Diabetes Leads to Alterations in Normal Metabolic Transitions of Pregnancy as Revealed by Time-Course Metabolomics.

Jacquelyn M Walejko,Arthur S Edison,Anushka Chelliah,Mark Atkinson,Maureen Keller-Wood,Clive Wasserfall,Anthony Gregg

doi:10.3390/metabo10090350

Abstract

Women with diabetes during pregnancy are at increased risk of poor maternal and neonatal outcomes. Despite this, the effects of pre-gestational (PGDM) or gestational diabetes (GDM) on metabolism during pregnancy are not well understood. In this study, we utilized metabolomics to identify serum metabolic changes in women with and without diabetes during pregnancy and the cord blood at birth. We observed elevations in tricarboxylic acid (TCA) cycle intermediates, carbohydrates, ketones, and lipids, and a decrease in amino acids across gestation in all individuals. In early gestation, PGDM had elevations in branched-chain amino acids and sugars compared to controls, whereas GDM had increased lipids and decreased amino acids during pregnancy. In both GDM and PGDM, carbohydrate and amino acid pathways were altered, but in PGDM, hemoglobin A1c and isoleucine were significantly increased compared to GDM. Cord blood from GDM and PGDM newborns had similar increases in carbohydrates and choline metabolism compared to controls, and these alterations were not maternal in origin. Our results revealed that PGDM and GDM have distinct metabolic changes during pregnancy. A better understanding of diabetic metabolism during pregnancy can assist in improved management and development of therapeutics and help mitigate poor outcomes in both the mother and newborn.

Highlights

During pregnancy, adaptations in endocrine and cardiovascular physiology contribute to a dynamic metabolic state for the mother
Pregnancy can lead to the development of diabetes, termed gestational diabetes mellitus (GDM), which often resolves following delivery; women who develop GDM are at a 60% increased risk of developing type 2 diabetes (T2D) later in life [6]
Glutamine, which is diminished in non-pregnant T2D populations [45], was significantly lower in PGDM compared to controls. These results suggest that women with PGDM during pregnancy have similar amino acid metabolic profiles to individuals with diabetes in the general population, especially in early pregnancy and these amino acid metabolic profiles disappear in the immediate post-partum period

Summary

Introduction

Adaptations in endocrine and cardiovascular physiology contribute to a dynamic metabolic state for the mother. In addition to an increase in basal metabolic rate, maternal lipids rise in the serum throughout healthy gestation [1,2]. These lipids serve as an energy source for the mother, resulting in increased glucose and amino acid delivery to the developing fetus. The emergence of metabolomics studies has confirmed these metabolic alterations in the mother throughout gestation, providing additional evidence of decreasing amino acids and increasing tricarboxylic acid (TCA) cycle intermediates during healthy pregnancy [3,4]. The effect of excess glucose on fetal growth is not completely understood Both gestational and pre-gestational diabetes account for significant maternal and perinatal morbidity and mortality [7,8,9]. Pre-existing diabetes (T1D or T2D) complicates 1–2 percent of all pregnancies [11], with the number of pregnancies complicated by T2D projected to rise in the coming years [12], while GDM affects up to 10 percent of all pregnancies in the United States [13]

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