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

Marwan Ismail,1,2 Mutaz Ibrahim Hassan,1 Akhtamova Shahzoda Fozilovna,3 Namoz Xalimovich Mavlonov,4 Nuriddin Nuritdinov,5 Elmotaz Abdelfatah61Department of Clinical Chemistry, College of Medical Laboratory, Clinical Chemistry, Shendi University, Shendi, River Nile State, Sudan; 2Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates; 3Department of Medical Rehabilitation, Sports Medicine and Traditional Medicine, Samarkand State Medical University, Samarkand, Uzbekistan; 4Department of Internal Disease in Family Medicine, Bukhara State Medical Institute, Bukhara, Uzbekistan; 5Department of Internal Diseases, Tashkent State Medical University, Tashkent, Uzbekistan; 6Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Marwan Ismail, Department of Medical Laboratory Sciences, Gulf Medical University, P.O. Box 4184, Ajman, United Arab Emirates, Email [email protected]: 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