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Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx ISSN 1948-9358 (online)
DOI: 10.4239/wjd.v7.i1.1 © 2016 Baishideng Publishing Group Inc. All rights reserved.

MINIREVIEWS

Milestones in the history of diabetes mellitus: The main

contributors

Marianna Karamanou, Athanase Protogerou, Gregory Tsoucalas, George Androutsos,

Effie Poulakou-Rebelakou

Marianna Karamanou, Gregory Tsoucalas, George And­ Abstract

routsos, Effie Poulakou-Rebelakou, Depart­ment of History of
Medicine, Medical School, University of Athens, 11527 Athens, Diabetes mellitus is a group of metabolic diseases
Greece involving carbohydrate, lipid, and protein metabolism.
It is characterized by persistent hyperglycemia which
Athanase Protogerou, Department of Pathophysiology, “Laiko” results from defects in insulin secretion, or action or
Hospital, Medical School, University of Athens, 11527 Athens, both. Diabetes mellitus has been known since antiquity.
Greece Descriptions have been found in the Egyptian papyri, in
ancient Indian and Chinese medical literature, as well
Author contributions: All authors equally contributed to this as, in the work of ancient Greek and Arab physicians.
paper with conception and design of the study, literature review nd
In the 2 century AD Aretaeus of Cappadocia provided
and analysis, drafting and critical revision and editing, and final the first accurate description of diabetes, coining the
approval of the final version. th
term diabetes, while in 17 century Thomas Willis
added the term mellitus to the disease, in an attempt
Conflict-of-interest statement: There is no conflict of interest to describe the extremely sweet taste of the urine. The
associated with any of the senior author or other coauthors th
important work of the 19 century French physiologist
contributed their efforts in this manuscript.
Claude Bernard, on the glycogenic action of the liver,
Open-Access: This article is an open-access article which was paved the way for further progress in the study of the
selected by an in-house editor and fully peer-reviewed by external disease. In 1889, Oskar Minkowski and Joseph von
reviewers. It is distributed in accordance with the Creative Mering performed their famous experiment of removing
Commons Attribution Non Commercial (CC BY-NC 4.0) license, the pancreas from a dog and producing severe and fatal
which permits others to distribute, remix, adapt, build upon this diabetes. In 1921, Frederick Banting and Charles Best
work non-commercially, and license their derivative works on extended Minkowski’s and Mering’s experiment. They
different terms, provided the original work is properly cited and isolated insulin from pancreatic islets and administrated
the use is non-commercial. See: http://creativecommons.org/ to patients suffering from type 1 diabetes, saving thus
licenses/by-nc/4.0/ the lives of millions and inaugurating a new era in
diabetes treatment.
Correspondence to: Marianna Karamanou, MD, PhD, Depart­
ment of History of Medicine, Medical School, University of Key words: History of endocrinology; Metabolic disorder;
Athens, Greece 4 str, Themidos, Kifissia, 11527 Athens, Diabetes mellitus; Aretaeus of Cappadocia; Insulin
Greece. mkaramanou@med.uoa.gr
Telephone: +30-210-7461437 © The Author(s) 2016. Published by Baishideng Publishing
Fax: +30-210-8235710
Group Inc. All rights reserved.
Received: August 13, 2015
Peer-review started: August 13, 2015 Core tip: Diabetes mellitus has been known since
First decision: September 17, 2015 antiquity and despite therapeutic advances it still
Revised: December 5, 2015 remains an incurable chronic disease. In our historical
Accepted: December 17, 2015 article, we attempt to provide the most important steps
Article in press: December 18, 2015 in the history of diabetes mellitus from antiquity till
Published online: January 10, 2016 nowadays. The contribution of leading medical figures

