Since antiquity, diabetes has always been an enigmatic metabolic disease. Its prevalence spans the entire medical era: The ancient Hindus writings referred to the sweetness of diabetic urine as “honey urine” and a disciple of Hippocrates, Aretaeus, coined the word “diabetes” which means, “siphon” to explain the condition of excessive urination associated with the disease. In what appeared to be a helpless observation of the combination of excessive urination and uncontrolled weight loss, Aretaeus went on to describe diabetes as “…a wonderful affection, not very frequent among men, being a melting down of the flesh and limbs into urine”. The direct supernatural medical era description was noted by Thomas Willis in 1674 who referred to diabetes as “pissing evil” but the symptom of sugar did not escape him as he also observed that the urine was “wonderfully sweet, as if it were imbued with honey or sugar”.
Diabetes was a rare fatal disease before the discovery of insulin 100 years ago by Frederick Banting and Charles Best at the University of Toronto in 1921. According to the International Diabetes Federation, “the only treatments available at the time were fasting and calorie-restricted diets but nothing was really effective to maintain adequate levels of blood glucose and keep people with a severe form of diabetes (today known as type 1 diabetes) alive for more than a few months.” Recounting his clinical experience before the insulin era, Dr. Elliott P. Joslin, one of the prominent American diabetologists of the early 20th century stated in a 1943 address that “diabetic coma took all the children” adding, “life was not a joy…no fun to starve a child to let him live”.
Since 1921, thanks to insulin discovery, diabetes was no longer a fatal disease and the cause and control of “honey urine” that had remained elusive since antiquity was finally resolved. However, there was no distinction between Type 1 and Type 2 diabetes when insulin was discovered. In 1936, Harrod Percival Himsworth, in what he described as his tentative opinions, labelled diabetes into 2 groups: insulin-insensitive and insulin-sensitive. About 15 years later, Robert Daniel Lawrence, a physician who had diabetes, also categorized diabetes into two: “The first starts in young people who are often underweight; it is severe in that the patient depends on the administration of insulin. The second is mild and characteristically arises in the middle-aged patients who are often obese and seldom require insulin”.
The first and second categories as described by Dr. Lawrence was for the first time referred to as Type 1 and Type 2 diabetes respectively by Philip Hugh-Jones in 1955. Type 1 diabetes is an autoimmune condition that occurs when the body’ immune system attacks and destroys the insulin producing cells in the pancreas. The removal of pancreas in dogs induced diabetes which mimicked the symptoms of diabetes observed in humans and eventually led to the discovery and successful purification of insulin by Banting and Best. On the other hand, according to the International Diabetes Federation, type 2 diabetes is characterized by insulin resistance where the body does not fully respond to insulin produced by the pancreas causing persistent high blood sugar levels.
Insulin extracts from cow and pig’s pancreas which were used initially have been replaced with biosynthetic human insulin produced from recombinant technology that harvests human insulin from microorganisms. Insulin is produced and stored inactively in the body as a cluster of six insulin molecules called a hexamer. This hexamer is disintegrated to release free active insulin molecules or monomers into the bloodstream. Since 1996, we have taken advantage of this cluster property of insulin to control its time-action by twigging the amino acid sequence to make analogous human insulin, often called insulin analogs, by causing a quick or delay disintegration of inactive insulin cluster to produce rapid-acting, short-acting, intermediate-acting, and long-acting insulins. Apart from insulin, which is considered a biologic medication from living cells, there are more than 50 anti-diabetes drugs of different classes targeting different tissues.
However, despite all these medications and insulin therapy, diabetes continues to be as enigmatic as ever. In 2000, diabetes was projected to rise globally from 171 million to 366 million by 2030. In 2019, the global prevalence was already estimated at 463 million people and now with a staggering projection to climb to 578 million by 2030. The failing projection has also been noted in the United States where the prevalence of diabetes rose from 11 million in 2000 to 34.2 million in 2018 against the projected 29 million by 2050. Adjusted for inflation to today’s dollars, the United States spent about $342 billion in World War 2 that lasted about 4 years, according to Parramatta History and Heritage. As we speak, within its shores, the United States is spending $237 billion every year on direct medical costs of diabetes and a loss of another $90 billion on reduced productivity.
May I repeat the enigmatic history of diabetes even in the 21st century where the medical community seems to be paying emphasis on evidence-based care and yet applying same intervention to two causes of a disease, loss of pancreas (type 1) and ineffectiveness of insulin (type 2), because both result in high blood sugar. Unquestionably, type 1 diabetes which is about 10% of all diabetes incidence is fatal without lifelong external insulin replacement, but should we continue to induce insulin resistance in type 2 diabetes with more insulin in so much as rewarding an alcoholic with more alcohol?
Before the insulin era, fasting and calorie-restricted were the only treatment options for diabetes type 1 and 2 but we have flipped the therapy in this insulin era by correctly treating type 1 diabetes with insulin and frequently, and I dare say incorrectly, doing the same with type 2 diabetes. Just like water follows salt, insulin is secreted following the presence of blood glucose. It is noteworthy to state that dietary glucose is the only macronutrient that breaks fasting state and therefore high levels of blood glucose is metabolically a feeding or absorptive state. Type 2 diabetes, an abnormal state of persistently high blood glucose, therefore violates the feeding and fasting cycle with persistent and toxic mix of high levels of blood glucose and insulin called insulin resistance. The opposite of insulin resistance is insulin sensitivity and can be effectively induced by reducing blood glucose through dietary fats, exercise, fasting and combination of exercise/fasting under health professional supervision.
While Dr. Joslin, described the incredible sadness of starvation diets on children in the 1943 address, he however added that “…adults did better with a restrictive carbohydrate and high fat ration”. Every health professional has seen anecdotal incidences of where some patients with type 2 diabetes lost weight with restored normal blood sugar either because they lost appetite or did not like the food served in the facilities where they were being admitted even for other conditions besides diabetes. And to quote Dr. Lawrence again, who described type 2 diabetes, in early 1951s as “…mild and characteristically arises in the middle-aged patients who are often obese and seldom require insulin.” Type 2 diabetes is a disease of civilization and would continue to rise in the face of polypharmacy if we do not revert to circadian feeding and fasting cycle which assists in preventing fuel overload to maintain normal metabolic state. Driving glucose out of the bloodstream with intensive insulin therapy to keep normal blood glucose does not address insulin resistance. It only facilitates production of endogenous fats leading to increased body weight and putting the metabolic tissues in constant overdrive.
When it comes to type 2 diabetes care, more insulin is not better!
