Gestational Diabetes (GDM) and Childhood Disorders of Glucose Metabolism—Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study (HAPO FUS)

Abstract

While overt diabetes during pregnancy is associated with a higher childhood risk of altered glucose metabolism, the contribution of GDM to this disorder is less clear. Using data from HAPO FUS, we examined associations of maternal GDM not confounded by treatment with childhood glucose metabolism. Maternal glycemic status was based on a 75 g oral glucose tolerance test (OGTT) at ∼28 weeks gestation. Offspring disorders of glucose metabolism (impaired glucose tolerance or type 2 diabetes using American Diabetes Association criteria) were assessed at the HAPO FUS visit using an OGTT in 41children at mean age 11.4 (range 7.9-15.5) years. Insulin sensitivity (IS) was calculated using the Matsuda index and insulin secretion using the insulinogenic index. GDM was defined by International Association of Diabetes in Pregnancy Study Groups criteria. Among offspring of mothers with and without GDM, 10.6% and 5.2%, respectively, had a disorder of glucose metabolism. After adjusting for field center, maternal pregnancy variables and child age, Tanner stage and family history of diabetes at HAPO FUS, the odds ratio and 95% confidence interval (CI) for a disorder of glucose metabolism was 1.98 (1.44-2.74), p=3.1 x 10-5. Adjusting for maternal BMI at OGTT, child’s BMI z score, or both did not attenuate risk. Offspring of GDM mothers had lower IS (29.7 ± 12.5, mean ± SD) compared to offspring of non-GDM mothers (33.7 ± 13.8) with a mean difference of -2.1 (95% CI -3.2 - -1.0), p= 1.9 x 10-4 after adjusting for field center, maternal pregnancy variables and child age, Tanner stage and family history of diabetes at HAPO FUS. The association was attenuated but still significant after adjusting for maternal BMI and/or child BMI z score. Maternal GDM was not associated with insulinogenic index. In summary, exposure to untreated GDM in utero is significantly and independently associated with childhood disorders of glucose metabolism, in part through insulin resistance. Disclosure W. Brickman: None. P. Catalano: None. P.E. Clayton: None. C. Deerochanawong: None. J. Hamilton: None. P.M. Lashley: None. J.M. Lawrence: None. Y. Lebenthal: Speaker's Bureau; Self; Novo Nordisk Inc.. Consultant; Self; Kamada. D.R. McCance: None. W.H. Tam: None. A. Kuang: None. L.P. Lowe: None. B.E. Metzger: None. D. Scholtens: None. W. Lowe: None.