scholarly journals Metabolomics and Type 2 Diabetes: Translating Basic Research into Clinical Application

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Matthias S. Klein ◽  
Jane Shearer
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Aromatic Amino Acids ◽  
Predictive Biomarkers ◽  
Basic Research ◽  
New Approach ◽  
Branched Chain ◽  
Small Biomolecules ◽  
Overt Disease

Type 2 diabetes (T2D) and its comorbidities have reached epidemic proportions, with more than half a billion cases expected by 2030. Metabolomics is a fairly new approach for studying metabolic changes connected to disease development and progression and for finding predictive biomarkers to enable early interventions, which are most effective against T2D and its comorbidities. In metabolomics, the abundance of a comprehensive set of small biomolecules (metabolites) is measured, thus giving insight into disease-related metabolic alterations. This review shall give an overview of basic metabolomics methods and will highlight current metabolomics research successes in the prediction and diagnosis of T2D. We summarized key metabolites changing in response to T2D. Despite large variations in predictive biomarkers, many studies have replicated elevated plasma levels of branched-chain amino acids and their derivatives, aromatic amino acids andα-hydroxybutyrate ahead of T2D manifestation. In contrast, glycine levels and lysophosphatidylcholine C18:2 are depressed in both predictive studies and with overt disease. The use of metabolomics for predicting T2D comorbidities is gaining momentum, as are our approaches for translating basic metabolomics research into clinical applications. As a result, metabolomics has the potential to enable informed decision-making in the realm of personalized medicine.

scholarly journals Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

Diabetologia ◽  
2018 ◽  
Vol 61 (7) ◽  
pp. 1560-1571 ◽  
Author(s):  
Miguel Ruiz-Canela ◽  
Marta Guasch-Ferré ◽  
Estefanía Toledo ◽  
Clary B. Clish ◽  
Cristina Razquin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Cohort Study ◽  
Mediterranean Diet ◽  
Aromatic Amino Acids ◽  
Diabetes Case ◽  
Branched Chain

scholarly journals Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus

Metabolism ◽  
2013 ◽  
Vol 62 (12) ◽  
pp. 1772-1778 ◽  
Author(s):  
Geoffrey A. Walford ◽  
Jaclyn Davis ◽  
A. Sofia Warner ◽  
Rachel J. Ackerman ◽  
Liana K. Billings ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Type 2 Diabetes Mellitus ◽  
Aromatic Amino Acids ◽  
Medical Therapies ◽  
Branched Chain

Dietary branched-chain amino acids intake exhibited a different relationship with type 2 diabetes and obesity risk: a meta-analysis

2018 ◽  
Vol 56 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Akinkunmi Paul Okekunle ◽  
Meng Zhang ◽  
Zhen Wang ◽  
Justina Ucheojor Onwuka ◽  
Xiaoyan Wu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Meta Analysis ◽  
Branched Chain Amino Acids ◽  
Obesity Risk ◽  
Branched Chain ◽  
Diabetes And Obesity

scholarly journals A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaoyu Liao ◽  
Bingyao Liu ◽  
Hua Qu ◽  
LinLin Zhang ◽  
Yongling Lu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Aromatic Amino Acids ◽  
Gas Chromatography Mass Spectrometry ◽  
Glucose Levels ◽  
Increased Risk ◽  
Normal Glucose ◽  
Potential Strategy ◽  
High Level

