Vasoactive mediators of hypertension in obesity.

Obesity is associated with hypertension. However, the mechanisms involved are not fully understood. Therefore, we investigated the relationship between obesity and vasoactive mediators.

Dapagliflozin reduces systolic blood pressure and modulates vasoactive factors.

Aim: To investigate the mechanisms underlying improvements in blood pressure (BP) and congestive heart failure outcomes following treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor.

Research Design And Methods: A total of 52 patients with type 2 diabetes (T2D) with an HbA1c of less than 8% participated in this prospective, double-blind and placebo-controlled study. Patients were randomized (1:1) to either dapagliflozin 10 mg daily or placebo for 12 weeks.

Liraglutide treatment in overweight and obese patients with type 1 diabetes: A 26-week randomized controlled trial; mechanisms of weight loss.

Aim: To investigate the effects of liraglutide treatment on glycaemic control and adipose tissue metabolism in overweight and obese people with type 1 diabetes (T1DM).

Research Design And Methods: A total of 84 adult overweight and obese patients with T1DM, with no detectable C-peptide, were randomized (1:1) to either placebo or 1.8 mg/d liraglutide for 6 months.

Dapagliflozin Suppresses Hepcidin And Increases Erythropoiesis.

Context: Dapagliflozin and other SGLT2 inhibitors are known to increase hematocrit, possibly due to its diuretic effects and hemoconcentration.

Objective: Since type 2 diabetes is a proinflammatory state and since hepcidin, a known suppressor of erythropoiesis, is increased in proinflammatory states, we investigated the possibility that dapagliflozin suppresses hepcidin concentrations and thus increases erythropoiesis.

Design: Prospective, randomized, and placebo-controlled study.

Testosterone Increases the Expression and Phosphorylation of AMP Kinase α in Men With Hypogonadism and Type 2 Diabetes.

Context: Adenosine 5'-monophosphate-activated protein kinase-α (AMPKα) is a mediator of exercise-induced glucose uptake in skeletal muscle.

Objective: We evaluated whether AMPKα expression and phosphorylation are reduced in skeletal muscle and adipose tissue of patients with hypogonadotropic hypogonadism (HH), and whether testosterone replacement therapy results in restoration of the expression and phosphorylation of AMPKα.

Design: This is a secondary analysis of a previously completed trial that showed an insulin-sensitizing effect of testosterone therapy in men with type 2 diabetes and HH.

Acute effects of insulin on skeletal muscle growth and differentiation genes in men with type 2 diabetes.

Aims: Insulin has anabolic effects on skeletal muscle. However, there is limited understanding of the molecular mechanisms underlying this effect in humans. We evaluated whether the skeletal muscle expression of satellite cell activator fibroblast growth factor 2 (FGF2) and muscle growth and differentiation factors are modulated acutely by insulin during euglycemic-hyperinsulinemic clamp (EHC).

Increase in Osteocalcin Following Testosterone Therapy in Men With Type 2 Diabetes and Subnormal Free Testosterone.

Context: One-third of men with type 2 diabetes have subnormal free testosterone concentrations. We evaluated the following: (i) whether bone mineral density (BMD) and bone strength are affected by gonadal status in type 2 diabetes and (ii) the effect of testosterone replacement on markers of osteoblast and osteoclast activity.

Design: This is a econdary analysis of a previously completed, randomized, placebo-controlled trial.

Effect of Testosterone on FGF2, MRF4, and Myostatin in Hypogonadotropic Hypogonadism: Relevance to Muscle Growth.

Context: Fibroblast growth factor (FGF)2 is an important stimulatory modulator of satellite cells in skeletal muscle. Satellite cells play a cardinal role in muscle growth and repair.

Objective: We evaluated whether skeletal muscle expression of FGF2 and muscle growth and differentiation factors are reduced in patients with hypogonadotropic hypogonadism (HH) and whether testosterone replacement therapy results in their restoration.

Decreases in neprilysin and vasoconstrictors and increases in vasodilators following bariatric surgery.

The aim of this study was to determine if weight loss following Roux-en-Y gastric bypass (RYGB) surgery in morbidly obese patients is associated with a decrease in plasma concentrations of neprilysin, mediators of the renin angiotensin system (RAS), catecholamines and endothelin-1, and also with an increase in the concentrations of vasodilators. Fasting blood samples were obtained from 15 patients with morbid obesity and diabetes prior to and 6 months after RYGB surgery. Circulating levels of neprilysin, vasoconstrictors, vasodilators, and the mRNA expression of related genes in circulating mononuclear cells (MNC) were measured.

Exenatide Increases IL-1RA Concentration and Induces Nrf-2‒Keap-1‒Regulated Antioxidant Enzymes: Relevance to β-Cell Function.

