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Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis.

ABSTRACT: OBJECTIVE:Diabetic neuropathy (DN) is one of the most common complications of diabetes that occurs in more than 67% of individuals with diabetes. Genetic polymorphisms may play an important role in DN development. However, until now, the association between genetic polymorphisms and DN risk has remained unknown. We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of the association between all genetic polymorphisms and DN risk. METHODS:Relevant published studies examining the relationship between all genetic polymorphisms and DN were obtained based on a designed search strategy up to 28 February 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess overall pooled effects of genetic models as well as in subgroup analyses. Sensitive analysis and publication bias were applied to evaluate the reliability of the study. Moreover, TSA was conducted to estimate the robustness of the results. RESULTS:We conducted a systematic review of a total of 1256 articles, and then 106 publications reporting on 136 polymorphisms of 76 genes were extracted. We performed 107 meta-analyses on 36 studies involving 12,221 subjects to derive pooled effect estimates for eight polymorphisms. We identified that ACE I>D, MTHFR 1298A/C, GPx-1 rs1050450, and CAT -262C/T were associated with DN, while MTHFR C677T, GSTM1, GSTT1, and IL-10 -1082G/A were not. Sensitivity analysis, funnel plot, and Egger's test displayed robust results. Furthermore, the results of TSA indicated sufficient sample size in studies of ACE, GPx-1, GSTM1, and IL-10 polymorphisms. INTERPRETATION:Our study assessed the association between ACE I>D, MTHFR C677T, MTHFR 1298A/C, GPx-1 rs1050450, CAT -262C/T, GSTM1, GSTT1, and IL-10 -1082G/A polymorphisms and DN risk. We hope that the data in our research study are used to study DN genetics.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6801182 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis.

Zhao Yating Y Zhu Ruixia R Wang Danni D Liu Xu X

Annals of clinical and translational neurology 20190926 10

<h4>Objective</h4>Diabetic neuropathy (DN) is one of the most common complications of diabetes that occurs in more than 67% of individuals with diabetes. Genetic polymorphisms may play an important role in DN development. However, until now, the association between genetic polymorphisms and DN risk has remained unknown. We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of the association between all genetic polymorphisms and DN risk.<h4>Methods</h4>Relevant pub ...[more]

PMID: 31557408

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Project description:BackgroundCurrently, diabetic peripheral neuropathy (DPN) is one of the most severe complications of diabetes mellitus (DM). Despite the seriousness of this problem, limited evidence is available on the prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia. In Ethiopia, there were no updated studies that estimate the national prevalence of DPN. Hence, this systematic review and meta-analysis provided a national prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia.MethodsThis study was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) in March 2020 and accepted with the registration number CRD42020173831. Different database searching engines were searched online to retrieve related articles, including PubMed, Scopus, Google Scholar, African Journals Online, World Health Organization (WHO) Afro Library, and Cochrane Review. The reviewers used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline in the reviewing process. In this systematic review and meta-analysis, all published and unpublished articles were analyzed. The reviewers used the random effects model to estimate the pooled prevalence of diabetic peripheral neuropathy among diabetes mellitus patients. The reviewers conducted the statistical analysis using the R version 3.5.3 and RStudio version 1.2.5033 software for Windows. The reviewers evaluated the heterogeneity across the included studies by the inconsistency index (I 2). The reviewers examined the publication bias by the funnel plot.ResultsThe search of the databases produced 245 papers. After checking the inclusion and exclusion criteria, 38 articles with 14029 total patients with diabetes mellitus were found suitable for the review. Except for three (retrospective cohort study), all studies were cross-sectional. The overall pooled prevalence of diabetic peripheral neuropathy was 22% (95% CI 18% to 26%). The subgroup analysis of diabetic peripheral neuropathy among patients with diabetes in the different regions was 23% (95% CI 17% to 29%) in Addis Ababa, 27% (95% CI 16% to 38%) in Oromia, 16% (95% CI 14% to 18%) in South nation and nationalities, and 15% (95% CI 6% to 24%) in Amhara.ConclusionsMore than one-fifth of patients with diabetes have diabetic peripheral neuropathy. According to this study, the prevalence of diabetic peripheral neuropathy in Ethiopia is considerably high. This evidence suggests that attention should be given to patients with diabetes in monitoring patients' blood glucose.

