Insulin’s Role in Diabetes Management: After 90 Years, Still Considered the Essential “Black Dress”

It has been 93 years since Banting and Best extracted insulin in Scottish physiologist J.J.R.Macleod’s laboratory and,with the help of their fellow Canadian chemist James B. Collip, used it to successfully treat a cachectic boy, Leonard Thompson, who suffered from life-threatening diabetes. Since that time, insulin therapy has become the mainstay of treatment for patients with type 1 diabetes and a cornerstone therapy for many individuals with type 2 diabetes. Over the years,many changes in insulin therapy have occurred, including new formulations, new delivery systems, and additional therapeutic tactics.Weare on the brink of a new and exciting era with increasingly reliable and easy-to-use continuous glucose monitoring as part of a closed-loop delivery system. This new “artificial pancreas” system, with its carefully modulated insulin (which remains the key component), may soon be ready for clinical use. In addition, an impressive array of neworal and injectable agents for type 2 diabetes has been developed over the past 20 years. Many thought that these could replace injected insulin in a therapeutic regimen, or at least delay its use. Yet, the reality is that insulin will always beneeded for type 1 diabetes until a cure is found and progressive insulin deficiency is a fundamental defect of type 2 diabetes. Furthermore, supplementation of endogenous insulin continues to be necessary for large numbers of individuals with type 2 diabetes. Meanwhile, the other classes of therapeutic agents are vying for a strategic position alongside insulin in clinical regimens for type 2 diabetes, and there is an unmet need for adjuvant therapies to mitigate the treatment challenges in type 1 diabetes as well. To dramatize the continuing role of insulin in the management of diabetes, we propose an analogy from the world of clothing and fashion: Insulin is and will remain the simple “black dress” that will never be out of fashion, can go with almost anything, and remains the basis of one’s wardrobedsomething we learned from our wives! Just like the “black dress,” by simple additions or modifications it can be adapted to nearly all occasions. To illustrate this point, our editorial team is featuring a collection of articles that displays the diversity of and recent innovations in the clinical use of insulin in this issue of Diabetes Care. These selected articles touch on the versatility of insulin in general, as well as new concepts regarding older formulations, new formulations, the advantages of using insulin in combination with the newer agents both in type 1 and type 2 diabetes, and new insulin delivery systems. This issue’s review of insulin begins with articles evaluating an old classic, NPH insulin. Whereas this insulin has been used for decades, it might be asked whether anything new about it can possibly be demonstrated. Yet a simple study by Lucidi et al. (1) provided quantitative support for an old clinical observation that has direct relevance to clinical efficacy. The authors described how NPH insulin comes in a two-phase solution, including both soluble and crystalline components that require adequate mixing (resuspension of the crystalline phase) prior to injection to provide consistent results. In this pharmacokinetics/pharmacodynamics study, lack of resuspension profoundly altered the action profiles of human NPH insulin (1). Given the continuing widespread use of NPH throughout the world, either alone or in premixed formulations with rapid insulins, this modest but elegant study reminds us that attending to resuspension of NPH before injectionmay improve day-to-day glycemic stability. Another study in this issue also evaluated an older formulation for in-hospital insulin management. In an inpatient setting, Bellido et al. (2) evaluated premixed insulin (30% regular and 70% NPH insulin [Mixtard 30; Novo Nordisk]) as compared with a basal-bolus regimen with insulin glargine once daily (Lantus;