Glycated hemoglobin variability and the risk of cardiovascular events in patients with prediabetes and type 2 diabetes mellitus: A post‐hoc analysis of a prospective and multicenter study

AIMS/INTRODUCTION: High glycated hemoglobin (HbA1c) variability has been reported to be linked with cardiovascular events in type 2 diabetes patients. Only a few studies have been carried out on Asian patients. This study aimed to investigate the association of prediabetes and type 2 diabetes in Asian patients by performing a post‐hoc analysis of a multicenter, prospective, observational study. MATERIALS AND METHODS: Data for prediabetes and type 2 diabetes patients were retrieved from a multicenter national registry entitled “CORE‐Thailand study.” The primary outcome was 4P‐MACE (major adverse cardiovascular events, including non‐fatal myocardial infarction, heart failure hospitalization, non‐fatal stroke and all‐cause death). Patients were stratified according to quartiles of HbA1c standard deviation. The Cox proportional hazards regression model was used to estimate the association of HbA1c variability with incident cardiovascular disease. RESULTS: A total of 3,811 patients with prediabetes and type 2 diabetes were included. The median follow‐up duration was 54 months. In the fully adjusted model, the highest quartile of HbA1c variability showed a statistically significant association with 4P‐MACE (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.77–4.35), fatal and non‐fatal myocardial infarction (HR 6.91, 95% CI 1.90–25.12), hospitalization for heart failure (HR 3.34, 95% CI 1.20–9.26) and all‐cause death (HR 3.10, 95% CI 1.72–5.57). All these outcomes were statistically significantly different among four quartiles of HbA1c (log‐rank P‐value <0.05). Fatal and non‐fatal stroke showed no statistically significant association with high HbA1c variability. CONCLUSION: High HbA1c variability in the highest quartile showed a statistically significant association with multiple adverse cardiovascular events in an Asian population. Minimizing HbA1c fluctuation during long‐term follow up should be another important objective for type 2 diabetes patients.