IDENTIFICATION OF GLUCOKINASE MUTATIONS IN SUBJECTS WITH GESTATIONAL DIABETES-MELLITUS

Recent studies have shown that mutations in the glucokinase gene on ch romosome 7 can cause an autosomal dominant form of NIDDM with a variab le clinical phenotype and onset during childhood. The variable clinica l phenotype includes mild fasting hyperglycemia (i.e., a plasma glucos e value of >110 mg/dl, a value that is at least 2-3 SDs above normal), impaired glucose tolerance, gestational diabetes mellitus, as well as overt NIDDM as defined using National Diabetes Data Group or World He alth Organization criteria. Because gestational diabetes mellitus was a clinical feature associated with glucokinase mutations, we have scre ened a group of women with gestational diabetes who also had a first-d egree relative with diabetes mellitus for the presence of mutations in this gene. Among 40 subjects, we identified two mutations, suggesting a prevalence of approximately 5% in this group. Extrapolating from th is result, the prevalence of glucokinase-deficient NIDDM among America ns may be approximately 1 in 2500.