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Lower serum prohepcidin levels associated with lower iron and erythropoietin requirements in hemodialysis patients with chronic hepatitis C.
Caliskan, Y, Yelken, B, Ozkok, A, Gorgulu, N, Yazici, H, Telci, A, Yildiz, A
BMC nephrology. 2012;:56
Abstract
BACKGROUND Patients with chronic HCV infection have increased liver iron. Recently identified protein hepcidin synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. Lower erythropoietin and iron supplementation requirements were previously reported in HD patients with HCV infection. We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection. METHODS Sixty patients (27 male, 33 female, mean age 50±15 years) on chronic HD were included. Parameters related to iron metabolism (ferritin, serum iron and total iron binding capacity (TIBC)), inflammation (hs-CRP, TNF-α and IL-6) and prohepcidin levels were measured. The response to treatment (erythropoiesis-stimulating agent (ESA) resistance index) was assessed from the ratio of the weekly erythropoietin (rhuEPO) dose to hemoglobin (Hb) per unit weight. RESULTS Serum prohepcidin levels of HCV positive patients (135±25 ng/mL) were significantly lower than HCV negative patients [148±18 ng/mL, (p=0.025)]. Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients (p=0.016). Serum prohepcidin levels were positively correlated with ferritin (r=0.405, p=0.001) and IL-6 (r=0.271, p=0.050) levels in HD patients. In the HCV positive group, serum prohepcidin levels significantly correlated with ferritin levels (r=0.514 p=0.004). In the HCV negative group, serum prohepcidin levels significantly correlated with serum IL-6 levels (r=0.418, p=0.027). In multiple regression analysis performed to predict prohepcidin in HCV positive patients, serum ferritin was found to be an independent variable (r=0.28, p=0.008). CONCLUSIONS HCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation together with lower iron and rhuEPO requirements in these patients.
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Influence of physical exercise and relationship with biochemical variables of NT-pro-brain natriuretic peptide and ischemia modified albumin.
Lippi, G, Salvagno, GL, Montagnana, M, Schena, F, Ballestrieri, F, Guidi, GC
Clinica chimica acta; international journal of clinical chemistry. 2006;(1-2):175-80
Abstract
BACKGROUND The diagnostic approach and the clinical management of patients presenting with suspected acute coronary syndrome or cardiac dysfunction are as yet challenging. Although ischemia modified albumin (IMA) and natriuretic peptides were recently proposed for detection of myocardial ischemia and cardiac dysfunction, little information is available on preanalytical and metabolic sources of variability of these markers. METHODS To establish the influence of a regular endurance training and the relationship with conventional biochemical variables, NT-pro-brain natriuretic peptide (NT-proBNP) and IMA were assayed, along with cardiac troponin T (cTnT), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine and albumin, in 35 sedentary healthy individuals and 50 male professional road cyclists, 12-24 h following the last demanding training session. RESULTS Athletes displayed higher values of both LDH (299+/-61 vs. 257+/-36 U/l, P=0.002) and CK (184+/-123 vs. 115+/-74 U/l, P=0.011), and slightly lower concentrations of creatinine (82+/-12 vs. 87+/-9 micromol/l, P=0.044). No athlete or sedentary control displayed cTnT concentrations exceeding the lower sensitivity limit of the assay. As compared to the sedentary controls, main IMA concentration was increased in athletes (100+/-13 vs. 94+/-6 KU/l, P=0.035), whereas that of NT-proBNP appeared significantly decreased (2.8+/-1.6 vs. 4.3+/-34, P=0.005). The percentage of subjects displaying values exceeding the upper reference limit for the IMA assay was significantly different between athletes and sedentary controls (50% vs. 7%; P<0.001). Pearson correlation analysis revealed an inverse association between IMA and albumin in both athletes (r=-0.640; P<0.001) and sedentary controls (r=-0.583; P=0.001). CONCLUSIONS Results of our investigation indicate that a demanding and regular aerobic training regimen, though able to trigger skeletal muscle sufferance, is not associated with any biochemical sign of severe and irreversible chronic cardiac involvement. Moreover, we suggest the adoption of specific IMA diagnostic thresholds following patients' stratification according to serum albumin concentration and physical activity.
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Glucagon-like peptide 1 (GLP-1) secretion and plasma dipeptidyl peptidase IV (DPP-IV) activity in morbidly obese patients undergoing biliopancreatic diversion.
