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Diabetes Care Apr 2022Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.
PURPOSE
To conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes.
DATA SOURCES
We searched PubMed and Embase until 6 March 2021.
STUDY SELECTION
We selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes.
DATA EXTRACTION
Baseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies.
DATA SYNTHESIS
A total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate-corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07-2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69-0.90).
LIMITATIONS
Substantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites.
CONCLUSIONS
Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.
Topics: Amino Acids; Carbohydrates; Diabetes Mellitus, Type 2; Humans; Metabolomics; Observational Studies as Topic; Prospective Studies; Risk Factors
PubMed: 35349649
DOI: 10.2337/dc21-1705 -
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 -
International Journal of Molecular... Feb 2023Around 40-50% of all triple-negative breast cancer (TNBC) patients achieve a pathological complete response (pCR) after treatment with neoadjuvant chemotherapy (NAC).... (Review)
Review
Around 40-50% of all triple-negative breast cancer (TNBC) patients achieve a pathological complete response (pCR) after treatment with neoadjuvant chemotherapy (NAC). The identification of biomarkers predicting the response to NAC could be helpful for personalized treatment. This systematic review provides an overview of putative biomarkers at baseline that are predictive for a pCR following NAC. Embase, Medline and Web of Science were searched for articles published between January 2010 and August 2022. The articles had to meet the following criteria: patients with primary invasive TNBC without distant metastases and patients must have received NAC. In total, 2045 articles were screened by two reviewers resulting in the inclusion of 92 articles. Overall, the most frequently reported biomarkers associated with a pCR were a high expression of Ki-67, an expression of PD-L1 and the abundance of tumor-infiltrating lymphocytes, particularly CD8+ T cells, and corresponding immune gene signatures. In addition, our review reveals proteomic, genomic and transcriptomic markers that relate to cancer cells, the tumor microenvironment and the peripheral blood, which also affect chemo-sensitivity. We conclude that a prediction model based on a combination of tumor and immune markers is likely to better stratify TNBC patients with respect to NAC response.
Topics: Humans; Neoadjuvant Therapy; Triple Negative Breast Neoplasms; Proteomics; Lymphocytes, Tumor-Infiltrating; Biomarkers; Tumor Microenvironment
PubMed: 36769287
DOI: 10.3390/ijms24032969 -
Survey of Ophthalmology 2022The human tear film is at the interface between the ocular surface and the external environment. Although investigation has been hindered by its small volume,... (Review)
Review
The human tear film is at the interface between the ocular surface and the external environment. Although investigation has been hindered by its small volume, improvements in preanalytical and analytical methods have allowed the omics approach to represent an innovative biomarker search strategy. There is still a significant lack of standardization, representing a barrier for performing between-studies comparisons and transferring experimental findings into clinical use and trials. We summarize the preanalytical and analytical procedures, describe the biomarkers that can be found using the metabo-lipidomics approach, and provide our expert opinion for omics investigations in human tears. For this systematic review of 38 studies, we searched PubMed by combining Boolean operators with the following keywords: tear, metabolomic, lipidomic, -omics. The human tear metabo-lipidome has been well-characterized in normal individuals using high-resolution liquid chromatography coupled with mass spectrometry. Lipid and metabolite profiles were influenced by ocular (e.g., dry eye disorders; Meibomian gland dysfunction; contact lens wear; glaucoma; keratoconus; pterygium) and systemic conditions (e.g., multiple sclerosis). Investigating the tear metabo-lipidome could improve our understanding of the pathogenesis of both ocular and systemic diseases, but also provide diagnostic as well as prognostic biomarkers.
Topics: Biomarkers; Dry Eye Syndromes; Humans; Lipidomics; Meibomian Glands; Metabolomics; Tears
PubMed: 35093405
DOI: 10.1016/j.survophthal.2022.01.010 -
Sports Medicine (Auckland, N.Z.) Mar 2022Metabolomics is a field of omics science that involves the comprehensive measurement of small metabolites in biological samples. It is increasingly being used to study...
BACKGROUND
Metabolomics is a field of omics science that involves the comprehensive measurement of small metabolites in biological samples. It is increasingly being used to study exercise physiology and exercise-associated metabolism. However, the field of exercise metabolomics has not been extensively reviewed or assessed.
OBJECTIVE
This review on exercise metabolomics has three aims: (1) to provide an introduction to the general workflow and the different metabolomics technologies used to conduct exercise metabolomics studies; (2) to provide a systematic overview of published exercise metabolomics studies and their findings; and (3) to discuss future perspectives in the field of exercise metabolomics.
METHODS
We searched electronic databases including Google Scholar, Science Direct, PubMed, Scopus, Web of Science, and the SpringerLink academic journal database between January 1st 2000 and September 30th 2020.
