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OBJECTIVE—In animals, experimentally induced maternal hyperglycemia during pregnancy results in hyperglycemic offspring. Similarly, Pima Indian offspring with mothers who are diabetic at the time of pregnancy have increased risk of early-onset diabetes. We hypothesized that exposure to hyperglycemia in utero would decrease the age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY) due to a mutation in the hepatocyte nuclear factor 1α (HNF-1α) gene. RESEARCH DESIGN AND METHODS—We analyzed the affect of maternal diabetes on age at diagnosis of diabetes in 150 HNF-1α gene mutation carriers from 55 families. RESULTS—Age at diagnosis in HNF-1α mutation carriers was younger when the mother was diagnosed before pregnancy compared with when the mother was diagnosed after pregnancy (15.5 ± 5.4 vs. 27.5 ± 13.1 years, P &amp;lt; 0.0001). This is unlikely to represent a generalized familial decrease in age at diagnosis due to a more severe mutation, because no difference was seen in age of the offspring at diagnosis of diabetes when the father was diagnosed at a young age, and a similar trend was seen when only the single common mutation, P291fsinsC, was analyzed. CONCLUSIONS—We conclude that maternal hyperglycemia during pregnancy probably increases the penetrance of HNF-1α mutations. The potential role of exposure to hyperglycemia in utero in a monogenic diabetic subgroup warrants prospective study.

Intrauterine Hyperglycemia Is Associated With an Earlier Diagnosis of Diabetes in HNF-1α Gene Mutation Carriers