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 Karamanou M et al . Protagonists in diabetes mellitus

such as Aretaeus of Cappadocia, Thomas Willis, Claude that diabetes affects primarily the rich castes and is
Bernard, Oskar Minkowski, Joseph von Mering, Frederick related to the excessive food consumption as the rice,
Banting and Charles Best is mentioned, in an attempt to cereals and sweets .
[6]

highlight the development of our current knowledge in In ancient China, Chang Chung-Ching (ca. 160-ca.
diabetes mellitus. 219), referred to as “the Chinese Hippocrates”, des­
cribed polyuria, polydipsia and loss of weight as
th
symptoms of a specific disease, while in 7 century
Karamanou M, Protogerou A, Tsoucalas G, Androutsos G, AD Chen Chuan recorded the sweet urine in diabetes
Poulakou-Rebelakou E. Milestones in the history of diabetes mellitus and named the disease Hsiao kho ping
mellitus: The main contributors. World J Diabetes 2016; 7(1): 1-7
mentioning its characteristic symptoms: intense thirst,
Available from: URL: http://www.wjgnet.com/1948-9358/full/
copious drinking and large amounts of urine which is
v7/i1/1.htm DOI: http://dx.doi.org/10.4239/wjd.v7.i1.1
tasted sweet. In an attempt to treat that disease his
colleague Li Hsuan proposed the abstinence from wine,
[6]
salt and sex .
th
From the 8 century onwards, physicians observed
INTRODUCTION the tendency of diabetic patients to develop skin
Diabetes mellitus is a group of metabolic diseases infections as furuncles, rodent ulcers and troubles of
th
involving carbohydrate, lipid, and protein metabolism. the eyesight. In 11 century AD, the celebrated Arabo-
It is characterized by persistent hyperglycemia, as a islamic physician Avicenna (980-1037) in his textbook
result of defects in insulin secretion, insulin action or a El-Kanun (Canon of Medicine) described diabetes and
combination of both, defective secretion and incorrect mentioned gangrene and sexual dysfunction as its
action. There are two main types of diabetes mellitus: complication. Years later, the medieval scholar Moises
Type 1 (insulin-dependent), and type 2 (non-insulin- Maimonides (1138-1204) described in detail diabetes,
[6]
dependent). Type 1 diabetes results by the autoimmune including the symptoms of acidosis .
destruction of the β-cells of the pancreatic islets Ancient Egyptians, Indians, Chinese and Arabs tried
and type 2 diabetes is caused from impaired insulin to describe the clinical signs and symptoms of diabetes
[1]
secretion and resistance to the action of insulin . mellitus. However, few are the main protagonists in the
Current epidemiological data reveal that 9% of adults, history of diabetes mellitus who contributed significantly,
18 years of age and older, has diabetes mellitus while not only to its diagnosis and treatment but also to the
it was estimated that in 2012, 1.5 million people died development of our current notions on the disease,
due to the disease. According to the World Health paving the way for further study and establishing a new
th
Organization, diabetes will be the 7 leading cause of medical sub specialty, diabetology.
[2-4]
death in 2030 .
The disease has a long history reaching back into
antiquity. However, during that period, due to a poor ARETAEUS OF CAPPADOCIA (2nd
knowledge of anatomy, pathophysiology and lack CENTURY AD) AND THE FIRST
of diagnostic tools, the disease remained extremely
perplexing to physicians. ACCURATE DESCRIPTION OF DIABETES
Nevertheless, physicians in antiquity observed the Aretaeus, surnamed the Cappadocian, is probably the
distinctive features of diabetes and proposed several greatest physician of the Greco-Roman antiquity after
therapeutic approaches. In Ebers papyrus, dated back Hippocrates, and at least equal of Galen. He was born
to 1500 BC, we may find passages describing patients in Cappadocia, a region in eastern Asia Minor, studied
who suffer from excessive thirst, copious urination and medicine in Alexandria and practiced in Rome probably
nd
they are treated by plants’ extracts. However, according during the 2 century AD. Areataeus’ medical practice
to the Egyptian endocrinologist, historian of medicine was based on the principals of the Pneumatic school
and translator of the Ebers papyrus Paul Ghalioungui believing not only in the vital role of pneuma (air) but
(1908-1987), the description of a probable diabetes, embracing also the theory of the four humors (heat,
in Ebers, is regarded as unsatisfactory and probably coldness, moisture, dryness). In his two treatises, De
wrong. In Kahun papyrus (c. 2000 BC) there is just causis et signis morborum acutorum et diuturnorum (on
the title of a recipe for the “Treatment of a thirsty the causes and symptoms of acute and chronic diseases)
[5]
woman”, but the text is missing . So, we may assume and De curatione morborum acutorum et diuturnorum
that ancient Egyptians could not recognize behind the (on the cure of acute and chronic diseases), written in
symptoms of specific disease entity such as diabetes. Ionic dialect, Aretaeus impresses us by the vividness
th
Around the 5 century BC, the famous Indian and the simplicity of his descriptions. Among others
surgeon Sushruta, in his work Samhita, identified he described, in an accurate way for his time, leprosy,
diabetes, by using the term madhumeha (honey-like asthma, pneumonia cancer, tetanus, hysteria, epilepsy,
[7,8]
urine) and pointed out not only the sweet taste of the gout (Figure 1).
urine but also its sticky feeling to the touch and its Before Aretaeus, ancient Greek medical authors
st
ability to attract the ants (!). Sushruta further mention such as Rufus of Ephesus (c. 1 century AD) and

