Maternal effect and familial aggregation in NIDDM. The CODIAB Study. CODIAB-INSERM-ZENECA Study Group.

Non-insulin-dependent diabetes mellitus (NIDDM) is known to have a strong genetic basis, but the mode of inheritance is still unknown. Recent studies have suggested that maternal inheritance is important; this complicates the transmission pattern of NIDDM. In our study, the familial aggregation of diabetes and the maternal effect were investigated through three generations. The CODIAB Study recruited 536 NIDDM patients between 35 and 74 years of age from 10 diabetes centers in France. Familial aggregation was confirmed: among 218 NIDDM patients, 66% had at least one diabetic relative. Mothers were implicated 2 times more frequently than fathers (P < 0.001). This maternal effect was confirmed because more diabetic cases were noted among maternal than paternal aunts and uncles (P < 0.02). When we considered the next generation, women had more diabetic offspring than men (P < 0.01). Other factors susceptible to modify the familial aggregation were considered. The maternal effect was not significantly related to the patients' ages (P > 0.2). The genetic component was more important when the diagnosis was made earlier, but the maternal effect was homogeneous (P > 0.3). In conclusion, we found a familial aggregation of diabetes that suggests a strong genetic component with a mode of inheritance that may be influenced by a maternal environment.