TY - JOUR

T1 - Metabolomics in prediabetes and diabetes

T2 - A systematic review and meta-analysis

AU - Guasch-Ferré, Marta

AU - Hruby, Adela

AU - Toledo, Estefanía

AU - Clish, Clary B.

AU - Martínez-González, Miguel A.

AU - Salas-Salvadó, Jordi

AU - Hu, Frank B.

N1 - Publisher Copyright: © 2016 by the American Diabetes Association.

PY - 2016

Y1 - 2016

N2 - 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 multivariableadjusted 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]; I2 = 9.5%), 36% for leucine (1.36 [1.17-1.58]; I2 = 37.4%), 35% for valine (1.35 [1.19-1.53]; I2 = 45.8%), 36% for tyrosine (1.36 [1.19-1.55]; I2 = 51.6%), and 26% for phenylalanine (1.26 [1.10-1.44]; I2 = 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 I2 = 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.

AB - 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 multivariableadjusted 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]; I2 = 9.5%), 36% for leucine (1.36 [1.17-1.58]; I2 = 37.4%), 35% for valine (1.35 [1.19-1.53]; I2 = 45.8%), 36% for tyrosine (1.36 [1.19-1.55]; I2 = 51.6%), and 26% for phenylalanine (1.26 [1.10-1.44]; I2 = 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 I2 = 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.

U2 - 10.2337/dc15-2251

DO - 10.2337/dc15-2251

M3 - Review

C2 - 27208380

AN - SCOPUS:84964746576

VL - 39

SP - 833

EP - 846

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 5

ER -