Lugari, R, Dei Cas, A, Ugolotti, D, Barilli, AL, Camellini, C, Ganzerla, GC, Luciani, A, Salerni, B, Mittenperger, F, Nodari, S, et al
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2004;(2):111-5
Abstract
BACKGROUND The physiological inhibitory control of glucagon-like Peptide 1 (GLP-1) on gastric emptying and the contribution of this peptide in the regulation of food intake as a satiety factor suggest that impaired secretion and/or activity of GLP-1 may be involved in the pathogenesis of obesity. We investigated food-mediated GLP-1 secretion as well as plasma activity of dipeptidyl-peptidase IV (DPP-IV), the enzyme responsible for rapid inactivation of the circulating peptide, in morbidly obese patients, before and after weight loss resulting from biliopancreatic diversion. METHODS Twenty-two morbidly obese non-diabetic patients (BMI = 47.5 +/- 1.8) and 9 age-matched healthy volunteers were studied. A mixed meal (700 kcal) was administered to all subjects and blood samples were collected at 0, 15, 30, 60, 120 min for the determination of circulating glucose, insulin, GLP-1 (7 - 36 amide) concentrations and plasma DPP-IV activity. The patients repeated the test meal after 50 % overweight reduction resulting from surgical treatment (BMI = 33.8 +/- 1.1). RESULTS While nutrient ingestion significantly increased plasma GLP-1 levels in the control group (30', 60': p < 0.01), the test-meal failed to modify basal peptide values in the obese patients, and an overall reduction in circulating GLP-1 occurred during the observation period (p < 0.001). Plasma DPP-IV activity in the same patients resulted as being significantly higher than controls, both at fasting and in response to the meal (p < 0.05). With respect to preoperative values, an overall increase in circulating GLP-1 levels occurred in all patients following biliopancreatic diversion (p < 0.001). Plasma DPP-IV activity, on the other hand, continued to be abnormally increased, even after considerable weight loss (p < 0.05 vs. controls). CONCLUSIONS First: In morbid obesity, the accelerated inactivation of circulating GLP-1 could at least partially account for plasma peptide levels lower than normal, the defective availability of such a satiety factor possibly contributing to eating behaviour abnormalities; Second: plasma DPP-IV hyperactivity in the obese did not seem to be affected by the overweight degree, the increase in postoperative GLP-1 levels mainly resulting from hyperstimulation of GLP-1 secretory cells due to surgical manipulation of gastrointestinal tract. If the abnormally accelerated degradation of GLP-1 in obesity is confirmed, selective DPP-IV inhibitors could actually represent an ideal approach to obesity management.
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Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study.
Zander, M, Madsbad, S, Madsen, JL, Holst, JJ
Lancet (London, England). 2002;(9309):824-30
Abstract
BACKGROUND Glucagon-like peptide 1 (GLP-1) has been proposed as a treatment for type 2 diabetes. We have investigated the long-term effects of continuous administration of this peptide hormone in a 6-week pilot study. METHODS 20 patients with type 2 diabetes were alternately assigned continuous subcutaneous infusion of GLP-1 (n=10) or saline (n=10) for 6 weeks. Before (week 0) and at weeks 1 and 6, they underwent beta-cell function tests (hyperglycaemic clamps), 8 h profiles of plasma glucose, insulin, C-peptide, glucagon, and free fatty acids, and appetite and side-effect ratings on 100 mm visual analogue scales; at weeks 0 and 6 they also underwent dexascanning, measurement of insulin sensitivity (hyperinsulinaemic euglycaemic clamps), haemoglobin A(1c), and fructosamine. The primary endpoints were haemoglobin A(1c) concentration, 8-h profile of glucose concentration in plasma, and beta-cell function (defined as the first-phase response to glucose and the maximum insulin secretory capacity of the cell). Analyses were per protocol. FINDINGS One patient assigned saline was excluded because no veins were accessible. In the remaining nine patients in that group, no significant changes were observed except an increase in fructosamine concentration (p=0.0004). In the GLP-1 group, fasting and 8 h mean plasma glucose decreased by 4.3 mmol/L and 5.5 mmol/L (p<0.0001). Haemoglobin A(1c) decreased by 1.3% (p=0.003) and fructosamine fell to normal values (p=0.0002). Fasting and 8 h mean concentrations of free fatty acids decreased by 30% and 23% (p=0.0005 and 0.01, respectively). Gastric emptying was inhibited, bodyweight decreased by 1.9 kg, and appetite was reduced. Both insulin sensitivity and beta-cell function improved (p=0.003 and p=0.003, respectively). No important side-effects were seen. INTERPRETATION GLP-1 could be a new treatment for type 2 diabetes, though further investigation of the long-term effects of GLP-1 is needed.