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

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).