Context: The insulin-mimetic adipocytokine visfatin has been linked to obesity. The influence of weight loss on plasma visfatin concentrations in obese subjects is unknown yet.
Objectives: In this ...study we investigated whether plasma visfatin concentrations are altered by weight loss in patients with obesity.
Design and Patients: In a prospective study, fasting plasma visfatin, leptin, and adiponectin concentrations were measured before and 6 months after gastric banding in 31 morbidly obese patients aged 40 ± 11 yr with a body mass index (BMI) of 46 ± 5 kg/m2. Fourteen healthy subjects aged 29 ± 5 yr with a BMI less than 25 kg/m2 served as controls.
Results: Visfatin plasma concentrations were markedly elevated in obese subjects (0.037 ± 0.008 μg/ml), compared with controls (0.001 ± 0.000 μg/ml, P < 0.001). Gastric banding reduced BMI to 40 ± 5 kg/m2, visfatin to 19.2 ± 10.9 ng/ml, and leptin from 39.0 ± 12.4 to 29.7 ± 10.0 ng/ml and increased adiponectin from 0.015 ± 0.007 to 0.017 ± 0.007 μg/ml (all P < 0.05) after 6 months. Insulin sensitivity as estimated by the homeostasis model assessment insulin resistance index was unchanged from 5.8 ± 3.1 to 4.6 ± 1.9 (P = 0.13), but individual changes of insulin resistance and visfatin were significantly associated (P < 0.05, r = −0.43).
Conclusions: Elevated plasma visfatin concentrations in morbidly obese subjects are reduced after weight loss. This may be related to changes in insulin resistance over time.
BACKGROUND—Obesity is generally accepted as a risk factor for premature atherosclerosis. Subclinical inflammation as quantified by blood levels of C-reactive protein (CRP) contributes to the ...development and progression of atherosclerosis. We hypothesized that inflammation in obese children is related to functional and early morphological vascular changes.
METHODS AND RESULTS—Blood levels of high sensitivity (hs) CRP, hsIL-6, the soluble intercellular adhesion molecule1 (ICAM-1), vascular cell adhesion molecule (VCAM)-1, and E-selectin were measured in 145 severely obese (body mass index BMI, 32.2±5.8 kg/m) and 54 lean (BMI, 18.9±3.2 kg/m) children 12±4 years old. Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measured by high-resolution ultrasound as markers of early vascular changes were assessed in 92 (77 obese and 15 lean) and 59 (50 obese and 9 lean) children, respectively. Obese children had significantly higher levels of hsCRP, hsIL-6, and E-selectin than healthy controls (4.1±4.8 versus 0.9±1.5 mg/L, P<0.001 for hsCRP; 1.99±1.30 versus 1.42±1.01 pg/mL, P=0.05 for hsIL-6; and 78±38 versus 59±29 ng/mL, P=0.01 for E-selectin). There were no differences in the levels of ICAM-1 and VCAM-1 between groups. Obese children had lower peak FMD response (7.70±6.14 versus 11.06±3.07%, P=0.006) and increased IMT (0.37±0.04 versus 0.34±0.03 mm, P=0.03) compared with controls. Morbidly obese children (n=14, BMI 44.1±3.9 kg/m) had highest levels of hsCRP (8.7±0.7 mg/L), hsIL-6 (3.32±1.1 pg/mL), and E-selectin (83±40 ng/mL).
CONCLUSIONS—A proinflammatory state is detectable in obese children, which is accompanied by impaired vascular endothelial function and early structural changes of arteries, even in young subjects at risk. It remains to be determined whether high hsCRP in obese children predicts cardiovascular events.
Therapeutic intervention programs for somatic symptom disorder (SSD) show only small-to-moderate effect sizes. These effects are partly explained by the motivational problems of SSD patients. Hence, ...fostering treatment motivation could increase treatment success. One central aspect in SSD patients might be damage to motivation because of symptomatic relapses. Consequently, the aim of the present study was to investigate associations between motivational relapse struggle and therapeutic outcome in SSD patients.
We assessed 84 inpatients diagnosed with SSD in the early, middle and late stages of their inpatient treatment. The maintenance subscale of the University of Rhode Island Change Assessment-Short (URICA-S) was applied as a measure to assess motivational relapse struggle. Additionally, patients completed measures of treatment outcome that focus on clinical symptoms, stress levels and interpersonal functioning.
The results from multiple regression analyses indicate that higher URICA-S maintenance scores assessed in early stages of inpatient treatment were related to more negative treatment outcomes in SSD patients.
SSD patients with ambivalent treatment motivation may fail in their struggle against relapse over the course of therapy. The URICA-S maintenance score assessed at therapy admission facilitated early identification of SSD patients who are at greater risk of relapse. Future studies should incorporate randomized controlled trials to investigate whether this subgroup could benefit from motivational interventions that address relapse.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
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.