Background. High levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were associated with an increased risk of hyperglycemia and the onset of diabetes. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patients and high-fat diet- (HFD-) fed mice treated with the hypoglycemic agent sitagliptin (Sit) and analyzing the association of valine concentrations with metabolic parameters. Methods. Metabolomics in HFD-fed mice were analyzed by gas chromatography-mass spectrometry (GC-MS) systems. Plasma valine concentrations were detected with a commercial kit in 53 subjects with normal glucose levels (n=19), newly diagnosed T2D (n=20), placebo-treated T2D (n=7), or Sit-treated T2D (n=7). Biochemical parameters were also assessed in all participants. Results. Sit treatment markedly changed the pattern of amino acid in HFD-fed mice, especially by reducing the level of the BCAA valine. Compared with the healthy controls, the plasma valine concentrations were significantly higher in the T2D patients (p<0.05). Correlation analysis showed that the plasma valine concentration was positively correlated with the level of fasting plasma glucose (p<0.05). Moreover, the plasma valine concentrations were notably reduced after Sit treatment in T2D patients (p<0.05). Conclusions. Our findings demonstrate an important effect of Sit on the BCAA valine in T2D patients and HFD-fed mice, revealing a new hypoglycemic mechanism of it. Furthermore, the results suggest that the circulating valine level might be a novel biomarker for T2D and restoring the level of valine might be a potential strategy for diabetes therapy.

scholarly journals Early metabolic features of genetic liability to type 2 diabetes: cohort study with repeated metabolomics across early life

2020 ◽  
Author(s):  
Joshua A. Bell ◽  
Caroline J. Bull ◽  
Marc J. Gunter ◽  
David Carslake ◽  
Anubha Mahajan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Early Life ◽  
Genome Wide Association Study ◽  
Genetic Risk Score ◽  
Lipoprotein Subclass ◽  
Adult Type ◽  
Genetic Liability ◽  
Branched Chain

<b>Objective:</b> Type 2 diabetes develops for many years before diagnosis. We aimed to reveal early metabolic features characterising liability to adult disease by examining genetic liability to adult type 2 diabetes in relation to metabolomic traits across early life. <p><b>Research Design and Methods:</b> <a>Up to 4,761 offspring from the Avon Longitudinal Study of Parents and Children</a> were studied. Linear models were used to examine effects of a genetic risk score (162 variants) for adult type 2 diabetes on 229 metabolomic traits (lipoprotein-subclass-specific cholesterol and triglycerides, amino acids, glycoprotein acetyls, others) measured at age 8y, 16y, 18y, and 25y. Two-sample Mendelian randomization (MR) was also conducted using genome-wide association study data on metabolomic traits in an independent sample of 24,925 adults. </p> <p><b>Results:</b> At age 8y, associations were most evident for type 2 diabetes liability (per SD-higher) with lower lipids in high-density lipoprotein (HDL) subtypes, e.g. -0.03 SD (95% CI=-0.06, -0.003) for total lipids in very-large HDL. At 16y, associations were stronger with pre-glycemic traits including citrate and with glycoprotein acetyls (0.05 SD, 95% CI=0.01, 0.08), and at 18y, associations were stronger with branched chain amino acids. At 25y, associations had strengthened with VLDL lipids and remained consistent with previously altered traits including HDL lipids. Two-sample MR estimates among adults indicated persistent patterns of effect of disease liability. </p> <p><b>Conclusions:</b> Our results support perturbed HDL lipid metabolism as one of the earliest features of <a>type 2 diabetes liability, alongside higher branched chain amino acid and inflammatory levels. Several features are apparent in childhood as early as age 8y, decades before the clinical onset of disease. </a></p>

scholarly journals Dietary Intakes and Circulating Concentrations of Branched-Chain Amino Acids in Relation to Incident Type 2 Diabetes Risk Among High-Risk Women with a History of Gestational Diabetes Mellitus

2018 ◽  
Vol 64 (8) ◽  
pp. 1203-1210 ◽  
Author(s):  
Deirdre K Tobias ◽  
Clary Clish ◽  
Samia Mora ◽  
Jun Li ◽  
Liming Liang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Gestational Diabetes ◽  
Plasma Concentrations ◽  
Branched Chain Amino Acids ◽  
High Risk Women ◽  
History Of ◽  
Branched Chain

