 (164, 369). In 1936 Sir Harold
Himsworth (1905-1993), a professor of medicine at London University,
identified two types of diabetes mellitus—insulin-sensitive (type 1) and
insulin-insensitive (insulin resistance, type 2) (371-374).
The term, insulin, came from the Latin word, “insula” for island (149).
Further work on the insulin molecule occurred as the 20th century continued
by double Nobel prize winner, British biochemist Frederick Sanger (1918-
2013)---he identified the molecular structure of insulin in the 1940s and 1950s
including the amino acid sequence of the protein insulin (164, 267, 375-377).
Prior to that Protamine zinc insulin was introduced in the 1930s and neutral
protamine Hagedorn (NPH) insulin in the late 1930s and early 1940s. Hans
Christian Hagedorn (1888-1971) was a Danish physician who was influential
in obtaining the legal rights for insulin from Banting and Best, developed NPH
insulin, and helped form a company for insulin production now called Novo
Nordisk (378-380).
Research in the 1940s and 1950s led to insulin syringes, urine testing
methods (i.e., tablets, test strips), blood-glucose testing strips beginning in
1962, and oral sulfonylureas starting in 1958. Giants of medicine and research
continued to come in the 20th century as noted with American physician and
biochemist Donald Frederick Steiner (1930-2014) who discovered proinsulin
at the University of Chicago in 1965 that allowed production of more pure
insulin with less adverse effects (381).
Insulin pumps improved in the 1970s from earlier pumps by being
portable and were complemented by new blood-glucose meters. The 1970s
also saw the availability of U-100 insulin in 1973 and the first recombinant
DNA insulin (1978). Research in the 1970s and 1980s ushered in the first
biosynthetic human insulin that led in 1996 to FDA approval of the first
recombinant DNA human insulin analog, lispro (Humalog). Simple-to-use
insulin pens arrived in 1986 and self-monitoring of blood glucose was
advancing from the 1980s into the 21st century.
The last decade of the 20th century and the early 21st century saw the
fruition of years of research with new medications for type 2 diabetes
including metformin, acarbose, repaglinide, and others (382, 383). Research
continues to explore the mechanisms of the pancreas on glucose metabolism
(384), the impact of diet on glucose control (385), management of gestational
diabetes mellitus (386), genetic factors in diabetes (387), the potential
association of diabetes mellitus with statins (388), control of hypertension in
persons with diabetes (389), and the role of the gastrointestinal flora in
diabetes management (390). Future issues of this book can detail 21st century
advances that include different insulin delivery systems (i.e., inhalation,
patch), improved insulins, genetic engineering to develop insulin-secreting
cells, pancreatic transplantation, and others amazing advances (391-393).
No human being is constituted to know the truth, the whole truth, and
nothing but the truth; and even the best of men must be content with
fragments, with partial glimpses, never the full fruition.
(William Osler MD:1849-1919)
FINAL CHAPTER DENOUEMENT

To suffer woes which Hope thinks infinite;
To forgive wrongs darker than death or night;
To defy Power, which seems omnipotent;
To love, and bear; to hope till Hope creates
From its own wreck the thing it contemplates;
Neither to change, nor falter, nor repent;
This, like thy glory, Titan, is to be
Good, great and joyous, beautiful and free;
This is alone Life, Joy, Empire, and Victory.
Percy Bysshe Shelley's Prometheus Unbound, 1820
The current and future shortage of pediatric endocrinologists necessitates

steady, rejuvenated information on diabetes and other endocrine disorders for
primary care clinicians as they care for the child and adolescent with complex
endocrine dilemmas and disorders (394-396). In view of this shortage and the
rapidly increasing knowledge in pediatric diabetes as well understanding
indications for referral to pediatric endocrinologists in the 21st century, au
courant assiduous information aimed at primary care clinicians in these areas
becomes increasingly important (397-400).
Mine is the first step and therefore a small one, though worked out
with much thought and hard labor. You, my readers or hearers of my
lectures, if you think I have done as much as can fairly be expected
of an initial start. . . will acknowledge what I have achieved and will
pardon what I have left for others to accomplish.
Aristotle (385 BC-322 BCE)
REFERENCES
[1] Early modern homo sapiens. URL: http://anthro.palomar.edu/homo2/mod_
homo_4.htm.
[2] Magner LN. A history of the life sciences, 3rd ed. New York: Marcel Dekker, 2002.
[3] Kramer SN. The Sumerians. Chicago: The University of Chicago Press, 1963:225-6.
[4] Jastrow M. The liver in antiquity and the beginnings of anatomy. Tranasactions Coll
Physicians 1907;XXIX:117.
[5] Roth MT. Law collections from Mesopotamia and Asia Minor. Atlanta, GA:
Scholars Press, 1997.
[6] Geller MJ, Horstmanshoff HFJ, Stol M, Tilburg C, eds. West Meets East: Early
Greeks and Babylonian diagnosis. Magic and rationality in ancient Near Eastern and
Graeco-Roman Medicine. Boston, MA: Brill Publishers, 2004.
[7] Taylor JH, ed. Ancient Egyptian book of the dead: Journey through the afterlife.
London: British Museum Press, 2010:54.
[8] Hallmann-Mikolajczak A. Ebers papyrus. The book of the medical knowledge of the
16th century BC Egyptians. Arch Hist Filoz Med 2004;67(1):5-14. [Polish].
[9] Stiefel M, Shaner A, Schaefer SD. The Edwin Smith papyrus: The birth of analytical
thinking in medicine and otolaryngology. Laryngoscope 2006;116(2):182-8.
[10] Zajac J, Shrestha A, Patel P, Poretsky L. The main events in the history of diabetes
mellitus. In: Poretsky L, ed. Principles of diabetes mellitus. New York: Springer
Science, 2002:1-16.
[11] Loukas M, Lanteri A, Ferrauiola J, Tubbs RS, Maharaja G, Shoja MM, et al.
Anatomy in ancient India: a focus on the Susruta Samhita. J Anat 2010;217(6):646-
50.
[12] Frank LL. Diabetes mellitus in the texts of old Hindu medicine (Charaka, Susruta,
Vagbhata). Am J Gastroenterol 1957;27(1):76-95.
[13] Sharma HS, Sharma HI, Sharma HA. Sushruta-samhitA: A critical review part-I:
historical glimpse. Ayu 2012;33(2):167-73.
[14] Codellas PS. Alcmaeon of Croton: his life, work, and fragments. Proceed Royal Soc
Med 1931;25(4):1041-6.
[15] Schiefsky MJ. Hippocrates: On ancient medicine. Leiden, Netherlands: Brill
Publishers, 2005.
[16] Unguru S, Fried MN. Apollonius, Davidoff, Rorty, and Zeuthen: from A to Z, or,
what else is there? Sudhoffs Arch 2007;91(1):1-19.
[17] André J. Remarks on the translation of Greek words into medical texts of the fifth
century (Cassius Felix et Caelius Aurelianus). Rev Philol Litt Hist Anc 1963;37:47-
67. [French].
[18] Coturri E. Surgery in Aurelianus Caelius [Vari XXXX]. Minerva Med
1959;50(35):Varia 898-914. [Italian].
[19] Saba MM, Ventura HO, Saleh M, Mehra MR. Ancient Egyptian medicine and the
concept of heart failure. J Card Fail 2006;12(6):416-21.
[20] Van Praagh R, Van Praagh S. Aristotle’s “triventricular” heart and the relevant
history of the cardiovascular system. Chest 1983;84(4):462-8.
[21] Loukas M, Hanna M, AlsaieMason Stephen F. gh N, Shoja MM, Tubbs RS. Clinical
anatomy as practiced by ancient Egyptians. Clin Anat 2011;24(4):409-15.
[22] Witters LA, Luciano M, Williams C, Yang J. Diabetes detectives. Dartmouth Med
2008;Winter:1-2.
[23] Wilson JC. Aulus Cornelius Celsus and some remarks concerning rare editions of
old books and medical libraries. Bull Med Libr Assoc 1913;3(1):1-10.
[24] Androutsos G. Urology in the work De re medical of Aulus Cornelius Celsus (1st
century AD). Prog Urol 2005;15(2):344-52. [French].
[25] Trancas B, Borja Santos N. Ethics, knowledge and psychiatry: in Aulus Cornelius
Celsus’ De Medicina. Acta Med Port 2007;20(5):431-7. [Portuguese].
[26] Finlayson J. Galen: [A bibliographical demonstration in the library of the faculty of
physicians and surgeons of Glasgow, December 9th, 1891.]. Br Med J
1892;1(1628):573-5.
[27] Kempf EJ. From Hippocrates to Galen. Med Library Hist J 1904;2(4):282-307.
[28] Larkey SV. Galen: Greek, medievalist and modern: Part II. Cal West Med
1931;34(5):366-9.
[29] Hankinson RJ. Galen on Hippocratic physics. Stud Anc Med 2016;46:421-43.
[30] Kühn CG, ed. Claudii Galeni Opera Omnia. Leipzig: C Cnobloch, 1821.
[31] Bujalkova M. Rufus of Ephesus and his contribution to the development of
anatomical nomenclature. Acta Med Hist Adriat 2011;9(1):89-100.
[32] Eknoyan G. Rufus of Ephesus and his “Diseases of the kidneys.” Nephron
2002;91(3):383-90.
[33] Adams F, ed. Arataeus the Cappadocian: the extant works. London: Sydenham
Society, 1856.
[34] Roselli A. Arataeus of Cappadocia’s reading of the Hippocratic Corpus. Stud Anc
Med 2005;31:413-32. [Italian].
[35] Laios K, Karamanou M. Saridaki Z, Androutsos G. Arataeus of Cappadocia and the
first description of diabetes. Hormones (Athens) 2012;11(1):109-13.
[36] Garcia-Albea Ristol E. Arataeus of Cappadociaa (2nd century D) and the earliest
neurological descriptions. Rev Neurol 2009;48(6):322-7. [Spanish].
[37] Tekiner H. Arataeus of Cappadocia and his treatises on diseases. Turk Neurosurg
2015;25(3):508-12.
[38] Reed JA. Arataeus the Cappadocian: History enlightens the present. Diabetes
1954;3:419-21.
[39] Greydanus DE, Hofmann AD. Psychological factors in diabetes mellitus: a review of
the literature with emphasis in adolescence. Am J Dis Child 1979;133:1061-6.
[40] Cordell EF. Arateus of Cappadocia. Bull Johns Hopkins Hosp 1909;20:371-7.
[41] Pearce JMS. The neurology of Arateus: Radix pedis neuralgia. Eur Neurol 2013;106-
112.
[42] Bongartz LG, Cramer J, Joles JA. Origins of the cardiorenal syndrome and the
cardiorenal connection. Chronic Kidney Disease. URL: http://cdn..intechopen.com/
pdfs-wm/32307/pdf.
[43] Kirchhof M, Popat N, Malowany J. A historical perspective of the diagnosis of
diabetes. Univ West Ontario Med J 2008;78(1):1-4.
[44] Guthrie DW, Humpheys SS. Diabetes urine testing: an historical perspective.
Diabetes Educ 1988;14(6):521-6.
[45] Laron Z. Childhood diabetes towards the 21st century. J Pediatr Endocrinol Metabol
1998;11(3):387-402.
[46] Karamanou M, Protogerou A, Tsoucalas G, Androutsos G, Poulakou-Rebelakou E.
Milestones in the history of diabetes mellitus: The main contributors. World J
Diabetes 2016;7(1):1-7.
[47] Bestetti RB, Baraldi C, Restini BA, Couto LB. Development of anatomophysiologic
knowledge regarding the cardiovascular system: from Egyptians to Harvey. Arq Bras
Cardiol 2014;103(6):538-45.
[48] Christopoulou-Aletra H, Papavramidou N. ‘Diabetes’ as describe by Byzantine
writers from the fourth to the ninth century AD: the Graeco-roman influence.
Diabetologia 2008;51(5):892-6.
[49] Baldwin B. The career of Oribasius. Acta Cl 1975;18:85-97.
[50] Riou YF. Un fragment d’un manuscript disparu d’Oribase, C.L.A. 116 (Vatican,
Urb. lat. 293, ff. 95-96, VIIIe siècle). Scriptorium 1979;33:235-7.
[51] Lascaratos J, Poulakou-Rebelakou E. Oribasius (fourth Century) and early Byzantine
perinatal nutrition. J Pediatr Gastroenterol Nutr 2003;36(2):186-9.
[52] Mikic Z. Famous physicians from the past—Oribasisus from Pergamum. Med Pregl
2013;66(3-4):189-92. [Serbian].
[53] Shirodkar JA, Sayyad MG, Nanal VM, Yajnik CS. Anguli parimana in Ayurveda
and its association with adiposity and diabetes. J Ayurveda Integr Med
2014;5(3):177-84.
[54] Irmer D. Bearbeitungen von Schriften des iatrosophisten palladius unter den namen
des Johannes, Stephanus, und Theophilus. Medizinhist J 1973;8(2-3):179-81.
[German].
[55] Papathanassiou MK. Stephanus of Alexandria: pharmaceutical notions and
cosmology in his alchemical work. Ambix 1990;37(3):121-33.
[56] Papathanassiou MK. Stephanus of Alexandria; on the structure and date of his
alchemical work. Med Secoli 1996;8(2):247-66.
[57] Bouras-vallianatos P. Clinical experience in late antiquity: Alexander of Tralles and
the therapy of epilepsy. Med Hist 2014;58(3):337-53.
[58] Puschmann T. Nachträge zu Alexander Trallianus. Fragmente aus philumenus und
philagrius, nebst einer Bisher noch ungedruckten abhandlung über
augenkrankheiten. Berlin: Verlag von S Calvary, 1886. [German].
[59] Delisle L, Le cabinet des manuscrits de la Bibliothèque nationale, 4 tomes, Paris,
Imprimerie Nationale, 1868-1891 (réimpression 1978).
[60] Ongaro G. Le conoscenze elmintologiche de Alessandro di Tralle. Acta Med Hist
Patav 1964-5;11:119-43. [Italian].
[61] Nutton V.The Latin Alexander Trallianus: the text and transmission of a Latin
medical book (review). Bull Hist Med 2009;83(2):388-9.
[62] Papavramidou N, Christopoulou-Aletra H. Greco-Roman and Byzantine views on
obesity. Obes Surg 2007;17(1):112-6.
[63] Mylonas AI, Poulakou-Rebelakou EF, Androutsos GI, Seggas I, Skouteris CA,
Papadopoulou EC. Oral and cranio-maxillofacial surgery in Byzantium.
Craniomaxillofac Surg 2014;42(2):159-68.
[64] Poulakou-Rebelakou E, Marketos SG. Kidney disease in Byzantine medical texts.
Am J Nephrol 1999;19(2):172-6.
[65] Diamandopoulos A. Twelve centuries of nephrological writings in the Graeco-
Roman world of the Eastern Mediterranean (from Hippocrates to Aetius Amidanus).
Nephrol Dial Transplant 1999;14(Suppl 2):2-9.
[66] Scarborough J. Teaching surgery in late Byzantine Alexandria. Stud Anc Med
2010;35:235-60.
[67] 67 Sideras A. Aetius und Oribasius: Ihre gemeinsamen Exzerpte aus der Schrift des
Rufus von Ephesos “Ueber die Nieren- und Blasenleiden” und ihr
Abhängigkeitsverhältnis. Byzantinische Z 1974;67:110-30. [German].
[68] Conti Bizzarro F. Per l’edizione dei libri medicinali di Aezio Amideno. Koinonia
1978;2:169-97. [Italian].
[69] Durling RJ. Addenda lexicis, primary from Aëtius of Amida and Paul of Aegina.
Glotta 1986;44(1-2):30-6.
[70] Lascaratos J, Tsirou M, Fronimopoulos J. Ophthalmology according to Aetius
Amidenus. Doc Ophthalmol 1990;74(1-2):37-48.
[71] Karenberg A, Hort I. Medieval descriptions and doctrines of stroke: preliminary
analysis of select sources. Part I: The struggle for terms and theories—late antiquity
and early Middle Ages. J Hist Neurosci 1998;7(113 Pt 2):162-73.
[72] Gamillscheg E. Copyists of manuscripts for medicine. Med Secoli 1999;11(3):477-
86. [German]
[73] Ramoutsaki IA, Dimitriou H, Kalmanti M. Management of childhood diseases in the
Byzantine period: I—analgesia. Pediatr Int 2002;44(3):335-7.
[74] Bieganowski L. Ophthalmology in Byzantium between the 4th and the 7th century.
Klin Oczna 2005;107(1-3):177-81. [Polish]
[75] Mylonas AI, Poulakou-Rebelakou EF, Androutsos GI, Seggas I, Skouteris CA,
Papadopoulou EC. Oral and cranio-maxillofacial surgery in Byzantium. J
Craniomaxillofac Surg 2014;42(2):159-68.
[76] Francis A. The medical works of Paulus Aegineta, the Greek physician: Translated
into English with a copious commentary containing a comprehensive view of the
knowledge possessed by the Greeks, Romans, and Arabians, on all subjects
connected with medicine and surgery. First Edition. London: Welsh Treuttel Würtz,
1834. Book found in the collections of Oxford University. URL: https://archive.org/
details/medicalworkspau00paulgoog.
[77] Pormann PE. The oriental tradition of Paul of Aegina’s Pragmateia. Stud Anc Med
2004;29:1-337.
[78] Coturri E. Considerations on the surgical doctrinaire of Paul of Aegina. Minerva
Med 1959;50:1665-8. [Italian].
[79] Gurunluoglu R, Gurunluoglu A. Paulus Aegineta, a seventh century encyclopedist
and surgeon: his role in the history of plastic surgery. Plast Reconstruc Surg
2001;108(7):2072-9.
[80] Lascaratos J, Cohen M. Paul of Aegina. Plast Reconstr Surg 2002;110(5):1600-1.
[81] Papadakis M, de Bree E, Trompoukis C, Manios A. Paul of Aegina’s surgical

