Misread and mistaken: Étienne Lancereaux’s enduring legacy in the classification of diabetes mellitus

Abstract

Historians of diabetes have long claimed that physicians were aware of two distinct types of diabetes mellitus by the 1880s, and that these were the direct forerunners of type 1, juvenile-onset and type 2, adult-onset diabetes. French physician Étienne Lancereaux (1829–1910), based on autopsy and clinical studies, classified diabetes either as diabète maigre (thin, or more accurately emaciated, diabetes), which he believed to be pancreatic in origin with a poor prognosis, or diabète gras (fat diabetes), which he believed had a much better prognosis and was not pancreatic in origin. Historians citing Lancereaux have claimed that he observed the former to occur in young and the latter in middle-aged and elderly people. We review the papers of Lancereaux to clarify his clinical observations and understanding of diabetes. Lancereaux’s description of diabète maigre bores little resemblance to juvenile diabetes and all of his thin patients were middle-aged or older. On the other hand, his diabète gras is akin to type 2 diabetes and he might well deserve credit for its characterization.

Keywords

Medical history diabetes mellitus classification type 1 type 2 juvenile-onset adult-onset Étienne Lancereaux

It has been our observation that classic articles are cited much more often than they are actually carefully read. As a result, some have been seriously misinterpreted and, sometimes, these misinterpretations are perpetuated. So in the context of the upcoming 100th anniversary of the discovery of insulin, we decided to read and analyze three closely related classic articles about diabetes mellitus (DM) to determine what they actually say and mean. The articles,^1
–3 often cited interchangeably as the forerunners to the distinction between type 1, juvenile-onset and type 2, adult-onset DM, were published by the famous French physician Étienne Lancereaux (Figure 1).⁴

Figure 1.

Étienne Lancereaux (1829–1910). Credit: https://commons.wikimedia.org/wiki/File:Professeur_Lancereaux_CIPH0240.jpg.

Referring to one or another of these articles, standard textbooks, book chapters, and articles on the history of DM generally include statements like this:

From the middle of the nineteenth century many physicians believed that there were two distinct types of diabetes. That which had just been described in young people with an acute onset and bad outcome the French physician Étienne Lancereaux (1829–1910) called diabète maigre (thin diabetes). By contrast, the diabetes of middle aged overweight people, diabète gras (fat diabetes), came on gradually and was relatively indolent, so that sufferers could live with it for many years.⁵

None of the above-mentioned types of sources provide more details than this simple statement, and most far less. For instance, N.S. Papaspyros, in his book The History of Diabetes Mellitus, when listing historical landmarks, simply notes Lancereaux divides DM into two main groups “diabète maigre” and “diabète gras” in 1877.⁶ Another source states that Lancereaux “described in depth the clinical differences between diabetes type 1 and type 2 (“le diabète maigre et le diabète gras) in 1876.”⁷ Even, non-historians writing papers or chapters on classification of DM have dogmatically begun with statements such as: “In the late 19th century, two categories were recognized, one category was described as occurring in young people with a short time course before ketoacidosis occurred and the second one was described as common in older and obese people.”⁸

Who was Étienne Lancereaux?

Lancereaux was born on 27 November 1829 in the Ardennes region of Northern France, where he initially worked on his father’s farm. At age 20, he sustained a head injury in a farming accident and was so impressed with his medical care that he decided to become a physician. He received his bachelor degree in medicine at Reims at age 21 and moved to Paris to continue his studies, eventually writing a thesis on cerebral embolism and thrombosis and receiving his medical doctorate in 1862.^4,9 He worked in several prestigious hospitals in Paris; like many 19th century “Paris School” French academic physicians,¹⁰ Lancereaux was both a clinician and a morbid anatomist, a combination that promoted clinico-pathological correlation. Lancereaux was a nosologist. He fervently believed that medicine is a science, and as such it has general laws, and that diseases can be classified. His principal focus was to look for these laws and shine a light on characteristic elements necessary to establish an etiologic classification of diseases. Although we are unaware of Lancereaux having directly studied under Claude Bernard (1813–1878), he was a follower of his scientific methods which he tried to invoke in his studies.⁴

In 1868–1869, he published his two volume treatise on syphilis, which was immediately translated into English.¹¹ In 1875, he published the first volume of his massive three volume Traité d'anatomie pathologique ¹² and was a candidate for a professorship in anatomical pathology, but he lost out to Jean-Martin Charcot (1825–1893). He nonetheless held considerable prestige and for many years, he was the President of the French Academy of Medicine.