Abstract BACKGROUND Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, valine) are consistently associated with increased type 2 diabetes (T2D) risk, but the relationship with dietary intake of BCAAs is less clear. METHODS The longitudinal Nurses' Health Study II cohort conducted a blood collection from 1996 to 1999. We profiled plasma metabolites among 172 incident T2D cases and 175 age-matched controls from women reporting a history of gestational diabetes before blood draw. We estimated dietary energy-adjusted BCAAs from food frequency questionnaires. We used conditional logistic regression models to estimate odds ratios (OR) and 95% CI of T2D risk across quartiles (Q1–Q4) of BCAAs, adjusting for age, body mass index (BMI), physical activity, family history, and other established risk factors. We also assessed joint exposure to below/above medians of diet and plasma concentrations, with lower diet/lower plasma as reference. RESULTS Dietary and plasma BCAA concentrations were positively associated with incident T2D (diet Q4 vs Q1 OR = 4.6, CI = 1.6, 13.4; plasma Q4 vs Q1 OR = 4.4, CI = 1.4, 13.4). Modeling the joint association indicated that higher diet BCAAs were associated with T2D when plasma concentrations were also higher (OR = 6.0, CI = 2.1, 17.2) but not when concentrations were lower (OR = 1.6, CI = 0.61, 4.1). Conversely, higher plasma BCAAs were associated with increased T2D for either lower or higher diet. CONCLUSIONS Independent of BMI and other risk factors, higher diet and plasma BCAA concentrations were associated with an increased incident T2D risk among high-risk women with a history of gestational diabetes, supporting impaired BCAA metabolism as conferring T2D risk.

scholarly journals Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes

2021 ◽  
Vol 22 (23) ◽  
pp. 12846
Author(s):  
Lixiang Zhai ◽  
Jiayan Wu ◽  
Yan Y. Lam ◽  
Hiu Yee Kwan ◽  
Zhao-xiang Bian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Gut Microbiota ◽  
Aromatic Amino Acids ◽  
Microbial Metabolites ◽  
High Blood Glucose ◽  
Gaseous Products ◽  
Glucose Levels ◽  
Novel Therapeutic Strategies

Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota.

scholarly journals Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study

2018 ◽  
Vol 7 (12) ◽  
pp. 513 ◽  
Author(s):  
Jose Flores-Guerrero ◽  
Maryse Osté ◽  
Lyanne Kieneker ◽  
Eke Gruppen ◽  
Justyna Wolak-Dinsmore ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Cell Function ◽  
Cox Regression ◽  
Branched Chain Amino Acids ◽  
Resonance Spectroscopy ◽  
Net Reclassification Improvement ◽  
Increased Risk ◽  
Branched Chain

Plasma branched-chain amino acids (BCAAs) are linked to metabolic disease, but their relevance for prediction of type 2 diabetes development is unclear. We determined the association of plasma BCAAs with type 2 diabetes risk in the prevention of renal and vascular end-stage disease (PREVEND) cohort. The BCAAs were measured by means of nuclear magnetic resonance spectroscopy. We evaluated the prospective associations of BCAAs with type 2 diabetes in 6244 subjects. The BCAAs were positively associated with HOMA-IR after multivariable adjustment (p < 0.0001). During median follow-up for 7.5 years, 301 cases of type 2 diabetes were ascertained. The Kaplan-Meier plot demonstrated that patients in the highest BCAA quartile presented a higher risk (p log-rank < 0.001). Cox regression analyses revealed a positive association between BCAA and type 2 diabetes; the hazard ratio (HR) for the highest quartile was 6.15 (95% CI: 4.08, 9.24, p < 0.0001). After adjustment for multiple clinical and laboratory variables, the association remained (HR 2.80 (95% CI: 1.72, 4.53), p < 0.0001). C-statistics, Net reclassification improvement, and −2 log likelihood were better after adding BCAAs to the traditional risk model (p = 0.01 to <0.001). In conclusions, high concentrations of BCAAs associate with insulin resistance and with increased risk of type 2 diabetes. This association is independent of multiple risk factors, HOMA-IR and β cell function.

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