instruments: a complete surgical instrumentarium in the seventh century AD. Anz J
Surg 2015 Mar 2. doi:10.1111/ans.13027.
[82] Peumery JJ. Histoire illustrée du diabète. De l’Antiquitéa nos jours. Paris: Roger
Dacosta, 1987.
[83] Eknoyan G, Naby J. A history of diabetes mellitus or how a disease of the kidneys
evolved into a kidney disease. Adv Chronic Kidney Dis 2005;12(2):223-9.
[84] Needham J, Lu G-D. Proto-endocrinology: Medieval preparations of urinary steroid
and protein hormones. Science and Civilization in China, Volume 5: Chemistry and
chemical technology, Part 5: Spagyrical discovery and invention. Physiological
alchemy, Cambridge, UK: Cambridge University, 1983:301-37.
[85] Androutsos G. Theophilus Protospatharius: Byzantine forerunner of urology. Hist
Sci Med 2007;41(1):41-8. [French].
[86] Gorgieva GS. Kidney disease in medieval Serbian manuscripts from the Chilandar
monastery (Mount Athos, Greece). J Nephrol 2006;19(Suppl 10):S30-7.
[87] Iorio L, Lamagna M. Foam in urine: from Hippocrates to the medical school of
Salerno. G Ital Nefrol 2014;31(2). pii: gin/31.2.14. [Italian]
[88] Theophilus: De urinis. Édition gréco-latine. Traduction par Thomas Guidot, 1703.
[89] Touwaide A. Sephanus of Athens. The encyclopedia of ancient history, 2012. doi:
1002/9781444338386.wbeah21306.
[90] Nutton V. Stepanus of Athens, Commentary on Hippocrates’ Aphorisms, Section 1-
2, Corpus Medicorum Graecorum XI 1,3,1. Med Hist 1986;30(2):228-9.
[91] Westerink Leendert G, ed. Stepanus of Athens, Commentary on Hippocrates’
Aphorisms, Section III-IV, Corpus Medicorum Graecorum XI 1,3,2. Berlin:
Akademie Verlag, 1992.
[92] Westerink Leendert G, ed. Stepanus of Athens, Commentary on Hippocrates’
Aphorisms, Section V-VI, Corpus Medicorum Graecorum XI 1,3,3. Berlin:
Akademie Verlag, 1995.
[93] Garofalo I. The Arabic translations of Alexandrian compendia of the works of
Galen’s Canon. The ad glauconem compendium. Med Secoli 1994;6(2):329-48.
[Italian].
[94] Angeletti LR, Cavarra B. The Peri ouron treatise of Stephanus of Athens: Byzantine
uroscopy of the 6th-7th centuries AD. Am J Nephrol 1997;17(3-4):228-32.
[95] Flaws B, L Kurchinski L, Casanas RJ. The treatment of diabetes mellitus with
Chinese medicine: A textbook and clinical manual. Boulder, CO: Blue Poppy Press,
2002.
[96] Bowersock G. The vanishing paradigm of the Fall of Rome. Bull Amer Acad Arts
Sciences 1996;49(8):29–43.
[97] Masic I, Dilic M, Solakovic E, Rustemepasic N, Ridjanovic Z. Why historians of
medicine called Ibn al-Nafis the second Avicenna? Med Arh 2008;62(4):244-9.
[98] Greydanus DE, Raj VMS, Merrick J. From the Kition, Cyprus and Aristotelian
kidney to the 21st century pediatric kidney: standing on the shoulders of giants. In:
Greydanus DE, Raj VMS, Merrick J, eds. Chronic illness and disability: The
pediatric kidney. New Yok: Nova Biomedical, 2016:3-26.
[99] Eknoyan G. Arabic medicine and nephrology. Am J Nephrol 1994;14:270-8.
[100] Changizi Astivani S, Shamsi M, Cyrus A, Bastani B, Tabatabayei SM. A critical

review of the works of pioneer physicians on kidney diseases in ancient Iran:
Avicenna, Rhazes, Al-akhawayni, and Jorjani. Iran J Kidney Dis 2011;5(5):300-8.
[101] Dunea G. History of nephrology: beginnings. Hektoen Internat: J Med Humanities.
URL: http://www.hektoeninternational.org/index/php?option=com.
[102] Muntner Z. Persian medicine and its relation to Jewish and other medical science;
commemorating the millennium of Avicenna. Harofe Haivri Heb Med J 1951;2:171-
6.
[103] Chamsi-Pasha MAR, Chamsi-Pasha H. Avicenna’ contribution to cardiology.
Avicenna J Med 2014;4(1):9-12.
[104] Faridi P, Zarshenas MM. Ibn Sina’s book on drugs for cardiovascular diseases. Int J
Cardiol 2010;145:223.
[105] Tekol Y. The medieval physician Avicenna used an herbal calcium channel blocker,
Taxus baccata L. Phytother Res 2007;21:701-2.
[106] Eknoyan G. A history of diabetes mellitus—a disease of the kidneys that became a
kidney disease. J Nephrol 2006;19(Suppl 10):S71-4.
[107] The history of diabetes. URL www.med.uni-giessen.de/itr/history/diabhis.html.
[108] Majeed A. How Islam changed medicine. BMJ 2005;331:1486-7.
[109] West JB. Ibn al-Nafis, the pulmonary circulation, and the Islamic Golden age. J Appl
Physiol 1985;105(6):1877-80.
[110] Siahpoosh M, Ebadiani M, Shah Hosseini G, Isafhani M, Nasrabadi AN, Dadgostar
H. Avicenna the first to describe diseases which may be prevented by exercise. Iran J
Public Health 2012;41(11):98-101.
[111] Osler W. Suggested scheme for the restoration of the Tomb of Avicenna. Proc R Soc
Med 1914;7(Sect Hist Med):280.
[112] O’sullivan PM. The Canon Medicinae of Avicenna. Bull Med Libr Assoc
1928;17(3):14-5.
[113] Lichtwardt HA. Avicenna—philosopher and genius, teacher and surgeon. J Mich
State Med Soc 1950;49(5):568-72.
[114] Weaver AD. Avicenna, 980-1037. Works in the library of the New York Academy
of Medicine. Bull NY Acad Med 1955;31(4):334.
[115] Huard P. Avicenne (980-1037); Abou Ali al-Housayn ibn-Abdoullah ibn-Sina.
Concours Med 1956;78(50):5357-63. [French].
[116] Galdston I. Avicenna and Islamic science. Bull NY Acad Med 1955; 31(4): 300-1.
[117] Levy R. Avicenna—his life and times. Med Hist 1957;1(3):249-61.
[118] Kuprilanov VV. Outstanding contribution of the works of Avicenna to the history of
anatomy (on the occasion of the 1,000th anniversary of the birth of Avicenna). Arkh
Anat Gistol Embriol 1980;79(9):109-11. [Russian].
[119] Mannan AA, Kahvic M. Ibn Sina: a tribute. Gulf J Oncolog 2010;(7):60-3.
[120] Shamsi M, Haghverdi F, Changizi Ashtiyani S. A brief review of Rhazes, Avicenna,
and Jorjani’s views on diagnosis of diseases through urine examination. Iran J
Kidney Dis 2014;8(4):278-85.
[121] Bittar EE. A study of Ibn Nafis. Bull Hist med 1955;29:352-68.
[122] Coppola ED. The discovery of the pulmonary circulation: a new approach. Bull Hist
Med 1957;31:44-77.
[123] Masic I, Dilic M, Solakovic E, Rustemepasic N, Ridjanovic Z. Why historians of

