Metabolomics Signatures in Type 2 Diabetes: A Systematic Review and Integrative Analysis

Abstract Objective Metabolic signatures have emerged as valuable signaling molecules in the biochemical process of type 2 diabetes (T2D). To summarize and identify metabolic biomarkers in T2D, we performed a systematic review and meta-analysis of the associations between metabolites and T2D using high-throughput metabolomics techniques. Methods We searched relevant studies from MEDLINE (PubMed), Embase, Web of Science, and Cochrane Library as well as Chinese databases (Wanfang, Vip, and CNKI) inception through 31 December 2018. Meta-analysis was conducted using STATA 14.0 under random effect. Besides, bioinformatic analysis was performed to explore molecule mechanism by MetaboAnalyst and R 3.5.2. Results Finally, 46 articles were included in this review on metabolites involved amino acids, acylcarnitines, lipids, carbohydrates, organic acids, and others. Results of meta-analysis in prospective studies indicated that isoleucine, leucine, valine, tyrosine, phenylalanine, glutamate, alanine, valerylcarnitine (C5), palmitoylcarnitine (C16), palmitic acid, and linoleic acid were associated with higher T2D risk. Conversely, serine, glutamine, and lysophosphatidylcholine C18:2 decreased risk of T2D. Arginine and glycine increased risk of T2D in the Western countries subgroup, and betaine was negatively correlated with T2D in nested case-control subgroup. In addition, slight improvements in T2D prediction beyond traditional risk factors were observed when adding these metabolites in predictive analysis. Pathway analysis identified 17 metabolic pathways may alter in the process of T2D and metabolite-related genes were also enriched in functions and pathways associated with T2D. Conclusions Several metabolites and metabolic pathways associated with T2D have been identified, which provide valuable biomarkers and novel targets for prevention and drug therapy.

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Anti-diabetic agents for prevention of type 2 diabetes mellitus in people with pre-diabetes: a systematic review and network meta-analysis protocol

BMJ Open ◽

10.1136/bmjopen-2019-029073 ◽

2019 ◽

Vol 9 (10) ◽

pp. e029073 ◽

Cited By ~ 1

Author(s):

Xianzhe Wang ◽

Jiabin Liu ◽

Lijin Huang ◽

Hai Zeng ◽

Guoxin He ◽

...

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetes Prevention ◽

Meta Analysis ◽

Cochrane Library ◽

Glucose Lowering ◽

Increased Risk

IntroductionType 2 diabetes mellitus (T2DM) is a substantial health problem worldwide. Pre-diabetic state is associated with increased risk for the development of diabetes. There are various pharmacological therapies with glucose-lowering activity for diabetes prevention. Of those, most are being compared with placebo instead of active agents. The relative effects and safety of different glucose-lowering drugs still remain uncertain. To address this gap, we will conduct a systematic review and network meta-analysis (NMA) to evaluate comparative efficacy and safety of glucose-lowering agents for T2DM prevention in patients with pre-diabetes.Methods and analysisPubMed, the Cochrane library and Embase will be searched from inception to December 2019 for relevant randomised controlled trials (RCTs) that examined anti-diabetic drugs for diabetes prevention in patients with pre-diabetes. Two reviewers working independently will screen titles, abstracts and full papers. Data extraction will also be completed by two independent authors. The primary outcome will be the incidence of T2DM in patients with pre-diabetes at baseline. Secondary outcomes will include the achievement of normoglycaemia, all-cause mortality, cardiovascular mortality and hypoglycaemic event. Pairwise meta-analysis and NMA will be conducted for each outcome using a frequentist random-effects model. Additionally, subgroup analyses will also be performed. The comparison-adjusted funnel plot will be used to assess publication bias. The overall quality of evidence will be rated with the Grading of Recommendations Assessment, Development and Evaluation framework. Data analysis will be conducted using Stata V.14.0.Ethics and disseminationEthics approval is not required. We plan to submit the results of this study to a peer-review journal.PROSPERO registration numberCRD42019119157.

