Dataset Information

Acute Exenatide Therapy Attenuates Postprandial Vasodilation in Humans with Prediabetes: A Randomized Controlled Trial.

ABSTRACT: Background: The state of prediabetes comprises atherosclerotic changes leading to decreased vascular function in humans. This study examined the effects on incretin mimetics on vascular physiology in the prediabetic postprandial state. Methods: Fifteen obese adults with prediabetes participated in a randomized, crossover, double-blinded trial comparing the postprandial effects of exenatide, saxagliptin, and placebo on peripheral vasodilation. All studies utilized a standardized high-fat meal. Resting and peak forearm blood flow (FBF) were measured via strain gauge venous occlusion plethysmography, and makers of vascular dysfunction were measured in plasma. Results: Exenatide attenuated resting FBF at 3 hr (P = 0.003) and 6 hr (P = 0.056) postmeal, compared to placebo. Nonsignificant reductions in resting FBF were observed between saxagliptin and placebo at the same time points. No group differences were observed for peak FBF, plasma nitrotyrosine, and plasma 8-iso-prostaglandin F2alpha. A transient increase in plasma triglyceride was abated in the exenatide group, when compared to saxagliptin and placebo groups. Only exenatide group showed no significant upsurge in plasma insulin. Plasma-free fatty acids significantly declined in all three groups, although less markedly for exenatide. Postmeal glucose increased at 2 hr with placebo and saxagliptin, but simultaneously decreased with exenatide. Conclusions: Acute treatment with exenatide blunted the postprandial vasodilatory effect of a high-fat meal in prediabetes. Exenatide's acute effects derived primarily from multiple endothelium-independent processes. Trial Registration Number: NCT02104739.

SUBMITTER: Hamidi V

PROVIDER: S-EPMC7262649 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:High-fat diets may contribute to metabolic disease via postprandial changes in serum endotoxin and inflammation. It is unclear how dietary fat composition may alter these parameters. We hypothesized that a meal rich in n-3 (?3) fatty acids would reduce endotoxemia and associated inflammation but a saturated or n-6 (?6) fatty acid-rich meal would increase postprandial serum endotoxin concentrations and systemic inflammation in healthy adults.Healthy adults (n?=?20; mean age 25?±?3.2 S.D. years) were enrolled in this single-blind, randomized, cross-over study. Participants were randomized to treatment and reported to the laboratory, after an overnight fast, on four occasions separated by at least one week. Participants were blinded to treatment meal and consumed one of four isoenergetic meals that provided: 1) 20 % fat (control; olive oil) or 35 % fat provided from 2) n-3 (?3) (DHA?=?500 mg; fish oil); 3) n-6 (?6) (7.4 g; grapeseed oil) or 4) saturated fat (16 g; coconut oil). Baseline and postprandial blood samples were collected. Primary outcome was defined as the effect of treatment meal on postprandial endotoxemia. Serum was analyzed for metabolites, inflammatory markers, and endotoxin. Data from all 20 participants were analyzed using repeated-measures ANCOVA.Participant serum endotoxin concentration was increased during the postprandial period after the consumption of the saturated fat meal but decreased after the n-3 meal (p?<?0.05). The n-6 meal did not effect a different outcome in participant postprandial serum endotoxin concentration from that of the control meal (p?>?0.05). There was no treatment meal effect on participant postprandial serum biomarkers of inflammation. Postprandial serum triacylglycerols were significantly elevated following the n-6 meal compared to the n-3 meal. Non-esterified fatty acids were significantly increased after consumption of the saturated fat meal compared to other treatment meals.Meal fatty acid composition modulates postprandial serum endotoxin concentration in healthy adults. However, postprandial endotoxin was not associated with systemic inflammation in vivo.This study was retrospectively registered at clinicaltrials.gov as NCT02521779 on July 28, 2015.

