Association of hemoglobin glycation index with the risk of chronic lung disease in individuals with CKM stages 0-3: evidence from two large prospective cohorts in Europe and East Asia.

AIMS: To examine the prospective association between hemoglobin glycation index (HGI) and incident chronic lung disease (CLD) in individuals with cardiovascular-kidney-metabolic syndrome (CKM) stages 0-3. METHODS: We examined the association between HGI and incident CLD in the UK Biobank and CHARLS. After exclusions, 275,389 and 7,042 participants were included, respectively. HGI was calculated as observed minus predicted HbA1c based on cohort-specific fasting blood glucose-HbA1c regression equations. Cox models, Kaplan-Meier analysis, restricted cubic spline models, two-piecewise Cox regression, and subgroup analyses were performed. RESULTS: During follow-up of 7.29 years in UK Biobank and 9.00 years in CHARLS, 20,273 and 603 CLD cases occurred, respectively. Higher HGI was associated with increased CLD risk in both cohorts. In the fully adjusted model, each 1-SD increase in HGI was associated with higher CLD risk in the UK Biobank (HR 1.044, 95% CI 1.031-1.057) and CHARLS (HR 1.097, 95% CI 1.020-1.181). Compared with the lowest quartile, highest quartile had increased CLD risk in the UK Biobank (HR 1.118, 95% CI 1.074-1.165) and CHARLS (HR 1.414, 95% CI 1.126-1.776). Exploratory subgroup analyses suggested possible heterogeneity by diabetes status, although the interaction was not robust after correction for multiple testing. CONCLUSIONS: Higher baseline HGI was prospectively associated with increased CLD risk among adults aged ≥45 years with CKM stages 0-3, with directionally consistent findings across the UK Biobank and CHARLS. These findings support further evaluation of HGI as a research-based epidemiological marker for potential risk stratification.