Purpose: We previously demonstrated the anti-inflammatory and antioxidant effects of exenatide. We now hypothesized that exenatide also increases the plasma concentration of interleukin-1 receptor antagonist (IL-1RA), an endogenous anti-inflammatory protein, and modulates the nuclear factor erythroid 2‒related factor‒Kelchlike ECH-associated protein 1‒antioxidant response element (Nrf-2‒Keap-1‒ARE) system to induce key antioxidant enzymes to suppress inflammatory and oxidative stress.

Methods: Twenty-four patients with obesity and type 2 diabetes receiving combined oral and insulin therapy were randomly assigned to receive either exenatide 10 μg or placebo twice a day for 12 weeks.

Diminished androgen and estrogen receptors and aromatase levels in hypogonadal diabetic men: reversal with testosterone.

Aims: One-third of males with type 2 diabetes (T2DM) have hypogonadism, characterized by low total and free testosterone concentrations. We hypothesized that this condition is associated with a compensatory increase in the expression of androgen receptors (AR) and that testosterone replacement reverses these changes. We also measured estrogen receptor and aromatase expression.

Ezetimibe and simvastatin combination inhibits and reverses the pro-inflammatory and pro-atherogenic effects of cream in obese patients.

Background And Aims: Inflammation and postprandial lipemia are associated with increased cardiovascular disease. We investigated whether ezetimibe and simvastatin combination, a lipid lowering combination of simvastatin and ezetimibe, exerts an anti-inflammatory effect in the fasting state and after dairy cream intake.

Methods: Twenty obese patients were randomized to either ezetimibe and simvastatin combination or placebo treatment for 6 weeks.

Liraglutide acutely suppresses glucagon, lipolysis and ketogenesis in type 1 diabetes.

In view of the occurrence of diabetic ketoacidosis associated with the use of sodium-glucose transport protein-2 inhibitors in patients with type 1 diabetes (T1DM) and the relative absence of this complication in patients treated with liraglutide in spite of reductions in insulin doses, we investigated the effect of liraglutide on ketogenesis. Twenty-six patients with inadequately controlled T1DM were randomly divided into 2 groups of 13 patients each. After an overnight fast, patients were injected, subcutaneously, with either liraglutide 1.

Antiinflammatory and ROS Suppressive Effects of the Addition of Fiber to a High-Fat High-Calorie Meal.

Background: Fiber intake is associated with a reduction in the occurrence of cardiovascular events and diabetes.

Objective: To investigate whether the addition of fiber to a high-fat, high-calorie (HFHC) meal prevents proinflammatory changes induced by the HFHC meal.

Design: Ten normal fasting subjects consumed an HFHC meal with or without an additional 30 g of insoluble dietary fiber on 2 separate visits.

Exenatide induces an increase in vasodilatory and a decrease in vasoconstrictive mediators.

In view of the known vasodilatory effects of glucagon-like peptide-1 and exenatide, we investigated the effects of exenatide on vasoactive factors. We analysed blood samples and mononuclear cells (MNCs) from a previous study, collected after a single dose and 12 weeks of exenatide or placebo treatment in a series of 24 patients with type 2 diabetes mellitus. After exenatide treatment, plasma concentrations of atrial natriuretic peptide, cyclic guanyl monophosphate (cGMP) and cyclic adenyl monophosphate increased significantly at 12 weeks.

Effect of testosterone on hepcidin, ferroportin, ferritin and iron binding capacity in patients with hypogonadotropic hypogonadism and type 2 diabetes.

Context: As the syndrome of hypogonadotropic hypogonadism (HH) is associated with anaemia and the administration of testosterone restores haematocrit to normal, we investigated the potential underlying mechanisms.

Design: Randomized, double-blind, placebo-controlled trial.

Methods: We measured basal serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin and transferrin receptor (TR) in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes.

Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes.

Objective: One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH.

Research Design And Methods: A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH.

Suppressive effect of insulin on the gene expression and plasma concentrations of mediators of asthmatic inflammation.

Background And Hypothesis: Following our recent demonstration that the chronic inflammatory and insulin resistant state of obesity is associated with an increase in the expression of mediators known to contribute to the pathogenesis of asthma and that weight loss after gastric bypass surgery results in the reduction of these genes, we have now hypothesized that insulin suppresses the cellular expression and plasma concentrations of these mediators.

Methods: The expression of IL-4, LIGHT, LTBR, ADAM-33, and TSLP in MNC and plasma concentrations of LIGHT, TGF-β1, MMP-9, MCP-1, TSLP, and NOM in obese patients with T2DM were measured before, during, and after the infusion of a low dose (2 U/h) infusion of insulin for 4 hours. The patients were also infused with dextrose or saline for 4 hours on two separate visits and served as controls.

