JMS Pearce
Hull, England

There are many excellent descriptions of the history of diabetes, and of the nineteenth- and particularly twentieth-century discoveries of the secretion of insulin by the beta cells of the pancreatic islets of Langerhans.^1,2 (See Table) However, the earlier history of diabetes is less known.

The Egyptian papyrus (c. 1550 BC) discovered by George Ebers around 1873 is often cited. It described remedies “to eliminate urine which is too plentiful; a melting down of the flesh,” but sweet tasting urine was not mentioned. That this was diabetes is questionable. Ayurvedic physicians Sushruta and Charaka (5^th – 6^th century BC) more convincingly noted the sweet taste of urine and called the condition madhumeha (“honey urine”), noting that ants and flies were drawn to the urine of afflicted individuals.^3,4 It was associated with thirst and general weakness. In traditional Chinese medicine, xiāo kě characterized thirst, hunger, frequent urination, and weight loss.

The word diabetes comes from the Greek verb διαβαίνειν (diabain), a siphon, implying the passage of fluid—an apt description of polyuria. Aulus Cornelius Celsus (c. 25 BC – c. AD 50) related excessive urination to wasting and weight loss:

But when the urine exceeds in quantity the fluid taken, even if it is passed without pain, it gives rise to wasting and danger of consumption.

The naming of diabetes is variously attributed to the Greek Apollonius of Memphis in 230 BC and Demetrius of Apamea c. 100 BC,⁵ reported by Caelius Aurelianus:

But Demetrius of Apamea more properly distinguishes from dropsy the disease in which everything that is drunk is immediately discharged as urine and he [Demetrius] calls this disease diabetes.

Thirst, polyuria, and wasting were recognized; kidney disease was thought to be the cause of this malady.

Aretaeus (Aretaios) was a physician born in Cappadocia around the 2nd century AD.^6] He used the word diabetes³ and gave the first clear description:

Diabetes is a wonderful affection, not very frequent among men… The course is the common one, namely, the kidneys and the bladder; for the patients never stop making water, but the flow is incessant…. The nature of the disease, then, is chronic, and it takes a long period to form; but the patient is short-lived, if the constitution of the disease be completely established; for the melting is rapid, the death speedy. Moreover, life is disgusting and painful; thirst; excessive drinking, which, however, is disproportionate to the large quantity of urine, for more urine is passed; and one cannot stop them either from drinking or making water. Or if for a time they abstain from drinking, their mouth becomes parched and their body dry; they are affected with nausea, restlessness, and a burning thirst; and at no distant term they expire…⁷

Galen, too, mentioned the Greek word diabetes but failed to mention Aretaeus by name. Galen did not describe the sweet taste of the urine, but believed diabetes was a kidney disease.

I am of the opinion that the kidneys too are affected in the rare disease which some people call chamber-pot dropsy, others diabetes or violent thirst. I have seen the disease only twice, when the patients’ thirst forced them to drink enormous quantities; the fluid was urinated swiftly with a urine resembling the drink… Diabetes is a genuine kidney disease, analogous to voracious appetite.⁸

Interestingly he stressed its rarity, which suggests he may have been dealing with other causes of thirst and polyuria, possibly diabetes insipdus.

The Persian physician Avicenna in The Canon of Medicine in 1025 also recognized thirst, polyuria, and impaired sexual function along with sweet urine and diabetic gangrene. Various diets and herbal remedies were often prescribed. He was also the first to describe diabetes insipidus.

Long before modern research identified the etiology as autoimmune insulin deficiency and insulin resistance, in 1674 Thomas Willis made a major advance by distinguishing it from kidney disease^9,10:

But for a principal share in this malady, we may justly bring in the nervous juice;

…The disease which is called diabetes, or the Pissing Evil, is an unusual and deplorable distemper, in which there is a great and frequent discharge of urine, with an insatiable thirst, and an extraordinary wasting of the body, accompanied with the decay of strength.

Willis’s prescient idea was that the cause of diabetic symptoms was a disturbance in the blood and nervous system, not the kidneys:

Causa huius morbi non in renibus sita est…

The cause of this disease is not situated in the kidneys, but rather in the blood and the animal spirits, whose errors arise in the very brain and spinal cord. From this, there results a defect in the flow of urine, especially in that sweetness which is found in the urine, as if it were honey.

It was not until 1776 that Matthew Dobson (1732–1784), physician to the Liverpool Infirmary, examined the blood and urine in a thirty-three-year-old man and showed it was sugar that caused the sweet taste:

The urine is sweet, & two quarts yielded four ounces of an extract exactly resembling thick treacle, but not so sweet. After the evaporation, a white cake which … was granulated, and broke easily between the fingers; it smelled like brown sugar, neither could it, by the taste, be distinguished from sugar white cake.

At the time of his report he had seen nine patients with the disease. The term mellitus, often ascribed to John Rollo’s “An account of two cases of the diabetes mellitus” in 1797, had been chronicled earlier by William C. Cullen in 1788: “Diabetes mellitus; when the urine has the smell, colour, and taste of honey.”

For many centuries, diabetes was recognized by its symptoms but little was known of its cause or mechanisms.¹¹ Nor was there any effective treatment, and patients often died within weeks or months after diagnosis. It was the remarkable Guy’s physician Richard Bright who as early as 1833 described diabetes in pathologically verified pancreatic cancer, although he did not speculate about their putative relationship. His patient was James Barnes, a forty-nine-year-old clerk:

Case 1. Diabetes, with supervening icterus from obliteration of the common bile duct, caused by disease of the pancreas, malignant ulceration of the duodenum.