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TheType 2 Deiodinase Thr92Ala PolymorphismIs Associated with Worse Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Journal of Diabetes Research ◽

10.1155/2016/5928726 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Xiaowen Zhang ◽

Jie Sun ◽

Wenqing Han ◽

Yaqiu Jiang ◽

Shiqiao Peng ◽

...

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycemic Control ◽

Meta Analysis ◽

Increased Risk ◽

Design And Methods ◽

Hba1c Levels

Objective. Type 2 deiodinase (Dio2) is an enzyme responsible for the conversion of T4 to T3. The Thr92Ala polymorphism has been shown related to an increased risk for developing type 2 diabetes mellitus (T2DM). The aim of this study is to assess the association between this polymorphism and glycemic control in T2DM patients as marked by the HbA1C levels.Design and Methods.The terms “rs225014,” “thr92ala,” “T92A,” or “dio2 a/g” were used to search for eligible studies in the PubMed, Embase, and Cochrane databases and Google Scholar. A systematic review and meta-analysis of studies including both polymorphism testing and glycated hemoglobin (HbA1C) assays were performed.Results. Four studies were selected, totaling 2190 subjects. The pooled mean difference of the studies was 0.48% (95% CI, 0.18–0.77%), indicating that type 2 diabetics homozygous for the Dio2 Thr92Ala polymorphism had higher HbA1C levels.Conclusions. Homozygosity for the Dio2 Thr92Ala polymorphism is associated with higher HbA1C levels in T2DM patients. To confirm this conclusion, more studies of larger populations are needed.

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The association between insulin therapy and depression in patients with type 2 diabetes mellitus: a meta-analysis

BMJ Open ◽

10.1136/bmjopen-2017-020062 ◽

2018 ◽

Vol 8 (11) ◽

pp. e020062 ◽

Cited By ~ 10

Author(s):

Xiaosu Bai ◽

Zhiming Liu ◽

Zhisen Li ◽

Dewen Yan

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Therapy ◽

Depressive Disorders ◽

Meta Analysis ◽

Epidemiological Studies ◽

Cochrane Library ◽

Increased Risk

ObjectivesSeveral patients with type 2 diabetes mellitus (T2DM) have depressive disorders. Whether insulin treatment was associated with increased risk of depression remains controversial. We performed a meta-analysis to evaluate the association of insulin therapy and depression.DesignA meta-analysis.MethodsWe conducted a systematic search of PubMed, PsycINFO, Embase and the Cochrane Library from their inception to April 2016. Epidemiological studies comparing the prevalence of depression between insulin users and non-insulin users were included. A random-effects model was used for meta-analysis. The adjusted and crude data were analysed.ResultsTwenty-eight studies were included. Of these, 12 studies presented with adjusted ORs. Insulin therapy was significantly associated with increased risk of depression (OR=1.41, 95% CI 1.13 to 1.76, p=0.003). Twenty-four studies provided crude data. Insulin therapy was also associated with an odds for developing depression (OR=1.59, 95% CI 1.41 to 1.80, p<0.001). When comparing insulin therapy with oral antidiabetic drugs, significant association was observed for adjusted (OR=1.42, 95% CI 1.08 to 1.86, p=0.008) and crude (OR=1.61, 95% CI 1.35 to 1.93, p<0.001) data.ConclusionsOur meta-analysis confirmed that patients on insulin therapy were significantly associated with the risk of depressive symptoms.

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Impact of Common Spices on Glycemia in Individuals with Type 2 Diabetes: Systematic Review and Meta-Analysis of Clinical Trials

Current Developments in Nutrition ◽

10.1093/cdn/nzaa040_002 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 2-2

Author(s):