medicine called Ibn al-Nafis the second Avicenna? Med Arh 2008;62(4):244-9.
[124] Masic I. On the occasion of 800th anniversary of birth of Ibn al-Nafis—discoverer of
cardiac and pulmonary circulation. Med Arh 2010;64(5):309-13.
[125] Akmal M, Zulkifle M, Ansari A. Ibn Nafis—a forgotten genius in the discovery of
pulmonary blood circulation. Heart Views 2010;11(1):26-30.
[126] Rodin FH. Moses Maimonides: Great physician, scientist, and philosopher. Cal West
Med 1936;44(3):192-6.
[127] Barr SE. Moses Maimonides. N Engl J Med 154;250(18):779-80.
[128] Rosner F. Nephrology and urinalysis in the writings of Moses Maimonides. Am J
Kidney Dis 1994;24:222-7.
[129] Gesundheit B. Maimonides’ appreciation for medicine. Rambam Maimonides Med J
2011;2(1):e0018. doi: 10.5041/RMMJ.10018.
[130] Connor H. Moses Maimonides (1135-1204). J Med Biogr 2009;17(1):13. doi:
10.1258/jmb.2008.008005.
[131] Cantwell JD. On camel rides and Moses Maimonides. Proc (Bayl Univ Med Cent).
2015;28(3):406-8.
[132] Rosner F, Muntner S. Moses Maimonides’ aphorisms regarding analysis of urine.
Ann Intern Med 1969;71(1):217-20.
[133] Massry SG. Maimonides: physician and nephrologist. Am J Neprhol 1994;14(4-
6):307-12.
[134] Kaltenstadler W. Life is short, art is long: Medical works of Moses Maimonides.
Dtsch Med Wochenschr 2010;135(51-52):2563-6. [German].
[135] Rosner F, Muntner S, eds. The medical aphorisms of Moses Maimonides.
NewvYork: Yeshiva Universtiy Press, 1971.
[136] Eknoyan G. On the contributions of Paracelsius to nephrology. Nephrol Dial
Transplant 1996;11:1138-94.
[137] Medvei VC. The 16th century and the Renaissance. In: Medvei VC, ed. The history
of clinical endocrinology: A comprehensive account of endocrinology from earliest
times to the present day. New York: Parthenon Publishing, 1993:55-6,97.
[138] Morley H. The life of Girolamo Cardano of Milan, Physician 2 volumes. London:
Chapman Hall, 1854.
[139] Ongaro G. Girolamo Cardano and Andreas Vesalius. Riv Stor Med 1969;13(1):51-
61. [Italian].
[140] Regöly-Mérei G. The life and scientific activity of Girolamo Cardano. Orv Hetil
1971;112(38):2291-3. [Hungarian].
[141] Simili A. The figure and work of Girolamo Cardano. Riv Stor Med 1970;14(1):3-18.
[Italian].
[142] Scarani P. Out of control: the life of Gerolamo Cardano (1501-1576). Pathologica
2001;93(5):565-74. [Italian].
[143] Antonello A, Calo L, Bonfante L, Mennella G, Abaterusso C, Spinello M, et al.
Giovanni Battista Morgagni, a pioneer of clinical nephrology. Am J Nephrol
1999;19:222-5.
[144] Fischer WJ. Thomas Sydenham, the English Hippocrates: (1624-1689). Can Med
Assoc J 1913;3(11):931-46.
[145] No Authors listed. Thomas Sydenham (1624-1689). Can Med Assoc J

1924;14(10):983-4.
[146] Bloch H. Thomas Sydenham, MD (1624-1689): the father of clinical observation. J
Fam Pract 1994;38(1):80-1.
[147] Low G. Thomas Sydenham: the English Hippocrates. Aust NZ J Surg
1999;69(4):258-62.
[148] Anstey P. The creation of the English Hippocrates. Med Hist 2011;55(4):457-78.
[149] Hamid A, Mohd A, Tanzeel A, Naghma C. Diabetes mellitus from antiquity to
present scenario and contribution of Greco-Arab physicians. JISHIM 2006;5:46-50.
[150] Willis T. Pharmaceutice rationalis or an exercitation of the operations in humane
bodies. London: Dring Harper Leigh, 1678.
[151] Willis T. Founders of modern medicine. I Thomas Willis, MA, MD (1621-1675).
Med Library Hist J 1903;1(4):264-70.
[152] van Gijn J, Gijselhart JP. Willis and his circle. Ned Tijdschr Geneeskd
2012;156(12):A4653. [Dutch].
[153] Feindel W. Thomas Willis (1621-1675)-The founder of neurology. Can Med Assoc J
1962;87(6):289-96.
[154] Ahmed AM. History of diabetes mellitus. Saudi Med J 2002;23(4):373-8.
[155] Stylianou C, Kelnar C. The introduction of successful treatment of diabetes mellitus
with insulin. J R Soc Med 2009;102(7):298-303.
[156] Allan FN. The writings of Thomas Willis, MD; Diabetes 300 years ago. Diabetes
1953;2(1):74-7.
[157] Greydanus DE, Hofmann AD. Psychological factors in diabetes mellitus. Am J Dis
Child 1979;133:1061-6.
[158] Bosmia AN, Tubbs RI, Clapp DC, Batzdorf U, Loukas M, Tubbs RS. Johann Conrad
Brunner (1653-1727) and the first description of syringomyelia. Child Nerv Syst
2014;30(2):193-6.
[159] Keck FS, Pfeiffer EF. The first experimental diabetes mellitus. Acta Diabetol Lat
1989;26(1):79-81.
[160] Brunner JC. Experimenta nova circa pancreas, accedit diatribe de lympha et gemino
pancreatis usu. Amsterdam: Apud H Wetstenium, 1683.
[161] Keck FS, Duntas LH. Brunner’s missing ‘Aha experience’ delayed progress in
diabetes research by 200 years. Hormones (Athens) 2007;6(3):251-4.
[162] Dobson M. Experiments and observations on the urine in diabetes. In: Medical
Observations and Inquiries. Volume 5. London: T Cadell, 1776:298-316.
[163] Williamson RT. English physicians of the past. Newcastle: Andrew Reid, 1923:47-
52.
[164] Polonsky KS. The past 200 years in diabetes. N Engl J Med 2012;367:1332-40.
[165] Furdell EL. Fatal thirst. Diabetes in Britain until insulin. Leiden, Netherlands: Brill,
2009:81-92.
[166] Sanders LJ. From Thebes to Toronto and the 21 st century: an incredible journey.
Diabetes Spectrum 2002;15(1):56-60.
[167] Kerr CE, Milne I, Kaptchuk TJ. William Cullen and a missing mind-body link in the
early history of placebos. J R Soc Med 2008;101(2):89-92.
[168] Cawley TA. Singular case of diabetes, consisting entirely in the quality of urine;
with an inquiry into the different theories of that disease. London Med J 1788;9:286-
308.
[169] Longo LD. Classic pages in obstetrics and gynecology: an account of a particular
change of structure in the human ovarium. Matthew Baillie, 1789. Am J Obstet
Gynecol 1975;123(7):770.
[170] Young RH. The history of British gynaecological pathology. Histopathology.
2009;54(2):144-55.
[171] Somebody. The introduction of successful treatment of diabetes mellitus with
insulin. R Soc Med 2009;102(7):298-303.
[172] Baillie M. The morbid anatomy of some of the most important parts of the human
body, 2nd ed. London: J Johnvson, 1797.
[173] Rollo J. Causes of the diabetes mellitus, 2nd ed. London: C Dilly, 1798.
[174] Rollo J. An account of two cases of the diabetes mellitus,with remarks as they arose
during the progress of the cure. London: C Dilly, 1797.
[175] Lemay P. Michel Eugene Chevreul (1786-1889). J Chem Educ 1948;25(2):62.
[176] Bourgougnon A. Michel Eugéne Chevreul. 1786-1889. J Am Chem Soc
1989;11(5):71-79.
[177] Chevreul ME. Note sur le sucre de diabetes. Ann Chim 1815;95:319-20.
[178] Fehling H. Die quantitative Bestimmung von Zucker und Stärkmehl mittelst
Kupfervitriol. Ann Chemie Pharmacie 1849;72(1):106-13.
[179] Elliotson J. The principles and practice of medicine. London: J Butler, 1839.
[180] Ridgway ES. John Elliotson (1791-1868): a bitter enemy of legitimate medicine?
Part II: The mesmeric scandal and later years. J Med Biogr 1994;2:1-7.
[181] Todd EM. An itinerant mermerist. Anaesth Intensive Care 2012;40(Suppl 1):5-9.
[182] Wittke G. Claude Bernard (1813-1878)-remarks on his methodology. Berl Munch
Tierarztl Wochenschr 1994;107(2):37-42. [German]
[183] Jörgens V, Grüsser M. Happy birthday, Claude Bernard. Diabetes 2013;62(7):2181-
2.
[184] Bernard C. Introduction ? l’étude de la Médecine Expérimentale. Paris: J-B Bailliére,
1865.
[185] Bernard C. De l’origine du sucre dans l’?conomie animale. Arch Gen Med
1848;18:303-319. [French].
[186] Foster M. Claude Bernard: a lecture. BMJ 1878;1(903):559-60.
[187] Rodriquez de Romo AC, Borgstein J Claude Bernard and fat emulsion (or the
Sleeping Beauty 150 years later). Gac Med Mex 2000;136():379-86. [Spanish]
[188] Han KW. The formation and background of Claude Bernard’s general physiology.
Uisahak 2010;19(2):507-52. [Korean].
[189] Noble D. Claude Benard, the first systems biologist, and the future of physiology.
Exp Physiol 2008;93(1):16-26.
[190] Bernard C. Mémoire sur le pancréas et sur le rôle du suc pancréatique dans les
phénomènes digestifs, particulièrement dans la digestion des matières grasses
neutres. Comptes rendus hebdomadaires de l’Académie des sciences 1856;1:379–
563.
[191] Friedman A. Fluid and electrolyte therapy: a primer. Pediatr Nephrol