RESULTS
Based on our detailed analysis of the field, exercise metabolomics studies fall into five major categories: (1) exercise nutrition metabolism; (2) exercise metabolism; (3) sport metabolism; (4) clinical exercise metabolism; and (5) metabolome comparisons. Exercise metabolism is the most popular category. The most common biological samples used in exercise metabolomics studies are blood and urine. Only a small minority of exercise metabolomics studies employ targeted or quantitative techniques, while most studies used untargeted metabolomics techniques. In addition, mass spectrometry was the most commonly used platform in exercise metabolomics studies, identified in approximately 54% of all published studies. Our data indicate that biomarkers or biomarker panels were identified in 34% of published exercise metabolomics studies.
CONCLUSION
Overall, there is an increasing trend towards better designed, more clinical, mass spectrometry-based metabolomics studies involving larger numbers of participants/patients and larger numbers of metabolites being identified.
Topics: Biomarkers; Exercise; Humans; Metabolome; Metabolomics; Sports
PubMed: 34716906
DOI: 10.1007/s40279-021-01582-y -
Journal of the American Academy of... Feb 2019Previous studies found conflicting results about the commonality of different atopic dermatitis (AD) signs and symptoms. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies found conflicting results about the commonality of different atopic dermatitis (AD) signs and symptoms.
OBJECTIVE
To determine the prevalences of AD characteristics and differences by region and age.
METHODS
A systematic review was performed of all published studies in MEDLINE, EMBASE, SCOPUS, LILACS, Cochrane, China National Knowledge Infrastructure, Taiwan Electronic Periodical Services, and CiNii that analyzed the proportion of AD characteristics. Two reviewers performed a review study titles and/or abstracts and data abstraction.
RESULTS
In all, 101 studies reported proportion of AD features with sufficient data for meta-analysis. The most prevalent AD features were pruritus, lichenification, and xerosis. There were differences in AD characteristics by study region. Flexural involvement was less commonly reported in India, the Americas, and Iran. Studies from East Asian reported more erythroderma and truncal, extensor, scalp, and auricular involvement. Studies from Southeast Asia reported more exudative eczema, truncal involvement, lichenification, and prurigo nodularis. Studies from Iran reported more head, face, and neck involvement; pityriasis alba; and xerosis. Studies from Africa reported more papular lichenoid lesions, palmar hyperlinearity, ichthyosis, and orbital darkening.
LIMITATIONS
Heterogeneity between studies and limited reporting of certain AD clinical characteristics.
CONCLUSIONS
AD characteristics are heterogeneous and vary by region and age.
Topics: Adolescent; Adult; Age of Onset; Biopsy, Needle; Child; Dermatitis, Atopic; Disease Progression; Female; Humans; Immunohistochemistry; Internationality; Male; Prevalence; Prognosis; Risk Assessment; Severity of Illness Index; Young Adult
PubMed: 30287309
DOI: 10.1016/j.jaad.2018.09.035 -
Journal of Neurochemistry Mar 2021Similar to dementia, the risk for developing type 2 diabetes mellitus (T2DM) increases with age, and T2DM also increases the risk for dementia, particularly Alzheimer's...
Similar to dementia, the risk for developing type 2 diabetes mellitus (T2DM) increases with age, and T2DM also increases the risk for dementia, particularly Alzheimer's disease (AD). Although T2DM is primarily a peripheral disorder and AD is a central nervous system disease, both share some common features as they are chronic and complex diseases, and both show involvement of oxidative stress and inflammation in their progression. These characteristics suggest that T2DM may be associated with AD, which gave rise to a new term, type 3 diabetes (T3DM). In this study, we searched for matching peripheral proteomic biomarkers of AD and T2DM based in a systematic review of the available literature. We identified 17 common biomarkers that were differentially expressed in both patients with AD or T2DM when compared with healthy controls. These biomarkers could provide a useful workflow for screening T2DM patients at risk to develop AD.
Topics: Alzheimer Disease; Animals; Biomarkers; Diabetes Mellitus, Type 2; Humans; Proteomics
PubMed: 32909269
DOI: 10.1111/jnc.15166 -
Journal of Neurology, Neurosurgery, and... Jul 2017Genetic studies have shown that , , and are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genetic studies have shown that , , and are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the mutation frequencies of these major ALS-related genes in patients with ALS.
METHODS
We performed an extensive literature research to identify all original articles reporting frequencies of , , and mutations in ALS. The mutation frequency and effect size of each study were combined. Possible sources of heterogeneity across studies were determined by meta-regression, sensitivity analysis and subgroup analysis.
RESULTS
111 studies were included in the meta-analysis. The overall pooled mutation frequencies of these major ALS-related genes were 47.7% in familial amyotrophic lateral sclerosis (FALS) and 5.2% in sporadic ALS (SALS). A significant difference was identified regarding the frequencies of mutations in major ALS genes between European and Asian patients. In European populations, the most common mutations were the repeat expansions (FALS 33.7%, SALS 5.1%), followed by (FALS 14.8%, SALS 1.2%), (FALS 4.2%, SALS 0.8%) and mutations (FALS 2.8%, SALS 0.3%), while in Asian populations the most common mutations were mutations (FALS 30.0%, SALS 1.5%), followed by (FALS 6.4%, SALS 0.9%), (FALS 2.3%, SALS 0.3%) and (FALS 1.5%, SALS 0.2%) mutations.