Between 1877 and 1880, Lancereaux published his three primary papers on DM.^1
–3 Lancereaux mused in each of these papers that DM was not a syndrome but was an actual disease that could have associated clinical lesions, and he was convinced that gross pancreatic lesions, particularly calculi, caused thin diabetes based upon relatively few observations (see below). This was apparently not his only strongly held opinion; endocrinology historian Victor Medvei (1905–2000) notes that Lancereaux “not only denied that there was a casual connection between … [acromegaly] and the pituitary, but also that acromegaly was a morbid condition at all!”¹³

However, as we will demonstrate below, Lancereaux did not describe two distinct types of DM that were direct forerunners of type 1 and type 2 DM. All of the patients he studied were middle-aged or older and appear to have had type 2 DM; however, some subsequently became emaciated. But, Lancereaux is correctly remembered for two other things. The WHO International Classification of Disease (ICD)-9 assigned a specific code for “Lancereaux's diabetes” (i.e. diabetes mellitus with marked emaciation) (ICD9, 2014).¹⁴ In addition to his concepts of diabète maigre and diabète gras, Lancereaux had one other important link to the history of DM; one of his former pupils was Nicolae Paulescu (1869–1931), who most Romanians and some historians claim discovered insulin before Banting, Best, Collip, and Macleod.^13,15,16 Paulescu, who completed medical school in Paris in 1897, served as an intern and then an assistant to Lancereaux before returning to Bucharest, where he later made pancreatic extracts and injected these into diabetic dogs.

Lancereaux died on 26 October 1910; although he had been retired for many years, the tireless Lancereaux continued to see patients, and, at the age of 81, he developed pneumonia after falling down stairs in a patient’s home.⁴ As one of France’s greatest late 19th century physicians, there is also a street named after him in the 8e arrondissement of Paris, Rue du Docteur-Lancereaux.

Lancereaux’s 1877 paper

So for the record, what exactly did Lancereaux believe and what did his classic papers say? In his 1877 paper, he relates two cases of DM in middle-aged adults. His first patient was a 61-year-old woman who presented with vomiting and colic acutely for 36 hours. Upon hospitalization, glycosuria and hyperphagia were documented and she was believed to have an epigastric tumor. Her course of disease until death was 25 months; her autopsy revealed severe pancreatic atrophy, but despite meticulous description of the pancreatic pathology, the paper does not mention pancreatic duct calculi. The autopsy also showed disseminated pneumonia and did not reveal an epigastric tumor. His second patient was a 42 year old previously healthy man who suddenly developed DM, rapidly became emaciated despite eating and drinking voraciously, and whose disease course was almost three years. His autopsy showed the presence of pancreatic fibrocalculous disease. Grossly, his pancreas was “atrophied, flattened, and ribbon-like” and the “conduits of the gland were dilated and full of white calculi, not dense, composed of carbonate of chalk” (all quotations of Lancereaux hereinafter are the authors’ translation). The autopsy showed that this patient also had bilateral lobular pneumonia and syphilitic gummas.¹

Whether either patient experienced ketoacidosis or diabetic coma is unclear from reading this paper. Three years earlier, Adolf Kussmaul (1822–1902), then professor of medicine at Freiburg (and who relocated to Strasbourg in 1876), described the classic deep, desperate breathing pattern associated with diabetic ketoacidosis that often progresses to diabetic coma and death.¹⁷ This respiratory pattern, now known as Kussmaul breathing, would have been known to Lancereaux, and so, he almost certainly would have described this if he observed it. Likely, he was not present when either patient slipped into coma and died or possibly the patients did not experience ketoacidosis terminally.