Sepideh Alasvand ◽

William Bridges ◽

Vivian Haley-Zitlin

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Blood Glucose ◽

Meta Analysis ◽

Cochrane Library ◽

P Value ◽

Significant Heterogeneity ◽

P Values ◽

Common Spices

Abstract Objectives This study examined the effect of common spices cardamom, ginger, cumin, curcuminoids and cinnamon on improving glucose levels in individuals with type 2 diabetes by systematic review and meta-analysis. Methods PubMed, FSTA, Web of Science, CINAHEL, MEDLINE and Cochrane Library database of systematic review databases were searched using keywords (fasting blood glucose OR hemoglobin A1c OR HbA1c OR homeostasis) AND (Ginger or zingiber or “zingiber officinale” or “cinnamomum zeylanicum” or “cinnamomum aromaticum” or “cinnamomum cassia” or “cinnamomum verum” or curcumin or turmeric or curcuminoids or “curcuma longa” or langas or “curcuma zedoarias” or turmeric) AND (diabetes* OR “diabetes mellitus” OR “type 2” OR “blood glucose” OR insulin* OR antidiabet* OR “glucose level”) up to January 2020. Statistical calculations used SAS software version 9.2 (SAS, Cary NC, USA). P-values < 0.05 were considered significant, P-values < 0.10 were considered weakly significant. Results Twenty-three studies with 2237 trial participants were selected out of a 512 study pool. Spices decreased FBG and HbA1c %. The estimated reduction in intervention change vs. control change is as follows: A1c was −0.264 mg/dl, 95% CI (−0.5503, −0.02), P value 0.069; FBG was −9.9370 mg/dl, 95% CI (−20.79, 0.91), P value 0.07. A significant heterogeneity was observed overall among the all studies, indicating that not all studies had similar levels of decrease. Conclusions A correlation between consumption of certain common spices and significant reduction in glycemic indices among diabetes patients was proved. Funding Sources Clemson University.

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ABCA1 69C>T Polymorphism and the Risk of Type 2 Diabetes Mellitus: A Systematic Review and Updated Meta-Analysis

Frontiers in Endocrinology ◽

10.3389/fendo.2021.639524 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ha Young Yoon ◽

Min Hye Lee ◽

Yubin Song ◽

Jeong Yee ◽

Gonjin Song ◽

...

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cell Function ◽

Meta Analysis ◽

Asian Population ◽

Increased Risk ◽

Β Cell Function

BackgroundThe ATP-binding cassette transporter A1 (ABCA1) is likely associated with the risk of type 2 diabetes mellitus (T2DM) via β cell function modification, but the evidence on the association remains unclear. This study aimed to investigate the relationship between the ABCA1 69C>T polymorphism and the risk of T2DM through a systematic review and meta-analysis.Materials and MethodsThe PubMed, Web of Science, and Embase databases were searched for qualified studies published until August 2020. Studies that included the association between the ABCA1 69C>T polymorphism and the risk of T2DM were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated.ResultsWe analyzed data from a total of 10 studies involving 17,742 patients. We found that the CC or CT genotype was associated with increased risk of T2DM than the TT genotype (OR, 1.41; 95% CI, 1.02-1.93). In the Asian population, the C allele carriers had a higher risk of T2DM than those with the TT genotype; the ORs of the CC and CT genotypes were 1.80 (95% CI, 1.21-2.68) and 1.61 (95% CI, and 1.29-2.01), respectively.ConclusionsThis meta-analysis confirmed that the ABCA1 69C>T genotype showed a decrease risk of T2DM compared to the CC or CT genotypes.

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Effect of DPP-IV Inhibitors on Glycemic Variability in Patients with T2DM: A Systematic Review and Meta-Analysis

Scientific Reports ◽

10.1038/s41598-019-49803-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Subin Lee ◽

