U-500 Insulin: When More With Less Yields Success

Syndromes of severe insulin resistance were first reported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 1976,¹ with either inherited insulin receptor abnormalities or the presence of autoantibodies to the insulin receptor. These patients were some of the first with severe insulin resistance who were treated with U-500 insulin first used clinically in 1952.^2,3 Initially, patients requiring this concentrated insulin preparation were those with type 1 diabetes with high antibodies to insulin resulting from the use of animal-source insulin causing antibody formation. The introduction of sulfated insulin in the 1970s and the availability of human insulin preparations starting in the 1980s has shifted the use of U-500 insulin to patients with extreme forms of insulin resistance.^1,2 With the prevalence of obesity and the growing epidemic of type 2 diabetes, the utility of U-500 insulin can be expanded from syndromic forms of insulin resistance to patients with type 2 diabetes who require > 200 units of insulin per day. However, these syndromic patients have taught us a great deal about how to administer and manage U-500 insulin in patients.

The American Diabetes Association (ADA) has four standard classifications of diabetes mellitus: 1) type 1 diabetes, 2) type 2 diabetes, 3) other specific types of diabetes, and 4) gestational diabetes.⁴ Regardless of the cause, the four classifications have one symptom in common: hyperglycemia. Chronic hyperglycemia from diabetes is associated with macrovascular and microvascular complications such as heart, kidney, nerve, and eye disease. Several long-term diabetes complication trials (i.e., the Diabetes Control and Complications Trial, the Epidemiology of Diabetes Interventions and Complications Trial, the Action to Control Cardiovascular Risk study, and the Action in Diabetes and Vascular Disease study) provide the fundamentals for treating hyperglycemia as close to ADA targets …