DIABETES COMPLICATIONS IN NIDDM KINDREDS LINKED TO THE MODY3 LOCUS ONCHROMOSOME 12Q

OBJECTIVE - To assess the prevalence of diabetes complications and the severity of diabetes in kindreds with NIDDM linked to the MODY3 locus (chromosome 12q) and to compare these parameters with data obtained i n glucokinase (GCK)-deficient and other-MODY (unlinked to any of the t hree known loci) families, as well as with data from families with a l ate age of onset of NIDDM. RESEARCH DESIGN AND METHODS - Clinical and biological data were obtained from 667 affected members of 7 MODY3, 25 GCK-deficient, 6 other-MODY, and 81 NIDDM families. Severity of diabe tes (glucose tolerance status and insulin secretion) was assessed by a n oral glucose tolerance test. Neurological examination and eye fundus examination were performed in 349 and 251 subjects, respectively, and proteinuria was tested with strips in 282 family members. RESULTS - A higher prevalence of proliferative retinopathy was observed in MODY3 (21%) and NIDDM subjects (23%) than in GCK-deficient (3%) and other-MO DY subjects (8%; P = 0.004). Proteinuria was detected in 19, 7, 5, and 0% (P = 0.07) of subjects, respectively. Prevalence of neuropathy was higher in NIDDM (17%; P = 0.005) than in MODY3 (4%), GCK-deficient (5 %) and other-MODY (0%) subjects. MODY3 and NIDDM subjects had signific antly higher fasting glucose levels than subjects in the other groups. Glucose levels after 2 h were significantly higher, and the ratios of insulin to glucose levels were significantly lower in MODY3 subjects than in the other three groups. CONCLUSIONS - The MODY3 subtype of NID DM is characterized by a severe insulin secretory defect and by major hyperglycemia that progresses rapidly to overt diabetes. Microvascular complications of diabetes were frequently observed in the MODY3 subje cts and the subjects with a late age of onset of NIDDM in this cohort. Both the duration and the severity of diabetes were independently ass ociated with these complications.