Heeyoung Lee ◽

Yoonhye Kim ◽

EunYoung Kim

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Meta Analysis ◽

Glycemic Variability ◽

Mean Difference ◽

Systematic Evaluation ◽

Cochrane Library ◽

Significant Heterogeneity ◽

Dpp Iv

Abstract Glycemic variability (GV) has been an emerging target for preventing complications related to type 2 diabetes. For reducing GV, DPP-IV inhibitors have shown effectiveness compared to other oral anti-hyperglycemic drugs (OADs), but systematic evaluation has yet to be existed. A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to evaluate the effect of DPP-IV inhibitors compared with other OADs, on GV as measured by mean amplitude of glycemic excursions (MAGE). Searches were conducted using Pubmed, EMBASE, and the Cochrane Library, from which eligible studies were retrieved; seven RCTs were included in the analysis. DPP-IV inhibitors were found to significantly reduce MAGE compared to other OADs (mean difference = −14.61; 95% CI = −19.00 to −10.21; p < 0.0001) without significant heterogeneity among sulfonylureas (mean difference = −14.93; 95% CI = −21.60 to −8.26; p < 0.0001). Initial combination therapy with DPP-IV inhibitors more effectively reduced MAGE than stepwise add-on therapies (p = 0.006), although no differences in MAGE were found based on HbA1c values. These findings indicate that DPP-IV inhibitors are promising alternatives for reducing GV in type 2 diabetes patients. However, further studies utilizing larger numbers of patients and longer-term follow-ups are needed.

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Protocol for systematic review and meta-analysis of sex hormones and diabetes risk in ageing men and women of African ancestry

BMJ Open ◽

10.1136/bmjopen-2018-024446 ◽

2019 ◽

Vol 9 (1) ◽

pp. e024446 ◽

Cited By ~ 2

Author(s):

Nyuyki Clement Kufe ◽

Maphoko Masemola ◽

Tinashe Chikowore ◽

Andre Pascal Kengne ◽

Tommy Olsson ◽

...

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Sex Hormones ◽

Meta Analysis ◽

Risk Of Bias ◽

Diabetes Risk ◽

Cochrane Library ◽

Men And Women ◽

Inconsistency Index

AimTo present the protocol of a systematic review and meta-analysis of the available evidence examining the association between sex hormones and type 2 diabetes risk in ageing men and women of African descent.MethodsWe shall conduct a comprehensive search of published studies that examined the association between sex hormones and type 2 diabetes risk in men and women aged ≥40 years from 01/01/1980 to 31/03/2018 with no language restriction. Databases to be searched include: PubMed, Scopus, Cochrane Library, Cumulative Index to Nursing and Allied Health, ISI Web of Science, Clinical Trial registries, Google Scholar and institutional websites such as the WHO, American Diabetes Association, International Diabetes Federation, World Diabetes Foundation, European Association for the Study of Diabetes, African Journal Online and ProQuest databases. This protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Independent screening for eligible studies using defined criteria and data extraction, will be completed in duplicate. Discrepancies will be resolved by consensus or consultation with a third researcher. Risk of bias of included studies will be assessed by the appropriate Cochrane risk of bias tool. The overall association estimates will be pooled using appropriate meta-analytic techniques. Heterogeneity will be assessed using Cochrane Q statistic and the inconsistency index (I2). The random effects model will be used to calculate a pooled estimate.Ethics and disseminationNo ethics clearance is required as no primary data will be collected. The systematic review and meta-analysis are part of a PhD project at WITS University (Johannesburg, South Africa) and results will be presented at conferences and published in a peer-review journal. The results will guide future population specific interventions.PROSPERO registration numberCRD42017074581.

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The Effectiveness of Telemedicine Solutions for the Management of Type 2 Diabetes: A Systematic Review, Meta-Analysis, and Meta-Regression

Journal of Diabetes Science and Technology ◽

10.1177/19322968211064633 ◽

2021 ◽

pp. 193229682110646

Author(s):

Stine Hangaard ◽

Sisse H. Laursen ◽

Jonas D. Andersen ◽

Thomas Kronborg ◽

Peter Vestergaard ◽

...

