Novel Proteome Targets Marking Insulin Resistance in Metabolic Syndrome.

Context/objective: In order to better understand which metabolic differences are related to insulin resistance in metabolic syndrome (MetSyn), we used hyperinsulinemic-euglycemic (HE) clamps in individuals with MetSyn and related peripheral insulin resistance to circulating biomarkers.

Design/methods: In this cross-sectional study, HE-clamps were performed in treatment-naive men (n = 97) with MetSyn. Subjects were defined as insulin-resistant based on the rate of disappearance (Rd).

Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk.

Metabolic syndrome (MetSyn) is an important risk factor for type 2 diabetes and cardiovascular diseases (CVD). This study aimed to find distinct plasma metabolite profiles between insulin-resistant and non-insulin resistant subjects with MetSyn and evaluate if MetSyn metabolite profiles are related to CVD risk and lipid fluxes. In a cross-sectional study, untargeted metabolomics of treatment-naive males with MetSyn ( = 132) were analyzed together with clinical parameters.

Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.

The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce.

Plasma Metabolites Related to Peripheral and Hepatic Insulin Sensitivity Are Not Directly Linked to Gut Microbiota Composition.

Plasma metabolites affect a range of metabolic functions in humans, including insulin sensitivity (IS). A subset of these plasma metabolites is modified by the gut microbiota. To identify potential microbial-metabolite pathways involved in IS, we investigated the link between plasma metabolites, gut microbiota composition, and IS, using the gold-standard for peripheral and hepatic IS measurement in a group of participants with metabolic syndrome (MetSyn).

The effect of dapagliflozin on apolipoprotein B and glucose fluxes in patients with type 2 diabetes and well-controlled plasma LDL cholesterol.

Aim: To dissect the effects of the sodium-glucose linked transporter 2 inhibitor dapagliflozin on lipid metabolism and assess whether these effects could potentially offset cardiovascular benefit with this drug-class.

Materials And Methods: We assessed the effect of dapagliflozin on lipid metabolism in 11 adults with uncomplicated type 2 diabetes. After 4 weeks of statin wash-out and 4 weeks of rosuvastatin 10 mg treatment, participants were treated with dapagliflozin 10 mg once-daily for 5 weeks.

Akkermansia muciniphila Exerts Lipid-Lowering and Immunomodulatory Effects without Affecting Neointima Formation in Hyperlipidemic APOE*3-Leiden.CETP Mice.

Scope: Akkermansia muciniphila (A. muciniphila) is an intestinal commensal with anti-inflammatory properties both in the intestine and other organs. The aim is to investigate the effects of oral administration of A.

Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography.

Trillions of microorganisms inhabit the human gut and are regarded as potential key factors for health. Characteristics such as diet, lifestyle, or genetics can shape the composition of the gut microbiota and are usually shared by individuals from comparable ethnic origin. So far, most studies assessing how ethnicity relates to the intestinal microbiota compared small groups living at separate geographical locations.

Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects.

Background: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism.

Intestinal Ralstonia pickettii augments glucose intolerance in obesity.

An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects.

Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition.

The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition.

Role of the Gut Microbiome in the Pathogenesis of Obesity and Obesity-Related Metabolic Dysfunction.

The potential role of intestinal microbiota in the etiology of various human diseases has attracted massive attention in the last decade. As such, the intestinal microbiota has been advanced as an important contributor in the development of obesity and obesity-related metabolic dysfunctions, amongst others. Experiments in animal models have produced evidence for a causal role of intestinal microbiota in the etiology of obesity and insulin resistance.

Insights into the role of the microbiome in obesity and type 2 diabetes.

The worldwide prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise at an alarming pace. Recently the potential role of the gut microbiome in these metabolic disorders has been identified. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome seems to be more efficient in harvesting energy from the diet.

Therapeutic potential of fecal microbiota transplantation.

There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal conditions that were not previously considered to be associated with the intestinal microbiota. Although it is not clear if changes in the microbiota cause these conditions, we review the most current and best methods for performing fecal microbiota transplantation and summarize clinical observations that have implicated the intestinal microbiota in various diseases.

Ethnicity influences weight loss 1 year after bariatric surgery: a study in Turkish, Moroccan, South Asian, African and ethnic Dutch patients.

Several studies conducted in the USA have demonstrated that the effectiveness of bariatric surgery differs between patients from African and European origin. However, little is known on differences in outcomes after bariatric surgery between individuals from other ethnic backgrounds. In this retrospective study, we found that, in terms of weight loss, gastric bypass surgery is less effective in African, South Asian, Turkish and Moroccan patients than in their ethnic Dutch counterparts.

Infection-induced inflammatory response of adipocytes in vitro.

Background: Abdominal obesity plays an important role in the development of insulin resistance, diabetes mellitus and atherosclerosis. The exact pathophysiological mechanisms are unclear but adipocyte dysfunction is thought to be crucial. Infections are associated with the development of atherosclerosis as well as diabetes.

Infection induced inflammation is associated with erectile dysfunction in men with diabetes.

