Abstract
BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a major cause of morbidity and mortality in diabetes patients. Although several risk factors for CAN progression have been established, whether CAN is reversible remains unclear and the clinical factors associated with CAN recovery have not been identified. This study aimed to determine clinical factors related to CAN recovery. METHODS: Type 2 diabetes patients with CAN but free of cardiovascular disease at baseline were enrolled and followed for 2-3 years in this retrospective longitudinal study. CAN was classified as early (one abnormal parasympathetic test), definite (two or more abnormal parasympathetic tests), severe (definite plus orthostatic hypotension), or atypical (early plus orthostatic hypotension or orthostatic hypotension alone) based on Ewing's method. CAN recovery was classified as partial or complete: Partial recovery was defined as one-step improvement in CAN stage (early to normal, definite to early, or severe to definite), including the disappearance of only one abnormal result in any stage. Complete recovery was defined as normalization from definite or severe CAN. RESULTS: Among 759 subjects with CAN, 29.9% (n = 227) experienced CAN recovery, and 1.2% (n = 9) recovered completely. In a multivariate model, younger age (odds ratio [OR] per 5-year decrease 1.49; 95% confidence interval [CI] 1.25-1.78, P < 0.001), shorter duration of diabetes (OR per 5-year decrease 1.33; 95% CI 1.05-1.67, P = 0.016), presence of micro/macroalbuminuria (OR 0.34; 95% CI 0.15-0.78, P = 0.011), body weight reduction (OR per 1-kg decrease 1.11; 95% CI 1.02-1.21, P = 0.016), and HbA1c reduction (OR per 1% decrease 1.32; 95% CI 1.05-1.67, P = 0.019) were significantly associated with composite events of partial and complete CAN recovery. Age had the highest relative significance among the associated clinical factors. In addition, younger age was the only significant factor in complete CAN recovery. CONCLUSIONS: Younger age was the most important factor in CAN recovery in subjects with type 2 diabetes, including recovery from the definite or severe stage. HbA1c reduction, body weight reduction, no concurrent micro/macroalbuminuria, and shorter duration of diabetes were also significantly associated with CAN recovery.