Project description:IntroductionGlucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light on this clinically important question.MethodsA systematic review was conducted according to a published protocol and The Cochrane Handbook methodology including meta-analyses, TSA of randomised clinical trials, and external validity estimation (GRADE). Randomised clinical trials evaluating steroids were included for sepsis patients (systemic inflammatory response syndrome, sepsis, severe sepsis or septic shock) aged >18 years. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/Medline, Embase, Web of Science and Cinahl were searched until 18 February 2015. No language restrictions were applied. Primary outcomes were mortality at longest follow-up and serious adverse events.ResultsA total of 35 trials randomising 4682 patients were assessed and reviewed in full text. All trials but two had high risk of bias. No statistically significant effect was found for any dose of steroids versus placebo or no intervention on mortality at maximal follow-up [relative risk (RR) 0.89; TSA adjusted confidence interval (CI) 0.74-1.08]. Two trials with low risk of bias also showed no statistically significant difference (random-effects model RR 0.38, 95% CI 0.06-2.42). Similar results were obtained in subgroups of trials stratified according to high (>500 mg) or low (? 500 mg) dose hydrocortisone (or equivalent) (RR 0.87; TSA-adjusted CI 0.38-1.99; and RR 0.90; TSA-adjusted CI 0.49-1.67, respectively). There were also no statistically significant effects on serious adverse events other than mortality (RR 1.02; TSA-adjusted CI 0.7-1.48). The effects did not vary according to the degree of sepsis. TSA showed that many more randomised patients are needed before definitive conclusions may be drawn.ConclusionEvidence to support or negate the use of steroids in any dose in sepsis patients is lacking. The results of ongoing and future well-designed, large randomised clinical trials are needed.

Project description:Whether the lipid profile in diabetic patients is associated with diabetic neuropathy (DN) development remains ambiguous, as does the predictive value of serum lipid levels in the risk of DN. Here, we performed the first meta-analysis designed to investigate the relationship between DN and the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Candidate studies were comprehensively identified by searching PubMed, Embase, Cochrane Library and Web of Science databases up to May 2020. Observational methodological meta-analysis was conducted to assess the relationships of TG, TC, HDL, and LDL levels with DN. Changes in blood lipids were used to estimate the effect size. The results were pooled using a random-effects or fixed-effects model. Potential sources of heterogeneity were explored by subgroup analysis. Various outcomes were included, and statistical analyses were performed using STATA (Version 12.0). Mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The Newcastle-Ottawa Scale (NOS) was applied to assess the methodological quality. I2 statistics were calculated to evaluate statistical heterogeneity. Funnel plots were utilized to test for publication bias. A sensitivity analysis was performed by omitting each study one by one. Thirty-nine clinical trials containing 32,668 patients were included in the meta-analysis. The results demonstrated that DN patients showed higher TG and lower HDL levels (MD = 0.34, 95% CI: 0.20-0.48 for TG; MD = -0.05, 95% CI: -0.08--0.02, I2 = 81.3% for HDL) than controls. Subgroup analysis showed that patients with type 1 diabetes mellitus (T1DM) neuropathy had elevated TG levels in their serum (MD = 0.25, 95% CI: 0.16-0.35,I2 = 64.4% for T1DM). However, only patients with T1DM neuropathy had reduced serum HDL levels, and there was no significant difference in serum HDL levels between patients with T2DM neuropathy and controls (MD = -0.07, 95% CI: -0.10--0.03, I2 = 12.4% for T1DM; MD = -0.02, 95% CI: -0.07-0.03, I2 = 80.2% for T2DM). TC and LDL levels were not significantly different between DN patients and controls (MD = -0.03, 95% CI: -0.14-0.09, I2 = 82.9% for TC; MD = -0.00, 95% CI: -0.08-0.08, I2 = 78.9% for LDL). In addition, compared with mild or painless DN patients, those with moderate or severe pain DN pain had significantly reduced serum TC and LDL levels (MD = -0.31, 95% CI: -0.49--0.13, I2 = 0% for TC; MD = -0.19, 95% CI: -0.32--0.08, I2 = 0% for LDL). TG levels and HDL levels did not vary considerably between patients with mild or painless DN and those with moderate or severe DN pain patients (MD = 0.12, 95% CI: -0.28-0.51, I2 = 83.2% for TG; MD = -0.07, 95% CI:-0.14-0.01, I2 = 58.8% for HDL). Furthermore, people with higher TG and LDL levels had higher risk of DN (OR = 1.36, 95% CI: 1.20-1.54, I2 = 86.1% for TG and OR = 1.10, 95% CI: 1.02-1.19, I2 = 17.8% for LDL). Conversely, high serum HDL levels reduced the risk of DN (OR = 0.85, 95% CI: 0.75-0.96, I2 = 72.6%), while TC levels made no significant difference with the risk of DN (OR = 1.02, 95% CI: 1.00-1.04, I2 = 84.7%). This meta-analysis indicated that serum lipid profile changes are among the biological characteristics of DN. Lipid levels should be explored as routine laboratory markers for predicting the risk of DN, as they will help clinicians choose appropriate therapies, and thus optimize the use of available resources.

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Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis.

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Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis.

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