What Was Known About Childhood Diabetes Mellitus Before the Discovery of Insulin?

It has been widely reported by historians that physicians were aware of two distinct types of diabetes mellitus by the 1880s, and that these were both similar to and the direct forerunners of type 1, juvenile-onset and type 2, adult-onset diabetes. The writings of prominent specialist physicians practicing just prior to the discovery of insulin in 1921–1922 were reviewed and there is little evidence that experts believed that adult and childhood diabetes were different. In fact, more than a decade passed after the discovery of insulin before diabetes in children and adults even began to be distinguished. Childhood diabetes was exceedingly rare in the early 20th century and diabetes was believed to be primarily a chronic disease of adults. It is interesting to speculate about what might have happened if the first pancreatic extract tests had been performed on adult-onset diabetics with insulin-resistant diabetes mellitus. Clearly, the results would have been disappointing and the discovery of insulin delayed. This essay explores how the test subject decision was made. It is fortuitous that a 14 year old boy with what was unequivocally type 1 diabetes was selected to be the first insulin recipient, and the rest is history.

Differential Detection of Encapsidated versus Unencapsidated Enterovirus RNA in Samples Containing Pancreatic Enzymes—Relevance for Diabetes Studies

Using immunohistochemistry, enterovirus capsid proteins were demonstrated in pancreatic islets of patients with type 1 diabetes. Virus proteins are mainly located in beta cells, supporting the hypothesis that enterovirus infections may contribute to the pathogenesis of type 1 diabetes. In samples of pancreatic tissue, enterovirus RNA was also detected, but in extremely small quantities and in a smaller proportion of cases compared to the enteroviral protein. Difficulties in detecting viral RNA could be due to the very small number of infected cells, the possible activity of PCR inhibitors, and the presence—during persistent infection—of the viral genome in unencapsidated forms. The aim of this study was twofold: (a) to examine if enzymes or other compounds in pancreatic tissue could affect the molecular detection of encapsidated vs. unencapsidated enterovirus forms, and (b) to compare the sensitivity of RT-PCR methods used in different laboratories. Dilutions of encapsidated and unencapsidated virus were spiked into human pancreas homogenate and analyzed by RT-PCR. Incubation of pancreatic homogenate on wet ice for 20 h did not influence the detection of encapsidated virus. In contrast, a 15-min incubation on wet ice dramatically reduced detection of unencapsidated forms of virus. PCR inhibitors could not be found in pancreatic extract. The results show that components in the pancreas homogenate may selectively affect the detection of unencapsidated forms of enterovirus. This may lead to difficulties in diagnosing persisting enterovirus infection in the pancreas of patients with type 1 diabetes.

Diabetes mellitus: present by historical perspective

Diabetes mellitus has been known from antic period, due to the sweet taste of the urine of this patients. The modern era of diabetes started in 1815 with the discovery made by the French chemist Eugène Chevreul, who found that the sweet substance from the diabetic urine was the same with the grapes sugar. At this point, the study of diabetes has had aproached several succesive objectivs: the development of chemical methods from determination of urinary and blood glucose and its physiological signification (A. Bouchardat, Claude Bernard); the discovery of the organ involved in diabetes (E. Lancereaux, P. Langerhans, von Mering and Minkowsky, E. Laguèsse); indirectly demonstration of the presence of a pancreatic antidiabetic substance, produced possible in the Langerhans islets (E. Hédon, E. Gley, G.L. Zuelzer), the discovery of antidiabetic hormone and full description of its metabolic functions (N.C. Paulescu); purification of the pancreatic extract by J. B. Collip and it’s utilization in diabetes treatment by J. MacLeod, F.G. Banting and C.H. Best; in an unprecedental hurry, the 1923 Nobel Prize for the physiological and experimental discovery of insulin (in fact made by Paulescu) and for its clinical application (in fact due to the purification of the pancreatic extract made by J. B. Collip), without factual reasons the Nobel Prize was awarded to Banting and MacLeod.