Search

Diabet. Med. 29, 721-725 (2012) Abstract Background Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes. Methods In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded. Results The median duration of diabetes was 11 ± 10.35 years. Patients were in the mean 60 ± 13 years old and mean HbA1c was 62 ± 13 mmol/mol (7.8 ± 3.3%). At baseline, mean uric acid was 321.2 ± 101.1 μmol/l (range 101.1-743.5 μmol/l), median N-terminal pro-B-type natriuretic peptide was 92 ± 412 pg/ml and median urinary albumin to creatinine ratio was 8 ± 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide ( r = 0.237, P < 0.001) and urinary albumin:creatinine ratio ( r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model. Conclusion Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro-B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes. [ABSTRACT FROM AUTHOR]

Presents information pertaining to the distribution and kinetics of amylin in humans. Performance of an intravenous injection; Analysis of the plasma levels of amylin concentrations; How amylin is secreted; Calculation of the noncompartmental parameters.

Presents information on a study which aimed to determine the apparent volume of distribution, total body clearance, fractional clearance and mean residence time (MRT) of the beta-cell hormone amylin in humans. Subjects and study design; Data analysis; Discussion of results.

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. [ABSTRACT FROM AUTHOR]

Background: Sunitinib and sorafenib are tyrosine kinase inhibitors that have important antitumor activity in metastatic renal cell carcinoma (mRCC). Hypothyroidism constitutes a commonly reported side effect of both drugs, and particularly of sunitinib. The objective of this analysis was to investigate whether the occurrence of hypothyroidism during treatment with sunitinib and sorafenib affects the outcome of patients with mRCC.Methods: Eighty-seven consecutive patients with mRCC who were to receive treatment with sunitinib or sorafenib were included in a prospective analysis. Thyroid function was assessed in each patient every 4 weeks during the first 2 months of treatment and every 2 to 4 months thereafter. Assessment included serum levels of thyroid-stimulating hormone (TSH), tri-iodthyronine (T3), and thyroxine (T4). Subclinical hypothyroidism was defined as an increase in TSH above the upper limit of normal (>3.77 μM/mL) with normal T3 and T4 levels.Results: Subclinical hypothyroidism was evident in 5 patients at baseline and occurred in 30 patients (36.1%) within the first 2 months after treatment initiation. There was a statistically significant correlation between the occurrence of subclinical hypothyroidism during treatment and the rate of objective remission (hypothyroid patients vs euthyroid patients: 28.3% vs 3.3%, respectively; P < .001) and the median duration of survival (not reached vs 13.9 months, respectively; hazard ratio, 0.35; 95% confidence interval, 0.14-0.85; P = .016). In multivariate analysis, the development of subclinical hypothyroidism was identified as an independent predictor of survival (hazard ratio, 0.31; P = .014).Conclusions: The current results indicated that hypothyroidism may serve as a predictive marker of treatment outcome in patients with mRCC. Thus, the interpretation of hypothyroidism during treatment with sunitinib and sorafenib as an unwanted side effect should be reconsidered. [ABSTRACT FROM AUTHOR]

Abstract Background The role of amylin, which is cosecreted together with insulin by the pancreatic B-cells, in the pathogenesis of type-2 diabetes is still unclear. To elucidate a possible relation between amylin and glucagon we directly evaluated the respective prehepatic secretions following administration of a 75-g oral glucose load (OGL) in humans. Materials and methods We studied six healthy controls (C), six obese, insulin resistant subjects (O) and six patients with type 2 diabetes (D). Catheters were placed in the femoral artery and hepatic vein according to the hepatic vein catheterization technique. Splanchnic blood flow was assessed by infusion of indocyanine-green dye. The measured variables were analyzed by a general circulatory model for calculation of prehepatic secretion. Results The total amount of released glucagon was not different between the respective groups (20·5 ± 2·3 in C, 27·7 ± 5·1 in O and 27·9 ± 5·4 µg/4 h in D). When considered as the difference from the fasting profile, however, glucagon secretion was reduced by 3·5 ± 14% in C, 25 ± 12% in O and increased by 36 ± 21% in D (P = 0·051, D vs. C). Amylin secretion was increased in O (1·10 ± 0·15) vs. C (0·63 ± 0·05, P < 0·05) and D (0·24 ± 0·10 nmol, P < 0·01). Following glucose administration, glucagon secretion significantly inversely correlated with secretion of amylin ( r = -0·6, P < 0·01), but not with that of insulin ( r =-0·23, P = 0·36). Conclusions The inverse correlation between amylin and glucagon secretion suggests that amylin modulates glucagon secretion following oral glucose administration. This study proves for the first time a role of endogenous amylin in the regulation of glucose homeostasis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the relation between plasma leptin concentrations and metabolic control in human diabetes mellitus. DESIGN AND SUBJECTS: Cross sectional study consisting of 156 patients with diabetes mellitus type 1 (n=42), type 2 (n=114), and non-diabetic subjects (n=74). RESULTS: Plasma leptin concentrations were lower (P<0.05) in type 1 (8.3±1.7 ng/ml) and type 2 diabetic (14.9±1.8 ng/ml) than in non-diabetic humans (18.3±1.9 ng/ml). Only female type 1 and type 2 diabetic subjects also had decreased leptin/BMI ratios (P<0.05 vs non-diabetic females). The log rank test identified age-adjusted correlation of plasma leptin concentration with sex (P<0.0004) and body mass index (P<0.0218), but not with glycosylated haemoglobin A1c (P>0.5) in all groups. Plasma leptin was correlated with age (P<0.0058) and serum triglycerides (P<0.0199) in type 1 diabetic patients, and with serum cholesterol (P<0.0059) and LDL (P<0.0013) in type 2 diabetic patients. CONCLUSIONS: Defective leptin production and/or secretion might be present independently of metabolic control in female patients with type 1 or type 2 diabetes mellitus. International Journal of Obesity (2000) 24, 976–981 [ABSTRACT FROM AUTHOR]

Background: Based on the complex pathophysiology of type 2 diabetes and atherosclerosis we hypothesized a dynamic change in prognostic value of cardiovascular biomarkers over time.Methods: In this prospective study 746 patients with type 2 diabetes mellitus, being followed up for 60 months were analysed. The primary endpoint was defined as unplanned hospitalization for cardiovascular disease or death. Beside others, especially the prognostic performance of the biomarkers of interest (GDF-15, NT-proBNP, hs-TnT) was evaluated in relation to quartiles of diabetes duration.Results: In patients having a diabetes duration below 7 years lnGDF-15 (HR 2.84; p < 0.01) and lnhs-TnT (HR 2.96; p < 0.01) were significant predictors of the primary endpoint. LnAge (HR 40.01; p < 0.01) and lnNT-proBNP (HR 1.56; p = 0.03) were significant predictors in patients with a diabetes duration between 7 and 12 years. In the third quartile (diabetes duration 12-22 years) lnurinary albumin to creatinine ratio (HR 1.25; p = 0.005) and lnNT-proBNP (HR 2.13, p < 0.001) predicted the endpoint. In patients with a diabetes duration above 22 years, lnAge (HR 75.35; p = 0.001) and lnNT-proBNP (HR 2.0; p < 0.01) were the only significant predictors of the endpoint.Conclusion: Prognostic power of cardiovascular biomarkers changes dynamically in relation to duration of type 2 diabetes mellitus. In patients with shorter duration of the disease markers of subclinical cardiovascular dysfunction and inflammation perform better than markers of systemic advanced organ dysfunction and cardiovascular disease. [ABSTRACT FROM AUTHOR]