Diabetes

Ancient Hindu writings, many thousands of years old, document how black ants and flies were attracted to the urine of diabetics. The Indian physician Sushruta in 400 BCE described the sweet taste of urine from affected individuals, and for many centuries to come, the sweet taste of urine was key to the diagnosis of diabetes. Around 250 BCE, the name “diabetes” was first used. It is a Greek word that means “to syphon”, reflecting how diabetes seemed to rapidly drain fluid from the affected individual. The Greek physician Aretaeus noted that as affected individuals wasted away, they passed increasing amounts of urine as if there was “liquefaction of flesh and bones into urine”. The complete term “diabetes mellitus” was coined in 1674 by Thomas Willis, personal physician to King Charles II. Mellitus is Latin for honey, which is how Willis described the urine of diabetics (“as if imbued with honey and sugar”). Up until the mid-1800s, the treatments offered for diabetes varied tremendously. Various “fad” diets were prescribed, and the use of opium was suggested, as were bleeding and other therapies. The most successful treatments were starvation diets in which calorie intake was severely restricted. Naturally, this was intolerable for the patient and at best extended life expectancy for a few years. A breakthrough in the puzzle of diabetes came in 1889 when German physicians Joseph von Mering and Oskar Minkowski surgically removed the pancreas from dogs. The dogs immediately developed diabetes. As the link was established between the pancreas gland and diabetes, research focused on isolating the pancreatic extract that could treat diabetes. When Dr. Frederick Banting took up the challenge of isolating a pancreatic extract, he was met with much skepticism. But Banting, a surgeon, persisted and in May 1921, he began work in the laboratory of Professor John Macloed in Toronto, Canada. Charles Best, a medical student at the time, worked as his assistant. To concentrate what we now know as insulin, Banting tied the pancreatic ducts of dogs. The pancreatic cells that released digestive enzymes (and could also destroy insulin) degenerated, but the cells that secreted insulin were spared. Over several weeks the pancreas degenerated into a residue from which insulin could be extracted. In July 1921, a dog that had had its pancreas surgically removed was injected with an extract collected from a duct-tied dog. In the two hours that followed the injection, the blood sugar level of the dog fell, and its condition improved. Another de-pancreatized (diabetic-like) dog was kept alive for eight days by regular injections until supplies of the extract, at that time called “isletin”, were exhausted. Further experiments on dogs showed that extracts from the pancreas caused a drop in blood sugar, caused glucose in the urine to disappear, and produced a marked improvement in clinical condition. So long as the extract was being given, the dogs were kept alive. The supply of the extract was improved: the pancreas of different animals were used until that of the cow was settled upon. This extract kept a de-pancreatized dog alive for 70 days. Dr. James B. Collip, a biochemist, was drafted to continue improving the purity of the pancreas extract, and later, Best carried on this work. A young boy, Leonard Thompson, was the first patient to receive insulin treatment. On January 11, 1922, aged 14 and weighing only 64 pounds, he was extremely ill. The first injections of insulin only produced a slight lowering of blood sugar level. The extract still was not pure enough, and abscesses developed at the injection site. Collip continued to refine the extract. Several weeks later, Leonard was treated again and showed a remarkable recovery. His blood sugar levels fell, he gained weight and lived for another 13 years. He died from pneumonia at the age of 27. During the spring of 1922, Best increased the production of insulin to enable the treatment of diabetic patients coming to the Toronto clinic. Over the next 60 years, insulin was further refined and purified, and long-acting and intermediate types were developed to provide more flexibility. A revolution came with the production of recombinant human DNA insulin in 1978. Instead of collecting insulin from animals, new human insulin could be synthesized. In 1923, Banting and Macloed were awarded the Nobel Prize for the discovery of insulin. Banting split his prize with Best, and Macloed split his prize with Collip. In his Nobel Lecture, Banting concluded the following about their discovery: “Insulin is not a cure for diabetes; it is a treatment. It enables the diabetic to burn sufficient carbohydrates, so that proteins and fats may be added to the diet in sufficient quantities to provide energy for the economic burdens of life.”

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