2010;25(5):843-6.
[192] Harrison HE, Darrow DC, Yannet H. The total electrolyte content of animals and its
probable relation to the distribution of body water. J Biol Chem 1936;113:515-29.
[193] Gamble JL. Chemical anatomy, physiology and pathology of extracellular fluid: a
lecture syllabus. Boston, MA: Harvard University Press, 1947.
[194] Granger A, Kushner JA. Cellular origins of beta cell regeneration: a legacy view of
historical controversies. J Intern Med 2009;266(4):326-38.
[195] Rosenfeld L. William Prout: early 19th century physician-chemist. Clin Chem
2003;49(4):699-705.
[196] Prout W. On the nature and treatment of stomach and renal diseases, 5th ed. London:
Churchill, 1848.
[197] Brock WH. The life and work of William Prout. Med Hist 1965;9:101-26.
[198] No authors listed. William Prout (1785-1850) analytical chemist. JAMA
1968;206(5):1079-80.
[199] Copeman WS. William Prout, M.D., FRS. Physician and chemist (1785- 850). Notes
Rec R Soc Lond 1970;24:273-80.
[200] No authors listed. William Prout (1785-1859). Nutrition classics: Philosophical
Transactions of the Royal Society of London. For the year MDCCCXXVII. Part I.
Volume CXVII:355-388, 1827. XXIII. On the ultimate composition of simple
alimentary substances; with some preliminary remarks on the analysis of organized
bodies in general. By William Prout. Nutr Rev 1975;33(4):112-4.
[201] Ahrens R. William Prout (1785-1850): a biographical sketch. J Nutr 1977;
107(1):17-23.
[202] Nwaneri C. Diabetes mellitus: a complete ancient and modern historical perspective.
WebmedCentral Diabetes 2015;6(2):WMC004831.
[203] Kark RM. A propect of Richard Bright on the centenary of his death, December 16,
1958. Am J Nephrol 1958;6:819-24.
[204] Dock W. Proteinuria: the story of 280 years of trials, errors, and rectifications. Bull
NY Acad Med 1974;50:659-66.
[205] Bright R. Reports of medical cases. Selected with a view of illustrating the
symptoms and cure of diseases by a reference to morbid anatomy. London: Longman
Rees Orme Brown Green, 1827.
[206] Weller RO, Nester B. Historical reassessment of three kidneys originally described
by Richard Bright in 1827-36. BMJ 1972;2(5816):761-3.
[207] Dunea G. History of nephrology: the middle period. Hektoen Internat: J Med
Humanities. URL: http://www.hektoeninternational.org/HON-beginnings.html.
[208] MacKenzie JC. Dr. Richard Bright—a man of many parts. His bicentenary year—
1789-1858. Bristol Med Chir J 1989;104(3):63-7.
[209] Mukhin NA. Richard Bright and the nephrological theory of E.M. Tareev. Klin Med
(Mosk) 1990;68(1):4-7. [Russian].
[210] Young RH. Dr. Richard Bright—father of medical renal disease. Arch Pathol Lab
Med 2009;133(9):136.
[211] Apollinaire B. De la Glycosurie ou diabète sucré, son traitement hygénigue. Paris:
Libraire Germer Bailliére, 1883.
[212] Bouchardat A. Nouveau mémoire sur la glycosurie. Comptes rendus des séances de
l’Académie des sciences 1845;20:1020.
[213] Chast F. Apollinaire Bouchardat, pharmacist, nutritionist. Ann Pharm Fr 2000;58(6
Suppl):435-42. [French].
[214] Chast F, Slama G. Apollinaire Bouchardat and diabetes. Hist Sci Med
2007;41(3):287-301. [French].
[215] Trépardoux F, Ségal A. Bouchardat and hygienic medicine. Hist Sci Med
2007;41(3):279-86. [French].
[216] Karamanou M, Koutsilieris M, Laios K, Marineli F, Androutsos G. Apollinaire
Bouchardat (1806-1886): founder of modern diabetology. Hormones (Athens)
2014;13(2):296-300.
[217] Lancereaux E. Note et réflexions sur deux cas de diabéte sucrè avec alteration du
pancrèas. Bull Acad Med 1877;6:1215.
[218] Lancereaux E. Le diabéte maigre: ses symptomes, son évolution, son prognostic et
son traitment; ses rapports avec les altérations du pancréas. Etude comparative du
diabéte maigre et du diabéte gras. In: Delahaye A, Lecrosnier E, eds. Lecons de
Clinique Médicale: Paris: 1883:5–16.
[219] Peumery JJ. Étienne Lancereaux (1829-1910) sa vie, son oeuvre, ses découvertes
scientifiques. Hist Sci Med 1989;23(4):279-84.
[220] Lestradet H. The 75th anniversary of the discovery of insulin. Diabetes Metab
1997;23(1):112-7. [French].
[221] Leickert KH. Insulin precursors—a historical synopsis. First diabetes treatment trials
using pancreatic extracts. Arzneimittelforschung 1975;25(3):439-42. [German].
[222] Wolf G. Friedrich Theodor von Frerichs (1819-1885) and Bright’s disease. Am J
Nephrol 2002;22(5-6):596-602.
[223] No authors listed. Friedrich Theodor von Frerichs (1819-1885). JAMA
1963;186:511-2.
[224] Martini GA. Friedrich Theodor von Frerichs (1819-1885). Clinical picture of acute
liver atrophy. Internist (Berl) 1969;10(3):74-8.
[225] Schwarz U, Ritz E. Glomerulonephritis and progression----Friedrich Theodor von
Frerichs, a forgotten pioneer. Nephrol Dial Transplant 1997;12:2776-8.
[226] Thormann J, Steinberg H. Friedrich Theodor von Frerichs (1819-1885). J Neurol
2014;261(1):248-9.
[227] Young P, Finn BC, Bruetman JE, Buzzi A, Zylberman M. The outstanding
achievements of Adolf Kussmaul. Rev Med Chil 2012;140(4):538-44. [Spanish].
[228] Hoffmann KF. Memories of the clinician Adolf Kussmaul (1822-1902); special
reference to hydrotherapy. Hippokrates 1952;23(15):419-20.
[229] No authors listed. Adolf Kussmaul (1822-1902) – country doctor to clinical
professor. JAMA 1964:189:54-9.
[230] Nogaller AM. Adolf Kussmaul (1822-1902) as a doctor, scientist, teacher. Klin Med
(Mosk) 1999;77(6):63-4. [Russian].
[231] Johnson SK, Naidu RK, Ostopowicz RC, Kumar DR, Bhupathi S, Mazza JJ, et al.
Adolf Kussmaul: distinguished clinician and medical pioneer. Clin Med Res
2009;7(3):107-12.
[232] Kussmaul A. Zur Lehre vom Bailliere. Uber eine eigenthumliche to desart bei
Diabetischen, Uber Acetonamie. Glycerin-behandlung des Diabetes und
Einspritzungen von Diastase ins blit bei dieser Kranicheit. Deutsche Arch Klin
Med1874;14:1-46. [German]
[233] Breathnach CS, Westphal W. Adolf Kussmaul (1822-1902): from youth to maturity
under the influence of Virchow. J Med Biogr 2003;11(1):55-61.
[234] Noyes HD. Retinitis in glycosuria. Trans Am Ophthalmol Soc 1869;4: 71-5.
[235] Kalantzis G, Angelou M, Poulakou-Rebelako E. Diabetic retinopathy: An historical
assessment. Hormones 2006;5(1):71-4.
[236] Nettleship E. On oedema or cystic disease of the retinal. Roy Ophthal Lond Hosp
Rep 1872;VII:343-41.
[237] Mackenzie S, Nettleship E. A case of glycosuric retinitis. Roy Ophth Lond Hosp
Rep 1877;9:134.
[238] Lawford JB. British masters of ophthalmology series: Edward Nettleship FRS,
FRCS (1845-1913) Br J Ophthalmol 1923;7:nil4-9. doi: 10.1136/bjo.7.1.nil4.
[239] Wolfensberger TJ, Hamilton AM. Diabetic retinopathy—an historical review. Semin
Ophthalmol 2001;16(1):2-7.
[240] Naunyn B. Der diabetes mellitus. Wien: Alfred Holder, 1898.
[241] Brogard JM, Vetter T, Blickle JF. Discovery of pancreatic diabetes in Strasbourgh.
Diabet Metab 1992;18(2):104-14.
[242] Caldwell J. Drug metabolism and pharmacogenetics: the British contribution to
fields of international significance. Br J Pharmacol 2006;147(Suppl 1):S89-S99.
[243] Barach JH. Paul Langerhans, 1847-1888. Diabetes 1952;1(5):411-3.
[244] Campbell WR. Paul Langerhans, 1847-1888. Can Med Assoc J 1958;79(10):855-6.
[245] Becker V. 100 hundred years after Paul Langerhans’ doctoral thesis on the cells of
the pancreas. Dtsch Med Wochenschr 1970;95(7):358-62. [German].
[246] Wolff G, Schadenwaldt H. 1877-1977: Bibliographic annotations on Paul
Langerhans—the islands were his destiny. Med Welt 1977;28(1):1-7. [German].
[247] Ebling FJG. Homage to Paul Langerhans. J Invest Dermatol 1980;75:3-5.
[248] Sakula A. Paul Langerhans (1847-1888): a centenary tribute. J R Soc Med
1988;81(7):414-5.
[249] Jollies S. Paul Langerhans. J Clin Pathol 2002;55(4):243.
[250] Langerhans P. Beiträge zur mikroscopischen anatomie der bauchspeichel druse.
Dissertation. Berlin: Gustav Lange, 1869. [German].
[251] Morrison H. Contributions to the microscopic anatomy of the pancreas by Paul
Langerhans (Berlin, 1869). Reprint of the German original with an English
translation and an introductory essay. Bull Inst Hist Med 1937;5:259-97.
[252] Fossati P. Edouard Laguesse at Lille in 1893 created the term “endocrine” and
opened the endocrinology era. Hist Sci Med 2004;38(4):433-9. [French].
[253] Laguesse E. Sur la formation des ilots de Langerhans dans le pancreas. Comptes
Rendus Hebdomadaires des Seances et Memoires de la Societe de Biologie
1893;5:819–820. [French].
[254] Laguesse E. Recherches sur l’histogénie du pancreas chez le mouton. J Anat Physiol
1895;31:475–500.
[255] Laguesse E. Sur la formation des ilots de Langerhans dans le pancreas. Comptes
Rendus Hebdomadaires des Seances et Memoires de la Societe de Biologie
1893;5:819–20.
[256] Debeyre A. How insulin was discovered; corollary on the scientific research of the
Dijon physician Gustave-Edouard Laguesse, former professor emeritus of the Lille
Univeristy Medical faculty. Prog Med (Paris) 1956;84(23):442.
[257] Goet JP. Gustave Edouard Laguesse; his demonstration of the significance of the
islands of Langerhans. Diabetes 1953;2(4):322-4.
[258] Dickinson WH. Diabetes. Disease of the kidney. London: Longsmans Green, 1875.
[259] von Mering JV, Minkowski O. Diabetes mellitus nach pankreasextirpation. Zbl Klin
Med 1889;10:393-4. [German]
[260] Von Mering JV, Minkowski O. Diabetes mellitus nach pankreasexstirpation. Arch
Pathol Pharmak 1889-1890;26:371-87. [German].
[261] Minkowski O. Die Lehre vom pancreas. Diabetes in ihrer geschichtlichen
Entwicklung. Munch Med Wschr 1929;76:311-5. [Germna].
[262] No authors listed. Oskar Minkowski (1858-1931): designer of experimental diabetes.
JAMA 1967;199:754-5.
[263] Kaiser W, Völker A. Oscar Minkowski (1858-1931). Z Gesamte Inn Med
1981;36(24):973-9. [German].
[264] Jörgens V. Oscar Minkowski (1858-1931): An outstanding master of diabetes
research. Hormones (Athens) 2006;5(4):310-1.
[265] Brogard JM, Blickle JF. History of the rhenish and alsacian contributions to the
understanding of diabetes. Hist Sci Med 2004;38(4):421-32. [French].
[266] Dittrich HM, Hahn Von Dorshe H. The anatomical and histological investigation of
the pancreas in the 19th century and till the discovery of insulin (1921). The
discovery of the pancreas-diabetes by von Mering and Minkowski (1889). Anat Anz
1978;143(5):509-17.
[267] Savona-Ventura C. The history of diabetes aellitus. A Maltese perspective. Malta:
Self Publication, 2002. URL: http://staff.wm.edu.mt/csav1/books/diabetes_hist.pdf.
[268] Kidd JG. Eugene Lindsay Opie, MD, 1873-1971. Am J Pathol 1971;65(3):483-92.
[269] Olcott CT. Introductory remarks on the presentation of the twenty-first Middleton
Goldsmith lecture. Bull Y Acad Med 1955;31(4):275-9.
[270] Menon S, Rajesh G, Balakrishman V. Pancreas and diabetes mellitus: The
relationship between the organ and the disease. J Assoc Phys India 2015;63:).1-5.
[271] Opie EL. Ssobolew and insulin. Can Med Assoc J 1952;67(5):482.
[272] Opie EL. Pathological changes affecting the islands of Langerhans of the pancreas. J
Boston Soc Med Soc 1900;4(10):251-60.
[273] Opie EL. On the relationship of chronic interstitial pancreatitis to the islands of
Langerhans and to diabetes mellitus. J Exp Med 1901;5(4):397-428.
[274] Opie EL. Diabetes mellitus associated with hyaline degeneration of the islands of
Langerhans of the pancreas. Johns Hopkins Hosp Bull 1901;12(125):263 .
[275] Rous P. An inquiriy into certain aspects of Eugene L Opie. Arch Path 1942;34:1-6.
[276] Hughes J. Eugene L. Opie. Diabetes 1958;7(6):496-9.
[277] Hirsch JG. Eugene L. Opie, 1873-1971. Trans Assoc Am Physicians 1971;84:31-4.
[278] Ssobolew LW. Zur normalen und pathologishen Morphologie der inneren Secretion
der Bauchspeicheldruse. Arch Pathol Anatomie Physiol Klin Med 1902; 168:91–
128. [German].
[279] Granger A, Kushne JA. Ceulluar origins of cell regeneration: a legacy view of
historical controversies. J Intern Med 2009;266(4):325-338. doi: 10.1111/j.1365-
2796.2009.02156.x.
[280] Schulze W. Die Bedeutung der Langerhansschen Inseln im Paukreas. Arch Mikr
Anat 1900;56:491–504. [German].
[281] Bayliss WM, Starling EH. The mechanism of pancreatic secretion. J Physiol
1902;28(5):325-53.
[282] Henriksen JH. Earnest Henry Starling (1866-1927): the scientist and the man. J Med
Biogr 2005;13(1):22-30.
[283] Henriksen JH, Schaffalitzky de Muckadell OB. Secretin—the first hormone. Ugeskr
Laeger 2002;164(3):320-5. [Danish].
[284] Scott RV, Tan TM, Bloom SR. Can Bayliss and Starling gut hormones cure a
worldwide pandemic? J Physiol 2014;592(1):5153-67.
[285] Zuelzer GL. Über versuche einer specifischen fermentherapie des diabetes. Zeitshrift
Exp Pathol Ther 1908;5:307-18. [German].
[286] Mellinghoff KH. Georg Ludwig Zuelzer’s contribution to the research on pancreatic
extracts. Med Welt 1972;23(16):622-6. [German].
[287] Saudek CD. 2002 Presidential address: A tide in the affairs of medicine. Diabetes
Care 2003;26(2):520-5.
[288] Bliss M. The discovery of insulin. Chicago, IL: Univ Chicago, 1982.
[289] Banting FG. Diabetes and insulin. Can Med Assoc J 1926;26(3):221-31.
[290] Lane MA. The cytological characters of the areas of Langerhans. Am J Anat
1907;7:409–22.
[291] Bensley RR. Studies on the pancreas of the guinea pig. Am J Anat 1911;12:297–388.
[292] Gupta V, Garg K, Raheja S, Choudhry R, Tuli A. The histogenesis of islets in the
human fetal pancreas. J Anat Soc India 2002;51(1):23-6.
[293] Granger A, Kushner JA. Cellular origins of beta cell regeneration: a legacy view of
historical controversies. J Intern Med 2009;266(4):325-38.
[294] Ferner H. The insular alpha and beta cells as the source of the antagonistic principles
glucagon and insulin. Mikroskopie 1951;6(1–2):1–8.
[295] No authors listed. Sir Edward Sharpey-Schafer, FRS, LLD, MD, DSc, FRCPEd.
BMJ 1935;1(3874):741-2.
[296] Schafer GMS. Sir Edward Sharpey-Schafer. BMJ 1935;1:801.
[297] Writer D. Resuscitation great. Sir Edward Sharpey-Schafer and his simple and
efficient method of performing artificial respiration. Resuscitation 2004;61(2):113-6.
[298] Sykes AH. Edward Schafer (1850-1935) and artificial respiration. J Med Biogr
2006;14(3):155-62.
[299] No authors listed. Old age the the vices. Russell L Cecil. J Am Geriatrics Soc
1953;1:604.
[300] Textbook Titan. MD Magazine 1958;March:78-9.
[301] In sedication to Dr. Cecil”. Arthritis Rheuma 1963;6:vii-viii.
[302] In memoriam. Walsh McDermott (plus brief vita). Arthritis Rheuma 1965;8:577-80.
[303] McDermott W. Russell Lafayette Cecil. Trans Am Clin Climatol Assoc

