Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis.
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Abstract | 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. |
Year of Publication | 2016
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Journal | Diabetes Care
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Volume | 39
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Issue | 5
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Pages | 833-46
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Date Published | 2016 May
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ISSN | 1935-5548
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URL | |
DOI | 10.2337/dc15-2251
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PubMed ID | 27208380
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PubMed Central ID | PMC4839172
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Links | |
Grant list | P30 DK046200 / DK / NIDDK NIH HHS / United States
R01 DK102896 / DK / NIDDK NIH HHS / United States
R01 HL060712 / HL / NHLBI NIH HHS / United States
R01 HL118264 / HL / NHLBI NIH HHS / United States
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