Dominik G. Haider

Increased visfatin concentrations in women with gestational diabetes mellitus

The recently discovered adipocytokine visfatin has insulin-like properties. It lowers blood glucose and improves insulin sensitivity; however, clinical data on visfatin are limited. To evaluate the role of visfatin in GDM (gestational diabetes mellitus), we determined visfatin levels in women with GDM and in healthy pregnant controls. Furthermore, visfatin concentrations were investigated longitudinally during pregnancy and after delivery in a subgroup of women with GDM. Blood for measurement of visfatin and metabolic parameters was obtained from 64 women with GDM [median week of gestation, 34 (interquartile range, 27-36) weeks] and 30 healthy pregnant controls [median week of gestation, 34 (interquartile range, 28-36) weeks]. In a subgroup of 24 women with GDM, visfatin, leptin and metabolic parameters were investigated twice during pregnancy (28-30 and 38-40 weeks of gestation) and 2 weeks after delivery. In the cross-sectional analysis, median visfatin levels were significantly elevated in women with GDM [64.0 (interquartile range, 50.9-74.8) ng/ml] compared with controls [46.0 (interquartile range, 36.9-54.6) ng/ml; P<0.0001]. In women with GDM, visfatin correlated with week of gestation at the time of blood draw (R=0.35, P=0.005). No association with fasting glucose, insulin, homoeostasis model assessment-insulin resistance or body mass index was observed. According to the longitudinal analysis, visfatin increased during pregnancy (P=0.002) and rose further after delivery (P=0.014), whereas leptin and insulin levels decreased after parturition (both P<0.001). In conclusion, visfatin is elevated in women with GDM and increases during the course of pregnancy as well as after delivery. Furthermore, visfatin shows no association with insulin and leptin in women with GDM.

The adipokine visfatin is markedly elevated in obese children.

Objective: The insulin-mimetic adipocytokine visfatin has been linked to adiposity and the metabolic syndrome. Design Cross-sectional study. Subjects: Eighty-three nondiabetic obese children and 40 healthy controls. Measurements: We analyzed plasma visfatin concentrations to assess whether this adipokine is associated with adiposity. Results: Plasma visfatin concentrations were nearly 2-fold higher in obese children (mean, 1.1 ng/mL; 95% CI, 0.2-6.6) than in controls (0.6 ng/mL, 95% CI, 0.6 to 0.6; P < 0.001). No relationship was detectable between visfatin and other subject characteristics, hsCRP or the lipid profile. Conclusions: Visfatin may be involved in the development of metabolic derangements in obese children.

Asymmetric Dimethylarginine Enhances Cardiovascular Risk Prediction in Patients With Chronic Heart Failure

Objective—The purpose of this study was to investigate whether elevated asymmetrical dimethylorginine (ADMA) concentrations are associated with increased cardiovascular risk in chronic heart failure (HF) patients. Methods and Results—253 patients with symptomatic chronic HF and impaired left ventricular function (median age 70 years, 202 males) were followed for a median of 14.2 months (interquartile range 6.8 to 21.2). ADMA and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assessed by high performance liquid chromatography and by an enzyme-linked immunosorbent assay, respectively. Subjects with ADMA concentrations in the highest tertile had a significantly higher adjusted hazard ratio (HR; 2.00; 95% confidence interval [CI] 1.01 to 3.97) for occurrence of an end point (cardiac decompensation, major adverse cardiovascular events or all-cause mortality) compared with patients in the lowest tertile (P=0.046) during the first 6 months of follow-up. NT-proBNP also identified subjects at risk before adjustment for confounders at 6 and 12 months of follow-up. HR for patients with ADMA and NT-proBNP in the highest tertile was significantly increased (3.68, CI 1.67 to 8.14; at 6 months follow-up) compared with patients without ADMA and NT-proBNP in the highest tertile (P<0.001). Conclusions—Elevated ADMA plasma concentrations are associated with adverse cardiovascular outcome in patients with chronic HF. Quantification of ADMA with NT-proBNP improves risk stratification in this cohort.

Angiotensin inhibition stimulates PPARγ and the release of visfatin

Background  Angiotensin converting enzyme inhibitors (ACE‐I) and angiotensin receptor blockers (ARB) exhibit beneficial antidiabetic effects in patients with type 2 diabetes independent of their blood pressure‐lowering effects. Some antidiabetic properties of ARB and ACE‐I might by exerted by activation of peroxisome proliferator‐activated receptor gamma (PPARγ). However, it is not clear whether this action is drug specific.

Plasma adipocyte and epidermal fatty acid binding protein is reduced after weight loss in obesity

Aim:  Plasma adipocyte fatty acid binding protein (A‐FABP) and epidermal fatty acid binding protein (E‐FABP) concentrations have been linked to obesity and the metabolic syndrome. In this study, we investigated whether plasma A‐FABP and E‐FABP concentrations are altered by weight loss in obese patients.

