Clinical and Genetic Risk Factors for Type 2 Diabetes at Early or Late Post Partum After Gestational Diabetes Mellitus

Context: Women with a history of gestational diabetes mellitus (GDM) are at increased risk of type 2 diabetes (T2DM). However, the time to progression to diabetes differs individually. Objective: We investigated the clinical and genetic risk factors that are associated with T2DM early or late post partum after GDM pregnancy. Design and Setting: This was a hospital-based prospective cohort study that enrolled GDM women. Patients and Outcome Measures: A total of 843 GDM subjects were followed for the development of T2DM. Clinical risk factors were investigated during pregnancy, 2 months post partum, and annually thereafter. GDM subjects were genotyped for 21 known T2DM-associated genetic variants, and their genotype frequencies were compared with elderly nondiabetic controls. Results: At 2 months post partum, 105 (12.5%) subjects had T2DM (early converters). Among the 370 remaining subjects who underwent more than 1 year of follow-up, 88 (23.8%) had newly developed T2DM (late converters). Independent risk factors for early converters were higher prepregnancy body mass index, higher area under the curve of glucose during an antepartum oral glucose tolerance test, lower fasting insulin concentration, and decreased ␤-cell function. Independent risk factors for late converters were higher prepregnancy body mass index and higher glucose area under the curve. Variants in CDKN2A/2B and HHEX were associated with early conversion, whereas variants in CDKAL1 were associated with late conversion. Conclusions: Obesity was a risk factor for both early and late T2DM converters. However, early converters had more pronounced defects in ␤-cell function, which might be explained, in part, by differences in genetic predisposition. (J Clin Endocrinol Metab 98: 0000 -0000, 2013) W omen with a history of gestational diabetes mellitus (GDM) are at increased risk of type 2 diabetes mellitus (T2DM). In a recent meta-analysis, women with a previous history of GDM had as much as a 7.43-fold relative risk of T2DM compared with those who had a normoglycemic pregnancy (1). However, there are ethnic differences in the risk of developing T2DM after GDM pregnancy. In addition, there are large individual varia