Women with a history of gestational diabetes mellitus (GDM) face increased long-term risk of type 2 diabetes and cardiovascular disease, yet molecular markers linking physical fitness to cardiometabolic health in this population remain incompletely characterized. A proteomics-based study published in Cardiovascular Diabetology evaluated circulating serum proteins associated with aerobic capacity and muscle strength a decade after GDM.

The study analyzed 38 women from the post-GDM PONCH cohort. Aerobic fitness was assessed using peak oxygen uptake (VO2peak) and peak fat oxidation, while maximal isometric strength was measured across five muscle groups. Serum proteins were quantified using mass spectrometry-based proteomics. Associations between proteins, fitness variables, and clinical markers were examined using Spearman correlations with false discovery rate correction and age- and medication-adjusted sensitivity analyses. Group comparisons across fitness-level and glycemic-status categories were conducted using regression models and nonparametric testing. Exercise responsiveness was evaluated in an independent cohort of 28 previously untrained men undergoing six weeks of supervised aerobic training.

Thirty-five proteins were associated with at least one fitness measure, and 21 remained significant after adjustment. Nine proteins correlated with both VO2peak and muscle strength. Identified proteins mapped to pathways related to metabolic regulation, immune response, complement activation, oxidative stress, and extracellular matrix remodeling. Five proteins, including PON3 and IGF1, demonstrated consistent associations with central adiposity, lipid levels, blood pressure, and insulin resistance. In the training cohort, nine proteins changed following aerobic training without significant weight loss.

These findings identify circulating proteins associated with physical fitness and cardiometabolic markers in women 10 years after GDM.