Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

Abstract

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

Hexokinase domain-containing protein-1 in metabolic diseases and beyond

“…Although a potential mechanism linking HKDC1 to lipid metabolism was not proposed, the HAPO GWAS study also found a nominal association between HKDC1 variant rs4746822 and the number of skinfolds in neonatesa common way to quantify body fat in neonates and young infants [28]. Because increases in neonatal adiposity have been described in infants exposed to uncontrolled GDM in utero, this study indirectly links HKDC1 to a glucometabolic role [29,30]. Taken altogether, genetic studies have begun to reveal the role of HKDC1 in metabolism and human disease.…”

Metformin: Sex/Gender Differences in Its Uses and Effects—Narrative Review

“…The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, for the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, data from the most robust meta-analyses of clinical studies have yet to confirm such beneficial effects [ 35 , 38 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 ]. A caveat is that any extrapolation of benefit to humans from animal or in vitro studies has to take into account the level of MTF concentration attained; the latter may differ considerably and be lower in humans [ 147 ].…”

Gestational and Developmental Contributors of Pediatric MASLD

“…18 Specifically, while there is a clear link between GDM and delivery of infants that are large for gestational age (LGA), increased adiposity is also seen in the offspring of women with GDM and optimal glycemic control. 49 In addition, neonatal percent body fat does not correlate with maternal glucose levels in offspring of women with GDM. 50 Women with obesity without GDM, who are known to have increased circulating triglyceride but not glucose levels, give birth to offspring with increased adiposity.…”