Accelerated up-titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [PONTIAC]; NCT00562952).

BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events. METHODS We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery. RESULTS Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A1c, and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001). CONCLUSIONS The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.

Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart–gut–brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

(NT-proBNP) increase in response to volume overload and help in the differential diagnosis of acute heart failure. Elevated plasma BNP levels are observed also in sepsis and do not always correspond to left ventricular dysfunction. Here, we investigated plasma NT-proBNP fluctuations in response to human bacterial endotoxinemia, an experimental model of systemic infection and inflammation. Escherichia coli endotoxin (LPS) (2 ng/kg) was administered to 10 healthy volunteers in a randomized, placebo-controlled, cross-over design. Plasma NTproBNP, C-reactive protein (CRP), COOH terminal pro-endothelin-1 (CT-proET-1), and midregional-pro-adrenomedullin (MR-proADM) were measured at hourly intervals for 6 h. LPS administration induced a continuous increase in plasma NT-proBNP that reached peak values after 6 h (40.7 Ϯ 7.9 vs. 16.1 Ϯ 3.2 pg/ml in placebo days, mean Ϯ SE; P ϭ 0.023). The profile of changes in NT-proBNP correlated to changes in body temperature (P Ͻ 0.001), heart rate (P ϭ 0.005), CRP (P Ͻ 0.001), and CT-proET-1 (P ϭ 0.008), but not to blood pressure values. Our results demonstrate that plasma NT-proBNP increases in a model of systemic infection/inflammation in healthy men with normal heart function. This finding emphasizes the necessity to consider concomitant infections when interpreting elevated circulating NT-proBNP concentrations.B-type natriuretic peptide; C-reactive protein; bacterial endotoxin; infection; inflammation; human B-TYPE NATRIURETIC PEPTIDE (BNP) is secreted from atria and ventricles in response to volume load and myocardial wall stress (6, 24). It promotes vasodilatation, natriuresis, and diuresis (6). In the circulation, the prohormone is cleaved into two peptides: the physiologically active BNP and the inactive NH 2 -terminal-proBNP (NT-proBNP) (1). NT-proBNP has higher plasma levels and a longer half-life and therefore slower fluctuations (6). BNP and NT-proBNP are both helpful in the diagnosis of cardiac dysfunction and heart failure (16, 29) and equivalent in the prognosis of ischemic heart disease (21). Even modest elevations of the peptides are associated with increased risk of cardiovascular events, heart failure, stroke, and all-cause mortality (2, 34).BNP and NT-proBNP plasma levels depend on age and gender, are altered in the presence of renal disease and obesity (6), and are elevated in sepsis (3, 4). NT-proBNP correlates to the Acute Physiology and Chronic Health Evaluation scores and is found to be a prognostic marker in sepsis and septic shock (3, 4). Elevated BNP levels in sepsis might be attributed to the underlying myocardial dysfunction (32). Nevertheless, BNP is elevated also in septic patients with neither clinical nor echocardiographic evidence of left ventricular systolic dysfunction (26). Moreover, increased plasma BNP is found also in patients with infections in the absence of severe sepsis or septic shock (18). The existence of a direct association between infections and BNP is supported by evidence from preclinical studies, since LPS and pro-inflammatory c...

This position statement presents the recommendations of the Austrian Diabetes Association for diabetes management of adult patients during inpatient stay. It is based on the current evidence with respect to blood glucose targets, insulin therapy and treatment with oral antidiabetic drugs during inpatient hospitalization. Additionally, special circumstances such as intravenous insulin therapy, concomitant therapy with glucocorticoids and use of diabetes technology during hospitalization are discussed.