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 Karamanou M et al . Protagonists in diabetes mellitus

of cereals, milk and wine, the topical application of

cataplasms and the administration of Theriac, the
[7,8]
famous cure all remedy of antiquity .
However, it remains unknown how Aretaeus made
such a precise description of a relatively rare disease
during that period, just by observation.

THOMAS WILLIS (1621-1675) AND THE

TERM “MELLITUS”
The English anatomist and physician Thomas Willis,
th
is considered one of the greatest physicians in 17
century. He lived in a period that England was in poli­
tical and religious turmoil and he needed to interrupt
several times his studies. Willis studied classics and then
medicine at Oxford where he was appointed Professor
of Natural Philosophy to the highly prestigious Sedleian
chair. During his career, he wrote several books and
Figure 1 The distinguished physician Aretaeus of Cappadocia. (Source: articles on medicine and his work on the anatomy of
Wellcome Library, London). the brain and nervous system, based on his own dissec­
tions, remains very celebrated. Willis provided the
description of the autonomic nervous system, the spinal
Galen (130-c.201) were mentioning that diabetes
cord, the vasculature at the base of the brain (circle of
was provoking excessive thirst, polyuria, emaciation
Willis) and the cranial nerves, including the accessory
of the human body, leading sometimes to death. The [9]
nerve (Willis’ nerve) .
symptom of polyuria gives the idea to Galen, who
Willis, as physician, belonged to the Iatrochemical
according to his own writings he has seen the disease
School of medicine which believed that chemistry was
only twice, to name diabetes diarrhea urinoma (diarrhea
the basis of human function. Concerning diabetes, in
of the urine). Later, the term diabetes was introduced
his Pharmaceutice rationalis, Willis devoted a chapter
into medical nomenclature by Aretaeus. It arises from
to the “pissing evil”. He commented on the sweetness
the Greek verb διαβαiνω (diabaino) which means I pass
of the urine in diabetic patients, coining also the term
through and diabetes, the condition that the fluid runs [10] th
mellitus . It was actually a rediscovery, as in the 7
through.
century BC the Indian physician Sushruta mentioned
In the following passage of Areateus’ work, we may
the sweet urine of the disease but this work apparently
admire the clinical presentation and interpretation of
diabetes: “Diabetes is a wonderful affection, not very was unknown to Willis. So, he was the first European
frequent among men… The course is the common one, medical writer who mentioned the sweet taste of the
namely, the kidneys and the bladder; for the patients urine in diabetes mellitus. It seems that he saw several
never stop making water, but the flow is incessant, cases of diabetes mellitus and he believed that it was
…. The nature of the disease, then, is chronic, and it due to an affection of the blood rather of the kidneys.
takes a long period to form; but the patient is short- He attributed it to the eating habits and psychological
lived, if the constitution of the disease be completely status “an ill manner of living and chiefly an assiduous
established; for the melting is rapid, the death speedy. and immoderate drinking of cider, beer and sharp
Moreover, life is disgusting and painful; thirst; excessive wines; sometimes sadness, long grief”. He recognized
drinking, which, however, is disproportionate to the also diabetic neuropathy in the sufferers describing it as
large quantity of urine, for more urine is passed; and “stinging and other…frequent contractions or convulsion,
one cannot stop them either from drinking or making twinging of the tendons and muscles and other distur­
[9-11]
water. Or if for a time they abstain from drinking, their bances” .
mouth becomes parched and their body dry; they Concerning the sweet taste of the urine, he reported
are affected with nausea, restlessness, and a burning a case of “a certain noble earl” who suddenly “became
thirst; and at no distant term they expire. Thirst, as if much inclined to excessive pissing… in the space of
scorched up with fire... But if it increase still more, the twenty-four hours, he voided almost a gallon and a half
heat is small indeed, but pungent, and seated in the of limpid, clear, and wonderful sweet water, that tasted
intestines; the abdomen shriveled, veins protuberant, as if it has been mixed with honey”. Therapeutically he
general emaciation, when the quantity of urine and the considered beneficial for the disease a “thickening and
thirst have already increased; and when, at the same moderately cooling diet and cordials” and he mentioned
time, the sensation appears at the extremity of the that slimy vegetables, rice, white starch may improve
member, the patients immediately make water”. For the patient’s status. He also suggested a milk drink which
treatment of the disease he proposes the consumption was distilled with cypress tops and egg whites, two

