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.