Lancereaux is often credited, by those citing this 1877 paper, for having first coined the term diabète pancréatique (pancreatic diabetes). However, as noted by Victor Medvei in his A History of Endocrinology, Thomas Cawley, an English physician, and Friedrich von Recklinghausen (1833–1910), a German pathologist, published autopsy case reports of DM associated with pancreatic calculi in 1788 and 1864, respectively. Lancereaux cites both of these papers in his review of the literature and does not claim priority for association of these entities. Medvei also notes that Richard Bright (1789–1858) and Apollinaire Bouchardat (1789–1858) had described gross pancreatic lesions other than calculi in patients with DM at least 25 years before Lancereaux. Medvei states unequivocally that Cawley was “the first observer” to suggest “a connection between the diabetes and the condition of the pancreas” but later notes that “Lancereaux was definite in connecting the two conditions causally.”¹³

It is not obvious to the present day reader how Lancereaux established causality. Furthermore, these first two cases of “pancreatic diabetes,” an entity which he would link to “thin diabetes” in his next paper, did not present in children nor were the clinical histories otherwise compatible with the current concept of type 1 DM. Within 25 years of Lancereaux’s papers, it was well established that, although there can be exceptions when the degree of pancreatic atrophy is extreme, pancreatic calculi do not usually cause DM but rather cause chronic interstitial pancreatitis with the relative preservation of the pancreatic islets.¹⁸ In fact, it was this very tendency that impressed Frederick Banting (1891–1941) when he read the literature review in Moses Barron’s case report on pancreatic duct obstruction that resulted in Banting approaching JJR Macleod (1876–1935), initiating the sequence of events culminating in the discovery of insulin in Toronto.^18,19

Lancereaux’s two papers in 1880

The first of these papers was published on 31 January 1880 and was based upon a clinical lesson presented at Pitié Hospital on 30 May 1879; it was collected and edited by his former intern, LaPierre.² Both this lesson and the second published shortly thereafter have the same précis, the first phrase of which is often incorrectly cited as their titles: “Thin diabetes: its symptoms, evolution, prognosis, and treatment; Reports with alterations of the pancreas.—A comparative study of thin diabetes with fat diabetes. –A brief retrospective on diabetes.” In the first lesson, in addition to reviewing the two cases described in his 1877 paper, Lancereaux describes two new patients. The first is a 35-year-old non-obese male who was previously healthy and then reported developing epigastric burning, followed by weakness, depression, and intellectual decline. Eleven months after onset of first symptoms, he was seen in hospital by Lancereaux and was diagnosed with severe polyuria (7–14 liters/day) with glycosuria (75–80 g of glucose/liter) and emaciation. He was treated but continued to progress, went home, and died 24 months after disease onset. No autopsy was performed. The second patient was a 35-year-old man who also reported an abrupt onset of polydipsia, polyphagia, polyuria, and rapid weight loss. Lancereaux saw him two years after his symptoms had begun and documented glycosuria (49 g of glucose/liter). He died at home 15 days later. No autopsy was performed. In his lecture, he compares these two cases including the abruptness of illness and the similar symptoms/course of disease. He states that “even though I believe it was a lesion of the pancreas, I have to justify my assertion. I think my presentation of two similar cases with autopsy findings will do so.” He then describes in detail the same two cases as in the 1877 paper, except this time, the 61-year-old woman has pancreatic atrophy associated with numerous pancreatic calculi.

These are Lancereaux’s four cases of thin diabetes. Their mean age was over 43 years of age, and there is no clinical similarity to our current understanding of type 1 DM. Furthermore, the documentation of these “pancreatic diabetes” cases is poor, since only two of four patients had autopsies and, in one of those (i.e. the 61 year old woman), the original 1877 report made no mention of the pancreatic calculi that were highlighted as an important autopsy finding when recounted in the 1880 paper. However, as additional evidence, Lancereaux also mentions that a colleague, Maurice Raynaud (1834-1881) sent him a pancreas with lithiasis removed at autopsy from a diabetic patient with a dry gangrenous toe who died of pulmonary phthisis (tuberculosis with wasting). Lancereaux further explains:

So there are many examples of diabetes with atrophy secondary to calculi of the pancreas; there are also in science cases of simple atrophy without calculi, and it is known that there is a diabetes where the pancreas is invaded by a cancerous tumor that obstructs the ducts. Of course, one could argue that there can be calculi of the pancreas without diabetes but this objection is not serious because if one examines these cases intentionally one will soon perceive that the urinalysis will prove the fault.²

In other words, Lancereaux either believed that these patients have DM that was missed or will soon develop DM. He also mentions animal studies by others which he believes support his premise. Finally, he states:

With the clinical and experimental results can we conclude with certainty that the patients who left my wards had an alteration of the pancreas? I cannot say so absolutely but their symptoms point in this direction: rapid progression, loss of physical, intellectual and reproductive strength, great sugar loss each day.²

