Diabetologia. 2026 Apr 30. doi: 10.1007/s00125-026-06727-0. Online ahead of print.
ABSTRACT
AIMS/HYPOTHESIS: Women with a history of gestational diabetes mellitus (GDM) have an elevated risk of type 2 diabetes in their later life, yet the underlying mechanisms of this remain unclear. We aimed to investigate the long-term impact of GDM on gut microbiota and related metabolites and to explore whether such alterations may contribute to type 2 diabetes risk.
METHODS: Among parous women from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we identified microbial species associated with a history of GDM (visit 2, 2014-2017, n=1525), and serum metabolites associated with both a history of GDM (visit 1, 2008-2011, n=2968) and GDM-related microbiota (visit 2, n=391). We further examined prospective associations of the GDM-related microbiome (visit 2, n=925) with incident type 2 diabetes over 6 years of follow-up, and of microbial-related metabolites (visit 1, n=2341) with incident type 2 diabetes over 12 years.
RESULTS: Among 1525 US Hispanic/Latino parous women (median age: 58 years), seven species differed between women with and without a history of GDM, including higher abundances of four species (e.g. Parabacteroides merdae CAG:48, a proinflammatory taxon) and lower abundances of three species (e.g. Dialister sp. CAG:588, a short-chain fatty acid producer). Fifteen metabolites were associated with both a history of GDM and the GDM-related microbiome in a consistent direction, nine of which (e.g. saturated sphingomyelins and unsaturated fatty acids) were associated with glycaemic traits and incident type 2 diabetes. Using these microbial-related metabolites as proxy measures, proxy analysis suggested a positive relationship between the GDM-related microbiome and type 2 diabetes (r=0.55, p=0.036). A metabolite score derived from the nine microbial-related metabolites mediated an estimated 20% (95% CI 9%, 42%) of the association between a history of GDM and type 2 diabetes.
CONCLUSIONS/INTERPRETATION: A history of GDM is associated with an unfavourable gut microbiota and related metabolites in US Hispanic/Latino women, suggesting a potential role of the gut microbiota in GDM-related type 2 diabetes.
PMID:42062589 | DOI:10.1007/s00125-026-06727-0
