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Diabetes Care May 2016To conduct a systematic review of cross-sectional and prospective human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a systematic review of cross-sectional and prospective human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on prediabetes and type 2 diabetes.
RESEARCH DESIGN AND METHODS
We searched MEDLINE and EMBASE databases through August 2015. We conducted a qualitative review of cross-sectional and prospective studies. Additionally, meta-analyses of metabolite markers, with data estimates from at least three prospective studies, and type 2 diabetes risk were conducted, and multivariable-adjusted relative risks of type 2 diabetes were calculated per study-specific SD difference in a given metabolite.
RESULTS
We identified 27 cross-sectional and 19 prospective publications reporting associations of metabolites and prediabetes and/or type 2 diabetes. Carbohydrate (glucose and fructose), lipid (phospholipids, sphingomyelins, and triglycerides), and amino acid (branched-chain amino acids, aromatic amino acids, glycine, and glutamine) metabolites were higher in individuals with type 2 diabetes compared with control subjects. Prospective studies provided evidence that blood concentrations of several metabolites, including hexoses, branched-chain amino acids, aromatic amino acids, phospholipids, and triglycerides, were associated with the incidence of prediabetes and type 2 diabetes. We meta-analyzed results from eight prospective studies that reported risk estimates for metabolites and type 2 diabetes, including 8,000 individuals of whom 1,940 had type 2 diabetes. We found 36% higher risk of type 2 diabetes per study-specific SD difference for isoleucine (pooled relative risk 1.36 [1.24-1.48]; I(2) = 9.5%), 36% for leucine (1.36 [1.17-1.58]; I(2) = 37.4%), 35% for valine (1.35 [1.19-1.53]; I(2) = 45.8%), 36% for tyrosine (1.36 [1.19-1.55]; I(2) = 51.6%), and 26% for phenylalanine (1.26 [1.10-1.44]; I(2) = 56%). Glycine and glutamine were inversely associated with type 2 diabetes risk (0.89 [0.81-0.96] and 0.85 [0.82-0.89], respectively; both I(2) = 0.0%).
CONCLUSIONS
In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.
Topics: Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Incidence; Metabolomics; Middle Aged; Prediabetic State; Prospective Studies
PubMed: 27208380
DOI: 10.2337/dc15-2251 -
Diabetes, Metabolic Syndrome and... 2021The clinical manifestations of overweight/obesity are heterogeneous and complex. In contrast to metabolically unhealthy overweight/obese (MUO), a particular sub-group of... (Review)
Review
The clinical manifestations of overweight/obesity are heterogeneous and complex. In contrast to metabolically unhealthy overweight/obese (MUO), a particular sub-group of obese patients who are considered as metabolically healthy overweight/obese (MHO), display favorable metabolic profiles characterized by high levels of insulin sensitivity, normal blood pressure, as well as favorable lipid, inflammation, hormone, liver enzyme, and immune profiles. While only a few available studies focused on the metabolic files underlying the obese phenotypes, the current review aimed to perform a systematic review of available studies focusing on describing the metabolomic signature between MUO and MHO. We did the systematic search for literature on MEDLINE (PubMed), the Cochrane Library, EMBASE, and searched for the references of relevant manuscripts from inception to 29 May 2020. After critical selection, 20 studies were eligible for this systematic review and evaluated by using QUADOMICS for quality assessment. Eventually, 12 of 20 studies were classified as "high quality". Branched-chain amino acids (isoleucine, leucine, and valine), aromatic amino acids (phenylalanine and tyrosine), lipids (palmitic acid, palmitoleic acid, oleic acid, eicosapentaenoic acid, and docosahexaenoic acid), and acylcarnitines (propionyl carnitine) levels might be elevated in MUO. The current results suggested that MHO showed a favorable trend in the overall metabolic signature. More longitudinal studies are needed to elaborate deeply on the metabolic pathway and the relationship between metabolic patterns and the occurrence of the disease.
PubMed: 33692630
DOI: 10.2147/DMSO.S294894 -
Metabolites Sep 2022Fetal growth restriction (FGR) is a common complication of pregnancy and a significant cause of neonatal morbidity and mortality. The adverse effects of FGR can last... (Review)
Review
Fetal growth restriction (FGR) is a common complication of pregnancy and a significant cause of neonatal morbidity and mortality. The adverse effects of FGR can last throughout the entire lifespan and increase the risks of various diseases in adulthood. However, the etiology and pathogenesis of FGR remain unclear. This study comprehensively reviewed metabolomics studies related with FGR in pregnancy to identify potential metabolic biomarkers and pathways. Relevant articles were searched through two online databases (PubMed and Web of Science) from January 2000 to July 2022. The reported metabolites were systematically compared. Pathway analysis was conducted through the online MetaboAnalyst 5.0 software. For humans, a total of 10 neonatal and 14 maternal studies were included in this review. Several amino acids, such as alanine, valine, and isoleucine, were high frequency metabolites in both neonatal and maternal studies. Meanwhile, several pathways were suggested to be involved in the development of FGR, such as arginine biosynthesis, arginine, and proline metabolism, glyoxylate and dicarboxylate metabolism, and alanine, aspartate, and glutamate metabolism. In addition, we also included 8 animal model studies, in which three frequently reported metabolites (glutamine, phenylalanine, and proline) were also present in human studies. In general, this study summarized several metabolites and metabolic pathways which may help us to better understand the underlying metabolic mechanisms of FGR.
