The role of late-onset autoimmune diabetes in white familial NIDDM pedigrees

OBJECTIVE - To determine whether autoimmunity is a prominent feature oi NIDDM among diabetic members in families with a strong history of NIDDM or in families with a mixture of NIDDM and IDDM. RESEARCH DESIGN AND METHODS - We determined GAD and islet cell (ICA512) autoantibodies from 215 NIDDM individuals and from 14 individuals with impaired glucose tolerance (IGT) of 68 families, including 1 family with maturity-onset diabetes of the young (MODY) and 3 families ascertained specifically for a mixture of NIDDM and IDDM. We tested 2 control populations: 50 unrelated spouses from Utah families, including 29 spouses with either IGT or NIDDM and 198 random nondiabetic white individuals from Colorado. RESULTS - We detected either GAD or ICA512 autoantibodies in 11 members of seven families and in one spouse used as a control subject. In two families, two affected individuals showed evidence of autoimmunity, but NIDDM individuals in each of the seven families showed no evidence of autoimmunity Among the five families with both IDDM and NIDDM individuals (three families ascertained for a mixture and two families ascertained with an incidental IDDM child), antibodies were detected in members of only one family Antibody-positive individuals were significantly younger at diabetes onset and had low waist-to-hip ratios, but were not more likely to be insulin treated. CONCLUSIONS - Autoimmunity is an important cause of apparent NIDDM, even among families with a strong history of NIDDM. However, autoimmunity among affected family members appeared to be a chance event and not the manifestation of a different genetic cause of diabetes.