Risk association of HbA1c variability with chronic kidney disease and cardiovascular disease in type 2 diabetes: prospective analysis of the Hong Kong Diabetes Registry

Background In type 2 diabetes, tight glycaemic control lowers the risk of diabetic complications, but it remains uncertain whether variability of glycaemia influences outcomes. We examined the association of glycated haemoglobin (HbA(1c)) variability with incident chronic kidney disease and cardiovascular disease in a prospective cohort of 8439 Chinese patients with type 2 diabetes recruited from 1994 to 2007. Methods Intrapersonal mean and SD of serially measured HbA(1c) were calculated. Chronic kidney disease was defined as estimated glomerular filtration rate <60ml/min per 1.73m(2). Cardiovascular disease was defined as events of ischemic heart disease, heart failure, ischemic stroke or peripheral vascular disease. Results Over a median follow-up period of 7.2years, 19.7 and 10.0% of patients developed chronic kidney disease and cardiovascular disease, respectively. Patients who progressed to chronic kidney disease had higher mean HbA(1c) (7.8 +/- 1.3% vs 7.4 +/- 1.2%, p<0.001) and SD (1.0 +/- 0.8% vs 0.8 +/- 0.6%, p<0.001) than nonprogressors. Similarly, patients who developed cardiovascular disease had higher mean HbA(1c) (7.7 +/- 1.3% vs 7.4 +/- 1.2%, p<0.001) and SD (1.4 +/- 1.1% vs 1.1 +/- 0.8%, p<0.001) than patients who did not develop cardiovascular disease. By using multivariate-adjusted Cox regression analysis, adjusted SD was associated with incident chronic kidney disease and cardiovascular disease with corresponding hazard ratios of 1.16 (95% CI 1.11-1.22), p<0.001) and 1.27 (95% CI 1.15-1.40, p<0.001), independent of mean HbA(1c) and other confounding variables. Conclusions Long-term glycaemic variability expressed by SD of HbA(1c) predicted development of renal and cardiovascular complications. Copyright (c) 2013 John Wiley & Sons, Ltd.