PubMed: 36144264
DOI: 10.3390/metabo12090860 -
Frontiers in Endocrinology 2021Dysregulation of amino acids is closely linked to the initiation and progression of sarcopenia. We summarized recent advancements in the studies of amino acid profiles... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dysregulation of amino acids is closely linked to the initiation and progression of sarcopenia. We summarized recent advancements in the studies of amino acid profiles in sarcopenia and systematically presented the clinical significance of amino acid flux in sarcopenia.
METHODS
We systematically searched in MEDLINE, EMBASE, and Cochrane library from inception to June 1, 2021 to capture all studies examining metabolomics of sarcopenia. We used the following keywords: sarcopenia, metabonomics, metabolomics, amino acid profile, and mass spectrometry. Original articles comparing amino acid patterns between persons with and without sarcopenia were included. Two independent investigators independently completed title and abstract screening, data extraction, and quality evaluation. We used a random effects model to examine the association between amino acids levels and sarcopenia. Sensitivity analyses restricted the analyses to studies in which muscle mass was measured by bioelectrical impedance analysis. Study quality was evaluated according to the Agency for Healthcare Research and Quality (AHRQ) checklist.
RESULTS
The systematic research yielded six eligible articles, comprising 1,120 participants. Five studies used muscle mass in combination with physical performance and/or muscle strength as the criteria to diagnose sarcopenia, while one study used muscle mass as a diagnostic criterion alone. We found that the concentrations of branched-chain amino acids leucine (standardized mean difference [SMD] -1.249; 95% confidence interval [CI]: -2.275, -0.223, = 0.02, I = 97.7%), isoleucine (SMD -1.077; 95% CI: -2.106, -0.049, = 0.04, I = 97.8%), and aromatic amino acid tryptophan (SMD -0.923; 95% CI: -1.580, -0.265, = 0.01, I = 89.9%) were significantly reduced in individuals with sarcopenia. Study results were robust in sensitivity analysis.
CONCLUSIONS
The homeostasis of amino acids is critical to maintaining muscle health. The profiles of amino acids might be useful biomarkers for the characterization of sarcopenia. Future studies are warranted to study the clinical significance of amino acids in the diagnosis and treatment of sarcopenia.
Topics: Amino Acids; Humans; Metabolome; Muscle, Skeletal; Sarcopenia
PubMed: 34589057
DOI: 10.3389/fendo.2021.725518 -
BMC Endocrine Disorders Nov 2020We aimed to explore metabolite biomarkers that could be used to identify pre-diabetes and type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to explore metabolite biomarkers that could be used to identify pre-diabetes and type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis.
METHODS
Four databases, the Cochrane Library, EMBASE, PubMed and Scopus were selected. A random effect model and a fixed effect model were applied to the results of forest plot analyses to determine the standardized mean difference (SMD) and 95% confidence interval (95% CI) for each metabolite. The SMD for every metabolite was then converted into an odds ratio to create an metabolite biomarker profile.
RESULTS
Twenty-four independent studies reported data from 14,131 healthy individuals and 3499 patients with T2DM, and 14 included studies reported 4844 healthy controls and a total of 2139 pre-diabetes patients. In the serum and plasma of patients with T2DM, compared with the healthy participants, the concentrations of valine, leucine, isoleucine, proline, tyrosine, lysine and glutamate were higher and that of glycine was lower. The concentrations of isoleucine, alanine, proline, glutamate, palmitic acid, 2-aminoadipic acid and lysine were higher and those of glycine, serine, and citrulline were lower in prediabetic patients. Metabolite biomarkers of T2DM and pre-diabetes revealed that the levels of alanine, glutamate and palmitic acid (C16:0) were significantly different in T2DM and pre-diabetes.
CONCLUSIONS
Quantified multiple metabolite biomarkers may reflect the different status of pre-diabetes and T2DM, and could provide an important reference for clinical diagnosis and treatment of pre-diabetes and T2DM.
