Serum Levels of Acylcarnitines Are Altered in Prediabetic Conditions

Mai, M.; Tönjes, Anke; Kovacs, Peter; Stümvoll, Michael; Fiedler, Georg Martin; Leichtle, Alexander Benedikt

doi:10.1371/journal.pone.0082459

Cited by 158 publications

(178 citation statements)

References 30 publications

Supporting

Mentioning

162

Contrasting

Order By: Relevance

“…Similarly, Satish C. Kalhan et al discovered that 14 carnitines in serum increased in NAFLD [6]. A study on serum levels of acylcarnitines showed that a lot of carnitines were higher in T2DM, especially tetradecenoylcarnitine and tetradecadienylcarnitine [15]. What's more, we discovered that serum tetradecenoylcarnitine and tetradecadienylcarnitine were higher in NAFLD + T2DM compared with NAFLD.…”

Section: Differential Metabolites From Both Populationssupporting

confidence: 58%

Serum metabonomics of NAFLD plus T2DM based on liquid chromatography–mass spectrometry

Chen

Liu

et al. 2016

Clinical Biochemistry

View full text Add to dashboard Cite

Section: Differential Metabolites From Both Populationssupporting

confidence: 58%

Serum metabonomics of NAFLD plus T2DM based on liquid chromatography–mass spectrometry

Chen

Liu

et al. 2016

Clinical Biochemistry

View full text Add to dashboard Cite

“…Moreover, significantly different acylcarnitine profiles were observed among subjects with normal glucose tolerance, prediabetic states, or type 2 diabetes in a German study (22). Recently, several prospective studies indicated that medium-and/or long-chain acylcarnitines predicted cardiovascular events or mortality in people aged .85 years or selected patients undergoing cardiac catheterization or dialysis (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

et al. 2016

View full text Add to dashboard Cite

OBJECTIVEAcylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach. RESEARCH DESIGN AND METHODSA population-based prospective study was conducted among 2,103 communityliving Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry. RESULTSOver the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents. CONCLUSIONSA panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated.The escalating global epidemic of type 2 diabetes has contributed considerably to socioeconomic burdens in both developed and developing countries (1). To understand biological mechanisms and improve clinical predictions, it is essential to identify novel biomarkers to enhance the capability to predict early pathophysiological changes (2). As a largely preventable disease, early prediction is the key to control the epidemic trend of type 2 diabetes, particularly in those countries with

show abstract

“…Although typically short‐lived, LCAC accumulate in states of inefficient fatty acid oxidation (FAO), which may be attributed to (1) defects in mitochondrial FAO enzymes or (2) increased FAO relative to tricarboxylic acid (TCA) flux; this leads to a bottleneck of carbon substrates at the TCA cycle 53, 54. Such defects can be caused or exacerbated by IR, which has, in turn, been associated with elevations in plasma LCAC 54, 55, 56, 57. However, we found no correlation between plasma LCAC and IR in this study; this suggests that the observed LCAC elevations were not driven by IR 54, 55, 56, 57.…”

Section: Discussionmentioning

confidence: 99%

“…Such defects can be caused or exacerbated by IR, which has, in turn, been associated with elevations in plasma LCAC 54, 55, 56, 57. However, we found no correlation between plasma LCAC and IR in this study; this suggests that the observed LCAC elevations were not driven by IR 54, 55, 56, 57. Regardless of the precise cause, LCAC are transported out to the plasma, where they are subsequently metabolized in several tissues (especially skeletal muscle, liver, and heart) or excreted in urine or bile 52, 56, 57.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Hunter

Kelly

McGarrah

et al. 2016

JAHA

201

137

View full text Add to dashboard Cite

BackgroundMetabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF).Methods and ResultsWe identified HFpEF cases, HFrEF controls, and no‐HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No‐HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long‐chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no‐HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance.ConclusionsWe identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.

show abstract

Serum Levels of Acylcarnitines Are Altered in Prediabetic Conditions

Cited by 158 publications

References 30 publications

Serum metabonomics of NAFLD plus T2DM based on liquid chromatography–mass spectrometry

Serum metabonomics of NAFLD plus T2DM based on liquid chromatography–mass spectrometry

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Contact Info

Product

Resources

About