There is growing evidence that statins exert anti-inflammatory and antioxidative vascular actions that are independent of lipid lowering. We tested whether hyporeactivity to the endothelium-dependent ...vasodilator acetylcholine (ACh) and the vasoconstrictor norepinephrine (NE) during acute experimental inflammation could be prevented by simvastatin.
In a randomized, placebo-controlled, parallel group study, forearm blood flow (FBF) responses to NE, ACh, and the endothelium-independent vasodilator nitroglycerin (NTG) were assessed at baseline, after 4 days of simvastatin 80 mg PO or placebo treatment, and during Escherichia coli endotoxin (lipopolysaccharide LPS)-induced inflammation in 20 healthy volunteers. Additionally, markers of inflammation and neutrophil oxidative burst were assessed. Simvastatin and placebo had no effect on FBF or oxidative/inflammatory markers. LPS administration decreased the responses of FBF to NE by 43% (P<0.05) and decreased responses to ACh by 48% (P<0.05) but did not decrease FBF responses to NTG. Simvastatin completely preserved responses to NE and to ACh. The LPS-induced increases in neutrophil oxidative burst and plasma tumor necrosis factor-alpha concentrations were mitigated by simvastatin (P<0.05 versus placebo).
This study demonstrates potent vasoprotective properties of high-dose simvastatin during endotoxemia that may be useful for patients with acute systemic inflammation and associated vascular hyporeactivity.
The stomach-derived peptide hormone ghrelin induces appetite and GH release. Several ghrelin actions are possibly mediated and modulated by the central cholinergic system. The aim of this study was ...to investigate the influence of the unspecific cholinergic antagonist atropine and the acetylcholine esterase inhibitor pyridostigmine, a cholinergic enhancer on ghrelin plasma concentrations and ghrelin-induced GH release. We investigated plasma ghrelin concentrations, ghrelin-induced GH release, and glucose and insulin concentrations after administration of atropine or pyridostigmine, and ghrelin (in two different doses, 0.25 and 1 μg/kg body weight), alone and in combination in a randomized, double-blind, placebo-controlled, crossover study design on 12 young, healthy male volunteers.
Atropine alone significantly reduced fasting ghrelin levels by 25%, whereas under pyridostigmine alone ghrelin levels were unaltered. Ghrelin in combination with atropine induced significantly reduced GH concentrations compared with ghrelin administration alone for both ghrelin doses, whereas ghrelin-induced GH peak concentrations and areas under the curve were not enhanced by pyridostigmine treatment. These results suggest that, in humans, fasting ghrelin concentrations might be under cholinergic control and that the cholinergic system appears to modulate ghrelin-induced GH release.
Ghrelin plasma concentrations increase during fasting and fall rapidly after nutrient ingestion. We hypothesized that insulin or glucose could regulate ghrelin secretion by a feedback mechanism. In ...this randomized, double-blind, placebo-controlled crossover study, three different study days were carried out in nine healthy volunteers (age 26 +/- 6 years). On each day, stepwise increasing systemic glucose concentrations of 5.0, 8.3, and 11.1 mmol/l were attained by intravenous infusion of glucose, representing fasting and postprandial conditions. Ghrelin plasma concentration was studied during concomitant exogenous hyperinsulinemia, inhibition of endogenous insulin production by somatostatin infusion, and placebo time control, respectively. Elevated glucose concentrations increased circulating insulin to 612 +/- 85 pmol/l (P < 0.01), but they did not affect ghrelin concentrations. Prolonged hyperinsulinemia by exogenous infusion resulted in circulating insulin of 1,602 +/- 261 pmol/l (P < 0.01) and suppressed plasma ghrelin to 49.6% of baseline (P < 0.01). During administration of somatostatin, insulin concentration remained constant, but an even greater decrease in ghrelin to 39.5% of baseline was noted (P < 0.01). Hyperglycemia does not decrease ghrelin, and a reduction in ghrelin is only seen at supraphysiological insulin concentrations. In contrast, systemic ghrelin concentrations are decreased by somatostatin. The meal-related suppression of ghrelin appears not directly regulated by glucose or insulin.
