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PloS One 2014Aldose reductase inhibitors (ARIs) can block the metabolism of the polyol pathway, and have been used to slow or reverse the progression of diabetic cardiovascular... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Aldehyde Reductase; Blood Pressure; Cardiovascular Diseases; Diabetes Complications; Diabetic Neuropathies; Enzyme Inhibitors; Glycated Hemoglobin; Heart Rate; Humans; Models, Statistical; Randomized Controlled Trials as Topic; Reproducibility of Results; Treatment Outcome
PubMed: 24533052
DOI: 10.1371/journal.pone.0087096 -
The Cochrane Database of Systematic... Oct 2007Polyneuropathy, a common complication of diabetes mellitus, causes pain and sensory and motor deficits in the limbs, and is also an important independent predictor of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polyneuropathy, a common complication of diabetes mellitus, causes pain and sensory and motor deficits in the limbs, and is also an important independent predictor of foot ulceration. Inhibiting the metabolism of glucose by the polyol pathway using aldose reductase inhibitors is a potential mechanism to slow or reverse the neuropathy's progression.
OBJECTIVES
To assess the effects of aldose reductase inhibitors on the progression of symptoms, signs or functional disability in diabetic polyneuropathy.
SEARCH STRATEGY
We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (from January 1966 to May 2007), EMBASE (from January 1980 to May 2007) and LILACS (from 1982 to May 2007). We reviewed bibliographies of randomized trials identified, and contacted authors and experts in the field.
SELECTION CRITERIA
We included randomized controlled trials comparing an aldose reductase inhibitor with control, and lasting at least six months. The primary outcome measure was change in neurological function, measured in various ways, including strength testing, sensory examination, and composite scores of neurological examination. Secondary outcome measures were nerve conduction studies, neuropathic symptoms, quality of life, occurrence of foot ulcers and adverse effects.
DATA COLLECTION AND ANALYSIS
Trials included in the review were selected and assessed independently by at least two of us. Methodological criteria and study results were recorded on data extraction forms.
MAIN RESULTS
Thirty-two randomized controlled trials meeting the inclusion criteria were identified. Many had significant methodological flaws. Change in neurological function, our primary outcome measure, was assessed in 29 trials, but sufficient data for meta-analysis were only available in 13 studies, involving 879 treated participants and 909 controls. There was no overall significant difference between the treated and control groups (SMD -0.25, 95% CI -0.56 to 0.05), although one subgroup analysis (four trials using tolrestat) favored treatment. A benefit for neuropathic symptoms was suggested by a group of trials using a dichotomized endpoint (improvement or not), but this was contradicted by another group of trials which measured symptoms on a continuous scale. There was no overall benefit on nerve conduction parameters (27 studies) or foot ulceration (one study). Quality of life was not assessed in any of the studies. While most adverse events were infrequent and minor, three compounds had dose limiting adverse events that lead to their withdrawal from human use: severe hypersensitivity reactions with sorbinil, elevation of creatinine with zenarestat, and alteration of liver function with tolrestat.
AUTHORS' CONCLUSIONS
We found no statistically significant difference between aldose reductase inhibitors and placebo in the treatment of diabetic polyneuropathy. Any future clinical trials of aldose reductase inhibitors should be restricted to compounds proven to have substantial biological or preclinical advantages over previously tested agents.
Topics: Aldehyde Reductase; Diabetic Neuropathies; Enzyme Inhibitors; Humans; Peripheral Nervous System Diseases; Polyneuropathies; Randomized Controlled Trials as Topic
PubMed: 17943821
DOI: 10.1002/14651858.CD004572.pub2 -
PloS One 2022To evaluate the clinical value of Aldo-keto reductase family 1 member B10 (AKR1B10) in the diagnosis and prognosis of hepatocellular carcinoma (HCC). (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the clinical value of Aldo-keto reductase family 1 member B10 (AKR1B10) in the diagnosis and prognosis of hepatocellular carcinoma (HCC).
METHODS
A search of the PubMed, China Biology Medicine, Cochrane, and Embase databases was performed to conduct meta-analyses to evaluate the accuracy of AKR1B10 in diagnosing HCC and to assess the impact on prognosis of patients after curative resection of HCC.