Topics: Biomarkers; Diabetes Mellitus, Type 2; Humans; Metabolome; Prediabetic State; Prognosis
PubMed: 33228610
DOI: 10.1186/s12902-020-00653-x -
Nutrients Oct 2022Introduction: Recent studies have concluded that elevated circulating branched chain amino acids (BCAA) are associated with the pathogenesis of type 2 diabetes mellitus... (Meta-Analysis)
Meta-Analysis Review
Introduction: Recent studies have concluded that elevated circulating branched chain amino acids (BCAA) are associated with the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. However, the development of this association over time and the quantification of the strength of this association for individual BCAAs prior to T2DM diagnosis remains unexplored. Methods: A systematic search was conducted using the Healthcare Databases Advance Search (HDAS) via the National Institute for Health and Care Excellence (NICE) website. The data sources included EMBASE, MEDLINE and PubMed for all papers from inception until November 2021. Nine studies were identified in this systematic review and meta-analysis. Stratification was based on follow-up times (0−6, 6−12 and 12 or more years) and controlling of body mass index (BMI) through the specific assessment of overweight cohorts was also undertaken. Results: The meta-analysis revealed a statistically significant positive association between BCAA concentrations and the development of T2DM, with valine OR = 2.08 (95% CI = 2.04−2.12, p < 0.00001), leucine OR = 2.25 (95% CI = 1.76−2.87, p < 0.00001) and isoleucine OR = 2.12, 95% CI = 2.00−2.25, p < 0.00001. In addition, we demonstrated a positive consistent temporal association between circulating BCAA levels and the risk of developing T2DM with differentials in the respective follow-up times of 0−6 years, 6−12 years and ≥12 years follow-up for valine (OR = 2.08, 1.86 and 2.14, p < 0.05 each), leucine (OR = 2.10, 2.25 and 2.16, p < 0.05 each) and isoleucine (OR = 2.12, 1.90 and 2.16, p < 0.05 each) demonstrated. Conclusion: Plasma BCAA concentrations are associated with T2DM incidence across all temporal subgroups. We suggest the potential utility of BCAAs as an early biomarker for T2DM irrespective of follow-up time.
Topics: Humans; Amino Acids, Branched-Chain; Diabetes Mellitus, Type 2; Isoleucine; Leucine; Biomarkers; Valine
PubMed: 36297095
DOI: 10.3390/nu14204411 -
PloS One 2015The lactotripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to decrease systolic blood pressure (SBP) in several populations,... (Meta-Analysis)
Meta-Analysis Review
Influence of the Lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline on Systolic Blood Pressure in Japanese Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
The lactotripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to decrease systolic blood pressure (SBP) in several populations, but the size of the effect varies among studies. We performed a meta-analysis including all published studies to evaluate the SBP-lowering effect of IPP/VPP in Japanese subjects more comprehensively.
METHODS AND FINDINGS
Eligible randomized controlled trials were searched for within four bibliographic databases, including two Japanese ones. Eighteen studies (including a total of 1194 subjects) were included in the meta-analysis. A random effect model using the restricted maximum likelihood (REML) estimator was used for the analysis. The analysis showed that consumption of IPP/VPP induced a significant reduction in SBP as compared with placebo in Japanese subjects, with an estimated effect of -5.63 mm Hg (95% CI, -6.87 to -4.39, P<0.0001) and no evidence of publication bias. A significant heterogeneity between series was evident, which could be explained by a significant influence of the baseline blood pressure status of the subjects, the effect of IPP/VPP on SBP being stronger in hypertensive subjects (-8.35 mm Hg, P<0.0001) than in non-hypertensive subjects (-3.42mm Hg, P<0.0001). Furthermore, the effect of IPP/VPP on SBP remained significant when limiting the analysis to series that tested the usual doses of IPP/VPP consumed daily (below 5 mg/d), with estimated effects of -6.01 mm Hg in the overall population and -3.32 mm Hg in non-hypertensive subjects.
CONCLUSIONS
Results from this meta-analysis show that IPP/VPP lactotripeptides can significantly reduce office SBP in Japanese subjects with or without overt hypertension, and for doses that can potentially be consumed as an everyday supplement. This suggests that these peptides could play a role in controlling blood pressure in Japanese subjects. The systematic review protocol was published on the PROSPERO register (CRD42014014322).
Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Humans; Hypertension; Japan; Middle Aged; Oligopeptides; Randomized Controlled Trials as Topic
PubMed: 26536628
DOI: 10.1371/journal.pone.0142235 -
Nutrients Sep 2017Amino acids and more precisely, branched-chain amino acids (BCAAs), are usually consumed as nutritional supplements by many athletes and people involved in regular and... (Review)
Review
Amino acids and more precisely, branched-chain amino acids (BCAAs), are usually consumed as nutritional supplements by many athletes and people involved in regular and moderate physical activities regardless of their practice level. BCAAs have been initially shown to increase muscle mass and have also been implicated in the limitation of structural and metabolic alterations associated with exercise damage. This systematic review provides a comprehensive analysis of the literature regarding the beneficial effects of BCAAs supplementation within the context of exercise-induced muscle damage or muscle injury. The potential benefit of a BCAAs supplementation was also analyzed according to the supplementation strategy-amount of BCAAs, frequency and duration of the supplementation-and the extent of muscle damage. The review protocol was registered prospectively with Prospective Register for Systematic Reviews (registration number CRD42017073006) and followed Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Literature search was performed from the date of commencement until August 2017 using four online databases (Medline, Cochrane library, Web of science and ScienceDirect). Original research articles: (i) written in English; (ii) describing experiments performed in Humans who received at least one oral BCAAs supplementation composed of leucine, isoleucine and valine mixture only as a nutritional strategy and (iii) reporting a follow-up of at least one day after exercise-induced muscle damage, were included in the systematic review analysis. Quality assessment was undertaken independently using the Quality Criteria Checklist for Primary Research. Changes in indirect markers of muscle damage were considered as primary outcome measures. Secondary outcome measures were the extent of change in indirect markers of muscle damage. In total, 11 studies were included in the analysis. A high heterogeneity was found regarding the different outcomes of these studies. The risk of bias was moderate considering the quality ratings were positive for six and neutral for three. Although a small number of studies were included, BCAAs supplementation can be efficacious on outcomes of exercise-induced muscle damage, as long as the extent of muscle damage was low-to-moderate, the supplementation strategy combined a high daily BCAAs intake (>200 mg kg day) for a long period of time (>10 days); it was especially effective if taken prior to the damaging exercise.
Topics: Adult; Amino Acids, Branched-Chain; Animals; Dietary Supplements; Exercise; Female; Humans; Male; Muscle, Skeletal; Muscular Diseases; Treatment Outcome; Young Adult
PubMed: 28934166
DOI: 10.3390/nu9101047 -
Journal of Diabetes Research 2016Recent studies have shown the positive association between increased circulating BCAAs (valine, leucine, and isoleucine) and insulin resistance (IR) in obese or diabetic... (Review)
Review
Recent studies have shown the positive association between increased circulating BCAAs (valine, leucine, and isoleucine) and insulin resistance (IR) in obese or diabetic patients. However, results seem to be controversial in different races, diets, and distinct tissues. Our aims were to evaluate the relationship between BCAA and IR as well as later diabetes risk and explore the phenotypic and genetic factors influencing BCAA level based on available studies. We performed systematic review, searching MEDLINE, EMASE, ClinicalTrials.gov, the Cochrane Library, and Web of Science from inception to March 2016. After selection, 23 studies including 20,091 participants were included. Based on current evidence, we found that BCAA is a useful biomarker for early detection of IR and later diabetic risk. Factors influencing BCAA level can be divided into four parts: race, gender, dietary patterns, and gene variants. These factors might not only contribute to the elevated BCAA level but also show obvious associations with insulin resistance. Genes related to BCAA catabolism might serve as potential targets for the treatment of IR associated metabolic disorders. Moreover, these factors should be controlled properly during study design and data analysis. In the future, more large-scale studies with elaborate design addressing BCAA and IR are required.
Topics: 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); Adaptor Proteins, Signal Transducing; Amino Acids, Branched-Chain; Diabetes Mellitus; Diet; Genotype; Humans; Insulin Resistance; Metabolome; Minor Histocompatibility Antigens; Obesity; Phenotype; Pregnancy Proteins; Protein Phosphatase 2C; Racial Groups; Sex Factors; Transaminases; Weight Loss
PubMed: 27642608
DOI: 10.1155/2016/2794591 -
The American Journal of Gastroenterology Jun 2015The genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is shown to be associated with alcoholic liver disease (ALD). We performed a systematic review and meta-analysis to examine association of this genetic polymorphism with ALD spectrum and its severity.
METHODS
Medline, Embase, and Cochrane Library were searched for studies on association of PNPLA3 polymorphism and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was assessed using the I(2) statistics and publication bias using Egger's test and Begg and Mazumdar's test. Individual participant data obtained from five studies were used for subgroup analyses.
RESULTS
Among 10 studies included in this pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant data analysis showed age to predispose to AC among ALI patients.
CONCLUSIONS
PNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics. PNPLA3 gene may potentially be a therapeutic target in ALD.
Topics: Carcinoma, Hepatocellular; Central Nervous System Depressants; Chemical and Drug Induced Liver Injury; Ethanol; Fatty Liver, Alcoholic; Genetic Predisposition to Disease; Humans; Lipase; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Liver Neoplasms; Membrane Proteins; Polymorphism, Single Nucleotide; Severity of Illness Index
PubMed: 25964223
DOI: 10.1038/ajg.2015.137