by Huong-Thao Le, 2011 Doctor of Pharmacy Candidate LEECOM, Bradenton, FL
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 have improved over the decades since the discovery of insulin. These initial insulins were all manufactured from bovine or porcine pancreata and production techniques have also become 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. 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 recombinant DNA technology, and by Novo A/S, using 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.
Better Monitoring Tools
At the same time as the development of human insulin and insulin pumps, improvements in glucose monitoring were introduced. Although there was initial skepticism as to whether home blood glucose monitoring would be accepted by patients with diabetes, history would confirm that this technology would revolutionize diabetes management and allow patients to titrate blood glucose to normal or near-normal levels.
While self monitoring of blood glucose (SMBG) allowed immediate evaluation of diabetes management, the introduction of hemoglobin A1c (A1c, or glycated hemoglobin) around the same time was used as a marker of objective longer-term (about 90 days) glucose control. When hemoglobin is exposed to glucose in the bloodstream, the glucose slowly becomes non-enzymatically bound to the hemoglobin in a concentration-dependent fashion. The percentage of hemoglobin molecules that are glycated (bound to glucose) indicates what the average blood glucose concentration has been over the life of the cell.
Perhaps as importantly, A1c made it possible for researchers to study the effects of long-term glucose control and the development of vascular complications.
New students of diabetes may now find it difficult to appreciate that one of the greatest medical controversies between the discovery of insulin and the early 1990s was the relationship between glucose control and diabetes complications and has driven us to improve care in all patients in the past 20 years.
Information from “The Management of Type 1 Diabetes” by Irl B Hirsch, MD Jay S Skyler, MD
Copyright © 2011 Diabetes In Control, Inc.