RESULTS
A total of 12 different cohorts from 11 studies including 2747 HCC patients and 2053 controls showed that the pooled specificity and the pooled sensitivity of AKR1B10 for the diagnosis of HCC were 0.78 (95% CI: 0.69-0.85) and 0.85 (95% CI: 0.77-0.90), respectively. The pooled sensitivity and specificity of serum AKR1B10 for the diagnosis of HCC were 0.80 (95% CI: 0.70-0.86) and 0.87 (95% CI: 0.77-0.93), respectively. The pooled sensitivity and specificity of AKR1B10 in malignant tumor tissue for the diagnosis of HCC were 0.78 (95% CI: 0.61-0.89) and 0.82 (95% CI: 0.69-0.90), respectively. The pooled sensitivity and specificity of AKR1B10 to distinguish HCC from benign liver disease were 0.71 (95% CI: 0.62-0.78) and 0.84 (95% CI: 0.77-0.89), respectively. The sensitivity and specificity of AKR1B10 combined with alpha fetoprotein (AFP) in the diagnosis of HCC were 0.84 (95% CI: 0.79-0.88) and 0.88 (95% CI: 0.73-0.95), respectively. The pooled sensitivity and specificity of AKR1B10 in malignant tumor tissue for the diagnosis of early-stage HCC were 0.85 (95% CI: 0.62-0.95) and 0.88 (95% CI: 0.81-0.93), respectively. A meta-analysis of five studies including 798 patients demonstrated that high AKR1B10 expression in liver malignant tumor was associated with better overall survival in patients with HCC after hepatectomy (HR = 0.54, 95% CI: 0.41-0.72, p < 0.001).
CONCLUSIONS
AKR1B10 exhibits a great clinical value in the diagnosis of HCC, especially for early-stage HCC, with excellent diagnostic accuracy. Furthermore, AKR1B10 expression can predict the prognosis of HCC patients after hepatic resection.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Aldo-Keto Reductases; Aldehyde Reductase; Biomarkers, Tumor
PubMed: 36584078
DOI: 10.1371/journal.pone.0279591 -
The Cochrane Database of Systematic... 2000To assess the efficacy of aldose reductase inhibitors in the prevention, reversal or delay in the progression of diabetic peripheral neuropathy. (Review)
Review
OBJECTIVES
To assess the efficacy of aldose reductase inhibitors in the prevention, reversal or delay in the progression of diabetic peripheral neuropathy.
SEARCH STRATEGY
The Cochrane Diabetes Group's database was searched and the citation lists of identified trials and previous reviews checked. Investigators identified as active in the field were approached for overlooked studies.
SELECTION CRITERIA
Randomised controlled trials of aldose reductase inhibitors versus placebo, no treatment or other treatment in diabetic patients with or without clinical neuropathy.
DATA COLLECTION AND ANALYSIS
Nerve conduction velocity was the only end point measured in all trials. Treatment effect was evaluated in terms of nerve conduction velocity mean difference in median and peroneal motor and median and sural sensory nerves.
MAIN RESULTS
19 trials, testing 4 different aldose reductase inhibitors for between 4 to 208 weeks duration (median 24 weeks), met the inclusion criteria for the meta-analysis. A small but statistically significant reduction in decline of median and peroneal motor nerve conduction velocities was present in the treated group when compared to the control group (weighted mean 0.66 m/s 95% CI 0.18-1.14 m/s and 0.53 m/s 95% CI 0.02-1.04m/s respectively). No clear benefit of aldose reductase inhibitor treatment was observed in either of the sensory nerves.
REVIEWER'S CONCLUSIONS
Although aldose reductase inhibitor treatment has been demonstrated to diminsh the reduction in motor nerve conduction velocity, the clinical relevance of such a change in this outcome measure is uncertain. There was no effect in terms of this outcome measure in the smaller sensory fibres, degeneration of which is primarily responsible for the most common neuropathic syndrome associated with diabetes, that of severe pain and loss of sensation in the extremity leading in some cases to ulceration and eventual amputation.
Topics: Aldehyde Reductase; Diabetic Neuropathies; Enzyme Inhibitors; Humans
PubMed: 10796870
DOI: 10.1002/14651858.CD002182