Lancereaux’s second paper was published on 7 February 1880 and was based upon a second clinical lesson presented at Pitié Hospital on 6 June 1879; it was also collected and edited by LaPierre.³ Lancereaux begins with a brief summary of DM, explaining that it is “a definitive entity,” “its cause is unknown,” and that “some affected persons live 40 years while others succumb in two or three years.” He explains:

What we call sugar diabetes today is not a single-caused entity but complex pathologically. I have tried to show you two forms of diabetes with distinct morbidities: thin diabetes and fat diabetes. In my last lesson, I spoke to you about thin diabetes, its symptoms, evolution, lesions. Today, I would like to discuss the principal phenomena of fat diabetes and show you the considerable differences that separate the two pathologic entities. Fat diabetes begins insidiously. There is a stoutness accompanied by polyuria and glycosuria as well as obesity that can continue in the first phase of the ailment. As I explained in my first lecture on thin diabetes, thin diabetes presents in a brusque manner, is not associated with stoutness, rather is associated with greater and greater weight loss, increased appetite and polyuria and glycosuria. The biggest difference between the two is their evolution. Fat diabetes has polyuria and polydipsia which advances little by little … [he describes 24 hour urine volumes of 4 liters and the urine glucose in the range of 15–30g/liter]. Polyphagia is insidious and does not show symptoms for a long time. Patients with fat diabetes remain strong and intellectually intact in the majority and can continue to work … [Lancereaux explains that the course of fat DM waxes and wanes] Glycosuria can manifest some times and not others and is not continuous and progressive until late in the disease.³

While it is clear that Lancereaux’s work had little to do with the current day classification of type 1, juvenile-onset DM, his description of fat diabetes seems entirely compatible with the current concept of type 2, adult-onset DM, although, unlike for thin diabetes, he does not describe individual cases. Importantly, Lancereaux’s papers do not suggest that thin diabetes and fat diabetes occur in different age groups.

How did Lancereaux’s work become misinterpreted?

The fact that history has credited Lancereaux with describing the direct forerunner of the current classification of DM is curious as there is little evidence that his ideas were even taken seriously in the decades just before the discovery of insulin.

For instance, Frederick Madison Allen (1879–1964), one of two preeminent North American diabetologists before the discovery of insulin, was clearly not a supporter of Lancereaux’s ideas. In a 78 page long historical chapter in his 1919 textbook Total Dietary Regulation in the Treatment of Diabetes, Allen explains:

Lancereaux, a pupil of Claude Bernard, described a form of diabetes characterized by sudden onset, marked emaciation, polyphagia and polydipsia, characteristic feces, and early death. He correctly interpreted this complex as evidence of a pancreatic lesion … But Lancereaux and his pupil Lapierre [sic] proceeded to assume that all diabetes with emaciation is due to a gross pancreatic lesion; to this diabète maigre or pancreatic diabetes they opposed the type of diabète gras or fat diabetes, supposedly not pancreatic in origin. They also added later a “constitutional” or “arthritic” diabetes and a “nervous” diabetes. This classification has been generally discredited but still persists to some extent in France.²⁰

Elliott P. Joslin (1869–1962), the other contemporary preeminent North American diabetologist prior to the discovery of insulin, did not comment on Lancereaux in his writings. However, he clearly did not believe there were two distinct types of DM.

Eugene L. Opie (1873–1971), a pathologist at Johns Hopkins Hospital who discovered a direct relationship between the presence or absence of significant islet pathology in autopsy pancreata and the presence or absence of DM,^18,21 had the following to say:

Lancereaux, more than twenty-five years ago, attempted to define clinically two types of diabetes: diabetes with emaciation due to disease of the pancreas and diabetes with obesity unaccompanied by lesion of the organ. Few clinicians have accepted the criteria proposed by Lancereaux and the existence of pancreatic disease is rarely established unless an autopsy is performed.²¹

This latter statement about the necessity of autopsies was likely meant to further discredit Lancereaux’s ideas, as a careful reading of his 1880 papers reveals that only two of the diabetic patients upon which his ideas were formulated actually had autopsies.

