Introduction and Objective: Pathways for maternal obesity and GDM exposure to offspring diabetes are unclear. We examined whether these exposures differentially affect insulin sensitivity and secretion. Methods: The BrainChild cohort did 3-hour OGTTs (n=212; age 8.7±1.1 years; 58% female; 102 GDM-exposed). Exposures were maternal pre-pregnancy BMI, GDM exposure (yes v. no), and timing (≤26 weeks, 26 weeks). Outcomes were insulin sensitivity (log whole body insulin sensitivity index (ISI) and secretion (log insulinogenic index at 30 minutes InsIndex30). Models adjusted for child age and sex, then further adjusted for % body fat (%BF); InsIndex30 also adjusted for ISI. Results: Insulin Sensitivity: Maternal obesity was associated with lower ISI (β=−0.41, p=0.02), but this was fully attenuated after adjusting for child %BF (β=-0.01, p=0.97). Maternal overweight showed no association before (β=-0.22, p=0.25) or after adjustment (β=0.09, p=0.60). Overall GDM exposure was not associated with ISI (β=−0.18, p=0.21), but exposure ≤26 weeks was associated with lower ISI (β=−0.43, p=0.023); attenuated after adjustment for child %BF (β=-0.21, p=0.18). Exposure 26 weeks was not associated before (β=-0.02, p=0.91) or after child %BF adjustment (β=0.18, p=0.19). Insulin Secretion: Maternal pre-pregnancy weight was not associated with InsIndex30 (obesity: β=0.12, p=0.32; overweight: β=0.18, p=0.17). Further adjustment for %BF did not change the results. Overall GDM exposure was associated with lower InsIndex30 before (β=-0.17, p=0.08) and after adjusting for child %BF (β=−0.23, p=0.01); exposure ≤26 weeks was associated with lower InsIndex30 (β=−0.25, p=0.02); exposure 26 weeks was directionally similar but non-significant (β=-0.21, p=0.10). Conclusion: Maternal obesity during pregnancy may influence child insulin sensitivity via increased adiposity. In contrast, GDM exposure is associated with impaired early-phase insulin secretion independent of adiposity and insulin sensitivity, supporting distinct intrauterine programming pathways. Disclosure E.C. Morgan: None. M. Sidell: None. T. Chow: None. J. Alves: None. B. Belcher: None. A. Xiang: None. K. Page: None. Funding American Diabetes Association (1-14-ACE-36), NIH (RO1DK116858, R01DK134079)
Morgan et al. (Fri,) studied this question.