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

Walford, Geoffrey; Davis, Jaclyn; Warner, Ana Sofia; Ackerman, Rachel; Billings, Liana K.; Chamarthi, Bindu; Fanelli, Rebecca R.; Hernández, Alicia; Huang, Chengdong; Khan, Sabina; Littleton, Katherine R.; Lo, Janet; McCarthy, Rita; Rhee, Eugene P.; Deik, Amy; Stolerman, Elliot; Taylor, Andrew M.; Hudson, Margo; Wang, Thomas J.; Altshuler, David; Grant, Richard W.; Clish, Clary B.; Gerszten, Robert E.; Florez, José C.

doi:10.1016/j.metabol.2013.07.003

Cited by 66 publications

(62 citation statements)

References 15 publications

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“…For each diet, we examined the direction of change in the concentrations of the metabolites that have been shown to predict the risk of type 2 diabetes (31,32,(38)(39)(40)(41)(42). We annotated each metabolite by whether the change by diet was in the direction that increased or decreased risk of disease.…”

Section: Disease Riskmentioning

confidence: 99%

“…Multiple metabolites that have been linked to risk of type 2 diabetes (31,32,(38)(39)(40)(41)(42) showed strong or moderate associations with diet, including amino acids (isoleucine, leucine, valine, tyrosine, serine and glutamine), lipids (C18:2 lysophosphatidylethanolamine (LPE), C22:6 LPE, C56:9 TAG, C58:10 TAG, and C60:12 TAG), and others (2-aminoadipate, betaine, and C3 carnitine) as depicted in Supplemental Figures 5 and 6. The concordance between the metabolite profile that predicts type 2 diabetes risk and the dietassociated changes varied across classes of metabolites.…”

Section: Effect Of Diet On Metabolites That Predict Disease Riskmentioning

confidence: 99%

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Metabolomic profiles as reliable biomarkers of dietary composition

Esko¹,

Hirschhorn

Feldman

et al. 2017

The American Journal of Clinical Nutrition

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Background: Clinical nutrition research often lacks robust markers of compliance, complicating the interpretation of clinical trials and observational studies of free-living subjects. Objective: We aimed to examine metabolomics profiles in response to 3 diets that differed widely in macronutrient composition during a controlled feeding protocol. Design: Twenty-one adults with a high body mass index (in kg/m 2 ; mean 6 SD: 34.4 6 4.9) were given hypocaloric diets to promote weight loss corresponding to 10-15% of initial body weight. They were then studied during weight stability while consuming 3 test diets, each for a 4-wk period according to a crossover design: low fat (60% carbohydrate, 20% fat, 20% protein), low glycemic index (40% carbohydrate, 40% fat, 20% protein), or very-low carbohydrate (10% carbohydrate, 60% fat, 30% protein). Plasma samples were obtained at baseline and at the end of each 4-wk period in the fasting state for metabolomics analysis by using liquid chromatography-tandem mass spectrometry. Statistical analyses included adjustment for multiple comparisons. Results: Of 333 metabolites, we identified 152 whose concentrations differed for $1 diet compared with the others, including diacylglycerols and triacylglycerols, branched-chain amino acids, and markers reflecting metabolic status. Analysis of groups of related metabolites, with the use of either principal components or pathways, revealed coordinated metabolic changes affected by dietary composition, including pathways related to amino acid metabolism. We constructed a classifier using the metabolites that differed between diets and were able to correctly identify the test diet from metabolite profiles in 60 of 63 cases (.95% accuracy). Analyses also suggest differential effects by diet on numerous cardiometabolic disease risk factors. Conclusions: Metabolomic profiling may be used to assess compliance during clinical nutrition trials and the validity of dietary assessment in observational studies. In addition, this methodology may help elucidate mechanistic pathways linking diet to chronic disease risk. This trial was registered at clinicaltrials.gov as NCT00315354.Am J Clin Nutr 2017;105:547-54.

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Section: Disease Riskmentioning

confidence: 99%

Section: Effect Of Diet On Metabolites That Predict Disease Riskmentioning

confidence: 99%

Metabolomic profiles as reliable biomarkers of dietary composition

Esko¹,

Hirschhorn

Feldman

et al. 2017

The American Journal of Clinical Nutrition

View full text Add to dashboard Cite

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“…Clinical intervention studies have also reported that decreased BCAA concentrations following an intervention (e.g. gastric bypass surgery or medical therapy) correlated with improvements in glucose homeostasis [41,42].…”

Section: Discussionmentioning

confidence: 99%

Lactation is associated with altered metabolomic signatures in women with gestational diabetes

et al. 2016

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Aims/hypothesis Lactation for >3 months in women with gestational diabetes is associated with a reduced risk of type 2 diabetes that persists for up to 15 years postpartum. However, the underlying mechanisms are unknown. We examined whether in women with gestational diabetes lactation for >3 months is associated with altered metabolomic signatures postpartum. Methods We enrolled 197 women with gestational diabetes at a median of 3.6 years (interquartile range 0.7-6.5 years) after delivery. Targeted metabolomics profiles (including 156 metabolites) were obtained during a glucose challenge test. Comparisons of metabolite concentrations and ratios between women who lactated for >3 months and women who lactated for ≤3 months or not at all were performed using linear regression with adjustment for age and BMI at the postpartum visit, time since delivery, and maternal education level, and correction for multiple testing. Gaussian graphical modelling was used to generate metabolite networks.Results Lactation for >3 months was associated with a higher total lysophosphatidylcholine/total phosphatidylcholine ratio; in women with short-term follow-up, it was also associated with lower leucine concentrations and a lower total branchedchain amino acid concentration. Gaussian graphical modelling identified subgroups of closely linked metabolites within phosphatidylcholines and branched-chain amino acids that were affected by lactation for >3 months and have been linked to the pathophysiology of type 2 diabetes in previous studies. Conclusions/interpretation Lactation for >3 months in women with gestational diabetes is associated with changes in the metabolomics profile that have been linked to the early pathogenesis of type 2 diabetes.

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“…A study by Walford et al [14] involved administering either metformin, glipizide or glucose challenge to type 2 diabetes patients. In patients who were insulin sensitive, branched chain amino acids and aromatic amino acids decreased in response to release of insulin, as happened when they were given either glipizide or glucose challenge.…”

Section: Anti-diabeticsmentioning

confidence: 99%

Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases

2014

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To refer to metabolomics as a new field is injustice to ancient doctors who used ants to diagnose the patients of diabetes having glycosuria. Measuring the levels of molecules in biological fluids believing them to be the representatives of biochemical pathways of carbohydrates, fats, proteins, nucleic acids or xenobiotic metabolism and deciphering meaningful data from it is what can be called as metabolomics, just as high glucose in urine suggests diabetes mellitus. Genomics, epigenetics, proteomics, transcriptomics finally converge to metabolomics, which are the signatures of mechanisms of bodily processes which is why understanding this science can have many applications. Just as a heap of stones does not make a house, having data of metabolite levels does not make it a science. Analyzing this data would help us in constructing biochemical pathways and their interactions. Analyzing the changes caused by a drug in the metabolite levels would help us in deriving the mechanisms by which the drug acts. Comparing metabolite levels in diseased with non-diseased, good-responders with poor-responders to a particular drug can help in identifying new markers of a disease or response to a drug respectively. Also, metabolite levels of an endogenous substrate can tell us the status of a person's metabolizing enzymes and help in drug dose titration. Generating hypothesis by identifying the new molecular markers and testing their utility in clinics seems to be the most promising approach in future. This review narrates the modes of quantifying and identifying metabolome, its proposed applications in diagnosis, monitoring and understanding the diseases and drug responses. We also intend to identify hindrances in using metabolomics in clinical studies or experiments.

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

Cited by 66 publications

References 15 publications

Metabolomic profiles as reliable biomarkers of dietary composition

Metabolomic profiles as reliable biomarkers of dietary composition

Lactation is associated with altered metabolomic signatures in women with gestational diabetes

Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases

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