The discovery of insulin in 1921 was one of the greatest medical breakthroughs in history. Individuals, mostly children with type 1 diabetes, whose life expectancies were measured in months were now able to prevent fatal ketoacidosis by taking injections of crude “soluble” (later known as regular) insulin. Of course, new problems were soon noted. Hypoglycemia, occasionally life-threatening, was encountered as diabetes monitoring by urine testing for glycosuria was crude at best during those first years after the discovery of insulin. The insulin itself was often impure and varied in potency from lot to lot. Allergic reactions were common and occasionally anaphylaxis would occur. Even more concerning was the appreciation that these patients often succumbed to chronic vascular complications which either dramatically reduced quality of life or resulted in a fatal cardiovascular event.

The tools to manage individuals with type 1 diabetes improved over the decades since the discovery of insulin. These initial insulins were all manufactured from bovine or porcine pancreata and production techniques also became more efficient. Insulins with longer durations of action were first introduced in the 1930s, and over time these insulins improved in their purity and consistency of potency. Nevertheless, “standard” animal insulins prior to 1972 contained 80,000 parts per million (8%) impurities, enough to elicit local reactions when injected as well as systemic effects. By way of comparison, all insulins sold in the United States today contain less than 10 parts per million impurities.

Major improvements in the tools to manage type 1 diabetes were developed in the late 1970s and early 1980s. First, not only was “purified” insulin introduced, but in 1982 the first insulins of human amino-acid sequence were marketed both by Eli Lilly and Company using a human insulin made by recombinant DNA technology and by Novo A/S using a human insulin made by a semi-synthetic methodology. These insulins were available as short-acting (regular) and longer-acting [Neutral protamine Hagedorn (NPH), lente, and ultralente] preparations. The other major advance with insulin therapy was delivery by continuous subcutaneous insulin infusion (CSII) pumps. While pumps were initially touted as providing less variable insulin absorption since only regular insulin was used, the use of CSII had a greater impact: both patients and clinicians used this tool to teach themselves how to best use “basal bolus” therapy, a strategy that would become a standard of care after the beginning of the next century with the development of insulin analogues.