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 middle-aged 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 person-years for Q1- to Q4-adjusted HbA(1c) SD, respectively (p for trend = 0.042). 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.
