Association of haemoglobin glycation index with all-cause and cardiovascular disease mortality in diabetic kidney disease: a cohort study

Abstract

While the high haemoglobin glycation index (HGI) has been extensively investigated in diabetic populations, its impact on patients with diabetic kidney disease (DKD) remains unclear. We examined data from the National Health and Nutrition Examination Surveys (NHANES) conducted between 1999 and 2018. HGI was determined using the formula recommended by Hempe et al., which calculates the difference between measured and predicted HbA1c. Predicted HbA1c was derived from the equation: 0.024 FPG + 3.1. National death index records up to December 31, 2019, were utilized to assess mortality outcomes. To estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for both all-cause and cardiovascular disease (CVD) mortality, we utilized Cox proportional hazard models. A restricted cubic spline analysis was performed to explore the potential nonlinear relationship between HGI levels and mortality. Our cohort study comprised data from 1,057 participants with DKD (mean [SE] age, 61.61 [0.57] years; 48.24% female). The mean HGI level was 0.44 (SE 0.04). Over a median follow-up period of 6.67 years, we observed 381 deaths, including 140 due to CVD. Compared with participants in the second tertile of HGI levels (0.03–0.74), those in the lowest tertile of HGI (-5.29–0.02) exhibited an all-cause mortality hazard ratio of 1.39 (95% CI, 1.02–1.88) and a CVD mortality hazard ratio of 1.10 (95% CI, 0.67–1.81). Conversely, participants in the highest tertile (0.75–9.60) demonstrated an all-cause mortality hazard ratio of 1.48 (95% CI, 1.05–2.08) and a CVD mortality hazard ratio of 2.06 (95% CI, 1.13–3.77) after further adjusting for HbA1c and other important variables. Additionally, a restricted cubic spline analysis revealed a U-shaped relationship between HGI and all-cause mortality (P < 0.001 for nonlinearity) and a J-shaped relationship between HGI and CVD mortality (P = 0.044 for nonlinearity). Our cohort study suggests that HGI in DKD populations exhibits a U-shaped association with all-cause mortality and a J-shaped association with CVD mortality, independent of HbA1c levels.