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 Karamanou M et al . Protagonists in diabetes mellitus

Bernard’s several discoveries we may cite: the vasomotor

innervation, the principle of physiological determinism,
the concept of internal secretion, the concept of milieu
intérieur or internal environment (meaning the interstitial
fluid, and its physiological capacity to ensure protective
stability for the tissues and organs), the nature and
function of curare, carbon monoxide and other poisons
(Figure 2). Unfortunately, the only way to understand and
discover all these phenomena, promoting our knowledge
to physiology, was through animals’ vivisections. This
was the reason for his wife to divorce him and join with
his children the antivivisection movement, campaigning
[12]
actively on the issue .
Bernard’s contribution in the study of metabolism
th
and diabetes remains leading. In 19 century, scientists
hypothesized on the role of pancreas in the physio­
pathology of diabetes as they found in the post-mortem
examination of the diseased, atrophic or stone filled
pancreases. However, as they believed that pancreas
Figure 2 Portrait of the French physiologist Claude Bernard. (Source: was an exocrine organ, they interpreted these post-
Wellcome Library, London).
mortem findings as a chance phenomenon. During that
period the French experimental physiologist, Claude
[1,12]
powders (a mixture of gum arabic and gum dragant), Bernard decided to test this hypothesis .
rhubarb and cinnamon. Following Willis’ therapeutic At the beginning, he falsely believed that “diabetes
advices, patient’s condition improved in a month but was a nervous affection of the lungs”. However, during
immediately after his recovery, he returned to his past an experiment, he injected grape sugar into the jugular
[9]
dietary habits . vein of a dog, extracting at the same time blood from
However Willis could not explain “why the urine is the carotid artery. This blood contained a large amount
wonderfully sweet like sugar or honey”. The explanation of sugar and he realized that glucose was not destroyed
was given 100 years later, by another English physician, in the lungs, because blood must pass by these organs
Matthew Dobson (1732-1784) of Liverpool, who in order to move from the jugular vein to the carotid
experimentally demonstrated the presence of sugar in artery. He was then fed dogs on a carbohydrate-rich
urine. He actually boiled urine to dryness and noticed diet, the blood from the hepatic veins and vena cava
that the residue, a crystalline material, had the taste of contained sugar which was not destroyed in the liver
[11]
brown sugar . and was also present in heart ventricles, so the theory
of lungs’ role in diabetes was rejected. In further
experiments, Bernard proved that animal blood contains
CLAUDE BERNARD’S (1813-1878) sugar even if it is not supplied by food. Testing the
BRILLIANT DISCOVERY ON THE theory that sugar absorbed from food was destroyed
when it was passing through tissues, Bernard put dogs
GLYCOGENIC ACTION OF THE LIVER in carbohydrate diet and killed them immediately after
Born to a poor family in Beaujolais region, south of feeding. To his surprise he observed large amounts
France, Claude Bernard at the age of 19 was apprenticed of sugar in hepatic veins. The same observation was
to an apothecary. His passion for the theatre led him done in the control group, animals that were fed only
to write two plays La Rose du Rhône and Arthur de by meat. He then moved to the analysis of liver tissue
Bretagne but soon after arriving to Paris, he was samples and in every liver he examined he found large
discouraged by the literary critic and politician Saint- quantities of glucose which was missing from other
Marc Girardin (1801-1873) who counseled him to enroll organs. He concluded that liver was storing a water
in medicine. In Medical School of Paris, Bernard was insoluble starchy substance that he named glycogen
not considered a brilliant student and unwilling to which was converted into sugar or glucose and secreted
practice medicine, he was appointed assistant to the into the blood. He assumed that it was an excess of this
[13,14]
Professor of Physiology and pioneer of experimental secretion that caused diabetes .
physiology François Magendie (1783-1855). However, Moving toward, Bernard demonstrated the con­
Bernard’s research career was very successful. In nection between the central nervous system and dia­
1854, he became member of the Academy of Sciences betes. Using a needle, he stimulated the floor of the
and later on he succeeded Magendie to the chair of fourth brain ventricle and produced temporary “artificial
experimental physiology at the College de France. The diabetes” which lasted less than one day. He named this
Emperor Napoleon III admired him so much that created procedure piqûre diabétique and linked for the first time
two laboratories for him and made him a Senator. Among glucose homeostasis and the brain to the pathogenesis

