Prognostic impact of visit-to-visit glycemic variability on the risks of major adverse cardiovascular outcomes and hypoglycemia in patients with different glycemic control and type 2 diabetes

The prognostic impact of visit-to-visit glycemic variability on clinical outcomes in patients with different glycemic control and type 2 diabetes remains obscure. We investigated glucose variability and clinical outcomes for patients in the groups of Good glycemic control (GC), Insufficient glycemic control (IC), and Poor glycemic control (PC) in a prospective cohort study. By using data from Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE), 930 patients were enrolled from 61 centers in China and grouped into GC, IC, and PC according to their glycated hemoglobin A1(c) (HbA1(c)) and fasting plasma glucose (FPG). Visit-to-visit glycemic variability was defined using the coefficient of variation (CV) of five measurements of HbA1(c) and FPG taken 3-24 months after treatment. Multivariable Cox proportional hazards models were employed to estimate adjusted hazard ratio (aHR). Among 930 patients in the intensive glucose control, 82, 538, and 310 patients were assigned to GC, IC, and PC, respectively. During the median of 4.8 years of follow-up, 322 patients were observed hypoglycemia and 244 patients experienced major adverse cardiovascular events (MACE). The CV of HbA1(c) and FPG was significantly lower for GC (6.0 +/- 3.8, 11.2 +/- 6.2) than IC (8.3 +/- 5.6, 17.9 +/- 10.6) and PC (9.5 +/- 6.3, 19.3 +/- 10.8). High glycemic variability was associated with a greater risk of MACE (aHR: 2.21; 95% confidence interval (CI): 1.61-3.03; p < 0.001) and hypoglycemia (aHR: 1.36; 95% CI: 1.04-1.79; p = 0.025) than low glycemic variability in total patients. The consistent trend was also found in subgroups of GC, IC, and PC. This prospective cohort study showed that glycemic variability was significantly lower for GC than IC and PC. Furthermore, glycemic variability was associated with the risk of MACE and hypoglycemia in total patients and subgroups of different glycemic control.