Diabetes Metab Syndr Obes. 2026 Oct 6;19:621983. doi: 10.2147/DMSO.S621983. eCollection 2026.
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.
PMID:42859675 | PMC:PMC13653552 | DOI:10.2147/DMSO.S621983