Association of visit-to-visit glycemic variability with risk of cardiovascular diseases in high-risk Japanese patients with type 2 diabetes: A subanalysis of the EMPATHY trial.

AIMS/INTRODUCTION Long-term glycemic variability is important to predict diabetic complications, but evaluation in a Japanese population is lacking. The aim of this study was to explore the relationship between visit-to-visit glycemic variability (VVV) and cardiovascular diseases (CV) in Japanese patients with type 2 diabetes (T2DM), using the prospective cohort of the EMPATHY trial. MATERIALS/METHODS Among 4532 participants with at least three HbA1c measurements, VVV was defined using the coefficient of variation (CV-HbA1c). The outcomes were the composite cardiovascular endpoints, including cardiac, cerebral, renal, and vascular events. The odds ratios (ORs) for the development of outcomes were estimated by using logistic regression models. RESULTS During a median follow-up of 38 months, 190 subjects developed CV events. The risk of developing CV events increased significantly with increasing quintile of CV-HbA1c, after multivariable adjustment including mean-HbA1c (OR for the fifth vs first quintile, 1.73; 95%CI, 1.03-2.91; P for trend test=0.003). There was a stronger association between CV-HbA1c and CV events in patients with mean-HbA1c <7% compared with those with mean-HbA1c ≥7% (OR per 1 standard deviation, 1.51; 95%CI, 1.23-1.85 and 1.13; 95%CI, 0.98-1.29, respectively; P for interaction=0.02). CONCLUSIONS Increases of VVV were associated with the risk of CV events in Japanese patients with T2DM independent of mean-HbA1c. The long-term variability of HbA1c as well as mean HbA1c might be an important glycemic indicator in the management of patients with T2DM, especially in those with mean-HbA1c <7%.