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Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index.

ABSTRACT: BACKGROUND:Quantifying mildly elevated ketone bodies is clinically and pathophysiologically relevant, especially in the context of disease states as well as for monitoring of various diets and exercise regimens. As an alternative assay for measuring ketone bodies in the clinical laboratory, a nuclear magnetic resonance (NMR) spectroscopy-based test was developed for quantification of ?-hydroxybutyrate (?-HB), acetoacetate (AcAc) and acetone. METHODS:The ketone body assay was evaluated for precision, linearity and stability and method comparisons were performed. In addition, plasma ketone bodies were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1198; 373 type 2 diabetes mellitus (T2DM) subjects). RESULTS:?-HB and AcAc quantified using NMR and mass spectrometry and acetone quantified using NMR and gas chromatography/mass spectrometry were highly correlated (R2 = 0.996, 0.994, and 0.994 for ?-HB, AcAc, acetone, respectively). Coefficients of variation (%CVs) for intra- and inter-assay precision ranged from 1.3% to 9.3%, 3.1% to 7.7%, and 3.8% to 9.1%, for ?-HB, AcAc and acetone, respectively. In the IRAS, ketone bodies were elevated in subjects with T2DM versus non-diabetic individuals (p = 0.011 to ?0.001). Age- and sex-adjusted multivariable linear regression analysis revealed that total ketone bodies and ?-HB were associated directly with free fatty acids (FFAs) and T2DM and inversely with triglycerides and insulin resistance as measured by the Lipoprotein Insulin Resistance Index. CONCLUSIONS:Concentrations of the three main ketone bodies can be determined by NMR with good clinical performance, are elevated in T2DM and are inversely associated with triglycerides and insulin resistance.

SUBMITTER: Garcia E

PROVIDER: S-EPMC7074331 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index.

Garcia Erwin E Shalaurova Irina I Matyus Steven P SP Oskardmay David N DN Otvos James D JD Dullaart Robin P F RPF Connelly Margery A MA

Journal of clinical medicine 20200123 2

<h4>Background</h4>Quantifying mildly elevated ketone bodies is clinically and pathophysiologically relevant, especially in the context of disease states as well as for monitoring of various diets and exercise regimens. As an alternative assay for measuring ketone bodies in the clinical laboratory, a nuclear magnetic resonance (NMR) spectroscopy-based test was developed for quantification of β-hydroxybutyrate (β-HB), acetoacetate (AcAc) and acetone.<h4>Methods</h4>The ketone body assay was evalu ...[more]

PMID: 31979327

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Project description:BackgroundCancer Anorexia Cachexia Syndrome (CACS) is a distinct atrophy disease negatively influencing multiple aspects of clinical care and patient quality of life. Although it directly causes 20% of all cancer-related deaths, there are currently no model systems that encompass the entire multifaceted syndrome, nor are there any effective therapeutic treatments.MethodsA novel model of systemic metastasis was evaluated for the comprehensive CACS (metastasis, skeletal muscle and adipose tissue wasting, inflammation, anorexia, anemia, elevated protein breakdown, hypoalbuminemia, and metabolic derangement) in both males and females. Ex vivo skeletal muscle analysis was utilized to determine ubiquitin proteasome degradation pathway activation. A novel ketone diester (R/S 1,3-Butanediol Acetoacetate Diester) was assessed in multifaceted catabolic environments to determine anti-atrophy efficacy.ResultsHere, we show that the VM-M3 mouse model of systemic metastasis demonstrates a novel, immunocompetent, logistically feasible, repeatable phenotype with progressive tumor growth, spontaneous metastatic spread, and the full multifaceted CACS with sex dimorphisms across tissue wasting. We also demonstrate that the ubiquitin proteasome degradation pathway was significantly upregulated in association with reduced insulin-like growth factor-1/insulin and increased FOXO3a activation, but not tumor necrosis factor-α-induced nuclear factor-kappa B activation, driving skeletal muscle atrophy. Additionally, we show that R/S 1,3-Butanediol Acetoacetate Diester administration shifted systemic metabolism, attenuated tumor burden indices, reduced atrophy/catabolism and mitigated comorbid symptoms in both CACS and cancer-independent atrophy environments.ConclusionsOur findings suggest the ketone diester attenuates multifactorial CACS skeletal muscle atrophy and inflammation-induced catabolism, demonstrating anti-catabolic effects of ketone bodies in multifactorial atrophy.

Dataset Information

Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index.

Publications

Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index.

Similar Datasets

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