The Treatment of Diabetes: A Brief History.
In 1910, British researcher Sir Edward Albert Sharpey-Shafer suggested that people with diabetes were deficient in a single chemical produced by the pancreas and proposed calling it insulin, from the Latin term "insula," meaning "island" and referring to the islets of Langerhans in the pancreas. Then in 1921-1922, Canadians Frederick Banting and Charles Best began treating diabetes with insulin. Banting, Best, a chemist named Collip and their colleagues at the University of Toronto went on to purify insulin from bovine pancreases.
By the fall of 1923, Eli Lilly and Co., along with the University of Toronto, began mass production of Insulin. Soon 25,000 patients in Canada and the U.S. were being treated with insulin.
For this work, in 1923 Banting and laboratory director John MacLeod received the Nobel Prize for Physiology in Medicine. They shared their prize money with others who were not recognized, particularly Best. More importantly, they made a decision that proved profoundly impactful. They had no interest in controlling insulin production and chose to share their insulin production patents without charge. As a result, insulin production and therapy spread rapidly around the world. To this day, Banting is honored on World Diabetes Day, celebrated each year on his birthday, November 14.
The 1920s continued to be an amazing period for the treatment of diabetes. In 1922, the biguanide metformin was discovered. While its blood glucose-lowering effects in laboratory animals were known by the late 1920s, its importance as a potential treatment for diabetes was obscured by the high-profile nature of insulin, which was relatively inexpensive, more understood than the biguanides, easily obtained and known to be effective.
Moreover, adding to the already high profile of insulin, in 1936 it was discovered that adding protamine to insulin prolonged its effect. This work by Hans Hagedorn led to the introduction in 1950 of neutral protamine Hagedorn, or NPH, insulin. Also in 1936 the concept of insulin resistance was recognized. That discovery opened an entirely new sector of diabetes treatment research.
Eventually the term "metabolic syndrome" was developed to define a condition putting a person at significant risk for diabetes and cardiovascular disease.
In 1941, a then simple diagnostic and patient management test for glucose in the urine was discovered and soon proven to be acceptably accurate. Tablets for testing urine glucose levels became widely available. In the 1950s urine test strips were marketed and slowly began to be accepted by patients.
Then in the 1960s, and particularly the 1970s, somewhat unsophisticated attempts to improve home glucose monitoring proved beneficial, particularly in type 1 patients. But it was not until 1981 that the first glucometers, Accu-Check from Roche and Glucometer from Bayer, were introduced and began to dominate the market.
In 1949 Becton Dickinson began producing a standardized insulin syringe designed and approved by the American Diabetes Association. These standardized syringes mitigated incorrect insulin dosages, thus greatly reducing the potential for hypoglycemic and hyperglycemic events.
On the medication research front, interest in metformin resumed in the late 1940s and '50s. As studies progressed, its ability to lower blood glucose levels without lowering either blood pressure or heart rate were noted. As well, metformin seemed to produce no weight gain. Unwelcome weight gain was a known side effect of insulin therapy. Metformin was also suspected to reduce the possibility of adverse cardiovascular events in overweight patients with type 2 diabetes.
The U.K. Prospective Diabetes Study, a large clinical study in the 1980s and '90s provided evidence to corroborate the cardiovascular benefit. However, newer and more recent studies mitigated belief in metformin's cardiovascular benefits.
Nevertheless, after first being introduced as a medicine in France in 1957, metformin was introduced in the U.S. in 1995. It is currently on the World Health Organizations List of Essential Medicines.
Other oral biguanides, phenformin and buformin, were introduced in subsequent years. But their propensity to produce lactic acidosis caused them to be withdrawn from the market.
Also in the 1940s, while metformin was attracting research attention, sulfonamides were being studied as possible antibiotic agents. In 1942, sulfonylureas were found to produce lower blood sugar levels in laboratory animals. Research showed they induced insulin production by the pancreas, so much so that hypoglycemia was a risk. Due to sulfonylureas increasing insulin production, it was not surprising they also produced weight gain. And similar to metformin, they were shown to reduce death from cardiovascular events.
In the mid-1950s, sulfonylureas became the first oral medications available for the treatment of diabetes. The first was tolbutamide under the trade name Orinase from Upjohn Co. Later came oral dosages of metformin, introduced in France in 1957, although, as mentioned earlier, not until 1995 in the U.S.
The 1970s produced amazing gains in diabetes patient management. The Ale test was developed to measure glycosolated hemoglobin. It became the gold standard test. E. coli bacteria were studied and used to produce synthetic insulin identical to human insulin. But it was not until 1982 that the FDA approved the production of insulin from genetically engineered bacteria.
Portable insulin pumps were introduced and proved to produce stable insulin levels in patients using them. However, because they were large and clumsy, it was not until 1983 that a miniaturized version much easier to use became more widely accepted.
In the late 1990s, three thiazolidinediones commonly known as glitizones were introduced. They were troglitizone, pioglitizone and rosiglitizone. While troglitizone had a short commercial life due to safety issues, pioglitizone and rosiglitizone remain on the market today but must be used with extreme caution.
Currently a near multitude of medications representing 11 different molecular categories are on the market. The potential permutations from combinations of these medications are of no less than serious concern.
So as we continue to struggle with patient efficacy of the various treatment regimens, it must be recognized that we have come a long way in diabetes management. In 1975 it was reported that life expectancy of patients with type 1 against those without was 27 years. In 2013 it was reported the differential had dropped to 11 to 14 years.
Yet the need for improved diabetes patient management can be said to be more extreme than ever. The term "diabetes epidemic" in the U.S. is well founded. From 1980 to 2010 the number of diagnosed cases of diabetes in the U.S. has risen from 5.6 million to 20.9 million.
Not even considering patient suffering, the annualized cost of treating this U.S. epidemic is calculated to be in a range of $175 billion to $200 billion. Economically unsustainable is a descriptor being used.
Robert Coopman is president of Robert Coopman Consultants, based in San Antonio. He can be contacted at firstname.lastname@example.org.
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|Publication:||Chain Drug Review|
|Date:||Oct 23, 2017|
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