Lancereaux’s terminology received some free advertising from Sir William Osler (1849–1919). Osler published the first edition of his classic textbook Principles and Practice of Medicine in 1892. In his chapter on DM, Osler does not mention Lancereaux specifically, but alludes to his classification as follows:

In spite of the enormous amount of food consumed a patient may become rapidly emaciated … Many, diabetics, however, do not show marked emaciation. Patients past the middle period of life may have the disease for years without much disturbance of health, and may remain well nourished. These are the cases of the diabète gras in contradistinction to diabète maigre.²²

In the next eight editions of Osler’s Principles and Practice of Medicine covering the time up to the discovery of insulin, Osler repeats his observations about the presence or absence of emaciation described in the paragraph above, again invoking the phrase “diabète gras in contradistinction to diabète maigre.” While there is no evidence in any of Osler’s writings that he believed there were two age-of-onset distinct types of DM,²³ mentioning these two terms in many successive editions of his textbook likely helped elevate Lancereaux’s profile. Regardless, Osler’s wording is precise and correct. Lancereaux’s term diabète maigre was not meant to imply that diabetes developed in thin patients, but rather these patients became emaciated during the course of their disease.

How, if Lancereaux and his ideas had essentially no North American followers in the first half of the 20th century, did historians in the latter half of the 20th century latch onto him and bestow priority for DM classification? Furthermore, none of the above-mentioned writers, including Lancereaux, suggest diabète maigre was a disease of young people; where did this idea come from? Addressing these questions is speculative. Greek physician and medical historian NS Papaspyros, who published first and second editions of his History of Diabetes in 1952 and 1964 likely played a role as this is the first history book we have identified that mentions Lancereaux’s two types of DM. We speculate that Lancereaux may have been brought to Papaspyros’ attention by Romanian diabetologists who revered him, primarily because of his association with Paulescu, whom they believed had been denied credit due to him for discovering insulin.^15,16 While Papaspyros may have resurrected the two terms in his book, he did not link these to 20th century DM classification schemes, which did not even exist when he wrote his book, nor did he associate diabète maigre with young people.

It seems likely the long précis, that is incorrectly cited as the title of his two 1880 papers is partially to blame. The papers, actually simply entitled Lesson and Lesson 2, became known as “Thin diabetes: its symptoms, evolution, prognosis, and treatment; Reports with alterations of the pancreas.—A comparative study of thin diabetes with fat diabetes. –A brief retrospective on diabetes.” Possibly, the suggestive wording of the précis implied to someone who did not bother to read his papers that these were equivalent to type 1, juvenile-onset and type 2, adult-onset DM. Subsequent authors, who also did not read Lancereaux’s papers, further embellished this by accidentally adding elements of their current understanding and attributing this to him.

Conclusion

In summary, we have demonstrated that there is no compelling evidence to support the concept that Lancereaux’s diabète maigre, which he attributed to pancreatic causes, was a direct predecessor of type 1 DM. Unfortunately, historians of diabetes appear to have latched onto his catchy terminology without reading his papers and then reinterpreted thin and fat diabetes using a present day understanding. However, in doing this, they were half right, as Lancereaux’s second 1880 paper provides a compelling description of classic signs and symptoms of type 2 DM, and perhaps Lancereaux should be credited for describing this entity and naming it diabète gras, which he attributed to non-pancreatic causes. Related to this later point, his vision was later proven to be correct, as type 2 DM in obese middle-aged patients is often due to insulin-resistance in peripheral tissues such as adipose and muscle.

While we established that Lancereaux did not discover type 1 DM, his descriptions of cases of diabete maigre bear striking clinical and pathological similarities to a more recently described diagnostic entity, type 3c (or pancreatogenic) DM. Type 3c DM would likely now encompass all of the cases described in his 1877 and first 1880 papers.^24,25

Footnotes

Acknowledgements

The authors thank Kristin Rodgers, MLIS, Collections Curator, The Ohio State University Health Sciences Library Medical Heritage Center; Lily Szczygiel, Osler Library of the History of Medicine, McGill University; Charlotte Monroe; Thomas Kryton, BFA; and the University of Calgary Interlibrary Loan Service.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

James R Wright Jr.

Author biographies

James R Wright Jr. is Professor of Pathology and Laboratory Medicine and also Professor of Paediatrics at the University of Calgary, Calgary, Alberta, Canada. He has written extensively on historical topics, especially the history of pathology.

Lynn McIntyre is Professor emerita of Community Health Sciences at the University of Calgary. Raised in an anglophone/francophone family, she is fluent in French and has published extensively in the social and public health sciences literatures.

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