First-Degree Relatives of Patients with Type I Diabetes Mellitus: Islet-Cell Antibodies and Abnormal Insulin Secretion

In a prospective study to evaluate the prevalence and predictive potential of circulating islet-cell antibodies, we have screened 1723 "normal" first-degree relatives (parents, siblings, and offspring) of patients with insulin-dependent diabetes mellitus. The prevalence of islet-cell antibodies on initial screening was 0.9 per cent (16 of 1723). Over a maximal follow-up period of two years, insulin-dependent diabetes mellitus developed in 2 of 16 relatives with islet-cell antibodies and in 1 of 1707 without antibodies. In addition, 6 of 12 nondiabetic relatives with islet-cell antibodies had abnormally low insulin responses — below the third percentile in 6 and below the first percentile in 4 — on their initial intravenous glucose challenge. Thus, prospective islet-cell antibody screening of high-risk first-degree relatives, in combination with intravenous glucose-tolerance testing, is capable of identifying immunologically abnormal persons with profoundly diminished beta-cell function, who are presumably at increased risk of insulin-dependent diabetes mellitus. (N Engl J Med 1985; 313:461–4.) OUR concepts regarding the chronology, natural history, and pathogenesis of Type I (insulin-dependent) diabetes mellitus are currently changing, in part as a result of several prospective studies involving subjects at high risk for the development of this disease. 1 2 3 4 5 6 Long-term follow-up studies of discordant monozygotic twins have documented a slowly progressive loss of the insulin response to intravenous glucose in the years before the onset of overt insulin-dependent diabetes mellitus. 3 , 4 Over the past two years we have enrolled 860 families in a new screening program for the presence of circulating islet-cell antibodies, and have prospectively evaluated 1723 nondiabetic first-degree relatives of . . .