First-degree relatives of patients with type I diabetes mellitus. Islet-cell antibodies and abnormal insulin secretion

N Engl J Med. 1985 Aug 22;313(8):461-4. doi: 10.1056/NEJM198508223130801.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoantibodies / analysis*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diseases in Twins
  • Female
  • Glucagon
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / immunology*
  • Male
  • Prospective Studies


  • Autoantibodies
  • Insulin
  • Glucagon