Physical Activity, Myokine–Adipokine Signatures and Haemoglobin Glycation Index in Adults with Type 2 Diabetes

Abstract

Background: The Hemoglobin Glycation Index (HGI) reflects variability in hemoglobin glycation beyond ambient glycaemia and is a marker of metabolic heterogeneity, cardiovascular risk and treatment response in type 2 diabetes mellitus (T2DM). Whether circulating myokines and adipokines are related to HGI, or whether relationships differ across exercise modalities, is unclear. Objective: To examine associations of circulating myokines (irisin, myostatin, myonectin, IL-6, IL-15) and adipokines (leptin, adiponectin) with HGI, and whether associations differ between physically active and sedentary individuals and across exercise modalities. Methods: Cross-sectional study of 185 adults with T2DM recruited at Thumbay Hospital, Ajman, United Arab Emirates, classified as physically active (n=98) or sedentary (n=87), with active individuals sub-grouped by predominant modality: aerobic (70), resistance (11), combined (17). Measurements were obtained after an overnight fast. HGI was calculated as the residual of HbA1c regressed on fasting plasma glucose. Mann–Whitney U, Kruskal–Wallis, Spearman correlations with false discovery rate (FDR) correction and median regression adjusted for age, sex, BMI and fasting glucose were used. Results: Active participants had lower HGI than sedentary participants (median −0.44 vs 0.12; p = 0.001), with lower BMI, fasting glucose and HbA1c. HGI differed by modality (p < 0.001), most favourable in the combined-training group and least favourable in the aerobic-only group. IL-6 was inversely correlated with HGI in active participants and leptin in sedentary participants (both FDR p < 0.05). Physical activity remained an independent predictor of lower HGI after adjustment for age, sex and BMI (β = −0.65;p< 0.001), and persisted after adjustment for IL-15 and leptin. Conclusion: Precludes causal inference; if confirmed prospectively, associations may inform individualized exercise prescription and HGI-based risk stratification. Distinct myokine–adipokine signatures were associated with glycation variability beyond mean glycaemia and combined aerobic- plus-resistance training with the most favourable HGI profile. The cross-sectional design precludes causal inference; if confirmed prospectively, associations may inform individualized exercise prescription and HGI-based risk stratification. Keywords: type 2 diabetes, hemoglobin glycation index, myokines, adipokines, exercise modality