1966;77:xlvi-xlvii.
[304] Cecil RL. On hypertrophy and regeneration of the islands of Langerhans. J Exp Med
1911;14(5):500-19.
[305] Cecil RL, Vaughan HF. Results of prophylactic vaccination against pneumonia at
Camp Wheeler. J Exper Med 1919;29:457–83.
[306] Cecil RL, Larsen NP. Clinical and bacteriologic study of one thousand cases of lobar
pneumonia. JAMA 1922;79:343–9.
[307] Cecil RL, Sutliff WD. The treatment of lobar pneumonia with concentrated anti-
pneumococcus serum. JAMA 1928;91:2036–40.
[308] Cecil RL, Plummer N. Pneumococcus Type 1 pneumonia: a study of eleven hundred
and sixty-one cases, with especial reference to specific therapy. JAMA
1931;95:1547–53.
[309] Neuhauser D, Diaz M, Chalmers I. A puzzling omission in a gret medical textbook
edited by a pioneer of controlled trials. J R Soc Med 2008;101(7):381-383.
[310] Cecil RL. Textbook of medicine. Philadelphia, PA: WB Saunders, 1927.
[311] Goldman L, Schafer AI, eds. Goldman-Cecil medicine, 25th ed. Philadelphia, PA:
Elsevier, 2016.
[312] Scott EL. The relation of pancreatic extract to the sugar in the blood. Proc Soc exp
Med Biol 1913;10:101-3.
[313] Boehm R, Hoffmann FA. Beiträge zur Kentniss des Kohlehydratsoff- wechsels.
Arch Exp Pathol Pharmakol 1878;8:295-304. [German].
[314] Macleod JJR. Studies in experimental glycosuria: I. On the existence of afferent and
efferent nerve fibers, controlling the amount of sugar in the blood. Am J Physiol
1907;19:388-406.
[315] Drinker CK. Walter Bradford Cannon 1871-1945. Science 1945; 102(2654):470-2.
[316] Iaroshevskiĭ MG. Chesnokova SA. Centenary of the birth of Walter Bradford
Cannon (1871-1945). Fiziol Zh SSSR Im I M Sechenova 1971;57(10):1559-62.
[Russian].
[317] Joaquin Izquierdo J. Walter Bradford Cannon (1871-1945). His human general
personality. In memoriam. Gac Med Mex 1972;104(1):73-6. [Spanish].
[318] Gorisch E, Gorisch R. Walter Bradford Cannon (1871-1945). The professional
activities of an outstanding physiologist. Z Gesamte Hyg 1990;36(7):368-70.
[German].
[319] Cooper SJ. From Claude Bernard to Walter Cannon. Emergence of the concept of
homeostatis. Appetite 2008;51(3):419-27.
[320] Cannon WB, Shohl AT, Wright WS. Emotional glucosuria. Am J Physiol
1911;29:280-7.
[321] Cannon WB. The secretion of the adrenal glands during emotional excitement.
Science 1911;2:907.
[322] Henderson Y, Underhill FP. Acapnia and glycosuria. Am J Physiol 1911; 28:275-89.
[323] Knox WE. Sir Archibald E Garrod. Genetics 1967;56(1):1-6.
[324] Dronamraju K. Profiles in genetics: Archibald E. Garrod (1857-1936). Am J Hum
Genet 1992;51(1):216-9.
[325] Garrod AE. Lettsomian lectures on glycosuria. Lancet 1912;1:480-8.
[326] Folin O, Denis W, Smillie WG. Some observations on “emotional glycosuria” in