Decreased insulin secretion and incretin concentrations and increased glucagon concentrations after a high-fat meal when compared with a high-fruit and -fiber meal.

This study was conducted to investigate whether a high-fat/high-carbohydrate (HFHC) meal induces an increase in plasma concentrations of glucagon, dipeptidyl peptidase-IV (DPP-IV), and CD26 expression in mononuclear cells (MNC) while reducing insulin, C-peptide, proinsulin, GIP, and GLP-1 concentrations. Ten healthy normal subjects were given either a 910-calorie HFHC meal or an American Heart Association (AHA) meal rich in fruit and fiber during the first visit and the other meal during the second visit in crossover design. Blood samples were collected at baseline and at 15, 30, 45, 60, 75, 90, 120, 180, and 300 min following the meal.

Increase in the mediators of asthma in obesity and obesity with type 2 diabetes: reduction with weight loss.

Objective: To determine whether the expression of key asthma related genes, IL-4, LIGHT, LTBR, MMP-9, CCR-2, and ADAM-33 in mononuclear cells and the plasma concentration of nitric oxide metabolites (NOM) and MMP-9 are increased in the obese, obese type 2 diabetics (T2DM) and in morbidly obese patients prior to and after gastric bypass surgery (RYGB).

Design And Methods: The expression of these genes in MNC and plasma concentrations of these indices was measured in healthy lean and in obese with and without T2DM and following RYGB in obese T2DM.

Results: The expression of IL-4, MMP-9, LIGHT and CCR-2 and plasma NOM concentrations was significantly higher in the obese subjects and in obese T2DM patients than in normal subjects.

Insulin infusion suppresses while glucose infusion induces Toll-like receptors and high-mobility group-B1 protein expression in mononuclear cells of type 1 diabetes patients.

The purpose of this study was to determine whether an insulin infusion exerts an anti-inflammatory effect and whether the infusion of small amounts of glucose results in oxidative and inflammatory stress in patients with type 1 diabetes. Ten patients with type 1 diabetes were infused with either 2 U/h of insulin with 100 ml 5% dextrose/h to or just dextrose (100 ml/h) or physiological saline (100 ml/h) for 4 h after an overnight fast on three separate days. Blood samples were collected at 0, 2, 4, and 6 h.

Sitagliptin exerts an antinflammatory action.

Context: Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-IV (DPP-IV), which degrades the incretins, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, and thus, sitagliptin increases their bioavailability. The stimulation of insulin and the suppression of glucagon secretion that follow exert a glucose lowering effect and hence its use as an antidiabetic drug. Because DPP-IV is expressed as CD26 on cell membranes and because CD26 mediates proinflammatory signals, we hypothesized that sitagliptin may exert an antiinflammatory effect.

Reduction in inflammation and the expression of amyloid precursor protein and other proteins related to Alzheimer's disease following gastric bypass surgery.

Objective: Obesity and type 2 diabetes are associated with an increase in the incidence and prevalence of Alzheimer's disease (AD) and an impaired cognitive function. Because peripheral blood mononuclear cells (MNC) express amyloid precursor protein (APP), the precursor of β-amyloid, which forms the pathognomonic plaques in the brain, we hypothesized that APP expression diminishes after the marked caloric restriction and weight loss associated with Roux-en-Y gastric bypass (RYGB) surgery.

Research Design And Methods: Fifteen type 2 diabetic patients with morbid obesity (body mass index, 52.

A resveratrol and polyphenol preparation suppresses oxidative and inflammatory stress response to a high-fat, high-carbohydrate meal.

Background: High-fat, high-carbohydrate (HFHC) meals are known to induce oxidative and inflammatory stress, an increase in plasma endotoxin concentrations, and an increase in the expression of suppressor of cytokine signaling-3 (SOCS-3).

Hypothesis: The intake of a nutritional supplement containing resveratrol and muscadine grape polyphenols reduces HFHC meal-induced oxidative and inflammatory stress and stimulates the activity of the antioxidant transcription factor, NF-E2-related factor-2 (Nrf-2), and its downstream targets.

Methods: Ten normal, healthy subjects were given a 930-kcal HFHC meal either with placebo or with the supplement.

An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol.

Background: Resveratrol have been shown to exert an antiinflammatory and antiaging effects in vitro and in animal models.

Objective: The objective of the study was to investigate the effect of a Polygonum cuspidatum extract (PCE) containing resveratrol on oxidative and inflammatory stress in normal subjects.

Research Design And Methods: Two groups (10 each) of normal-weight healthy subjects were randomized to placebo or PCE containing 40 mg resveratrol daily for 6 wk.