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It is estimated that 30 million Americans have diabetes. Some 86 million others have prediabetes, of which 30% will develop diabetes over a five year period. It is the fastest growing chronic disease in the United States. For the 6% and growing population of patients with type 1 diabetes (T1D), insulin is necessary for survival.
It is no exaggeration to call insulin a life-saving medicine. Since its discovery in 1923, millions of people have had longer lives than expected and fewer complications because of their disease. Patients with T1D were previously "treated" with diets close to famine and had a life expectancy of only a few years.
The basic diet, popularized during the decade before the discovery of insulin, was to completely limit calories for a while, resulting in considerable weight loss before reintroducing the patient into a high-fat diet. fats and protein without carbohydrates. In writing about the strategy, prominent physician Eliot Proctor Joslin, MD, noted that patients were starving with only "the faint hope that something new will appear".
Enter insulin, in 1923.
It had been known for half a century that blood sugar was at the heart of the problem of diabetes. The importance of the pancreas in carbohydrate metabolism had been known since 1880, when German doctors Joseph von Mering and Oskar Minkowski had successfully removed the pancreas from a dog and demonstrated that it was causing a syndrome high blood sugar, glucosuria and possible death.
Previously, in 1869, investigators had discovered two types of cells in the pancreas: acinar cells were responsible for digestive functions and islets of sugar secreted by Langerhans.
Around the same time, Romanian scientist Nicolae Paulescu was experimenting with an aqueous extract of pancreas that reduced blood sugar when it was injected into diabetic dogs. He called this pancreatic substance. When the First World War broke out, he stopped his experiments for several years. In fact, he patented his product in 1922 at the Romanian patent office, but he was never officially recognized for the discovery of insulin. At the same time, two Canadian researchers, Sir Frederick Grant Banting and John Macleod, published an article on the use of an alcohol-based pancreatic extract to normalize blood sugar levels in humans.
In addition to contributing to the development of insulin, Palescu also knew that the pancreas contained other enzymes that play a role in regulating blood sugar – an unexplored data over the next 50 years. They play today an important role in the treatment of diabetes.
Banting's work began with the discovery that by ligating the pancreatic duct to the dogs and then removing the intact pancreas, he could isolate the insulin without destroying it by the pancreatic digestive enzymes. He was able to isolate a small amount of a pancreatic enzyme – which he injected into a diabetic dog, showing a drop in glucose.
The process was repeated many times, but was tedious and yields low. This procedure only allowed to harvest a small amount of insulin and took a lot of time. So they decided to use cattle as a source of pancreatic enzymes.
The next step was to try to purify it and test it on rabbits. The work was done under the supervision of McCleod. Once a good insulin purification process has occurred, the first human test occurred in 1922 with insulin injection at a boy of 14 years old. Miraculously, his blood sugar level has fallen into a normal range and he is not dead. Several other tests on humans have been developed, which clearly showed that the extract could reduce blood sugar in humans.
Banting and McCleod were awarded the Nobel Prize in Medicine in 1923 for their work discovering insulin. This has created a controversy that continues to this day as to who really should have been recognized for this discovery. In the end, it is Banting who received the commercial rights to insulin, which he donated to the University of Toronto for one dollar.
Producing insulin in commerce was a gigantic undertaking. Banting asked the company Eli Lilly's help to help produce insulin that was now extracted from rabbits, giving them a non-exclusive license to develop insulin. . Non-exclusivity has allowed other companies to work with insulin as well.
At first, the reliability of the insulin extracts posed major problems. The extracts deteriorated rapidly and lacked consistency from batch to batch. The problem was solved by the discovery that insulin had to be prepared at a specific pH, which would guarantee purity and quality control. The method called "isoelectric precipitation" has allowed Eli Lily to produce insulin in large quantities, although problems of standardization remain. The University of Toronto has been able to maintain control of insulin, but has granted several companies the right to develop it.
Banting said repeatedly that he did not want a company to have complete control, to allow insulin to remain available at a great price for patients in need. Over time, new proportions of insulin have been developed to increase or decrease the duration of the effect.
In 1936, Hans Hagedorn and August Krogh obtained insulin rights from the University of Toronto. They formed Nordisk Insulin Laboratorium. They discovered that insulin could be prolonged by adding protamine obtained from river trout sperm. Protamine-zinc insulin lasted 24 to 36 hours, making it somewhat unmanageable due to prolonged hypoglycaemia.
A problem with all insulins produced until 1982 was that they came from animal sources and could cause allergic reactions, as well as reactions at injection sites. It also sometimes produced inconsistent results.
A major breakthrough occurred in 1978, when Genentech was able to synthesize the first human insulin molecule. Once the genetic code was known, Lilly scientists were able to insert the DNA sequence into E. coli and harvest human insulin in large quantities. Human insulin was patentable and was put on the market in 1982 in two forms: a normal or short-acting form or an intermediate-acting form. These products were unlikely to cause allergic reactions and their effects were very consistent. What was lacking, however, was the insulin's ability to behave like insulin when secreted by the pancreas in healthy subjects because the onset of action could not be matched.
Over the years, scientists have modified the amino acid sequences of human insulin to mimic more accurately the effect of insulin in vivo. They have created faster and more durable products. They have also developed new management systems, such as insulin pens and pumps, to make administration and storage of insulin convenient and painless.
As I said, insulin DT1 is a lifesaver. For many patients with type 2 diabetes, insulin can be added to other treatments to control glucose and reduce complications. The discovery of insulin has constituted a considerable scientific breakthrough, but as for many other great things, there are unexpected negative consequences.
Insulin prolongs patients' lives long enough for them to aggravate the complications of their disease, including blindness, kidney failure, and cardiovascular disease prematurely. There is no way to reduce the risk of transmitting a genetic predisposition to the children of patients. Finally, it can be said that the discovery of insulin ended diabetes research, neglecting some important hormones that play a key role in glucose metabolism.
Only in the last 20 years have we recognized and developed drugs other than insulin to treat type 2 diabetes. These products have changed the lives of people with T2DM and prevented complications of insulin therapy. It has been said, although it goes without saying, that the discovery of insulin was the worst thing that happened to type 2 diabetes.
But it can not be denied that insulin has saved millions of lives in T1D treatment and was perhaps the greatest medical miracle of this century. As with everything in life, nothing is black and white and all good things have unintended consequences.
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