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Background: Gender differences in metabolic response to lifestyle interventions remain poorly explored. This study aimed to evaluate the impact of a six-month Mediterranean diet (MD) intervention combined with regular physical activity on metabolic parameters in overweight adults., Methods: A prospective cohort study was conducted in an obesity clinic in Rome, Italy, involving overweight adults (BMI ≥ 25 kg/m 2 ) motivated to improve their lifestyle. Participants ( n = 205; 107 men and 98 women) self-selected into physical activity groups (aerobic, anaerobic, combined or no activity). Gender-specific metabolic changes were assessed, including lipid profiles, liver markers and fasting glucose., Results: Significant gender differences in metabolic results were observed. Men showed greater reductions in total cholesterol (TC) and LDL, as well as significant reductions in alanine aminotransferase (ALT). Women showed a significant increase in HDL cholesterol. Fasting blood glucose decreased significantly in both sexes, with no differences between the sexes. Activity-specific analysis revealed that anaerobic activity significantly improved lipid metabolism in men, while aerobic activity produced the greatest benefits in women, including increased HDL and improved liver marker profiles., Conclusions: Therapeutic strategies combining MD and physical activity must take into account gender-specific physiological differences and the type of sport activity to optimise metabolic benefits. Personalised approaches may improve the management of cardiovascular risk factors in overweight individuals., Study Registration: This study is registered on ClinicalTrials.gov (NCT06661330).

Context: The mechanisms underlying bone fragility and increased fracture risk observed in individuals with type 2 diabetes (T2D) are not yet fully elucidated. Previous research has suggested a role for neuropeptides in regulating bone metabolism; however, the contribution of the neuropeptide Neurotensin (NT), which is thoroughly implicated in T2D and cardiovascular disease, has not been investigated in this context., Objective: To study the relationship between circulating levels of the NT precursor proneurotensin (proNT) and bone mineralisation in T2D women., Materials and Methods: This is a cross-sectional investigation with a longitudinal prospective phase, involving 126 women with T2D who underwent bone density scans and had proNT levels measured. Biomarkers of bone metabolism and inflammation were also assessed. Data on bone mineral density (BMD) after 12 months were available for 49 patients., Main Outcome Measure: Plasma proNT levels in relation to BMD., Results: 32% of the participants had osteopenia/osteoporosis and exhibited higher proNT than those with normal BMD (200.8 ± 113.7 vs. 161.6 ± 108.8 pg/mL; p = 0.013). ProNT inversely correlated with femur BMD and T-score (p < 0.01) and was associated with degraded bone architecture (TBS, p = 0.02), and higher OPN, P1NP, TNF-α and IL-1β levels. Baseline proNT correlated with further BMD reduction at the 12-month follow-up, independently of potential confounders (p = 0.02)., Conclusions: In women with T2D, greater proNT levels are associated with impaired bone mineralisation and predict mineral density decline overtime. ProNT could potentially serve as a diagnostic tool for identifying patients at higher risk of osteopenia/osteoporosis, suggesting a significant connection between this neuropeptide and bone metabolism in diabetes., (© 2024 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)