man. J Biol Chem 1914;17:519-20.
[327] Allen FM. Studies concerning glycosuria and diabetes, Cambridge, MA: Harvard
University Press, 1913.
[328] Allen FM, Stillman E, Fitz R. Total dietary regulation in the treatment of diabetes.
New York: Rockefeller Institute Medical Research, Monograph 11, 1919.
[329] Duncan GG. Frederick Madison Allen 1879-1964. Diabetes 1964;13:318-9.
[330] No authors listed. Frederick Madison Allen 1879-1964. Metabolism 1964;13:383-5.
[331] Grott JW, Swiezawska E. Frederick Madison Allen (1879-1964) and his
contributions to the knowledge of diabetes mellitus. Pol Tyg Lek 1965;20(49):1872.
[Polish].
[332] Mazur A. Why were “starvation diets” promoted for diabetes in the pre-insulin
period? Nutr J 2011;10:23. doi: 10.1186/1475-2891-10-23.
[333] Westman EC, Yancy WS Jr., Humphreys M. Dietary treatment of diabetes mellitus
in the pre-insulin era (1914-1922). Perspect Biol Med 2006;49(1):77-83.
[334] Barnett DM. Elliot Proctor Joslin. American National Biography. New York: Oxford
Press, 1999:282–83.
[335] Joslin EP. The obligation and the opportunity of the chiropodist in the treatment of
diabetes. J Am Podiatr Med Assoc 2007;97(4):271-3.
[336] Joslin EP. Influence of bile on metabolism. J Boston Soc Med Sci 1899;3(10):259-
63.
[337] Joslin EP. Present day treatment and prognosis in diabetes. Am J Med Sci
1915;150:485-96.
[338] Beaser RS, Campbell A. The Joslin guide to diabetes. Boston, MA: Joslin Diabetic
Center, 2016.
[339] Kleiner IS, Meltzer SJ. Retention in the circulation of dextrose in normal and
depancreatized animsl and the effects of an intravension injection of an emulsion of
pancreas upon this retention. Proc Nat Acad Sc 1915;1:338-40.
[340] Kleiner IS. The actions of the intravenous injections of pancreatic emulsions in
experimental diabetes. J Biochem 1919;40:153-70.
[341] Kleiner IS. The action of intravenous injections of pancreas emulsions in
experimental diabetes. Am J Physiol 1919;29:306-10.
[342] Barthold SW. Unsung heroes in the battle against diabetes. ILAR J 2004;45(3):227-
30.
[343] Tattersal R. Pancreatic organotherapy for diabetes, 1889-1921. Med Hist
1995;39(3):288-316.
[344] James T. History of medicine. Paulesco. S Afr Med J 1992;82(2):123-5.
[345] Dominguez LJ, Licata G. The discovery of insulin: what really happened 80 years
ago. Ann Ital Med Int 2001;16(3):155-62. [Italian].
[346] Laron Z. Nicolae C. Paulescu—scientist and politician. Isr Med Assoc J
2008;10(7):491-3.
[347] Paulesco NC. Action de l’extrait pancreatique injecte dans le sang, chez un animal
diabetique. Comptes Rendus des Seances de la Societe de Biologie 1921;85:555–9.
[French].
[348] D Haulica I. Professor Nicolae C. Paulesc-the true discoverer of insulin. Rev Med
Chir Soc Med Nat Iasi 2001;105(3):602-5. [Romanian].
[349] Roth J, Qureshi S, Whitford I, Vranic M, Kahn CR, Fantus IG, et al. Insulin’s
discovery: new insights on its ninetieth birthday. Diabetes Metab Res Rev
2012;28(4):293-304.
[350] Bliss M. The eclipse and rehabilitation of JJR Macleod, Scotland’s insulin laureate. J
R Coll Physicians Edinb 2013;43(4):366-73.
[351] Pavel I, Sdrobici D. N. Paulescu, discoverer of insulin. 50th anniversary of the
discovery of that hormone. Med Interna (Bucur) 1972;24(11):1285-94. [Romanian].
[352] Kenéz J. Who invented insulin? (Charles H. Best, Frederick Grant Banting). Orv
Hetil 1978;119(44):2693-9. [Hungarian]
[353] No authors listed. Frederick Grant Banting (1891-1941), codiscovered of insulin.
JAMA 1966;198(6):660-1.
[354] Raju TN. A mysterious something: the discovery of insulin and the 1923 Nobel Prize
for Frederick G Banting (1891-1941) and John JR Macleod (1876-1935). Acta
Paediatr 2006;95(10):1155-6.
[355] Berche P, Lefrère JJ. The return to life with insulin. Ann Endocrinol (Paris)
2010;71(4):243-8. [French]
[356] De Herder WW. Heroes in endocrinology: Nobel Prizes. Endocr Connect
2014;3(3):R94-R104.
[357] Pai-Dhungat JV, Parikh F. Frederick Banting (1891-1941). J Assoc Physicians India
2015;63(3):114.
[358] Barron M. The relation of the islets of Langerhans to diabetes with special reference
to cases of pancreatic lithiasis. Surg Gynec Obstet 1920;31:437–448.
[359] Hobart A, Reimann MD. Moses Barron and Banting. JAMA 1967;199(1):48.
[360] Shampo MA, Kyle RA. Charles Best—codiscoverer of insulin. Mayo Clin Proc
2004;79(12):1546.
[361] Macleod J. Insulin and diabetes. BMJ 1922;2:833.
[362] Macleod JJR: History of the researches leading to the discovery of insulin (1922),
letter of Macleod to Col. Albert Gooderham. Bull History Med 1978;52:295-312.
[363] Shampo MA, Kyle RA. Macleod John J.R.--Nobel prize for discovery of insulin.
Mayo Clin Proc 2006;81(8):1006.
[364] Banting FG, Best CH. Pancreatic extracts. J Lab Clin Med 1922;7:464–72.
[365] Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA. Pancreatic extracts in
the treatment of diabetes mellitus. Preliminary report. Can Med Assoc J
1922;12:141–146.
[366] Noble RL. Memories of James Bertram Collip. Can Med Assoc J 1965;
93(26):1356-1364.
[367] Barr ML, Rossiter RJ. James Bertram Collip 1892-1965. Biogr Mem Fellows R Soc
1973;19:234.
[368] Bangham DR. H.H. Dale and the London Centre for WHO standards—some
milestones of the early years. Dev Biol Stand 1999;100:11-5.
[369] Harvey AM. Pharmacology’s giant: John Jacob Abel. Johns Hopkins Med J Suppl
1974;135(4):245-58.
[370] Murnaghan JH, Talalay P. John Jacob Abel and the crystallization of insulin.
Perspect Biol Med 1967;10(3):334-80.
[371] Himsworth HP. Diabetes mellitus: its differentiation into insulin-sensitive and
insulin-insensitive types. Diabet Med 2011;28(12):1440-4. (Reprinted from
Management of diabetes mellitus, BMJ 1936).
[372] Black D, Gray J. Sir Harold Percival Himsworth, K.C.B.-19 May 1905—1
November 1993. Biogr Mem Fellows R Soc 1995;41:199-218.
[373] Himsworth R. Sir Harold Himsworth. Diabet Med 2011;28(11):1438-9.
[374] Krentz AJ, Hitman GA. Sir Harold Himsworth and insulin insensitivity 75 years on.
Diabet Med 2011;28(12):1435.
[375] Sanger F. The free amino groups of insulin. Biochem J 1945;39(5):507-15.
[376] Sanger F, Thompson EO, Kitai R. The amide groups of insulin. Biochem J
1955;59(3):509-18.
[377] Sanger F. Chemistry of insulin: determination of the structure of insulin opens the
way to greater understanding of life processes. Science 1959;129(3359):1340-4.
[378] Deckert T. Hans Christian Hagedorn (1888-1971). Ugeskr Laeger
2007;169(35):2883. [Danish].
[379] Poulsen JE. Hans Christian Hagedorn (1888-1971. Dan Medicinhist Årbog 1978;9-
45. [Danish].
[380] Kruse PR. The hospital pharmacies in Copenhagen and their professional
importance. Dan Medicinhist Årbog 2005;33:163-70. [Danish].
[381] Philipson LH, Bell G, Polonsky KS. Donald F. Steiner MD, 1930-2014: Discoverer
of proinsulin. PNAS (Proc Nat Acad Sci) 2015;112(4):940-1.
[382] Frandsen CS, Dejgaard TF, Madsbad S. non-insulin drugs to treat hyperglycaemia in
type 1 diabetes mellitus. Lancet Diabetes Endocrinol 2016 Mar 8. pii: S2213-
8587(16)00039-5.
[383] Kooti W, Farokhipour M, Asadzadeh Z, Ashtary-Larky D, Asadi-Samani M. The
role of medicinal plants in the treatment of diabetes; a systematic review. Electron
Physician 2016;8(1):1832-42.
[384] Röder PV, Wu B, Liu Y, Han W. Pancreatic regulation of glucose homeostasis. Exp
Mol Med 2016;48:e219.
[385] Salas-Salvado J, Guasch-Ferré M, Lee CH, Estruch R, Clish CB, Ros E. Protective
effects of the Mediterranean diet on type 2 diabetes and metabolic syndrome. J Nutr
2016 Mar 9. pii:jn218487.
[386] Voormolen DN, Abell SK, James R, Hague WM, Mol BW. Diagnostic criteria and
treatment for gestational diabetes mellitus. Semin Reprod Med 2016;34(2):102-9.
[387] Luczynski W, Glowinska-Olszewska B, Bossowski A. The influence of clinical and
genetic factors on the development of obesity in children with type 1 diabetes.
Diabetes Metab Res Rev 2016 Mar 6. doi: 10.1002/dmrr.2797.
[388] Backes JM, Kostoff MD, Gibson CA, Ruisinger JF. Statin-assocviated diabetes
mellitus: review and clinical guide. South Med J 2016;109(3):167-73.
[389] Brunström M, Carlberg G. Effect of antihypertensive treatment at different blood
pressure levels in patients with diabetes mellitus: systematic review and meta-
analyses. BMJ 2016 Feb 24;352:i717. doi: 10.1136/bmj.i717.
[390] Knip M, Siljander H. The role of the intestinal microbiota in type 1 diabetes mellitus.
Nat Rev Endocrinol 2016;12(3):154-67.
[391] Clements JN, Bello L. Insulin glargine 300 units/mL: a new basal insulin product for
diabetes mellitus. Am J Health Syst Pharm 2016;73(6):359-66.
[392] Barnosky A, Shah L, Meah F, Emanuele N, Emanuele MA, Mazhari A. A primer on
concentrated insuins: what an internist should know. Postgrad Med 2016 Feb 27.
[393] Dholakia S, Mittal S, Quiroga I, Gilbert J, Sharples E, Pleog RF et al. Pancreas
transplantation: past, present, future. Am J Med 2016 Mar 7. pii; S0002-
9343(16)30199-1.
[394] Jewett EA, Anderson MR, Gilchrist GS. The pediatric subspecialty workforce:
public policy and forces for change. Pediatrics 2005;116(5):1192-202.
[395] Pierce JS, Kozikowski C, Lee JM, Wysocki T. Type 1 diabetes in very young
children: a model of parent and child influences on management and outcomes.
Pediatr Diabetes 2015 Dec 29. doi: 10.1111/pedi.12351.
[396] Kim SH. Maturity-onset diabetes of the young: what do clinicians need to know?
Diabetes Metab J 2015;39(6):468-77.
[397] Greydanus DE. Endocrine disorders. In: Hofman AD, ed. Adolescent medicine.
Menlo Park, CA: Addison-Wesley, 1983:160-80.
[398] Greydanus DE, Hofmann AD. Endocrine disorders. In: Hofman AD, Greydanus DE,
eds. Adolescent medicine, 2nd ed. Norwalk, CT: Appleton Lange, 1989:231-56.
[399] Greydanus DE. Exercise and insulin-requiring diabetes mellitus. In: Luckstead EF,
Greydanus DE, eds. Medical care of the adolescent athlete. Los Angeles, CA:
Professional Medical Information, 1993:177-8.
[400] Greydanus DE. Endocrine disorders. In: Hofman AD, Greydanus DE, ds. Adolescent
medicine, 3rd ed. Norwalk, CT: Appleton Lange, 1997:314-47.
SECTION TWO: ACKNOWLEDGMENTS
Chapter 3
ABOUT THE AUTHORS
Donald E. Greydanus, MD, Dr. HC (Athens), FAAP, FSAM (Emeritus),

FIAP (HON) is Professor and Founding Chair of the Department of Pediatric
and Adolescent Medicine, as well as Pediatrics Program Director at the
Western Michigan University Homer Stryker MD School of Medicine
(WMED), Kalamazoo, Michigan, USA. He is also Professor of Pediatrics and
Human Development at Michigan State University College of Human
Medicine (East Lansing, Michigan, USA) as well as Clinical Professor of
Pediatrics at MSU College of Osteopathic Medicine in East Lansing,
Michigan, USA. Received the 1995 American Academy of Pediatrics’ Adele
D. Hofmann Award for “Distinquished Contributions in Adolescent Health”,
the 2000 Mayo Clinic Pediatrics Honored Alumnus Award for “National
Contributions to the field of Pediatrics,” and the 2003 William B Weil, Jr.,
MD Endowed Distinguished Pediatric Faculty Award from Michigan State
University College of Medicine for “National and international recognition as
well as exemplary scholarship in pediatrics.” Received the 2004 Charles R
Drew School of Medicine (Los Angeles, CA) Stellar Award for contributions
to pediatric resident education and awarded an honorary membership in the
Indian Academy of Pediatrics—an honor granted to only a few pediatricians
outside of India. Was the 2007-2010 Visiting Professor of Pediatrics at Athens
University, Athens, Greece and received the Michigan State University
College of Human Medicine Outstanding Community Faculty Award in 2008.
In 2010 he received the title of Doctor Honoris Causa from the University of
Athens (Greece) as a “distinguished scientist who through outstanding work
has bestowed praise and credit on the field of adolescent medicine
(Ephebiatrics).” In 2010 he received the Outstanding Achievement in
Adolescent Medicine Award from the Society for Adolescent Medicine “as a
leading force in the field of adolescent medicine and health.” In 2014 he was
selected by the American Medical Association as AMA nominee for the
ACGME Pediatrics Residency Review Committee (RRC) in Chicago,
Illinois, USA. Past Chair of the National Conference and Exhibition Planning
Group (Committee on Scientific Meetings) of the American Academy of
Pediatrics and member of the Pediatric Academic Societies’ (SPR/PAS)
Planning Committee (1998 to Present). In 2011 elected to The Alpha Omega
Alpha Honor Society (Faculty member) at Michigan State University College
of Human Medicine, East Lansing, Michigan. Former member of the Appeals
Committee for the Pediatrics’ Residency Review Committee (RRC) of the
Accreditation Council for Graduate Medical Education (Chicago, IL) in both
adolescent medicine and general pediatrics. Numerous publications in
adolescent health and lectureships in many countries on adolescent health. E-
mail: [email protected]
Joav Merrick, MD, MMedSci, DMSc, born and educated in Denmark is

professor of pediatrics, child health and human development, Division of
Pediatrics, Hadassah Hebrew University Medical Center, Mt Scopus Campus,
Jerusalem, Israel and Kentucky Children’s Hospital, University of Kentucky,
Lexington, Kentucky United States and professor of public health at the Center
for Healthy Development, School of Public Health, Georgia State University,
Atlanta, United States, the medical director of the Health Services, Division
for Intellectual and Developmental Disabilities, Ministry of Social Affairs and
Social Services, Jerusalem, the founder and director of the National Institute of
Child Health and Human Development in Israel. Numerous publications in the
field of pediatrics, child health and human development, rehabilitation,
intellectual disability, disability, health, welfare, abuse, advocacy, quality of
life and prevention. Received the Peter Sabroe Child Award for outstanding
work on behalf of Danish Children in 1985 and the International LEGO-Prize
(“The Children’s Nobel Prize”) for an extraordinary contribution towards
improvement in child welfare and well-being in 1987. E-mail:
[email protected]
Chapter 4
ABOUT THE DEPARTMENT OF PEDIATRIC

AND ADOLESCENT MEDICINE,
WESTERN MICHIGAN UNIVERSITY
HOMER STRYKER MD SCHOOL OF
MEDICINE (WMED), KALAMAZOO,
MICHIGAN, USA
MISSION AND SERVICE

