Association of Pregnancy Oral Glucose Tolerance Test (OGTT) Glucose Response with Metabolic Profile in Mother and Child-Hyperglycemia and Adverse Pregnancy Outcomes Follow-up Study (HAPO-FUS)

The glucose response shape during an OGTT, monophasic or biphasic, can characterize physiologically distinct groups with differences in insulin secretion and sensitivity. Biphasic response (glucose rebound after nadir ≥ 0.025 mmol/L) has been associated with higher insulin sensitivity and β-cell function. We aimed to identify the association of the pregnancy OGTT response shape with follow-up maternal and offspring metabolic profiles. Method: Using HAPO-FUS study data from the NIH-NIDDK repository, monophasic glucose response was defined as 2-hr glucose - 1-hr glucose < 0. Multiple linear regression assessed the relationship of glucose response shape with maternal profile at 10-year follow-up and offspring metabolic profile at 10-12 years of age. Maternal covariates include age, gestational age, field center and BMI. Child covariates include age, sex, pubertal stage, and family history of diabetes. Results: 4,605 mothers (83.7% monophasic) and 3792 children were included. Mothers with monophasic shape were older (30.7 vs 29.8 years, p=.002), had higher BMI (26.7 vs 26.0 kg/m2, p=.003), HbA1c (4.80 vs 4.70 %, p <.001), 1-hour c-peptide level (9.60 vs 7.75 ug/dL, p <.001) and gestational diabetes (14 vs 9.5%, p <.001). At 10-year follow-up, pregnancy monophasic response was associated with higher fasting glucose level (0.06 [0.01, 0.11], p =.01) and log HOMA-IR (0.06 [0.02, 0.10], p=.007) in mothers at follow-up. Offspring had higher cord c-peptide (0.12 [0.04, 0.21], p=.005) and body fat percent (1.35 [0.50-2.21], p =.002). Offspring insulin sensitivity (-0.17 [-0.04, -0.3], p=.01) and Matsuda index (-0.46 [-0.15, -0.76], p=.003) were lower with monophasic response. Conclusion: Maternal glucose response profiles during pregnancy determined by both insulin secretion and whole-body insulin resistance are associated with long-term maternal and offspring metabolic profile. Disclosure V. V. Thaker: None. C. A. Leduc: None. R. Salem: Other Relationship; Travere Inc. Funding National Institutes of Health (K23DK110539)