HbA _1c variability is associated with microalbuminuria development in type 2 diabetes: A 7-year prospective cohort study

Aims/hypothesis HbA _1c variability has been shown to be an independent risk factor for nephropathy in patients with type 1 diabetes. In this study, we aimed to explore the association between HbA _1c variability and microalbuminuria development in patients with type 2 diabetes. We also intended to test the applicability of serially measured HbA _1c over 2 years for this risk assessment. Methods Between 2003 and 2005, we recruited 821 middleaged normoalbuminuric individuals with type 2 diabetes and followed them through to the end of 2010. The average follow-up time was 6.2 years. We defined microalbuminuria as a urine albumin to creatinine ratio of 30 mg/g (3.4 mg/mmol) or higher. HbA _1c variability was calculated by the SD of serially measured HbA _1c. The Cox proportional hazards model was used to evaluate the association between HbA _1c SD quartile and development of microalbuminuria. Results The incidence of microalbuminuria for the overall population was 58.4, 58.6, 60.8 and 91.9 per 1,000 personyears for Q1- to Q4-adjusted HbA _1c SD, respectively (p for trend00.042). Compared with patients in Q1, those in Q4 were about 37% more likely to develop microalbuminuria. The HR derived from a series of 2 year HbA _1c measurements was similar to that from data collection for longer than 4 years. Conclusions/interpretation In addition to mean HbA _1c values, HbA _1c variability, even measured as early as 2 years, is independently associated with the development of microalbuminuria in patients with type 2 diabetes.