Aims/hypothesis: The aim of this study was to examine the association between HbA(1c) variability and the development of microalbuminuria as defined by an albumin/creatinine ratio ≥ 3.4 mg/mmol (≥ 30 mg/g) in at least two of three consecutive urine samples in Japanese patients with type 2 diabetes.
Methods: HbA(1c) level was measured in 812 serially registered normoalbuminuric adults aged 21-79 years with type 2 diabetes. After registration, a 1-year period to establish baseline values for mean HbA(1c) and HbA(1c) variability (measured as the intrapersonal SD of serially collected HbA(1c)) was decided upon. The association between HbA(1c) variability and the development of microalbuminuria was determined by Cox regression analysis after adjustment for other risk factors for microalbuminuria.
Results: Microalbuminuria occurred in 193 patients during the observation period of (mean ± SD) 4.3 ± 2.7 years. Even after adjustment for mean HbA(1c), HbA(1c) variability was a significant predictor of microalbuminuria independently of the mean HbA(1c); the HR for every 1% (95% CI) increase in mean HbA(1c) was 1.22 (1.06, 1.40) (p = 0.005), and that for HbA(1c) variability was 1.35 (1.05, 1.72) (p = 0.019). The effects of these two variables were quite similar when 1 SD was used; the HR for every 1 SD increase (95% CI) in HbA(1c) was 1.23 (1.07, 1.43) (p = 0.005), and that for HbA(1c) variability was 1.20 (1.03, 1.39) (p = 0.019).
Conclusions/interpretation: HbA(1c) variability affects the development of microalbuminuria independently of mean HbA(1c) in type 2 diabetes. Further studies should be performed to evaluate the influence of HbA(1c) variability on other complications and in individuals of other ethnicities with type 2 diabetes.