Serum Carnitine Metabolites and Incident Type 2 Diabetes Mellitus in Patients With Suspected Stable Angina Pectoris

Strand, Elin; Rebnord, Eirik Wilberg; Flygel, Malin R; Lysne, Vegard; Svingen, Gard Frodahl Tveitevåg; Tell, Grethe S.; Løland, Kjetil Halvorsen; Berge, Rolf K.; Svardal, Asbjørn; Nygård, Ottar; Pedersen, Eva Ringdal

doi:10.1210/jc.2017-02139

Cited by 31 publications

(28 citation statements)

References 40 publications

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“…Furthermore, very recently Strand et al . 26 demonstrated that serum levels of gamma-butyrobetaine and trimethyllysine predict long-term risk of type 2 diabetes independently of traditional risk factors, possibly reflecting dysfunctional fatty acid metabolism.…”

Section: Discussionmentioning

confidence: 99%

A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants

Jääskeläinen

Kärkkäinen

Jokkala

et al. 2018

Sci Rep

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Preeclampsia (PE) is a complex pregnancy disorder. It is not extensively known how the metabolic alterations of PE women contribute to the metabolism of newborn. We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of plasma from umbilical cord differs between infants born to PE and non-PE pregnancies in the FINNPEC study. Cord plasma was available from 42 newborns born from PE and 53 from non-PE pregnancies. 133 molecular features differed between PE and non-PE newborns after correction for multiple testing. Decreased levels of 4-pyridoxic acid were observed in the cord plasma samples of PE newborns when compared to non-PE newborns. Compounds representing following areas of metabolism were increased in the cord plasma of PE newborns: urea and creatine metabolism; carnitine biosynthesis and acylcarnitines; putrescine metabolites; tryptophan metabolism and phosphatidylcholines. To our knowledge, this study is the first one to apply LC-MS based metabolomics in cord plasma of PE newborns. We demonstrate that this strategy provides a global picture of the widespread metabolic alterations associated with PE and particularly the elevated levels of carnitine precursors and trimethylated compounds appear to be associated with PE at birth.

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Section: Discussionmentioning

confidence: 99%

A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants

Jääskeläinen

Kärkkäinen

Jokkala

et al. 2018

Sci Rep

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“…For study‐specific analyses, serum and plasma were immediately prepared and stored in 2‐mL Vacutainer tubes (Becton, Dickinson and Company, United States) at −80 °C until thawed and analysed by laboratory staff, blinded to the clinical outcome of the patients. Plasma TML, plasma TMAO, serum γBB and plasma riboflavin were measured using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) [20,21].…”

Section: Methodsmentioning

confidence: 99%

Circulating trimethyllysine and risk of acute myocardial infarction in patients with suspected stable coronary heart disease

et al. 2020

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Background The carnitine precursor trimethyllysine (TML) is associated with progression of atherosclerosis, possibly through a relationship with trimethylamine‐N‐oxide (TMAO). Riboflavin is a cofactor in TMAO synthesis. We examined prospective relationships of circulating TML and TMAO with acute myocardial infarction (AMI) and potential effect modifications by riboflavin status. Methods By Cox modelling, risk associations were examined amongst 4098 patients (71.8% men) with suspected stable angina pectoris. Subgroup analyses were performed according to median plasma riboflavin. Results During a median follow‐up of 4.9 years, 336 (8.2%) patients experienced an AMI. The age‐ and sex‐adjusted hazard ratio (HR) (95% CI) comparing the 4th vs. 1st TML quartile was 2.19 (1.56–3.09). Multivariable adjustment for traditional cardiovascular risk factors and indices of renal function only slightly attenuated the risk estimates [HR (95% CI) 1.79 (1.23–2.59)], which were particularly strong amongst patients with riboflavin levels above the median (Pint = 0.035). Plasma TML and TMAO were strongly correlated (rs = 0.41; P < 0.001); however, plasma TMAO was not associated with AMI risk in adjusted analyses [HR (95% CI) 0.81 (0.58–1.14)]. No interaction between TML and TMAO was observed. Conclusion Amongst patients with suspected stable angina pectoris, plasma TML, but not TMAO, independently predicted risk of AMI. Our results motivate further research on metabolic processes determining TML levels and their potential associations with cardiovascular disease. We did not adjust for multiple comparisons, and the subgroup analyses should be interpreted with caution.

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“…In a later population-based prospective study of 2103 individuals, with a mean follow-up of six years, palmitoylcarnitine was included in a panel of acylcarnitines that demonstrated an AUC of 0.89 for the prediction of incident T2DM [ 28 ]. Palmitoylcarnitine was also associated with T2DM in a study of 2519 patients with coronary artery disease with a median follow-up of 7.7 years, and a three-metabolite panel that also contained trimethyllysine and γ-butyrobetaine was proposed for predicting the long-term risk of T2DM, based on the susceptibility to this disease of patients with dysfunctional fatty acid metabolism [ 29 ]. An in-depth study of the mechanism underlying this relationship described palmitoylcarnitine as a useful biomarker of excessive fatty acid oxidation, which leads to tissue lipid accumulation and ultimately insulin resistance, finding elevated concentrations of this metabolite in patients with T2DM during the insulin clamp at fasting [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Biomarkers to Distinguish between Type 3c and Type 2 Diabetes Mellitus by Untargeted Metabolomics

et al. 2020

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Pancreatogenic diabetes mellitus (T3cDM) is a highly frequent complication of pancreatic disease, especially chronic pancreatitis, and it is often misdiagnosed as type 2 diabetes mellitus (T2DM). A correct diagnosis allows the appropriate treatment of these patients, improving their quality of life, and various technologies have been employed over recent years to search for specific biomarkers of each disease. The main aim of this metabolomic project was to find differential metabolites between T3cDM and T2DM. Reverse-phase liquid chromatography coupled to high-resolution mass spectrometry was performed in serum samples from patients with T3cDM and T2DM. Multivariate Principal Component and Partial Least Squares-Discriminant analyses were employed to evaluate between-group variations. Univariate and multivariate analyses were used to identify potential candidates and the area under the receiver-operating characteristic (ROC) curve was calculated to evaluate their diagnostic value. A panel of five differential metabolites obtained an area under the ROC curve of 0.946. In this study, we demonstrate the usefulness of untargeted metabolomics for the differential diagnosis between T3cDM and T2DM and propose a panel of five metabolites that appear altered in the comparison between patients with these diseases.

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Serum Carnitine Metabolites and Incident Type 2 Diabetes Mellitus in Patients With Suspected Stable Angina Pectoris

Abstract: Serum levels of TML, γ-butyrobetaine, and the long-chained palmitoylcarnitine predict long-term risk of T2D independently of traditional risk factors, possibly reflecting dysfunctional fatty acid metabolism in patients susceptible to T2D development.

Cited by 31 publications

References 40 publications

A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants

A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants

Circulating trimethyllysine and risk of acute myocardial infarction in patients with suspected stable coronary heart disease

Novel Biomarkers to Distinguish between Type 3c and Type 2 Diabetes Mellitus by Untargeted Metabolomics

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