Exposure to gestational diabetes (GDM) and polymorphisms of the glucagon-like-peptide-1 receptor gene (GLP-1R) are both associated with type 2 diabetes risk. In adults, GLP-1R mutations were associated with altered first phase insulin secretion and glucose levels during an oral glucose tolerance test (OGTT). We explored a potential joint association between GLP-1R and GDM exposure on glucose regulation in youth. Exploring Perinatal Outcomes among Children (EPOCH) participants with (N = 86) and without (N = 189) GDM exposure had 2-hour 75g OGTT at ~17 years. DNA was genotyped by microarray. Plink 2.0 was used to extract genotyped and imputed GLP-1R polymorphisms. Glucose and insulin measured at 0, 30 and 120 minutes were used to calculate areas under the curve (AUC), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), insulinogenic index (IGI), and disposition index (DI). Linear models tested the interaction of GLP-1R rs1042044 homozygosity of the minor allele and GDM on each outcome. Homozygotes exposed to GDM had higher baseline, 30, 120 minute and AUC for glucose (p < 0.0001), and lower insulin AUC (p = 0.046) than others (Figure 1), but not significantly different HOMA-IR, IGI and DI. Our data indicates a joint effect of GDM exposure and GLP-1R on glucose levels in youth, potentially due to reduced first phase insulin secretion. Further studies are needed to replicate this finding.


K.K.Harrall: None. D.H.Glueck: None. K.A.Sauder: None. M.Cree-green: Consultant; Pollie Inc, Research Support; Amino Corp LLC. D.Dabelea: None.


National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068001)

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