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 Karamanou M et al . Protagonists in diabetes mellitus

Figure 3 Sites of punctures of 4th ventricle from Bernard’s book «Leçons Figure 4 The Nobel laureate Frederick Banting in his laboratory with a
sur la Physiologie et la Pathologie du Système Nerveux», 1858. (Source: dog. (Source: Wellcome Library, London).
Wellcome Library, London).

the dog developed diabetes due to the fact that von

[15]
of diabetes (Figure 3). Mering had treated it for a long time with phlorizin. So
The work of Claude Bernard on glycogenic action of he repeated the pancreatectomy in three more dogs
the liver illuminated the pathway of gluconeogenesis which had no sugar in their urine previous to operation
and promoted the study of diabetes. and all of them developed glycosuria
[13,16]
.
Furthermore Minkowski implanted a small portion
of pancreas subcutaneously, in depancreatized dogs,
OSKAR MINKOWSKI (1858-1931) AND
and observed that hyperglycemia was prevented
JOSEPH VON MERING (1849-1908): until the implant was removed or had spontaneously
[13]
degenerated .
THE DISCOVERY OF “PANCREATIC
Minkowski and von Mering experiment demonstrated
DIABETES” that pancreas was a gland of internal secretion
A turning point in the history of diabetes mellitus took important for the maintenance of glucose homeostasis.
place in 1889 after the experiments of Minkowski and They also paved the way for Banting and Best to
von Mering. conduct their experiments and to meet with success.
In 1886, three years before their first meeting,
von Mering discovered that phlorizin, a glucoside,
FREDERICK BANTING (1891-1941),
could cause transient glucuresis. In 1889, while von
Mering was working in Hoppe Seyler’s Institute at the CHARLES BEST (1899-1978), JAMES
University of Strasbourg, Minkowski, assistant at that
time to the German leading authority on diabetes
BERTRAM COLLIP (1892-1965) AND
Professor Bernard Naunyn (1839-1925), he visited JOHN MACLEOD (1876-1935): THE
the Institute to look at some chemical books of the
library. They met accidentally and talked about Lipanin,
DISCOVERY OF INSULIN
an oil containing free fatty acids and von Mering used In 1923 the Nobel Prize in Medicine was awarded to
to administrate to patients suffering from digestive Frederick Banting and John MacLeod for the discovery of
disturbances. Minkowski was not in favor of Lipanin insulin. It was actually a story of success that provoked
intake and then their conversation turned on whether a great scientific conflict.
the pancreas had a role in digestion and absorption of Frederick Banting was a young Canadian surgeon,
fats. As a result of the discussion, the two men decided who was admitted into the laboratory of the eminent
the same evening to perform a pancreatectomy in biochemist, interested in diabetes, Professor John
[13]
a dog in Naunyn’s laboratory. The animal remained Macleod, at the University of Toronto . In 1920,
alive and was closely observed by Minkowski, as von Moses Barron, physician in Minnesota, published an
Mering left urgently to Colmar because of a family article on “The relation of the islets of Langerhans to
issue. Soon after the operation, the dog developed dia­betes, with special reference to cases of pancreatic
[17]
polyuria. Minkowski examined the urine and found that lithiasis which was mentioning that the continuation of
it contained 12% sugar. Initially Minkowski believed that experiments of Minkowski and von Mering could lead to

