Serum metabolomic profile of incident diabetes

Rebholz, Casey M.; Yu, Bing; Zheng, Zihe; Chang, Patrick; Tin, Adrienne; Köttgen, Anna; Wagenknecht, Lynne E.; Coresh, Josef; Boerwinkle, Eric; Selvin, Elizabeth

doi:10.1007/s00125-018-4573-7

Cited by 104 publications

(89 citation statements)

References 38 publications

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“…Two prospective observational studies in the United States found that baseline plasma asparagine was a protective marker of diabetes (28,29). In these researches, ndings about aspartate were accordant with ours, but results about asparagine were opposite to ours.…”

Section: Discussionsupporting

confidence: 49%

Interactive effects of asparagine and aspartate homeostasis with sex and age for the risk of type 2 diabetes risk

Luo

Feng

Yang

et al. 2020

Preprint

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Background Asparagine and aspartate homeostasis link with type 2 diabetes (T2D). This study aimed to explore whether asparagine and aspartate metabolism interacted with sex and age to increase the risk of T2D.Methods From 27 May 2015 to 3 August 2016, we consecutively retrieved 1032 T2D patients and 1522 subjects without T2D from a tertiary care hospital in Liaoning, China. Restricted cubic spline nested in the logistic regression was used to draw odds ratio curves of plasma asparagine to aspartate ratio for T2D by sex and age. Cutoff point was select where curves went apart, indicating possible interaction. Addictive interactions of asparagine to aspartate ratio with sex or age and secondary interaction with copresence of unfavorable sex and age were further estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). Results Ratio of asparagine to aspartate >1.5 was associated with elevated risk of T2D (OR: 7.99, 95%CI: 5.50 to 11.6), which was enhanced by female gender to 13.6, (95%CI: 8.10-22.9) and by >50 years of age to 28.7 (14.6-56.3), with significant additive interactions. There was a significant secondary-interaction of copresence of female sex and > 50 years of age with high asparagine to aspartate ratio for increased T2D risk with the OR being further increased to 34.4 (20.5 - 57.5). Conclusions High asparagine to aspartate ratio was associated with markedly increased risk of T2D, which was further amplified by either female gender or >50 years of age, and especially both.

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Section: Discussionsupporting

confidence: 49%

Interactive effects of asparagine and aspartate homeostasis with sex and age for the risk of type 2 diabetes risk

Luo

Feng

Yang

et al. 2020

Preprint

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“…However, in humans the benefit of BCAA supplementation is less evident 23 , 24 . A possible reason might be that not only low levels of BCAAs associate with adverse health outcomes: In contrast to AD and mortality, higher levels of valine and further BCAA have been linked to prevalent and incident type 2 diabetes (T2D) 25 , 26 and incident CVD in women 27 . Thus, balancing the potential positive effects of BCAA supplementation with potential adverse effects 28 might be crucial.…”

Section: Discussionmentioning

confidence: 99%

Instability of personal human metabotype is linked to all-cause mortality

Lacruz

Kluttig

Tiller

et al. 2018

Sci Rep

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Disruption of metabolic homeostasis is an important factor in many diseases. Various metabolites have been linked to higher risk of morbidity and all-cause mortality using metabolomics in large population-based cohorts. In these studies, baseline metabolite levels were compared across subjects to identify associations with health outcomes, implying the existence of ‘healthy’ concentration ranges that are equally applicable to all individuals. Here, we focused on intra-individual changes in metabolite levels over time and their link to mortality, potentially allowing more personalized risk assessment. We analysed targeted metabolomics data for 134 blood metabolites from 1409 participants in the population-based CARLA cohort at baseline and after four years. Metabotypes of the majority of participants (59%) were extremely stable over time indicated by high correlation between the subjects’ metabolite profiles at the two time points. Metabotype instability and, in particular, decrease of valine were associated with higher risk of all-cause mortality in 7.9 years of follow-up (hazard ratio (HR) = 1.5(95%CI = 1.0–2.3) and 0.2(95%CI = 0.1–0.3)) after multifactorial adjustment. Excluding deaths that occurred in the first year after metabolite profiling showed similar results (HR = 1.8(95%CI = 1.1–2.8)). Lower metabotype stability was also associated with incident cardiovascular disease (OR = 1.2(95%CI = 1.0–1.3)). Therefore, changes in the personal metabotype might be a valuable indicator of pre-clinical disease.

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“…Previous work on metabolomics in T2D highlights the important role of amino acid profiling, particularly branched-chain amino acids (BCAA) for diabetes risk assessment [15][16][17] . Several other metabolites have been reported as significantly associated with diabetes prevalence; these include reduced levels of glycine, lysophosphatidylcholine (LPC) (18:2) as well as increased levels of acetylcarnitine 18 .…”

mentioning

confidence: 99%

Integration of whole-body [18F]FDG PET/MRI with non-targeted metabolomics can provide new insights on tissue-specific insulin resistance in type 2 diabetes

Diamanti

Visvanathar

Pereira

et al. 2020

Sci Rep

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Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific phenotypes requires a multi-omics approach. In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body mass index, we calculated associations between parameters of whole-body positron emission tomography (PET)/magnetic resonance imaging (MRI) during hyperinsulinemic euglycemic clamp and non-targeted metabolomics profiling for subcutaneous adipose tissue (SAT) and plasma. Plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Visceral adipose tissue (VAT) and SAT insulin sensitivity (K i), were positively associated with several lysophospholipids, while the opposite applied to branched-chain amino acids. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver K i. Bile acids and carnitines in adipose tissue were inversely associated with VAT K i. Furthermore, we detected several metabolites that were significantly higher in T2D than normal/prediabetes. In this study we present novel associations between several metabolites from SAt and plasma with the fat fraction, volume and insulin sensitivity of various tissues throughout the body, demonstrating the benefit of an integrative multi-omics approach. High-throughput metabolomics promises a deeper understanding of type 2 diabetes (T2D) mellitus 1. According to the World Health Organization's global report on diabetes, the age-standardized global prevalence of diabetes has nearly doubled from 1980 to 2014 2. Motivated by the necessity of progress to halt the diabetes epidemic, researchers have made significant discoveries to widen our understanding of T2D. A novel classification of T2D has been suggested, comprising of five clusters and reported to better correlate with disease progression and risk

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Serum metabolomic profile of incident diabetes

Abstract: Branched chain amino acids may play a role in diabetes development. Our study is the first to report asparagine as a protective biomarker of diabetes risk. The serum metabolome reflects known and novel metabolic disturbances that improve prediction of diabetes.

Cited by 104 publications

References 38 publications

Interactive effects of asparagine and aspartate homeostasis with sex and age for the risk of type 2 diabetes risk

Interactive effects of asparagine and aspartate homeostasis with sex and age for the risk of type 2 diabetes risk

Instability of personal human metabotype is linked to all-cause mortality

Integration of whole-body [18F]FDG PET/MRI with non-targeted metabolomics can provide new insights on tissue-specific insulin resistance in type 2 diabetes

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