Plasma Ghrelin Concentrations Are Not Regulated by Glucose or Insulin
A Double-Blind, Placebo-Controlled Crossover Clamp Study
Georg Schaller 1 ,
Adele Schmidt 2 ,
Johannes Pleiner 1 ,
Wolfgang ...Woloszczuk 3 ,
Michael Wolzt 1 and
Anton Luger 2 3
1 Department of Clinical Pharmacology, Vienna University, Vienna, Austria
2 Department of Endocrinology and Metabolism, Vienna University, Vienna, Austria
3 Ludwig Boltzmann Institute for Experimental Endocrinology, Vienna University, Vienna, Austria
Abstract
Ghrelin plasma concentrations increase during fasting and fall rapidly after nutrient ingestion. We hypothesized that insulin
or glucose could regulate ghrelin secretion by a feedback mechanism. In this randomized, double-blind, placebo-controlled
crossover study, three different study days were carried out in nine healthy volunteers (age 26 ± 6 years). On each day, stepwise
increasing systemic glucose concentrations of 5.0, 8.3, and 11.1 mmol/l were attained by intravenous infusion of glucose,
representing fasting and postprandial conditions. Ghrelin plasma concentration was studied during concomitant exogenous hyperinsulinemia,
inhibition of endogenous insulin production by somatostatin infusion, and placebo time control, respectively. Elevated glucose
concentrations increased circulating insulin to 612 ± 85 pmol/l ( P < 0.01), but they did not affect ghrelin concentrations. Prolonged hyperinsulinemia by exogenous infusion resulted in circulating
insulin of 1,602 ± 261 pmol/l ( P < 0.01) and suppressed plasma ghrelin to 49.6% of baseline ( P < 0.01). During administration of somatostatin, insulin concentration remained constant, but an even greater decrease in
ghrelin to 39.5% of baseline was noted ( P < 0.01). Hyperglycemia does not decrease ghrelin, and a reduction in ghrelin is only seen at supraphysiological insulin concentrations.
In contrast, systemic ghrelin concentrations are decreased by somatostatin. The meal-related suppression of ghrelin appears
not directly regulated by glucose or insulin.
Footnotes
Address correspondence and reprint requests to Dr. Michael Wolzt, Department of Clinical Pharmacology, Allgemeines Krankenhaus
Wien, Währinger Gürtel 18-20, A-1090 Wien, Austria. E-mail: michael.wolzt{at}univie.ac.at .
Received for publication 7 June 2002 and accepted in revised form 3 October 2002.
AUC G , area under the ghrelin concentration versus time curve; GH, growth hormone.
DIABETES
Intersections between Grawe's General Psychotherapy and Prochaska's Transtheoretical Model were investigated in group therapy in a longitudinal design. It was assumed that general change mechanisms ...have an impact on patients' stages of change. Specifically, the main hypotheses were that experiential change mechanisms (ECM; clarification of meaning, problem actuation, emotional bond and group cohesion) should be especially relevant for early stages of change (precontemplation and contemplation), whereas behavioral change mechanisms (BCM; resource activation, mastery/coping and task and goals) should be especially relevant for late stages of change (action and maintenance). Therefore, 140 outpatients attending different types of group therapy, with a typical duration of 8 sessions, were investigated. Patients completed the Form for the Evaluation of Therapeutic Processes in Group Therapy (FEPiG), the University of Rhode Island Change Assessment, short version (URICA-S) and several symptomatology measures (BDI-II, BSCL and IIP-32) at two measuring times. Intersections were analysed through correlational analyses, cross-lagged panels and a path-analytic model, supporting the hypotheses. Specifically, results suggested that experiencing ECM at t1 predicted higher levels of reported contemplation at t2. Patients experiencing higher levels of BCM at t1 reported higher levels of action at t2. Clinical implications of the results are discussed.
We sought to determine the role of oxidative stress in the development of vascular dysfunction in inflammation.
Hyporeactivity to catecholamines and other vasoconstrictors is present in acute ...inflammation. Because oxidative stress plays a significant role in inflammation, impaired responsiveness may be overcome by anti-oxidants.
In randomized, double-blind, cross-over studies, forearm blood flow (FBF) responses to norepinephrine (NE), angiotensin II (ANG II), and vasopressin (VP) were assessed before and 4 h after induction of systemic inflammation by low doses of Escherichia coliendotoxin (lipopolysaccharide LPS, 20 IU/kg intravenously) or after placebo in healthy volunteers. Furthermore, the effect of intra-arterial vitamin C (24 mg/min) or placebo on NE-induced or ANG II-induced vasoconstriction was studied after LPS.
Administration of LPS caused systemic and forearm vasodilation, increased white blood cell count, elevated body temperature, and reduced vitamin C plasma concentrations. Lipopolysaccharide decreased the responses of FBF to NE by 59%, to ANG II by 25%, and to VP by 51% (n = 9, p < 0.05, all effects). Co-administration of vitamin C completely restored the response to NE and to ANG II, which was comparable to that observed under baseline conditions (n = 8).
E. coli-endotoxemia reduces FBF responsiveness to vasoconstrictors. The hyporeactivity can be corrected by high doses of vitamin C, suggesting that oxidative stress may represent an important target for inflammation-induced impaired vascular function.
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