Gestational Diabetes Mellitus and Accelerated Biological Aging in Middle-Aged and Elderly Women

OBJECTIVE To evaluate the association between gestational diabetes mellitus (GDM) and accelerated biological aging in middle-aged and elderly women. RESEARCH DESIGN AND METHODS We included parous women with a baseline survey on history of GDM and biological aging biomarkers from the UK Biobank. Information regarding prior GDM was collected via a touchscreen questionnaire and linkage to hospital admission records. Biological aging was evaluated using validated phenotypic age (PhenoAge) based on chronological age and nine biomarkers measured at baseline (2006–2010). Biological aging acceleration was determined as the residual by regressing PhenoAge estimates on chronological age. All-cause mortality and incident cardiometabolic disease during follow-up were also assessed. RESULTS Among the 178,363 women (mean age, 57.0 [SD 7.9] years), 1,141 had a history of GDM. In a multivariable-adjusted model, a history of GDM was associated with an increase in PhenoAge acceleration by 2.34 (95% CI 2.02, 2.66) years. The association persisted regardless of the occurrence of type 2 diabetes and related comorbidities after GDM. Consistent results were observed across subgroups, while the GDM-related PhenoAge acceleration was more prominent among women with less physical activity and obesity (both Pinteraction < 0.01). The mediation analysis demonstrated that PhenoAge acceleration explained 57.0% (95% CI 21.0, 86.9), 12.4% (7.3, 20.4), and 21.9% (14.0, 32.5) of the positive associations between GDM and all-cause mortality, type 2 diabetes, and cardiovascular disease, respectively. CONCLUSIONS Women with a history of GDM were biologically older than their non-GDM counterparts. The biological aging acceleration partially accounted for the associations between GDM and adverse health outcomes.