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.
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