History of Diabetes

Dr Chakshu Chandel *

Diabetes mellitus which is more commonly known as diabetes comes from the Greek word diabetes, meaning 'siphon - to pass through', to explain polyuric state that means excessive urination and unquenchable thirst, and the Latin word 'mellitus' meaning sweet.

The Hindu physicians Charaka and Sushruta, who wrote between 400 BC and 500 BC, were the first to recognize the sweetness of diabetic urine. Both noted that the disease was most prevalent in those who were indolent, overweight and gluttonous and who indulged in sweet and fatty foods.

Physical exercise and liberal quantities of vegetables were the mainstays of treatment in obese, while lean people with more serious disease were given a nourishing diet.

Later on discoveries showed that a chemical produced by the pancreas regulate glucose metabolism in our body. The deficiency of this chemical substance leads to diabetes. In the latter part of the 19th century it was becoming apparent that there were at least two clinically distinct forms of diabetes.

In 1880, the French physician E. Lancereaux identified lean and obese patients as having diabete maigre (thin, or more accurately emaciated, diabetes) and diabete gras (fat diabetes). This observation laid foundation for subsequent etiologic classifications of the disease.

Doctors in the 19th century were theoretically important; their main role was as taxonomists who described symptoms, complexes and the natural history of disease. As a result, most of the complications of diabetes were well described before 1900.

In the 19th century, treatment regimes for diabetes were lifestyle modifications like starvation, diet, excessive exercise, "oatmeal" cure.

The story of how insulin was discovered in Toronto in 1921 is interesting. A young orthopaedic surgeon Fredric Banting inspired after reading an article by a pathologist about a pancreatic extract which could treat diabetes.

So he approached Professor of Physiology in Toronto JJR Macleod who was an authority on carbohydrate metabolism. Banting along with Physiology student Charles Best after 6 months of hard work, discovered the most important new therapy for diabetes. It was 'Insulin'; the term was coined by Macleod.

For the first decade after its discovery, insulin was available only in its soluble formations or regular insulin, whose short action profile required multiple daily injections. First delayed action preparation, protamine insulinate was introduced in 1936. Then NPH or isophane insulin in 1946.

These are delayed acting insulin used in different combinations or mixes. Then came long acting insulin in 1952,, lente insulin. Long acting insulin were welcomed by diabetes specialists and patients because only single daily injections required but they had their own side effects that is hypoglycemia.

From that time, main advances were in methods to produce highly purified preparations from porcine or bovine pancreas which remained till early 1980s.

Insulin was the first therapeutic protein to be produced by recombinant DNA technology initiated by David Goeddel. From there, genetic engineering has been used to produce "designer" insulin such as fast acting insulin analogs lispro and aspart and the "peakless" basal insulin such as glargine, detemir and degludec. These are more expensive but less clinical hyperglycemia with their use.

There are studies and research trials going on for oral and intranasal insulin. The first orally active glucose lowering drug Synthalin was developed in 1926 but it was withdrawn because of its toxicity.

After that many oral drugs were discovered including metformin, glimipride, gliclacide, gliptins and latest glifozines and semaglutide. These drugs work at various levels of glucose metabolism.

Some enhance insulin production, some mimic insulin actions, some decrease inflammation in body specially insulin producing islet cells of pancreas, some increase glucose excretion from kidneys.

Hope the future will be bright for diabetic patients as new treatment options are available.