Following RYGB surgery, changes in serum vaspin concentrations correlate significantly with the reduction of circulating leptin, insulin, and C-peptide levels and with the amelioration of insulin sensitivity. However, further studies have to elucidate whether vaspin is only a biomarker for body-weight-related changes of insulin sensitivity or whether it is implicated in the regulation of human glucose homeostasis.

Background and Aims Determinants of fatty liver (FL) might be predictive for further deterioration in insulin resistance (IR) in women with previous gestational diabetes (pGDM). The aim was to evaluate the association between pGDM, FL and future manifestation of type 2 diabetes (T2DM) by a detailed pathophysiological characterization early after pregnancy. Methods 68 pGDM and 29 healthy controls were included 3–6 months after delivery and underwent specific metabolic assessments: status of IR was determined via oral- and intravenous-glucose-tolerance-tests with analysis of proinflammatory factors and kinetics of free-fatty-acids (FFA). According to the fatty-liver-index (FLI), pGDMs were categorized into three groups with low (FLI≤20), intermediate (20

Our initial experience suggests that, without additional immunosuppressive measures, bortezomib has modest effects on circulating antibodies against HLA or blood group antigens. The reduced levels of antibody-triggered complement fixation, however, imply potential clinical relevance of proteasome inhibition for recipient desensitization.

Rationale: Left ventricular hypertrophy (LVH) is highly prevalent in patients with chronic kidney disease and increases their risk of cardiac events and mortality. Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) levels, which are associated with the development of LVH, rise progressively with declining renal function. Objective: To determine whether FGF23 suppression by calcimimetic therapy may reduce LVH progression in comparison to FGF23 elevation under vitamin D analogs at equal PTH suppression under either therapy as well as tight volume control. Methods and Results: We conducted a single-blinded trial with 1:1 block randomization to investigate the effect of the intravenous treatment with etelcalcetide (ETL) versus alfacalcidol (ALFA) on LVH progression in 62 maintenance hemodialysis patients with secondary hyperparathyroidism and LVH. In the intention-to-treat analysis of 59 patients, the mean difference in the change of left ventricular mass index (LVMI) determined by cardiac magnetic resonance imaging from baseline to 12 months of treatment was -6.9 g/m² (95% confidence interval [CI] -12.6 to -1.2, p=0.022) in the ETL compared to the ALFA group. The effect estimate was -8.2 g/m² (95% CI -14 to -2.4) in the per-protocol analysis on 52 patients. The trajectories of PTH, phosphate and Klotho were similar in both groups throughout follow-up. FGF23 levels, which showed a strong positive association with LVMI, were decreasing under ETL and increasing under ALFA at similar PTH suppression. Mild hypocalcemia was the most common adverse event under ETL. Blood pressure and the distribution of antihypertensive medications were similar between groups. Conclusions: In this trial we were able to show that FGF23 suppression by ETL inhibited the progression of LVH compared to ALFA in hemodialysis patients. A successful prevention of increasing hypertrophy may reduce the risk of sudden cardiac death in this population.

BackgroundAging and insulin resistance have been related to reduced mitochondrial function and oxidative stress. Muscular phosphodiesters (PDE) are comprised of metabolites of phospholipid breakdown and may reflect membrane damage. We aimed to test the hypothesis that myocellular PDE are increased in patients with type 2 diabetes (T2D) and correlate inversely with mitochondrial ATP turnover.MethodsA Cross-sectional study in the Clinical Research Facility of an University hospital was performed. 10 nonobese middle-aged patients with T2D, 10 healthy humans matched for sex, age and physical activity index (CONm) and 18 young healthy humans (CONy) were included. Myocellular PDE and unidirectional flux through ATP synthase (fATP) were measured with 31P magnetic resonance spectroscopy (MRS). Intramyocellular (IMCL) and hepatocellular lipid deposition (HCL) were quantified with 1H MRS. Insulin sensitivity (Rd) was assessed from hyperinsulinemic-euglycemic clamp tests in 10 T2D, 10 CONm and 11 CONy.ResultsDuring fasting, T2D and CONm had 1.5 fold greater PDE than CONy (2.8±0.2, 2.5±0.2, 1.7±0.1 mmol/l, P = 0.004). Stimulation by insulin did not affect PDE in any group. PDE correlated negatively with Rd (r = −0.552, p<0.005) and fATP (r = −0.396, p<0.05) and positively with age (r = 0.656, p<0.001) and body mass (r = 0.597, p<0.001). PDE also related positively to HbA1c (r = 0.674, p<0.001) and fasting plasma glucose (r = 0.629, p<0.001) within T2D and across all participants.ConclusionsMuscular PDE concentrations associate with age, lower resting mitochondrial activity and insulin resistance, which is determined mainly by body mass and glycemia.