Background: In diabetic patients with erectile dysfunction, endothelial dysfunction is a major underlying cause. Infection-induced inflammation may be associated with endothelial dysfunction. The goal of this study was to determine whether erectile dysfunction in patients with diabetes is associated with infections of Chlamydia pneumoniae or cytomegalovirus and/or with low-grade inflammation.

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial.

Aims: The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes.

Methods: The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively.

Azithromycin reduces Chlamydia pneumoniae-induced attenuation of eNOS and cGMP production by endothelial cells.

Background: Intracellular infections with cytomegalovirus (CMV) or Chlamydia pneumoniae (Cp) may play a role in the aetiology of atherosclerosis. Nitric oxide (NO) is a key regulator of endothelial function. Under pathological conditions uncoupling of endothelial nitric oxide synthase (eNOS) leads to vessel damage as a result of production of oxygen radicals instead of NO.

Cytomegalovirus and Chlamydia pneumoniae as predictors for adverse events and angina pectoris after percutaneous coronary intervention.

Background: The aim of our study was to investigate the influence of prior cytomegalovirus (CMV) or Chlamydia pneumoniae (CP) infection on prognosis after percutaneous coronary intervention (PCI).

Methods: Using the enzyme-linked immunosorbent assay technique preprocedural anti-CMV immunoglobulin G and anti-CP immunoglobulin A (CP IgA), immunoglobulin M, and immunoglobulin G antibodies were measured. Repeat anginal complaints and major adverse clinical events (MACE), including PCI, coronary artery bypass grafting, myocardial infarction, and death, were recorded at 8-month follow-up.

Preprocedural serum levels of acute-phase reactants and prognosis after percutaneous coronary intervention.

Objective: In this study we evaluate the value of baseline concentrations of acute-phase reactants on prognosis after percutaneous coronary intervention (PCI).

Methods: Blood samples were drawn immediately before PCI to measure baseline concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), lipoprotein(a) (Lp(a)), and fibrinogen. Follow-up data were collected at 8 months.

Procoagulant and inflammatory response of virus-infected monocytes.

Background: Monocytes play a prominent role in inflammation, coagulation and atherosclerosis by their ability to produce tissue factor (TF) and cytokines. The aim of the present study was to establish whether virus-infected monocytes initiate coagulation. In addition, the production of cytokines by monocytes may accelerate the chronic process of atherosclerosis and may contribute to coronary syndromes by eliciting plaque instability.

Procoagulant activity of endothelial cells after infection with respiratory viruses.

Influenza virus epidemics are associated with excess mortality due to cardiovascular diseases. There are several case reports of excessive coagulation during generalised influenza virus infection. In this study, we demonstrate the ability of respiratory viruses (influenza A, influenza B, parainfluenza-1, respiratory syncytial virus, adenovirus, cytomegalovirus) to infect lung fibroblasts and human umbilical vein endothelial cells in culture.

Rapid and short-acting mealtime insulin secretion with nateglinide controls both prandial and mean glycemia.

Objective: The objective of the study was to assess the efficacy and safety of four fixed doses of nateglinide compared with placebo in the treatment of patients with type 2 diabetes with focus on the prandial state.

Research Design And Methods: This randomized double-blind placebo-controlled multicenter study was conducted in 289 patients who received either nateglinide at doses of 30 mg (n = 51), 60 mg (n = 58), 120 mg (n = 63), or 180 mg (n = 57) or placebo (n = 60) before three main meals for 12 weeks. Levels of HbA1c, fasting plasma glucose (FPG), fructosamine, and plasma lipids were measured at predetermined intervals, and the effects of nateglinide on prandial glucose insulin, C-peptide, and triglyceride levels were measured after a liquid standard meal (Sustacal; Mead Johnson, Evansville, IN).

Asymptomatic bacteriuria may be considered a complication in women with diabetes. Diabetes Mellitus Women Asymptomatic Bacteriuria Utrecht Study Group.

Objective: To study the prevalence of and risk factors for asymptomatic bacteriuria (ASB) in women with and without diabetes.

Research Design And Methods: A total of 636 nonpregnant women with diabetes (type 1 and type 2) who were 18-75 years of age and had no abnormalities of the urinary tract, and 153 women without diabetes who were visiting the eye and trauma outpatient clinic (control subjects) were included. We defined ASB as the presence of at least 10(5) colony-forming units/ml of 1 or 2 bacterial species in a culture of clean-voided midstream urine from an individual without symptoms of a urinary tract infection (UTI).

Interleukin-6 production by endothelial cells after infection with influenza virus and cytomegalovirus.

Inflammation plays a role in the pathogenesis of cardiovascular diseases. Viruses may be a cause of chronic inflammation, and both influenza virus and CMV have been associated with cardiovascular diseases. IL-6, a proinflammatory cytokine with antiviral effects, has a pivotal role in the immune response, and under pathologic conditions, prohemostatic effects of IL-6 could lead to pathologic thrombosis and vascular plaque instability.