Metabolite profiles and the risk of developing diabetes

Wang, Thomas J.; Larson, Martin G.; Vasan, Ramachandran S.; Cheng, Susan; Rhee, Eugene P.; McCabe, Elizabeth L.; Lewis, Gregory D.; Fox, Caroline S.; Jacques, Paul F.; Fernandez, Céline; O’Donnell, Christopher J.; Carr, Stephen A.; Mootha, Vamsi K.; Florez, José C.; Souza, Amanda; Melander, Olle; Clish, Clary B.; Gerszten, Robert E.

doi:10.1038/nm.2307

Cited by 2,712 publications

(2,362 citation statements)

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“…21 More specifically, metabolomics is a global and noninvasive analysis of biomarkers that are indicators of normal biological or pathogenic process, or response to therapeutic intervention, thereby helping to monitor treatment response. 22 Recent advances in metabolomics might provide various types of novel tumor markers for HCC.…”

Section: Metabolomic Features Of Hccmentioning

confidence: 99%

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

2013

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Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy and the third most common cause of cancer-related death worldwide. Incidence remains highest in the developing world and is steadily increasing across the developed world. Current diagnostic modalities, of ultrasound and a-fetoprotein, are expensive and lack sensitivity in tumor detection. Because of its asymptomatic nature, HCC is usually diagnosed at late and advanced stages, for which there are no effective therapies. Thus, biomarkers for early detection and molecular targets for treating HCC are urgently needed. Emerging highthroughput metabolomics technologies have been widely applied, aiming at the discovery of candidate biomarkers for cancer staging, prediction of recurrence and prognosis, and treatment selection. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. Small-molecule metabolites have an important role in biological systems and represent attractive candidates to understand HCC phenotypes. The power of metabolomics allows an unparalleled opportunity to query the molecular mechanisms of HCC. This technique-driven review aims to demystify the metabolomics pathway, while also illustrating the potential of this technique, with recent examples of its application in

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Section: Metabolomic Features Of Hccmentioning

confidence: 99%

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

2013

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“…Glycerophospholipid and BCAA levels are reported to be related to insulin resistance, type 2 diabetes and obesity [29][30][31][32][33]. Moreover, population-based studies of previously healthy adults revealed that low lyso-PC C18:2 concentrations were associated with an increased risk of pre-type 2 diabetes and type 2 diabetes [30,34], while high concentrations of several diacyl-PCs (C32:1, C36:1, C38:3 and C40:5) were associated with a risk of type 2 diabetes independent of dietary, lifestyle and anthropometric factors.…”

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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“…It was envisaged from the point of discovery of pharmacometabonomics that the methodology would have this broader utility. [46] If the intervention is just passively the passage of time, the methodology can be used to predict disease onset in subsets of a population, and this has been demonstrated in several important cases, including the prediction of the onset of type-2 diabetes, [92][93][94] as well as in other diseases. [90] The power of metabolic profiling to provide prognosis of outcome in a wide variety of situations is one of the most exciting current aspects of this new science.…”

Section: Conclusion and The Future For Pharmacometabonomicsmentioning

confidence: 99%

NMR-based pharmacometabonomics: A new paradigm for personalised or precision medicine

Everett

2017

Progress in Nuclear Magnetic Resonance Spectroscopy

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Metabolic profiling by NMR spectroscopy or hyphenated mass spectrometry, known as metabonomics or metabolomics, is an important tool for systemsbased approaches in biology and medicine. The experiments are typically done in a diagnostic fashion where changes in metabolite profiles are interpreted as a consequence of an intervention or event; be that a change in diet, the administration of a drug, physical exertion or the onset of a disease. By contrast, pharmacometabonomics takes a prognostic approach to metabolic profiling, in order to predict the effects of drug dosing before it occurs. Differences in predose metabolite profiles between groups of subjects are used to predict postdose differences in response to drug administration. Thus the paradigm is inverted and pharmacometabonomics is the metabolic equivalent of pharmacogenomics. Although the field is still in its infancy, it is expected that pharmacometabonomics, alongside pharmacogenomics, will assist with the delivery of personalised or precision medicine to patients, which is a critical goal of 21 st century healthcare. Highlights metabonomics or metabolomics involves metabolic profiling by NMR or MS methods  metabonomics is used in a diagnostic mode to study the effects of an intervention  pharmacometabonomics is a prognostic method to predict the effects of drugs  pharmacometabonomics is a special case of predictive metabonomics  pharmacometabonomics will help to deliver personalised medicine in the future Graphical AbstractNMR-Based Pharmacometabonomics PNMRS 2017

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Metabolite profiles and the risk of developing diabetes

Cited by 2,712 publications

References 32 publications

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

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

NMR-based pharmacometabonomics: A new paradigm for personalised or precision medicine

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