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 (HbA1c ) 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 HbA1c were calculated. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min per 1.73 m². 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 7.2 years, 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 HbA1c (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 HbA1c (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 HbA1c and other confounding variables. CONCLUSIONS: Long-term glycaemic variability expressed by SD of HbA1c predicted development of renal and cardiovascular complications.