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Glial acetate metabolism is increased following a 72-h fast in metabolically healthy men and correlates with susceptibility to hypoglycemia.

ABSTRACT: AIMS:Prior exposure to insulin-induced hypoglycemia was shown to increase glial acetate metabolism (GAM) during subsequent exposure to hypoglycemia in diabetic individuals. However, it remained unclear whether this effect was dependent on the disease state or the antecedent cause of hypoglycemia. We aimed to establish whether exposure to fasting-induced hypoglycemia was sufficient to produce alterations in GAM in non-diabetic individuals. METHODS:GAM was measured via carbon-13 magnetic resonance spectroscopy during infusion of [1-13C] acetate before and after a 72-h fast in six metabolically healthy men. All participants were male, aged 18-40 years, with a Body Mass Index of 20.0-27.9 kg/m2, who consented to reside at Pennington Biomedical Research Center for 4 days. The main outcome measure was the percent enhancement of cerebral [1-13C] bicarbonate (the primary metabolic byproduct of glial oxidation of [1-13C] acetate). Continuous glucose monitoring was used to measure hypoglycemic episodes during the 72-h fast. RESULTS:As expected, 72 h of fasting significantly reduced blood glucose levels and resulted in a high frequency of hypoglycemic episodes. Steady-state GAM increased from 53.5?±?3.7 to 61.9?±?1.7% following the 72-h fast (p?=?0.005). This increase correlated with greater duration of hypoglycemia experienced during the fast (r?=?0.967). In addition, subjects with greater GAM at baseline experienced a greater increase in the duration of hypoglycemia experienced during the 72-h fast (r?=?0.979). CONCLUSIONS:GAM has potential as a biomarker for susceptibility to hypoglycemic episodes. TRAIL REGISTRATION:Clinicaltrials.gov ID: NCT02690168.

SUBMITTER: McDougal DH

PROVIDER: S-EPMC6153507 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Glial acetate metabolism is increased following a 72-h fast in metabolically healthy men and correlates with susceptibility to hypoglycemia.

McDougal David Harry DH Darpolor Moses Morakortoi MM DuVall Marina Andreyevna MA Sutton Elizabeth Frost EF Morrison Christopher David CD Gadde Kishore Murali KM Redman Leanne Maree LM Carmichael Owen Thomas OT

Acta diabetologica 20180622 10

<h4>Aims</h4>Prior exposure to insulin-induced hypoglycemia was shown to increase glial acetate metabolism (GAM) during subsequent exposure to hypoglycemia in diabetic individuals. However, it remained unclear whether this effect was dependent on the disease state or the antecedent cause of hypoglycemia. We aimed to establish whether exposure to fasting-induced hypoglycemia was sufficient to produce alterations in GAM in non-diabetic individuals.<h4>Methods</h4>GAM was measured via carbon-13 mag ...[more]

PMID: 29931424

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Project description:BackgroundIndividuals with "metabolically healthy obesity" (MHO) phenotype (i.e., obesity and absence of cardiometabolic abnormalities: favorable levels of blood pressure, lipids, and glucose) experience lower risk of cardiovascular disease compared with those with "metabolically at-risk obesity" (MAO) phenotype (i.e., obesity with concurrent cardiometabolic abnormalities). Among Hispanic/Latino women and men with obesity, limited data exist on the correlates of and body composition measures associated with obesity phenotypes.MethodsData from the Hispanic Community Health Study/Study of Latinos (2008-2011) were used to estimate the age-adjusted distribution of obesity phenotypes among 5,426 women and men (aged 20-74 years) with obesity (BMI ? 30?kg/m2) and to compare characteristics between individuals with MHO and MAO phenotypes. Weighted Poisson regression models were used to examine cross-sectional associations between 1-standard deviation (SD) increase in body composition measures (i.e., body fat percentage, waist circumference, and body lean mass) and MHO phenotype prevalence.ResultsThe age-adjusted proportion of the MHO phenotype was low (i.e., 12.5% in women and 6.5% in men). In bivariate analyses, women and men with the MHO phenotype were more likely to be younger, have higher education and acculturation levels, report lower lifetime cigarette use, and have fasting insulin and waist circumference levels than MAO. Adjusting for sociodemographic and lifestyle factors, among women, each 1-SD increase in body fat percentage, waist circumference, and lean body mass was, respectively, associated with a 21%, 33%, and 31% lower prevalence of the MHO phenotype. Among men, each 1-SD increase in waist circumference and lean body mass was, respectively, associated with a 20% and 15% lower prevalence of the MHO phenotype.ConclusionsWe demonstrated that higher waist circumference and higher lean body mass were independently associated with a lower proportion of the MHO phenotype in Hispanic/Latino women and men. Findings support the need for weight reduction interventions to manage cardiometabolic health among Hispanics/Latinos.

Project description:PurposeIn adolescents, the definition and clinical implications of metabolically healthy overweight (MHO) status have not been established. This study aimed to investigate the prevalence of MHO according to its most widespread definition, which is based on metabolic syndrome (MS), and to explore further metabolic indicators such as Homeostatic Model Assessment of Insulin Resistance, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and C-reactive protein levels, together with metabolic health predictors in a sample of adolescents attending a pediatric obesity clinic.MethodsData from 487 adolescents categorized as overweight (52.6% females, 88.1% white), with a mean body mass index (BMI) z-score of 2.74 (±1.07 standard deviation [SD]), and a mean age of 14.4 years (±2.2 SD) were cross-sectionally analyzed. From this original sample, a subsample of 176 adolescents underwent a second assessment at 12 (±6 SD) months for longitudinal analysis.ResultsFrom the 487 adolescents originally analyzed, 200 (41.1%) were categorized as MHO, but only 93 (19.1%) had none of the metabolic indicators considered in this study. According to longitudinal analysis, 30 of the 68 adolescents (44%) categorized as MHO at baseline became non-MHO over time. BMI z-score was the best predictor of metabolic health both in cross-sectional and longitudinal analyses. Increased BMI z-score reduced the odds of being categorized as MHO (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.4-0.9; P=.008) and increased the odds of having hypertension (OR 2.1, 95% CI: 1.4-3.3, P=0.001), insulin resistance (OR, 2.4; 95% CI, 1.4-4.1, P=0.001), or a proinflammatory state (OR, 1.2; 95% CI, 1.1-1.3, P=0.002).ConclusionDiagnosis of MHO should not be exclusively based on MS parameters, and other metabolic indicators should be considered. Adolescents categorized as overweight should participate in weight-management lifestyle interventions regardless of their metabolic health phenotype.

Dataset Information

Glial acetate metabolism is increased following a 72-h fast in metabolically healthy men and correlates with susceptibility to hypoglycemia.

Publications

Glial acetate metabolism is increased following a 72-h fast in metabolically healthy men and correlates with susceptibility to hypoglycemia.

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