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Systematic Reviews ◽

Meta Analysis ◽

Cochrane Library ◽

Controlled Trials ◽

Sufficient Information ◽

Meta Regression ◽

Meta Analyses

Background: Previous systematic reviews have aimed to clarify the effect of telemedicine on diabetes. However, such reviews often have a narrow focus, which calls for a more comprehensive systematic review within the field. Hence, the objective of the present systematic review, meta-analysis, and meta-regression is to evaluate the effectiveness of telemedicine solutions versus any comparator without the use of telemedicine on diabetes-related outcomes among adult patients with type 2 diabetes (T2D). Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We considered telemedicine randomized controlled trials (RCT) including adults (≥18 years) diagnosed with T2D. Change in glycated hemoglobin (HbA1c, %) was the primary outcome. PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials (CENTRAL) were searched on October 14, 2020. An overall treatment effect was estimated using a meta-analysis performed on the pool of included studies based on the mean difference (MD). The revised Cochrane risk-of-bias tool was applied and the certainty of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: The final sample of papers included a total of 246, of which 168 had sufficient information to calculate the effect of HbA1c%. The results favored telemedicine, with an MD of −0.415% (95% confidence interval [CI] = −0.482% to −0.348%). The heterogeneity was great (I2 = 93.05%). A monitoring component gave rise to the higher effects of telemedicine. Conclusions: In conclusion, telemedicine may serve as a valuable supplement to usual care for patients with T2D. The inclusion of a telemonitoring component seems to increase the effect of telemedicine.

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Effects of Urtica dioica on Metabolic Profiles in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Clinical Trials

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210929143112 ◽

2021 ◽

Vol 21 ◽

Author(s):

Reza Tabrizi ◽

Eghbal Sekhavati ◽

Peyman Nowrouzi-Sohrabi ◽

Shahla Rezaei ◽

Parinaz Tabari ◽

...

Keyword(s):

Systematic Review ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Clinical Trials ◽

Meta Analysis ◽

Hdl Cholesterol ◽

Urtica Dioica ◽

Cochrane Library ◽

Metabolic Profiles

Background: Several studies have investigated the effect of Urtica dioica (UD) consumption on metabolic profiles in patients with type 2 diabetes mellitus (T2DM); however, the findings are inconsistent. This systematic review and meta-analysis of clinical trials was performed to summarize the evidence of the effects of UD consumption on metabolic profiles in patients with T2DM. Methods: Eligible studies were retrieved from searches of PubMed, Embase, Scopus, Web of Science, Cochrane Library and Google Scholar databases until December 2019. Cochran (Q) and I-square statistics were used to examine heterogeneity across included clinical trials. Data were pooled by using fixed-effect or random-effects model and expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Results: Among 1485 citations, thirteen clinical trials were found to be eligible for the current meta-analysis. UD consumption significantly decreased levels of fasting blood glucose (FBG) (WMD= -17.17 mg/dl, 95% CI: -26.60, -7.73, I2= 93.2%), hemoglobin A1c (HbA1c) (WMD= -0.93, 95% CI: -1.66, -0.17, I2= 75.0%), C-reactive protein (CRP) (WMD= -1.09 mg/dl, 95% CI: -1.64, -0.53, I2= 0.0%), triglycerides (WMD = -26.94 mg/dl, 95 % CI = [-52.07, -1.82], P = 0.03, I2 = 90.0%), systolic blood pressure (SBP) (WMD= -5.03 mmHg, 95% CI = -8.15, -1.91, I2= 0.0%) in comparison to the control groups. UD consumption did not significantly change serum levels of insulin (WMD= 1.07 μU/ml, 95% CI: -1.59, 3.73, I2= 63.5%), total-cholesterol (WMD= -6.39 mg/dl, 95% CI: -13.84, 1.05, I2= 0.0%), LDL-cholesterol (LDL-C) (WMD= -1.30 mg/dl, 95% CI: -9.95, 7.35, I2= 66.1%), HDL-cholesterol (HDL-C) (WMD= 6.95 mg/dl, 95% CI: -0.14, 14.03, I2= 95.4%), body max index (BMI) (WMD= -0.16 kg/m2, 95% CI: -1.77, 1.44, I2= 0.0%), and diastolic blood pressure (DBP) (WMD= -1.35 mmHg, 95% CI: -2.86, 0.17, I2= 0.0%) among patients with T2DM. Conclusion: UD consumption may result in an improvement in levels of FBS, HbA1c, CRP, triglycerides and SBP, but did not affect on levels of insulin, total-, LDL-, and HDL-cholesterol, BMI, and DBP in patients with T2DM.

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