Importance of the Hemoglobin Glycation Index for Risk of Cardiovascular and Microvascular Complications and Mortality in Individuals with Type 2 Diabetes

Abstract

Backgruound: This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c).

Methods: Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence.

Results: During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53).

Conclusion: HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

Keywords: Cardiovascular events; Cohort studies; Diabetes mellitus, type 2; Hemoglobin glycation index; Microvascular complications; Mortality.

Fig. 1.

Kaplan-Meier curves of cumulative incidence of cardiovascular (CV) and mortality outcomes in patients grouped according to tertiles of mean 1st-year hemoglobin glycation index (top panels A, C, E, and G) and according to tertiles of mean 1st-year glycated hemoglobin levels (bottom panels B, D, F, and H). T1 is the lower tertile subgroup (blue line), T2 the middle tertile subgroup (green line), and T3 is the upper tertile subgroup (red line). CVE, cardiovascular event; MACE, major adverse cardiovascular event.

Fig. 2.

Kaplan-Meier curves of cumulative incidence of microvascular outcomes in patients grouped according to tertiles of mean 1st-year hemoglobin glycation index (top panels A, C, E, and G) and according to tertiles of mean 1st-year glycated hemoglobin levels (bottom panels B, D, F, and H). T1 is the lower tertile subgroup (blue line), T2 the middle tertile subgro up (green line), and T3 is the upper tertile subgroup (red line).