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 Karamanou M et al . Protagonists in diabetes mellitus

th th
17 century, 19 century,

Thomas Willis Oskar Minkowski

added the term and Joseph von
mellitus to describe Mering recognized
the extremely that diabetes is a
sweet taste of the disease of the
urine pancreas

th
nd
2 century AD, th
19 century, 20 century,

Aretaeus of Claude Bernard Frederick Banting,

cappadocia provided and the Charles Best and
the first accurate discovery of the John Macleod,
description of glycogenic action the discovery of
diabetes, coining the of the liver insulin
term diabetes

Figure 5 Timeline table presenting the main contributors in the history of diabetes mellitus.

the discovery of a substance capable to control diabetes. Leonard Thompson a 14-year-old boy treated for
[13]
Influenced by this article, Banting focused on the study diabetes in Toronto Hospital . It’s worth mentioning
[13]
of diabetes . During that period the distinguished that after the introduction of Apollinaire Bouchar­
English physiologist Ernest Starling (1886-1927) was dat’s (1806-1886) pioneering dietary treatment for
mentioning: “We don’t know yet how the pancreas diabetes, physicians repeated in several generations of
affects sugar production or utilization in the same diabetics his motto: “mangez le moins possible” (eat
[21,22]
animal. It is generally assumed that it secretes into the as little as possible) . Thomson was also following
bloodstream a hormone which may pass to the tissues a strict fasting diet proposed by Frederick Madison
and enable them to utilize sugar or pass to the liver Allen (1879-1964) and he was in critical state. He
and inhibit the sugar production of this organ… but we received 15 mL of insulin, injected in his buttock
have been unable to imitate the action of the pancreas but he developed abscesses at the injection site and
still in vascular connection with the body, by injection or became even sicker. Collip further improved the quality
[18]
administration of the extracts of this organ” . of insulin and on January 23, Thompson received a
On 16 May 1921, Banting started to collaborate with second injection. The results were excellent. His blood
Charles Best, a young medical student. Experimenting glucose from 520 mg/dL fell to 120 mg/dL in 24 h and
in dogs they initially ligate the pancreatic ducts, urinary ketones disappeared. Thompson continued
achieving atrophy of the exocrine region and almost ten the treatment with insulin and lived another 13 years.
[13]
weeks later they removed dog’s degenerated pancreas. He died of pneumonia at 27 years old . Similar is
They crushed the atrophied pancreatic glands in a cool the story of Elizabeth Hughes Gossett (1907-1981).
mortar and froze it in salt water. Then the mass was Daughter of the United States politician Charles Evans
ground down and added to 100 mL of physiological Hughes, Elisabeth was diagnosed with diabetes at age
salt. Afterwards, they administrated 5 mL of this extract 11. Initially she was also treated by Allen and in August
intravenously to a depangreatized dog. Within 2 h its 1922 began the use of insulin. She survived, graduated
blood sugar had considerably dropped. They repeated from College, got married, had three children and died
[23]
several times the experiment with other diabetic dogs, suddenly of a heart attack at 74 years old .
gaining similar results and they experimented also with The pioneering work of Banting and Best saved
fetal calf pancreas using different ways of administration millions of lives and diabetics started to live a normal
[19,20]
such as subcutaneous and rectal (Figure 4). life. Lilly Pharmaceutical Company collaborated with the
At the end of 1921 the skilled chemist James Collip two scientists and in 1923 introduced Iletin, the world’s
[13]
joined the team and developed a better extraction and first commercially available insulin product .
purification technique. Obtained substance was initially However in 1923 the Nobel Committee decided
named by the team insletin and later on by MacLeod to award Banting and MacLeod for insulin’s discovery.
[13]
insulin . Banting became furious as he believed that he should
The next step was to test insulin in humans. So share the prize with Best instead of MacLeod and he
on 11 January 1922, insulin was administrated to decided to share with Best his cash award. In his turn,

