Life-Table Analysis of Progression to Diabetes of Anti-Insulin Autoantibody-Positive Relatives of Individuals With Type I Diabetes

  1. George S Eisenbarth
  1. Joslin Diabetes Center, Brigham and Women's Hospital, New England Deaconess Hospital, and Harvard Medical School Boston, Massachusetts Rambam Medical Center, Haifa, Israel; and the University of California Davis, Sacramento, California
  1. Address correspondence and reprint requests to G.S. Eisenbarth, MD, PhD, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215.

Abstract

Cytoplasmic islet cell antibody–negative (ICA; <20 Juvenile Diabetes Foundation units, n = 1670) and ICA+ (n = 42) first-degree relatives of type I (insulindependent) diabetic individuals were studied for competitive insulin autoantibodies (ClAAs) with a radioassay. Overall, 3.7% of first-degree relatives (64 of 1712) were CIAA+. Of ICA relatives, 2.7% (45 of 1670) exceeded the upper limit of our normal CIAA range (>39 nU/ml), and 45% (19 of 42) of ICA+ relatives exceeded this normal range. Follow-up serums for repeat CIAA determination have been obtained from 16 of the nondiabetic CIAA/ICA individuals (time between samples, 0.4–5.8 yr). Fourteen of these 16 (87%) CIAA/ICA relatives were found to still be positive on follow-up, and 2 of the relatives who were positive on the first determination were negative on their follow-up test. With a mean follow-up of ∼2 yr, 4 of 45 (9%) of the CIAA+/ICA-relatives, 5 of 23 (22%) of the ICA/CIAA-relatives, and 12 of 19 (63%) of the CIAA+/ICA+ relatives developed diabetes. Life-table analysis indicated that, overall, 53% of CIAA+ relatives become diabetic after 5 yr of follow-up versus 65% of ICA+ relatives. Also by life-table analysis, the predicted risk after 5 yr of follow-up for progression to diabetes is 17% for CIAA+/ICA relatives, 42% for ICA+/CIAA relatives, and 77% for CIAA/ICA+ relatives. The highest rate of progression to diabetes was found in ICA+ relatives with CIAA levels >150 nU/ml (100% projected to be diabetic within 5 yr, P < .008 vs. ICA/CIAA relatives).

  • Received December 19, 1988.
  • Revision received June 14, 1989.
  • Accepted June 14, 1989.
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