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Diabetes Mellitus A Medical History Journey (Public Health Practices, Methods and Policies) 1st Edition 2016 PDF
Diabetes Mellitus A Medical History Journey (Public Health Practices, Methods and Policies) 1st Edition 2016 PDF
DIABETES MELLITUS
A MEDICAL HISTORY JOURNEY
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PUBLIC HEALTH: PRACTICES,
METHODS AND POLICIES
Series Editor: Joav Merrick, Medical Director,
Health Services, Division for Intellectual and
Developmental Disabilities, Ministry of Social Affairs
and Social Services, Jerusalem, Israel
DIABETES MELLITUS
A MEDICAL HISTORY JOURNEY
DONALD E. GREYDANUS
AND
JOAV MERRICK
New York
Copyright © 2016 by Nova Science Publishers, Inc.
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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
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
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.
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
12 Donald E. Greydanus and Joav Merrick
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)
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
A historical journey of diabetes mellitus 15
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:
Table 2. Key physicians from the first two centures in the history of
diabetes
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).
published in 1552 by Junius Paulus Crassus (Giunio Paolo Grassi) who died in
1575 (35, 42).
Aetius Amidenus
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).
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
22 Donald E. Greydanus and Joav Merrick
this article (10, 39, 83). Li-Hsuan also commented on the sweetness of urine in
these patents (84):
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).
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)
Rhazes
Avicenna
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)
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:
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)
A historical journey of diabetes mellitus 27
Parcelsus (1494-1541)
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).
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
A historical journey of diabetes mellitus 29
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 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.,
30 Donald E. Greydanus and Joav Merrick
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.
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!
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).
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).
34 Donald E. Greydanus and Joav Merrick
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)
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).
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 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!
38 Donald E. Greydanus and Joav Merrick
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).
A historical journey of diabetes mellitus 39
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.
blood glucose control and were the endocrine glands or tissue of the pancreas
(253-257).
(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)
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)
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
44 Donald E. Greydanus and Joav Merrick
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).
A historical journey of diabetes mellitus 45
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
46 Donald E. Greydanus and Joav Merrick
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 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 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-
A historical journey of diabetes mellitus 47
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.
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.
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
A historical journey of diabetes mellitus 49
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).
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
50 Donald E. Greydanus and Joav Merrick
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
A historical journey of diabetes mellitus 51
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)
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)
A historical journey of diabetes mellitus 53
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SECTION TWO: ACKNOWLEDGMENTS
Chapter 3
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]
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
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
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.
82 Donald E. Greydanus and Joav Merrick
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;
84 Donald E. Greydanus and Joav Merrick
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
Contact
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
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
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