Chapter 5 - Insulin therapy: a century of continuing progress

Abstract

By the end of the 19th century, there was indirect evidence that diabetes was the consequence of deficiency of the “internal secretion of the pancreas,” and several researchers extracted it from animal pancreas. In 1922 the first diabetic patient, Leonard Thompson, was successfully treated in Toronto with the pancreatic extract obtained by Banting and purified by Collip. Ever since, insulin extracted from animal pancreas was progressively purified until regular human insulin (RHI) was synthetized using the rDNA technique by the end of the 1970s. The first retarded insulin (basal), NPH, became available in 1950, soon followed by the lente class. Because of limitation of subcutaneous (s.c.) delivery of RHI, and the nonphysiological pharmacokinetics and pharmacodynamics of NPH, it was, however, difficult to maintain near-normoglycemia without hypoglycemia with human insulin preparations. Insulin analogs were introduced by the end of the 20th century to overcome these barriers. Rapid-acting analogs have improved the prandial blood glucose, reduced the risk of late prandial hypoglycemia, and offered the convenience of insulin administration directly at mealtime as compared to RHI. Long-acting analogs have quickly and fully replaced NPH by providing smooth 24-hour basal insulin supplementation with a low risk for hypoglycemia. Today, an optimal combination of rapid- and long-acting analogs as multiple daily injections or continuous s.c. infusion of insulin (rapid-acting analog) by pump, both options guided by continuous glucose monitoring, allow people with diabetes to target near-normoglycemia with low risk for hypoglycemia. Until future research breakthroughs liberate people with diabetes from the current need to inject insulin, insulin access should be universally guaranteed. Insulin should be used to mimic the physiology of endogenous secretion of insulin with the goal of near-normoglycemia, low risk for hypoglycemia, and quality of life no different from that of people without diabetes.