Effect of Rosiglitazone on Visfatin and Retinol‐Binding Protein‐4 Plasma Concentrations in HIV‐Positive Patients

Thiazolidinediones (TZD) may improve insulin resistance in patients with diabetes and HIV. The novel adipocytokines visfatin and retinol‐binding protein‐4 (RBP‐4) have been proposed to influence the development of impaired glucose tolerance. The impact of TZD on these cytokines is yet unknown. In this randomized, double‐blind, placebo‐controlled parallel group study, 37 lean HIV‐positive subjects aged 19–50 years were treated with 8 mg/day rosiglitazone (n=20) or placebo (n=17) for 6 months. Insulin sensitivity was estimated from the homeostasis model assessment (HOMA) index. Fasting visfatin, RBP‐4, leptin, and adiponectin plasma concentrations were analyzed by immunoassays. Rosiglitazone had no effect on impaired insulin sensitivity, but increased median plasma visfatin from 6.2 ng/ml (95% CI: 5.9; 6.5) to 13.7 ng/ml (12.6; 19.1) (P<0.001) and adiponectin from 3.2 ng/ml (2.2; 4.0) to 4.0 ng/ml (3.3; 8.5; P<0.001). RBP‐4 was lowered from 21.0 ng/ml (19.6; 23.1) to 16.3 ng/ml (15.2; 17.0; P<0.001), and leptin concentrations were unchanged. Adipocytokine concentrations were stable in subjects receiving placebo, where a deterioration in insulin sensitivity was detectable (P<0.05). Changes in visfatin and RBP‐4 were correlated in subjects receiving rosiglitazone (r=−0.64, P<0.01) but not placebo (r=0.12, P=0.15). TZD treatment affects circulating adipocytokine concentrations in subjects with HIV. Reductions in RBP‐4 and increases in visfatin may contribute to the pharmacodynamic action of TZD on glucose homeostasis. Quantification of adipocytokines might be useful to assess TZD treatment effectiveness in insulin‐resistant subjects with HIV.

Natriuretic Peptides in Chronic Kidney Disease and During Renal Replacement Therapy: An Update

Natriuretic peptides play a major role in sodium and body volume homeostasis in patients with adequate kidney function. Circulating B-type natriuretic peptide (BNP) and its amino-terminal fragment NT-proBNP provide important information on cardiac dysfunction, hypervolemia, and risk for hospitalization or death even in patients with severe impairment of kidney function. NT-proBNP acts also as significant independent predictor of progression of chronic kidney disease (CKD). Differences in elimination and degradation as well as molecular weight and half-life between BNP and NT-proBNP are responsible for different plasma levels, different membrane-dependent removal during hemodialysis, and different diagnostic and prognostic power to predict morbidity and mortality in patients at different stages of CKD and in those on hemodialysis or peritoneal dialysis. Serial estimations of natriuretic peptides will help in the identification of potential complications in CKD patients with or without renal replacement therapies and probably improve outcome of these patients.

Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects.

Background  To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat‐derived factor retinol‐binding protein‐4 (RBP‐4) in HIV‐infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART).

Plasma asymmetric dimethylarginine and cardiovascular events in patients with acute decompensated heart failure

This prospective study investigated whether plasma asymmetric dimethylarginine (ADMA) concentrations are related to cardiovascular events in patients with acute heart failure. It has been reported that increased plasma ADMA concentrations are associated with adverse cardiovascular outcome in chronic heart failure. In 118 patients with acute decompensated heart failure and impaired left ventricular function, ADMA and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assessed by high-performance liquid chromatography and by an enzyme-linked immunosorbent assay, respectively. Venous blood was collected at admission and after 1 week, and clinical events were observed during follow-up. All patients (median age 73 years, 96 males) were followed up for a median of 10.7 months. A clinical endpoint (cardiac decompensation, major adverse cardiovascular event, or all-cause mortality) occurred in 66 patients. In 81 patients, changes (Delta) in ADMA or NT-proBNP between admission and a median of 7 days were available. ADMA, NT-proBNP at admission, and DeltaADMA or DeltaNT-proBNP were comparable in patients with and without a clinical endpoint. In contrast to ADMA, NT-proBNP concentrations above the median were associated with higher adjusted hazard ratio for occurrence of an endpoint (HR 2.1; 95% confidence interval 1.2-3.9; P = 0.013). An inverse relationship was observed between DeltaNT-proBNP and endpoints before (P = 0.010) and after (P = 0.015) adjustment for confounders. In patients with acute heart failure, ADMA did not detect patients at future cardiovascular risk.

Hypermagnesemia is a strong independent risk factor for mortality in critically ill patients: results from a cross-sectional study.

BACKGROUND Patients with electrolyte imbalances or disorders have a high risk of mortality. It is unknown if this finding from sodium or potassium disorders extends to alterations of magnesium levels. METHODS AND PATIENTS In this cross-sectional analysis, all emergency room patients between 2010 and 2011 at the Inselspital Bern, Switzerland, were included. A multivariable logistic regression model was performed to assess the association between magnesium levels and in-hospital mortality up to 28days. RESULTS A total of 22,239 subjects were screened for the study. A total of 5339 patients had plasma magnesium concentrations measured at hospital admission and were included into the analysis. A total of 6.3% of the 352 patients with hypomagnesemia and 36.9% of the 151 patients with hypermagnesemia died. In a multivariate Cox regression model hypermagnesemia (HR 11.6, p<0.001) was a strong independent risk factor for mortality. In these patients diuretic therapy revealed to be protective (HR 0.5, p=0.007). Hypomagnesemia was not associated with mortality (p>0.05). Age was an independent risk factor for mortality (both p<0.001). CONCLUSION The study does demonstrate a possible association between hypermagnesemia measured upon admission in the emergency department, and early in-hospital mortality.