The metabolic phenotype of the infant of the mother with gestational diabetes

Abstract

Offspring of mothers with diabetes are at greater risk of adverse metabolic outcomes in later life. Altered adiposity in infancy is a plausible mediator. I aimed to compare the metabolic phenotype of infants of mothers with (IDM) and without gestational diabetes mellitus (NIDM).

I performed a meta-analysis of studies examining adiposity in offspring of mothers with and without diabetes (all types). In a prospective cohort study, I used magnetic resonance imaging and spectroscopy to compare the quantity and distribution of adipose tissue (AT) and intrahepatocellular lipid (IHCL), in IDM and NIDM in early infancy. I also used nuclear magnetic resonance (NMR) spectroscopy to explore urinary metabolic profiles.

Meta-analysis: Over 24,000 infants and 17,000 children were included in the body composition meta-analyses. Maternal diabetes was associated with greater fat mass in offspring (mean difference [95% CI]): 83g [49, 117], p<0.00001 in infants, and 1.69kg [0.96, 2.43], p<0.00001 in children. Prospective cohort study: Mothers with gestational diabetes had good pregnancy glycaemic control. There was no difference in AT volume between newborn IDM and NIDM. At a median age of 10 weeks, and following adjustment for body size, total AT was 16% greater in IDM (mean % difference [95% CI]); 16.0 [6.7, 24.1], p=0.002. This difference remained significant following adjustment for maternal pre-pregnancy BMI. There were no differences in AT distribution or IHCL between groups. Urinary metabolic profiles differed in newborn IDM, including alterations in the tricarboxylic acid cycle. No differences were apparent at <2 weeks or 10 weeks of life, although there was some evidence of a relationship between newborn urinary metabolic profile and adiposity at 8-12 weeks of life.

Adiposity in IDM is amplified in early infancy, despite good maternal glycaemic control. Reduction in postnatal adiposity may be a therapeutic target to reduce later health risks.