Effects of Insulin in Relatives of Patients with Type 1 Diabetes Mellitus

Persons who are at high risk for type 1 diabetes may be identified on the basis of islet-cell antibody levels, insulin antibody levels, and genetic studies. These investigators randomly assigned 339 high-risk first- and second-degree relatives of patients with diabetes (mean age, 11.2 years) either to observation or to low-dose subcutaneous ultralente insulin twice daily, plus an annual four-day continuous intravenous infusion of insulin. By the end of the study, diabetes had been diagnosed in 69 subjects in the intervention group and 70 in the observation group, an annualized rate of progression of 15.1 percent in the intervention group and 14.6 percent in the observation group. In this study of high-risk relatives, the insulin regimen neither delayed nor prevented type 1 diabetes. Type 1 diabetes mellitus occurs in genetically predisposed persons as a consequence of the immune-mediated destruction of pancreatic islet beta cells that secrete insulin. 1 The onset of clinically overt diabetes represents the end point of an insidious, progressive decline in the function of beta cells after the majority of beta cells have been damaged or destroyed. Risk can be predicted on the basis of immunologic markers and tests of beta-cell function. Parenteral insulin therapy prevents diabetes in animal models. 2 – 7 Moreover, pilot studies have suggested that insulin therapy also delays diabetes in humans. 8 – 10 Animal studies have suggested that insulin . . .