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Session: Diet, Body Size, and Diabetes in Pregnancy: Impact on Offspring Metabolic Health (Oral 12)

(OR12-07-23) Look at Those Curves! Metabolic Flexibility and Gestational Diabetes

Sunday, July 23, 2023
5:12 PM – 5:24 PM ET
Location:  Constitution A
Disclosure(s):
Emily W. Flanagan, MS, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Kristen E. Boyle, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Diana M. Thomas, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Leanne Redman, PhD: Abbott Nutrition: Grant/Research Support (Ongoing)
Advocare International, LP: Advisory Committee/Board Member (Ongoing)
Bobbie Labs: Advisory Committee/Board Member (Ongoing)
Everly Health: Consultant (Ongoing)
Willow Innovations, Inc: Consultant (Ongoing)
Objectives: Metabolic flexibility is the responsiveness to alter metabolism with metabolic demand or energy availability. Impaired metabolic flexibility during pregnancy results in elevations in circulating fuel sources (e.g., glucose and lipids) known to promote both maternal and fetal adipose tissue accretion. It is unknown how metabolic flexibility differs in gestational diabetes (GDM). The aim of this study was to identify metabolic flexibility in individuals with and without GDM.

Methods: Pregnant individuals with GDM (n=10; of which n=5 on glyburide) and pair-matched (for age, BMI, race, infant sex) healthy controls (n=8) completed a mixed meal tolerance test (Nestle Boost: 68% CHO, 15% fat, and 17% protein) between 33-35 weeks of pregnancy. Boost was scaled to metabolic size (33% of energy needs determined by resting metabolic rate) and fasting and postprandial (120 mins) plasma and RMR were collected. Metabolic flexibility was calculated as the difference between respiratory exchange ratio (RER) peak and nadir in the postprandial state and the ability to clear circulating substrates (AUC for FFA, glucose, and insulin).

Results: Control and GDM did not differ by maternal age, pre-pregnancy BMI, late-pregnancy weight, or baseline RER. Compared to individuals with GDM, control pregnancies exhibited greater metabolic flexibility (postprandial RER flux in control: 0.23±0.07 and GDM: 0.16±0.06, p=0.04) and lower postprandial RER nadir (control: 0.71±0.06 and GDM: 0.76±0.05, p=0.06). Postprandial FFA AUC (control: 28.8±9.9 GDM: 37.7±11.2 mg/dL/min p=0.10) tended to be lower and postprandial glucose AUC was significantly lower (control: 117±16 and GDM: 135±16 mg/dL/min, p=0.04) in control. Of other calculus-based curve shape markers, the maximum speed of incline for FFA also differed between groups (control: 95±42 and GDM: 45±51, p=0.04).

Conclusions: Individuals with GDM exhibit impaired metabolic flexibility and more pronounced postprandial excursions of FFA and glucose. Interventions tailored to improve metabolic flexibility, such as exercise or fat loss during pregnancy, are of high interest given downstream implications and obesity risk for offspring born to those with GDM.

Funding Sources: National Institutes of Health