Project description:BackgroundKetone monoester β-hydroxybutyrate (KEβHB) ingestion has emerged as an effective method of inducing acute ketosis. Although evidence suggests that KEβHB can offer several therapeutic benefits, whether KEβHB affects lipid profile is still unknown.AimsThe primary aim was to study the effect of KEβHB on plasma lipid profile in individuals with prediabetes. The secondary aim was to investigate the role of saturated fat intake in that effect.MethodsThis study was a randomized controlled trial with cross-over design. Following an overnight fast, 18 adults (six women and 12 men) with prediabetes (diagnosed based on the American Diabetes Association criteria) ingested a single dose of KEβHB drink or placebo drink. Blood samples were collected every 30 min, from baseline to 150 min. Outcome variables included changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, remnant cholesterol, triglycerides, and the triglycerides to HDL cholesterol ratio. The area under the curve (AUC) over 150 min was calculated for each outcome following ingestion of the drinks. Habitual saturated fat intake was ascertained using the EPIC-Norfolk food frequency questionnaire.ResultsSignificant elevation of blood β-hydroxybutyrate from 0.2 mmol/L to 3.5 mmol/L (p < 0.001) was achieved within 30 min. Acute ketosis resulted in significantly lower AUCs for remnant cholesterol (p = 0.022) and triglycerides (p = 0.022). No statistically significant differences in the AUCs for total cholesterol, HDL cholesterol, LDL cholesterol, and the triglycerides to HDL cholesterol ratio were found. The changes in remnant cholesterol and triglycerides were statistically significant in individuals with high, but not low, habitual saturated fat intake.ConclusionAcute ketosis had no untoward effect on plasma lipid profile. Moreover, it led to significantly reduced circulating levels of remnant cholesterol and triglycerides. This paves the way for investigating whether exogenous ketone supplementation reduces cardiovascular disease risk (via its actions on triglyceride-rich lipoproteins) in at-risk populations. Trial registration: ClinicalTrials.gov, NCT03889210.

Project description:AimsPatients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) exhibit considerable residual risk for cardiovascular disease (CVD). There is, therefore, increasing interest in targeting postprandial lipid metabolism and remnant cholesterol. Treatment with the glucagon-like peptide 1 (GLP-1) analogue liraglutide reduces CVD risk by mechanisms that remain unexplained in part. Here we investigated the effects of liraglutide intervention on ectopic fat depots, hepatic lipogenesis and fat oxidation, postprandial lipid metabolism and glycaemia in humans with type 2 diabetes.MethodsThe effect of liraglutide was investigated in 22 patients with adequately controlled type 2 diabetes. Patients were randomly allocated, in a single-blind fashion, to either liraglutide 1.8 mg or placebo once daily for 16 weeks. Because liraglutide is known to promote weight loss, the study included dietary counselling to achieve similar weight loss in the liraglutide and placebo groups. Cardiometabolic responses to a high-fat mixed meal were measured before and at the end of the liraglutide intervention.ResultsWeight loss at Week 16 was similar between the groups: -2.4 kg (-2.5%) in the liraglutide group and -2.1 kg (-2.2%) in the placebo group. HBA1c improved by 6.4 mmol/mol (0.6%) in the liraglutide group (P = 0.005). Liver fat decreased in both groups, by 31% in the liraglutide group and by 18% in the placebo group, but there were no significant changes in the rate of hepatic de novo lipogenesis or β-hydroxybutyrate levels, a marker of fat oxidation. We observed significant postprandial decreases in triglycerides only in plasma, chylomicrons and VLDL, and remnant particle cholesterol after treatment in the liraglutide group. Fasting and postprandial apoCIII concentrations decreased after liraglutide intervention and these changes were closely related to reduced glycaemia. In relative importance analysis, approximately half of the changes in postprandial lipids were explained by reductions in apoCIII concentrations, whereas less than 10% of the variation in postprandial lipids was explained by reductions in weight, glycaemic control, liver fat or postprandial insulin responses.ConclusionsIntervention with liraglutide for 16 weeks produces multiple improvements in cardiometabolic risk factors that were not seen in the placebo group, despite similar weight loss. Of particular importance was a marked reduction in postprandial atherogenic remnant particles. The underlying mechanism may be improved glycaemic control, which leads to reduced expression of apoCIII, a key regulator of hypertriglyceridaemia in hyperglycaemic patients.

Dataset Information

Acute Exenatide Therapy Attenuates Postprandial Vasodilation in Humans with Prediabetes: A Randomized Controlled Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets