Abstract
AimsDisrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity. Our aim was to study metabolism in such pregnancies.MethodsWe recruited a longitudinal cohort of very severely obese (n = 190) and lean (n = 118) glucose-tolerant women for anthropometric and metabolic measurements at early, mid and late gestation and postpartum. In case–control studies of very severely obese and lean women we measured glucose and glycerol turnover during low- and high-dose hyperinsulinaemic–euglycaemic clamps (HEC) at early and late pregnancy and in non-pregnant women (each n = 6–9) and body fat distribution by MRI in late pregnancy (n = 10/group).ResultsAlthough greater glucose, insulin, NEFA and insulin resistance (HOMA-IR), and greater weight and % fat mass (FM) was observed in very severely obese vs lean participants, the degree of worsening was attenuated in the very severely obese individuals with advancing gestation, with no difference in triacylglycerol (TG) concentrations between very severely obese and lean women at term. Enhanced glycerol production was observed in early pregnancy only in very severely obese individuals, with similar intrahepatic FM in very severely obese vs lean women by late gestation. Offspring from obese mothers were heavier (p = 0.04).Conclusions/interpretationPregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women. Increased glycerol production is confined to obese women in early pregnancy and obese and lean individuals have similar intrahepatic FM by term. When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3708-3) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Highlights
IntroductionMethodsThe prevalence of obesity is increasing in women of childbearing age [1, 2]. In the UK 20% of pregnant women are obese and 2% have very severe obesity (BMI ≥40 kg/m2) [3]
MethodsThe prevalence of obesity is increasing in women of childbearing age [1, 2]
Anthropometric and metabolic indices Body weight and fat mass (FM) were greater in the very severely obese women and increased during pregnancy in both groups, absolute weight gain was greater in lean controls at ~28 and ~36 weeks’ gestation (Fig. 1; Table 2)
Summary
MethodsThe prevalence of obesity is increasing in women of childbearing age [1, 2]. In the UK 20% of pregnant women are obese and 2% have very severe obesity (BMI ≥40 kg/m2) [3]. Pregnancy is an insulin-resistant state and the consequent mobilisation of fatty acids and glucose provide substrates for fetal growth [16,17,18,19,20]. Mothers with a diagnosis of gestational diabetes mellitus (GDM) are more likely to have LGA infants [21, 22], maternal glucose concentrations within the normal range are associated with neonatal adiposity [21]. Studies comparing metabolism in obese and lean pregnant women have yielded inconclusive results for insulin sensitivity [20, 23, 24], which likely reflect small sample sizes, differences in study design [20] and confounding by co-existing disease [24]
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