The Western Michigan University Homer Stryker MD School of Medicine
was started in 2012 and its first class of medical students began in 2014. The
Department of Pediatric and Adolescent Medicine has a pediatric residency
program which is accredited by the Accreditation Council for Graduate
Medical Education (ACGME) in Chicago, Illinois, USA and the current
residency program in Pediatrics started in 1990.
The WMED Department of Pediatric and Adolescent Medicine has a
commitment to a comprehensive approach to the health and development of
the child, adolescent, and the family. The Department has a blend of academic
general pediatricians and pediatric specialists. Our Pediatric Clinic team
provides a broad spectrum of general well and sick child care (birth through 18
years) including immunizations, monitoring general physical and emotional
growth, motor skill development, sports medicine (including participation
evaluations and evaluation of common sports injuries), child abuse
evaluations, and psychosocial or behavioral assessment. WMED Pediatrics
believes in immunizations as a protection against preventative disease

processes. Our Pediatrics Clinic is undergoing a transformation to a patient-
centered medical home (PCMH). A patient-centered medical home is a way to
deliver coordinated and comprehensive primary care to our infants, children,
adolescents and young adults. It is a partnership between individuals and
families within a health care setting, which allows for a more efficient use of
resources and time to improve the quality of outcomes for all involved through
care provided by a continuity care team.
RESEARCH ACTIVITIES
The Department has a variety of research projects in adolescent medicine,
neurobehavioral pediatrics, adolescent gynecology, pediatric diabetes mellitus,
asthma, and cystic fibrosis. The WMED Department of Pediatric
and Adolescent Medicine has published a number of medical textbooks:
Essential adolescent medicine (McGraw-Hill Medical Publishers),
The pediatric diagnostic examination (McGraw-Hill), Pediatric and adolescent
psychopharmacology (Cambridge University Press), Behavioral pediatrics,
2nd edition (iUniverse Publishers in New York and Lincoln, Nebraska),
Behavioral pediatrics 3rd edition (New York: Nova Biomedical Books);
4th Edition: In press. Pediatric practice: Sports medicine (McGraw-Hill),
Handbook of clinical pediatrics (Singapore: World Scientific), Neuro-
developmental disabilities: Clinical care for children and young adults
(Dordrecht: Springer), Adolescent medicine: Pharmacotherapeutics in medical
disorders (Berlin/Boston: De Gruyter), Adolescent medicine:
Pharmacotherapeutics in general, mental, and sexual health (Berlin/Boston: De
Gruyter), Pediatric psychodermatology (Berlin/Boston: De Gruyter),
Substance abuse in adolescents and young adults: A manual for pediatric and
primary care clinicians (Berlin/Boston: De Gruyter), and tropical pediatrics
(New York: Nova); Second edition in press.
The Department has edited a number of journal issues published by
Elsevier Publishers covering pulmonology (State of the Art Reviews:
Adolescent Medicine—AM:STARS), genetic disorders in adolescents
(AM:STARS), neurologic/neurodevelopmental disorders (AM:STARS),
behavioral pediatrics (Pediatric Clinics of North America), pediatric
psychopharmacology in the 21st century (Pediatric Clinic of North America),
nephrologic disorders in adolescents (AM:STARS), college health (Pediatric
Clinics of North America), adolescent medicine (Primary Care: Clinics in
About the Department of Pediatric and Adolescent Medicine 79
Office Practice), behavioral pediatrics in children and adolescents (Primary

Care: Clinics in Office Practice), adolescents and sports (Pediatric Clinics of
North America), and developmental disabilities (Pediatric Clinics of North
America). The Department has also edited a journal issue on musculoskeletal
disorders in children and adolescents for the American Academy of Pediatrics’
AM:STARs; in April of 2013 a Subspecialty Update issue was published in
AM:STARs.
The department has developed academic ties with a variety of
international medical centers and organizations, including the Queen Elizabeth
Hospital in Hong Kong, Indian Academy of Pediatrics (New Delhi, India), the
University of Athens Children’s Hospital (First and Second Departments of
Paediatrics) in Athens, Greece and the National Institute of Child Health and
Human Development in Jerusalem, Israel.
Contacts
Professor Dilip R Patel, MD, current chair and Professor Donald E Greydanus,
MD, founding chair, Department of Pediatric and Adolescent Medicine
Western Michigan University Homer Stryker MD School of Medicine
1000 Oakland Drive, D48G, Kalamazoo, MI 49008-1284, United States
E-mail: [email protected]
and [email protected]
Website: http://www.med.wmich.edu
Chapter 5
ABOUT THE NATIONAL INSTITUTE

OF CHILD HEALTH AND HUMAN
DEVELOPMENT IN ISRAEL
The National Institute of Child Health and Human Development (NICHD) in

Israel was established in 1998 as a virtual institute under the auspices of the
Medical Director, Ministry of Social Affairs and Social Services in order to
function as the research arm for the Office of the Medical Director. In 1998
the National Council for Child Health and Pediatrics, Ministry of Health and
in 1999 the Director General and Deputy Director General of the Ministry of
Health endorsed the establishment of the NICHD.
MISSION
The mission of a National Institute for Child Health and Human Development
in Israel is to provide an academic focal point for the scholarly
interdisciplinary study of child life, health, public health, welfare, disability,
rehabilitation, intellectual disability and related aspects of human
development. This mission includes research, teaching, clinical work,
information and public service activities in the field of child health and human
development.
SERVICE AND ACADEMIC ACTIVITIES

Over the years many activities became focused in the south of Israel due to
collaboration with various professionals at the Faculty of Health Sciences
(FOHS) at the Ben Gurion University of the Negev (BGU). Since 2000 an
affiliation with the Zusman Child Development Center at the Pediatric
Division of Soroka University Medical Center has resulted in collaboration
around the establishment of the Down Syndrome Clinic at that center. In 2002
a full course on “Disability” was established at the Recanati School for Allied
Professions in the Community, FOHS, BGU and in 2005 collaboration was
started with the Primary Care Unit of the faculty and disability became part of
the master of public health course on “Children and society”. In the academic
year 2005-2006 a one semester course on “Aging with disability” was started
as part of the master of science program in gerontology in our collaboration
with the Center for Multidisciplinary Research in Aging. In 2010
collaborations with the Division of Pediatrics, Hadassah Hebrew University
Medical Center, Jerusalem, Israel around the National Down Syndrome Center
and teaching students and residents about intellectual and developmental
disabilities as part of their training at this campus.
RESEARCH ACTIVITIES
The affiliated staff have over the years published work from projects and
research activities in this national and international collaboration. In the year
2000 the International Journal of Adolescent Medicine and Health and in 2005
the International Journal on Disability and Human Development of De Gruyter
Publishing House (Berlin and New York) were affiliated with the National
Institute of Child Health and Human Development. From 2008 also the
International Journal of Child Health and Human Development (Nova Science,
New York), the International Journal of Child and Adolescent Health (Nova
Science) and the Journal of Pain Management (Nova Science) affiliated and
from 2009 the International Public Health Journal (Nova Science) and Journal
of Alternative Medicine Research (Nova Science). All peer-reviewed
international journals.
About the National Institute of Child Health and Human Development 83
NATIONAL COLLABORATIONS
Nationally the NICHD works in collaboration with the Faculty of Health
Sciences, Ben Gurion University of the Negev; Department of Physical
Therapy, Sackler School of Medicine, Tel Aviv University; Autism Center,
Assaf HaRofeh Medical Center; National Rett and PKU Centers at Chaim
Sheba Medical Center, Tel HaShomer; Department of Physiotherapy, Haifa
University; Department of Education, Bar Ilan University, Ramat Gan, Faculty
of Social Sciences and Health Sciences; College of Judea and Samaria in Ariel
and in 2011 affiliation with Center for Pediatric Chronic Diseases and
National Center for Down Syndrome, Department of Pediatrics, Hadassah
Hebrew University Medical Center, Mount Scopus Campus, Jerusalem.
INTERNATIONAL COLLABORATIONS
Internationally with the Department of Disability and Human Development,
College of Applied Health Sciences, University of Illinois at Chicago; Strong
Center for Developmental Disabilities, Golisano Children's Hospital at Strong,
University of Rochester School of Medicine and Dentistry, New York; Centre
on Intellectual Disabilities, University of Albany, New York; Centre for
Chronic Disease Prevention and Control, Health Canada, Ottawa; Chandler
Medical Center and Children’s Hospital, Kentucky Children’s Hospital,
Section of Adolescent Medicine, University of Kentucky, Lexington; Chronic
Disease Prevention and Control Research Center, Baylor College of Medicine,
Houston, Texas; Division of Neuroscience, Department of Psychiatry,
Columbia University, New York; Institute for the Study of Disadvantage and
Disability, Atlanta; Center for Autism and Related Disorders, Department
Psychiatry, Children’s Hospital Boston, Boston; Department of Pediatric and
Adolescent Medicine, Western Michigan University Homer Stryker MD
School of Medicine, Kalamazoo, Michigan, United States; Department of
Paediatrics, Child Health and Adolescent Medicine, Children's Hospital at
Westmead, Westmead, Australia; International Centre for the Study of
Occupational and Mental Health, Düsseldorf, Germany; Centre for Advanced
Studies in Nursing, Department of General Practice and Primary Care,
University of Aberdeen, Aberdeen, United Kingdom; Quality of Life Research
Center, Copenhagen, Denmark; Nordic School of Public Health, Gottenburg,
Sweden, Scandinavian Institute of Quality of Working Life, Oslo, Norway;
The Department of Applied Social Sciences (APSS) of The Hong Kong

Polytechnic University Hong Kong.
TARGETS
Our focus is on research, international collaborations, clinical work, teaching
and policy in health, disability and human development and to establish the
NICHD as a permanent institute in Israel in order to conduct model research
and together with the four university schools of public health/medicine in
Israel establish a national master and doctoral program in disability and human
development at the institute to secure the next generation of professionals
working in this often non-prestigious/low-status field of work.
Contact
Joav Merrick, MD, MMedSci, DMSc

Professor of Pediatrics
Medical Director, Health Services,
Division for Intellectual and Developmental Disabilities,
Ministry of Social Affairs and Social Services,
POB 1260, IL-91012 Jerusalem, Israel.
Chapter 6
ABOUT THE BOOK SERIES

“PUBLIC HEALTH: PRACTICES,
METHODS AND POLICIES”
Public health is a book series with publications from a multidisciplinary group

of researchers, practitioners and clinicians for an international professional
forum interested in the broad spectrum of public health issues. Books already
published:
 Rubin IL, Merrick J, eds. Environment and public health:

Environmental health, law and international perspectives. New York:
Nova Science, 2014.
 Shek DTL, Siu AMH, Merrick J, eds. Tomorrow’s leaders: Service
leadership and holistic development in Chinese university students.
New York: Nova Science, 2015.
 Siziya S, Mazaba ML, Merrick J, eds. Arbovirus: Public health
experience from Zambia. New York: Nova Science, 2015.
 Obeng C, Obeng SG, Merrick J, eds. Health issues in diverse cultures.
New York: Nova Science, 2015.
 Friedman BD, Merrick J, eds. Public health, social work and health
inequalities. New York: Nova Science, 2015.
 Rubin IL, Merrick J, eds. Environmental health disparities: Costs and
benefits of breaking the cycle. New York: Nova Science, 2016.
 Mazaba ML, Siziya S, Merrick J, eds. Smoking and adolescence:
International public health experiences. New York: Nova Science,
2016.
 Merrick J, ed. Public health: Some international perspectives. New

York: Nova Science, 2016.
 Greydanus DE, Merrick J. Medical history: Some perspectives. New
 Rubin IL, Merrick J, eds. Public health: International aspects on
environment and health. New York: Nova Science, 2016.
 Shek DTL, Ma C, Lin L, Merrick J, eds. Education in Hong Kong:
Service leadership for university students. New York: Nova Science,
2016.
 Shek DTL, Siu AMH, Leung H, Merrick J, eds. Higher education in
Hong Kong: Nurturing students to be caring service leaders. New
 Marufu T, Siziya S, Mazaba ML, Merrick J, eds. Measles:
Epidemiology and control of measles in the Gweru urban district in
Zimbabwe. New York: Nova Science, 2016.
 Hegamin-Younger C, Merrick J, eds. Caribbean adolescents: Misuse
and abuse of alcohol. New York: Nova Science, 2016.
Contact
Professor Joav Merrick, MD, MMedSci, DMSc