CONCLUSIONS
These findings demonstrated that the genetic architecture of ALS in Asian populations is distinct from that in European populations, which need to be given appropriate consideration when performing genetic testing of patients with ALS.
Topics: Amyotrophic Lateral Sclerosis; Asian People; DNA-Binding Proteins; Genetic Predisposition to Disease; Humans; Molecular Epidemiology; Mutation; White People
PubMed: 28057713
DOI: 10.1136/jnnp-2016-315018 -
Clinical Gastroenterology and... Apr 2015Little is known about differences in rates of fibrosis progression between patients with nonalcoholic fatty liver (NAFL) vs nonalcoholic steatohepatitis (NASH). We... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND & AIMS
Little is known about differences in rates of fibrosis progression between patients with nonalcoholic fatty liver (NAFL) vs nonalcoholic steatohepatitis (NASH). We conducted a systematic review and meta-analysis of all studies that assessed paired liver biopsy specimens to estimate the rates of fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD) including NAFL and NASH.
METHODS
Through a systematic search of multiple databases and author contact, up to June 2013, we identified studies of adults with NAFLD that collected paired liver biopsy specimens at least 1 year apart. From these, we calculated a pooled-weighted annual fibrosis progression rate (number of stages changed between the 2 biopsy samples) with 95% confidence intervals (CIs), and identified clinical risk factors associated with progression.
RESULTS
We identified 11 cohort studies including 411 patients with biopsy-proven NAFLD (150 with NAFL and 261 with NASH). At baseline, the distribution of fibrosis for stages 0, 1, 2, 3, and 4 was 35.8%, 32.5%, 16.7%, 9.3%, and 5.7%, respectively. Over 2145.5 person-years of follow-up evaluation, 33.6% had fibrosis progression, 43.1% had stable fibrosis, and 22.3% had an improvement in fibrosis stage. The annual fibrosis progression rate in patients with NAFL who had stage 0 fibrosis at baseline was 0.07 stages (95% CI, 0.02-0.11 stages), compared with 0.14 stages in patients with NASH (95% CI, 0.07-0.21 stages). These findings correspond to 1 stage of progression over 14.3 years for patients with NAFL (95% CI, 9.1-50.0 y) and 7.1 years for patients with NASH (95% CI, 4.8-14.3 y).
CONCLUSIONS
Based on a meta-analysis of studies of paired liver biopsy studies, liver fibrosis progresses in patients with NAFL and NASH.
Topics: Biopsy; Disease Progression; Histocytochemistry; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Risk Factors
PubMed: 24768810
DOI: 10.1016/j.cgh.2014.04.014 -
Annals of Internal Medicine Feb 2014Performance characteristics of fecal immunochemical tests (FITs) to screen for colorectal cancer (CRC) have been inconsistent. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Performance characteristics of fecal immunochemical tests (FITs) to screen for colorectal cancer (CRC) have been inconsistent.
PURPOSE
To synthesize data about the diagnostic accuracy of FITs for CRC and identify factors affecting its performance characteristics.
DATA SOURCES
Online databases, including MEDLINE and EMBASE, and bibliographies of included studies from 1996 to 2013.
STUDY SELECTION
All studies evaluating the diagnostic accuracy of FITs for CRC in asymptomatic, average-risk adults.
DATA EXTRACTION
Two reviewers independently extracted data and critiqued study quality.
DATA SYNTHESIS
Nineteen eligible studies were included and meta-analyzed. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FITs for CRC were 0.79 (95% CI, 0.69 to 0.86), 0.94 (CI, 0.92 to 0.95), 13.10 (CI, 10.49 to 16.35), 0.23 (CI, 0.15 to 0.33), respectively, with an overall diagnostic accuracy of 95% (CI, 93% to 97%). There was substantial heterogeneity between studies in both the pooled sensitivity and specificity estimates. Stratifying by cutoff value for a positive test result or removal of discontinued FIT brands resulted in homogeneous sensitivity estimates. Sensitivity for CRC improved with lower assay cutoff values for a positive test result (for example, 0.89 [CI, 0.80 to 0.95] at a cutoff value less than 20 µg/g vs. 0.70 [CI, 0.55 to 0.81] at cutoff values of 20 to 50 µg/g) but with a corresponding decrease in specificity. A single-sample FIT had similar sensitivity and specificity as several samples, independent of FIT brand.
LIMITATIONS
Only English-language articles were included. Lack of data prevented complete subgroup analyses by FIT brand.
CONCLUSION
Fecal immunochemical tests are moderately sensitive, are highly specific, and have high overall diagnostic accuracy for detecting CRC. Diagnostic performance of FITs depends on the cutoff value for a positive test result.
PRIMARY FUNDING SOURCE
National Institute of Diabetes and Digestive and Kidney Diseases and National Cancer Institute.
Topics: Adult; Colorectal Neoplasms; Early Detection of Cancer; Feces; Humans; Immunochemistry; Occult Blood; Sensitivity and Specificity
PubMed: 24658694
DOI: 10.7326/M13-1484