…Afflicted by immoderate thirst and who made water very frequently, and his urine was of a pale colour. These symptoms accompanied by emaciation… his disorder was pronounced to be diabetes mellitus.¹²

Interestingly, four months later, increasing emaciation, jaundice, and hepatomegaly supervened but his diabetes remitted: “From this time forth the patient might be said to have lost altogether the diabetic disorder.” It is possible this was a remission caused by weight loss. He died one year after the onset.

In 1849, Claude Bernard showed that sugar was stored in the liver as glycogen. In an experiment when he needled the floor of the fourth ventricle, he produced transient glycosuria—piqûre diabétique (puncture diabetes)—thus implicating the nervous system. Later studies confirmed that the hypothalamus is a regulator of glucose homeostasis and, by acting through the parasympathetic nervous system, stimulates the pancreatic release of insulin.

The disordered secretion of the insulin was revealed in the nineteenth century, clinically by Lancereaux and experimentally by Minkowski and von Mering (Table 1). Subsequently, biosynthetic insulin preparations have been refined and become standard treatment principally but not exclusively for type 1 diabetes. In addition to diet and exercise regulation, sulfonylureas were succeeded by metformin and other therapies mainly applicable to type 2 diabetes.

Table 1. Selected landmarks in diabetes
1833: Richard Bright described diabetes in malignant pancreatic disease.12
1849: Claude Bernard needled the fourth ventricle producing transient glycosuria (“puncture diabetes”).
1869: Paul Langerhans discovered islets of cells in the pancreas, secretory function unknown.
1877: Lancereaux coined the term pancreatic diabetes to describe two young subjects who died with severe diabetes and pancreatic atrophy at autopsy.13
1890: Oscar Minkowski aided by Joseph von Mering removed the pancreas of dogs, which developed polyuria, hyperglycemia, and glycosuria. They deduced diabetes is due to the absence of a pancreatic active substance that is transported by the bloodstream.14
1900: Eugene L. Opie linked diabetes mellitus with hyaline degeneration of the islands of Langerhans in pancreatitis.15
1910: Edward Albert Sharpey-Shafer suggested that diabetes was due to the deficiency of a single chemical in the pancreas, which he named insulin.2
1922: Frederick Banting,16* Charles Best, James Collip, and John Macleod* induced diabetes in pancreatectomized dogs, reversed by injecting pancreatic islet cells of healthy dogs; they purified insulin from bovine pancreases and were first to use it to treat a patient.17
1936: Harold Himsworth distinguished insulin-sensitive type 1 and more common insulin-insensitive type 2 diabetes.18
1945: Frederick Sanger* sequenced the amino acids of insulin.
1969: Dorothy Hodgkin* showed the three-dimensional crystalline structure of insulin.
1977 Rosalyn Yalow* showed the immunogenic properties of insulin and its immunoassay.

* Received the Nobel Prize

References

1. Slingerland AS. The history of diabetes and insulin. Hektoen Int. Spring 2018.
2. Tattersall R. Diabetes: The Biography. Oxford University Press, 2009.
3. Henschen F. On the term diabetes in the works of Aretaeus and Galen. Med Hist. 1969;13(2): 190-2.
4. Hirsch A. Handbook of Geographical and Historical Geography, 3 vols, London, 1883-1886.
5. Gemmill, CL. The Greek Concept of Diabetes. Bulletin of the New York Academy of Medicine. 1972;48 (8):1033-36.
6. Aretaeus, the Cappadocian, The extant works, ed. and trans. by Francis Adams, London, 1856.
7. Leopold EJ. Aretaeus the Cappadocian his contribution to diabetes mellitus. Ann Med Hist. 1930;2(4): 424-35.
8. Galen. On the Affected Parts, trans. Rudolph E. Siegel, Loeb Classical Library No. 328. Book 8. Harvard University Press, 1976.
9. Willis T. Pharmaceutice rationalis sive Diatriba de medicamentorum operationibus in humano corpore. section IV chapter IIIThe Hague: A. Leers, 1675.
10. Willis T. De Diabetis, et Curatione Eius. London: H. Herringman, 1674.
11. Polonsky KS. The Past 200 Years in Diabetes. New Engl J Med 2012;367:1332-40.
12. Bright R. Cases and observations connected with disease of the pancreas and duodenum, Medico-chirurgical transactions 1833;18:3-12.
13. Lancereaux E. Notes et réflexions à propos de deux cas de diabète sucré avec altération du pancréas. Bull Acad Méd 2e série 1877;6:1215.
14. von Mering J, Minkowski O. Diabetes mellitus nach Pankreas extirpation. Arch Exp Pathol Pharmacol 1890;26:371-387.
15. Opie EL. The relation of diabetes mellitus to lesions of the pancreas. Hyaline degeneration of the islands of Langerhans. J Exp Med 190;5(5): 527-40.
16. Frederick G. Banting – Nobel Lecture. NobelPrize.org. Nobel Prize Outreach 2025. https://www.nobelprize.org/prizes/medicine/1923/banting/lecture/
17. Banting FG, Best CH. The internal secretion of the pancreas. J Lab Clin Med. 1922;7:251-66.
18. Himsworth, HP. Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types. Lancet 1936;1:127-30.