Medical Director, Health Services
Division for Intellectual and Developmental Disabilities
Ministry of Social Affairs and Social Services
PO Box 1260, IL-91012 Jerusalem, Israel
SECTION THREE: INDEX
INDEX
behavioral assessment, 77
# bicarbonate, 38
bile, 15, 68
20th century, 11, 13, 31, 33, 35, 41, 42, 43,
black teenagers, 6
44, 45, 46, 47, 50, 51
blood circulation, 59
21st century, 11, 15, 24, 43, 50, 51, 52, 55,
blood flow, 16, 19
57, 60, 78
blood pressure, 70
blood vessels, 17
A boils, 21
breathing, 37
active children, 3
adiposity, 55
C
adolescents, 3, 5, 7, 78, 86
adrenal glands, 67
cachexia, 36
adverse effects, 47, 51
calcium channel blocker, 58
albuminuria, 35
carbohydrate, 31, 36, 41, 46, 48
alcohol use, 4
cardiac tamponade, 24
allergic reaction, 49
cardiovascular disease, 4, 6, 58
amino acid, 51
ccardiovascular system, 53, 55
amino groups, 70
CDC (Center for Disese Control and
anastomosis, 19
Prevention), 6, 7
anatomy, 15, 17, 28, 53, 54, 58, 61, 62, 64
childhood adversity, 4
arteries, 15, 16, 19, 31
Chinese medicine, 57
autonomic nervous system, 29
cholelithiasis, 38
chronic diseases, 17
B chronic renal failure, 35
chyle, 29, 31
barbiturates, 40 circulation, 19, 24, 25, 68
beef, 49 controlled trials, 44, 67
beer, 12, 29 cystic fibrosis, 78
90 Index
epidemiology, 6
D epilepsy, 17, 20, 55
epinephrine, 46
deficiency, 44
esophagoscopy, 37
dehydration, 15
etiology, 27, 36, 40
Department of Education, 83
Europe, 16, 23, 27
diabetes, vii, 3, 4, 5, 6, 7, 11, 12, 13, 14, 15,
exercise, 24, 36, 58
16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 27,
28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,
39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, F
50, 51, 52, 53, 54, 55, 57, 58, 60, 61, 63,
64, 65, 66, 68, 69, 70, 71, 78 families, 78
diabetes insipidus, 17, 30 fasting, 5, 36
diabetic coma, 34 fat, 31, 36, 46, 61
diabetic ketoacidosis, 37 fatty acids, 32, 40
diabetic neuropathy, 29 FDA approval, 51
diabetic patients, 30, 31, 36 fever, 49
diabetic retinopathy, 37 fibers, 46, 67
diarrhea, 16, 17, 24 fibrosis, 48
diet, 24, 25, 31, 36, 41, 46, 47, 51, 70 fruits, 4
digestion, 24, 29, 40, 61
digestive enzymes, 43
disability, 39, 57, 76, 81, 82, 84 G
diseases, 12, 16, 17, 20, 24, 28, 35, 37, 38,
54, 56, 58, 62 gangrene, 24
disorder, 11, 12, 16, 24, 29, 31, 33, 34, 38, gastric lavage, 37
40 gastrointestinal tract, 43
drug treatment, 24 genetic disorders, 78
drugs, 24, 25, 40, 58, 70 genetic engineering, 52
duodenum, 29 genetic factors, 51, 70
dyslipidemia, 4 genetics, 67
geology, 24
gerontology, 82
E gestational diabetes, 51, 70
glomerulonephritis, 26, 35
edema, 27, 35 glucagon, 44, 66
efferent nerve, 46, 67 glucose, 5, 31, 32, 34, 40, 41, 42, 43, 44, 45,
electrolyte, 33, 62 47, 49, 51, 70
emulsions, 68 glucose testing, 5, 51
endocrine disorders, 52 Greece, 15, 18, 57, 75, 79
endocrine glands, 40 Greeks, 53, 56
endocrinologist, 34, 44
endocrinology, 37, 44, 57, 59, 64, 69
environmental factors, 6 H
enzyme, 43
epidemic, 6 Han dynasty, 18
Index 91
health, vii, 4, 6, 13, 15, 22, 47, 76, 77, 78,

81, 84, 85, 86 L
health care, 78
liver, 33, 34, 53, 63
healthy lifestyle, 3
longevity, 47
heart disease, 24
lymph node, 39
heart failure, 53
heart murmur, 17
heart valves, 15 M
heavy alcohol use, 4
hematuria, 27 medical care, 7
high fat, 46 medical history, 11, 30, 31
Hispanic teenagers, 6 medical science, 58
histogenesis, 66 medication, 18
history, vii, 9, 12, 14, 16, 17, 19, 27, 28, 32, medicine, 12, 13, 14, 15, 16, 17, 18, 19, 20,
35, 42, 48, 50, 53, 55, 56, 57, 58, 59, 60, 21, 23, 24, 25, 26, 29, 31, 33, 36, 37, 39,
61, 65, 86 40, 41, 43, 44, 51, 53, 56, 57, 58, 59, 60,
homeostasis, 33, 70 61, 63, 66, 67, 68, 71, 75, 77, 78, 84
Hong Kong, 79, 84, 86 Mediterranean, 56, 70
hyperglycemia, 30, 70 mellitus, vii, 4, 6, 7, 9, 11, 12, 17, 18, 19,
hypersensitivity, 24 29, 30, 31, 33, 35, 36, 38, 39, 40, 41, 42,
hypertension, 4, 24, 51 44, 45, 46, 48, 49, 51, 53, 54, 55, 57, 58,
hypertrophy, 67 60, 61, 62, 64, 65, 68, 69, 70, 71, 78
hypoglycemia, 44 metabolic syndrome, 70
metabolism, 37, 41, 42, 44, 46, 47, 51, 64,
68
I
metformin, 51
methodology, 44, 61
ILAR, 68
microbiota, 71
impotence, 24
molecular structure, 11, 51
inferior vena cava, 19
Moses, 11, 25, 26, 42, 48, 59, 69
insulin, 11, 36, 39, 44, 45, 46, 48, 49, 50,
Multi-Ethnic Study of Atherosclerosis
51, 52, 60, 61, 63, 65, 66, 68, 69, 70, 71
(MESA), 4, 6
insulin resistance, 51
multiple sclerosis, 36
internal environment, 33
musculoskeletal, 79
international standards, 50
interstitial nephritis, 42
intestinal tract, 43 N
National Health and Nutrition Examination

K
Survey, 5
National Health and Nutrition Examination
kidney, 15, 20, 21, 24, 27, 28, 29, 30, 57,
Survey (NHANES), 5
58, 65
nephritis, 35, 42
kidneys, 15, 16, 17, 19, 21, 22, 27, 30, 31,
nephrologist, 59
35, 54, 57, 58, 62
nephrotic syndrome, 35
nervous system, 29, 40
92 Index
Netherlands, 53, 60
neuralgia, 54 Q
neurodevelopmental disorders, 78
quality of life, 3, 76
North Africa, 26
North America, 78
Norway, 83 R
nutrients, 22, 28
nutrition, 30, 55 recombinant DNA, 51
regeneration, 62, 66, 67
rehabilitation, 69, 76, 81
O
retinitis, 37, 64
retinopathy, 64
obesity, 4, 5, 43, 55, 70
Romania, 47
oedema, 64
Russia, 48
P
S
pancreas, 17, 27, 29, 31, 33, 36, 39, 40, 41,
self-monitoring, 36, 51
42, 43, 44, 47, 48, 49, 50, 51, 60, 64, 65,
semilunar valve, 15
66, 68
sexual health, 78
pancreatitis, 65
side effects, 43
paralysis, 37
siphon, 15, 16, 18
pathologist, 31, 36, 38, 39, 41, 45
situs inversus, 31
pathology, 31, 38, 39, 61, 62
skin, 21, 22
peristalsis, 43
smoking, 4
pharmacogenetics, 64
SSB consumption, 4
pharmacology, 38, 50
sugar-sweetened beverages, 4
phrenology, 33
sympathetic nervous system, 46
physical activity, 3, 4, 6
symptoms, 17, 18, 19, 20, 21, 22, 26, 29, 37,
physical inactivity, 4
40, 62
Plato, 15
syringomyelia, 60
pneumococcus, 67
pneumonia, 17, 21, 44, 49, 67
polydipsia, 20, 21, 22, 30 T
polyuria, 16, 20, 21, 22, 24, 29, 30, 31, 41
population, 3, 5, 6 T1DM, 5
prediabetes, 3, 5, 6 T2DM, 3, 4, 5, 6, 7
premature death, 12 transmission, 55
prophylactic, 67 transplantation, 52, 71
psychopharmacology, 78 transportation, 4
psychosocial factors, 4 transportation policies, 4
public health, 3, 6, 76, 81, 82, 84, 85 trauma, 31
public policy, 71 treatment, 12, 14, 21, 27, 29, 30, 33, 36, 40,
pulmonary artery, 25 47, 57, 60, 61, 62, 63, 67, 68, 69, 70
pulmonary circulation, 25, 58, 59 Turkey, 18, 20, 21
Index 93
type 1 diabetes, 5, 6, 7, 49, 70, 71

type 2 diabetes, 3, 4, 6, 7, 51, 70 V
vasomotor, 33, 34
U vasovagal syncope, 24
vein, 15, 19, 25
United Kingdom, 83 ventricle, 34
United States, 3, 4, 5, 6, 7, 48, 75, 76, 77, vision, 23
79, 83 vomiting, 24
urban planning, 4
urethra, 12
urethritis, 12 W
urinalysis, 26, 27, 59
weight loss, 20, 22
urine, 12, 13, 15, 16, 17, 18, 21, 22, 26, 27,
28, 29, 30, 31, 34, 37, 40, 41, 45, 51, 55,
57, 58, 59, 60, 61 Z
US Department of Health and Human
Services, 6 Zimbabwe, iii, 86
Uzbekistan, 24 zinc, 51

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PUBLIC HEALTH: PRACTICES, METHODS AND POLICIES

Environment and Public Health Issues in Diverse

Education in Hong Kong:

NOTICE TO THE READER

Library of Congress Cataloging-in-Publication Data

Published by Nova Science Publishers, Inc. † New York

TRENDS IN CHILD AND YOUTH DIABETES

It is estimated that 86 million adult Americans have prediabetes and with

A study from Finland of 37,699 adults looked at childhood adverse

DIABETES, CHILDREN AND YOUTH

TRENDS IN PEDIATRIC AND ADOLESCENT DIABETES

Donald Frederick Steiner (1930-2014), and so much more as the 20th

ANCIENT PHYSICIANS OF INDIA

What is a scientist after all? It is a curious man looking through a

ANCIENT GREEK PHYSICIANS

Western civilization’s understanding of science is traced to the ancient

Table 1. Ancient physicians in the history of diabetes

Alcmaeon of Croton (born around 510 BC)

Bubbles appearing on the surface of the urine indicate disease of the

However, the Hippocrates dictum of observing the patient encouraged

no role after death, these Greek scientists at Alexandria began to dissect

THE FIRST AND SECOND CENTURIES AD

Aulus Cornelius Celsus (25 BC-50 AD)

Areteus of Capadocia (81-138 AD)

An important physician in the early history of diabetes is Arateus of

Diabetes is a remarkable affliction, not very frequent among

Chang Chung Ching (150-219 AD)

In 200 AD Chang Chung Ching (Zhang Zhongjing [150 AD-219AD)]), a Han

We have come to understand that we are who we are is also who we

BYZANTINE WRITERS (4TH TO 9TH CENTURY AD)

Byzantine nephrology and utilizing magnifying lenses, confirmed Erasistratus’

Table 3. Byzantine physicians/writers (4th to 9th Centuries AD) in the

Oribasius (325-403 AD)

He also identified circulation in the kidneys that including blood flow

Stephanus Alexandriensis (550 AD-622 AD)

Another Byzantine writer who commented on symptoms of diabetes was

Constantinople that had been founded by the Byzantine Emperor Theodosius

Alexander Traillianus (525-605 AD)

Alexander Traillianus (Alexander of Tralles; 525-605 AD) was a Greek

I like to use every possible means in treating my patients.

Alexander Traillianus wrote about symptoms of diabetes and epilepsy

I have assembled from my rich experience of treatments of various

An early to mid-6th century Byzantine physician who continued the Byzantine

Paulus Aegineta (625-690 AD)

Li-Hsuan and Chen Chuan

This disease is due to weakness of the renal and urogenital system. In

Stephanus’ aim is to imbue his pupils with proper method and he

GOLDEN AGES OF ISLAMIC ERA: 9TH TO 12TH CENTURIES

Table 4. Arab/Persian Clinicians of the Golden Age of the Islamic Era

Ali at-Taberi (838-870 AD)

Rhazes (Abu Bakr Muhammad ibn Zakariyya al-Razi; 865-925), a musician

Often acclaimed as the most influential Islamic physician/philosopher was Ibn

Geoffrey Chaucer (1340-1400) as translated by the English literary scholar

A Doctor too emerged as we proceeded;

Ibn al-Nafis (1213-1288)

Moses Maimonides (1138-1204)

A physician should begin with simple treatments trying to cure by

The great Jewish scholar, Moses Maimonides (1138-1204) was a

Galen’s art healed only the body,

Moses Maimonides provided much information on medicine such as

You must accept the truth from whatever source it comes

Moses Maimonides detailed various aspects of diabetes in patients

RENAISSANCE ERA AND THE PANCREAS