title: Efficacy and safety of aldose reductase inhibitor for the treatment of diabetic cardiovascular autonomic neuropathy: systematic review and meta-analysis.
abstract: BACKGROUND
  Aldose reductase inhibitors (ARIs) can block the metabolism of the polyol pathway, and have been used to slow or reverse the progression of diabetic cardiovascular autonomic neuropathy (DCAN). The purpose of this study was to review the effectiveness and safety of ARIs in the treatment of DCAN as determined by five cardiac autonomic neuropathy function tests.
  
  
  METHODS
  CENTRAL, MEDLINE, EMBASE, Scopus databases (inception to May 2012) were searched to identify randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) investigating ARIs for the treatment of DCAN with an English-language restriction. The data were analyzed using RevMan 5.0, and the heterogeneity between the trials was evaluated using the Cochrane's Q-test as well as the I² test. The type of model (random or fixed) used for analysis was based on heterogeneity. Weighted mean differences (WMD) with 95% confidence intervals (CI) were computed for the five cardiac automatic neuropathy function tests to evaluate the effects.
  
  
  RESULTS
  Ten articles met the prerequisites for this review. Analysis of the results showed that ARIs significantly improved function in at least three of the five automatic neuropathy tests, including the resting heart rate variation coefficients (WMD = 0.25, 95%CI 0.02 to 0.48, P = 0.040); the 30∶15 ratio (WMD = 0.06, 95%CI 0.01 to 0.10, P = 0.010) and the postural systolic blood pressure change (WMD = -5.94, 95%CI -7.31 to -4.57, P = 0.001). The expiration/inspiration ratio showed a marginally significant benefit (WMD = 0.05, 95%CI 0.00 to 0.09, P = 0.040). Glycaemic control was not significantly affected by ARIs. Adverse effects of ARIs except for Tolerestat were minimal.
  
  
  CONCLUSIONS
  Based on these results, we conclude that ARIs could ameliorate cardiac automatic neuropathy especially mild or asymptomatic DCAN but need further investigation.
authors.affiliation: Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Shengbing
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: The Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Guenther
authors.initials: G
authors.lastname: Boden
authors.affiliation: Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D048909:Diabetes Complications / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000737:chemistry; D006339:Heart Rate; D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D000449:Aldehyde Reductase; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human