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 Karamanou M et al . Protagonists in diabetes mellitus

[13]
MacLeod shared also his award with Collip . 2 Global status report on non communicable diseases 2014. Geneva:
Another black spot in the history of insulin discovery World Health Organization, 2012
3 World Health Organization. Global health estimates: Deaths by
was also the discovery of pancreatin, an extract of
cause, age, sex and country, 2000-2012. Geneva: World Health
bovine pancreas discovered by the Romanian Professor Organization, 2014
of Physiology Nicolae Constantin Paulescu (1869-1931) 4 Mathers CD, Loncar D. Projections of global mortality and burden
in 1916, published a few years later because of the war of disease from 2002 to 2030. PLoS Med 2006; 3: e442 [PMID:
in 1921 and patented in April 1922. Even if Paulescu 17132052 DOI: 10.1371/journal.pmed.0030442]
was the first to provide a detailed demonstration of the 5 Ghalioungui P. The Ebers papyrus: A new English translation,
commentaries and glossaries. Cairo: Academy of Scientific
antidiabetic and antiketogenic effect of a pancreatic
Research and Technology, 1987
extract, pancreatine was not used in humans and 6 Peumery JJ. Histoire illustrée du diabète. De l’Antiquité à nos
[24]
passed over silently . jours. Paris: Les Éditions Roger Dacosta, 1987
A crucial step in the history of diabetes has been 7 Laios K, Karamanou M, Saridaki Z, Androutsos G. Aretaeus
completed. Over the next years insulin purification of Cappadocia and the first description of diabetes. Hormones
methods improved and new insulin formulations were (Athens) 2012; 11: 109-113 [PMID: 22450352]
8 Adams F. The extant works of Aretaeus the Cappadocian. London:
developed such as Protamine–zinc insulin, a long-acting
Sydenham Society, 1856
insulin in 1930s, neutral protamine Hagedorn in 1940s 9 Furdell EL. Fatal Thirst. Diabetes in Britain until Insulin. Leiden:
[13]
and Lente series in 1950s . Brill, 2009: 81-92
10 Willis T. Opera Omnia. Coloniae: Sumptibus Gasparis Storti,
1694: 460
CONCLUSION 11 Williamson RT. English Physicians of the past. Newcastle:
Andrew Reid and Company, 1923: 47-52
For more than 3000 years physicians quested the
12 Grmek M. Le Legs de Claude Bernard. Paris: Fayard, 1997
causes and treatment of diabetes mellitus (Figure 13 von Engelhardt D, editor. Diabetes: Its medical and cultural
5). However, an important progress has been made history. Berlin: Springer-Verlag, 1989: 306-319, 350-358, 411-426
over the last two centuries thanks to the development 14 Bernard C. Du suc pancréatique et de son rôle dans les phéno­
of chemistry, physics and pharmacology. Over the mènes de la digestion. C R Soc Acad Sci (Paris) 1850; 1: 99-119
next years scientists continued to make significant 15 Grmek M. Examen critique de la genèse d’une grande découverte:
La piqûre diabétique de Claude Bernard. Clio med 1965; 1:
discoveries: The structure of insulin was delineated in
341-350
1955 by the Nobel laureate Fred Sanger (1918-2013); 16 von Mering J, Minkowski O. Diabetes mellitus nach Pankreas
in 1967 proinsulin was discovered by Donald Steiner extirpation. Arch f exper Path u Pharmakol 1889; 26: 371 [DOI:
(1930-2014) and with his colleagues he produced the 10.1007/BF01831214]
radioimmunoassay for C-peptide which is used today to 17 Barron M. The relation of the Islets of Langerhans to Diabetes.
measure endogenous insulin production; in the same Surg Gynecol Obstet 1920; 31: 437-448
18 Medvei VC. The History of Clinical Endocrinology: A Com­
year, the first pancreas transplant in a human was
prehensive Account of Endocrinology from Earliest Times to the
performed by William Kelly, Richard Lillehei (1927-1981) Present Day. New York: Parthenon, 1993: 253
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P- Reviewer: Charoenphandhu N, Hssan M, Masaki T, Tarantino G

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