Clinical Experience With U-500 Regular Insulin in Obese, Markedly Insulin-Resistant Type 2 Diabetic Patients

Abstract

On a clinical basis, severe insulin re-sistance is defined as a situation inwhich a patient requires 200 units of insulin daily for2 days (1). This definitionwas determined50 years ago, when it was erroneously believed that the human pancreas secreted 200 units of insulin a day. Although it is now known that the normal pancreas secretes only 20–40 units of insulin a day, this clinical definition is helpful because it delin-eates a very small group of patients, many with a number of unusual under-lying problems. In adults, the conditions associated with clinical insulin resistance are gross obesity, severe infection, Cushing’s syn-drome, acromegaly, hemochromatosis, li-podystrophic diabetes, genetic insulin receptor abnormalities, insulin receptor antibodies, Werner’s syndrome (adult form of progeria), insulin degradation at the injection site, and high titers of IgG insulin binding antibodies (immune me-diated). Gross obesity is by far the most common condition. Although a recent re-view (2) discussed the use of U-500 reg-ular insulin in states of severe insulin resistance, no detailed description of how to start and adjust doses of this concen-trated form of insulin was given. This ar-ticle provides a treatment algorithm for the use of U-500 regular insulin and sum-marizes our experience with obese, mark-edly insulin-resistant type 2 diabetic patients. RESEARCH DESIGN AND METHODS — Nine patients with type 2 diabetes from our diabetes clinic (five women and four men [eight Latino and one African American], aged 49.4 10.0 years [mean SD], diabetes duration