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1.  Effects of TNF-α neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome 
In a prior study, we have shown that tumor necrosis factor (TNF)-α neutralization improves inflammatory markers and total adiponectin in patients with the metabolic syndrome, without improving insulin sensitivity. In this study, we sought to extend our understanding of the effects of TNF-α neutralization in this human model of obesity by investigating the responses of high-molecular-weight (HMW) adiponectin, resistin, leptin, and muscle adiposity to etanercept in patients with the metabolic syndrome. Fifty-six men and women with the metabolic syndrome enrolled in a double-blind randomized placebo-controlled trial. Circulating concentrations of total and HMW adiponectin, resistin, and leptin were determined at baseline and after 4 wk of treatment with etanercept. Muscle adiposity was measured by computed tomography (CT). Although etanercept increased total adiponectin concentration, the HMW form, which is thought to mediate insulin sensitivity, was unchanged. Thus the ratio of HMW to total adiponectin decreased following etanercept treatment compared with placebo (−0.03 ± 0.03 vs. 0.06 ± 0.03, P = 0.02). Resistin tended to decrease in the etanercept-treated group compared with placebo (−0.6 ± 0.7 vs. 1.2 ± 0.7 ng/ml, P = 0.06), whereas leptin was not altered. Etanercept decreased muscle attenuation on CT [−0.61 ± 0.64 Hounsfield units (HU) vs. 1.54 ± 0.77 HU in placebo, P = 0.04], suggesting an increase in muscle adiposity. Together, these results demonstrate that neutralization of TNF-α in obese humans results in differential effects on critical adipokines and body composition indexes. These findings may help to explain the lack of effect on insulin sensitivity and extend our knowledge of the biological effects of TNF-α neutralization in obesity.
doi:10.1152/ajpendo.00089.2007
PMCID: PMC3196534  PMID: 17374698
tumor necrosis factor-α; adiponectin; resistin; muscle adiposity; metabolic syndrome
2.  Effects of Etanercept in Patients With the Metabolic Syndrome 
Archives of internal medicine  2006;166(8):902-908.
Background
Adipose-derived cytokines, including tumor necrosis factor α, may contribute to the inflammation that occurs in the metabolic syndrome. We investigated the effects of inhibition of tumor necrosis factor α with etanercept in patients with the metabolic syndrome.
Methods
Fifty-six subjects with the metabolic syndrome were randomized to administration of either etanercept or identical placebo, 50 mg subcutaneously once a week for 4 weeks. The C-reactive protein level was the primary end point. Effects on other inflammatory markers (including fibrinogen, interleukin 6, and adiponectin), insulin sensitivity, lipid levels, and body composition were also determined.
Results
Baseline characteristics were similar between the groups. Two subjects dropped out of each group, and etanercept was well tolerated throughout the study. The C-reactive protein levels decreased significantly in the treated compared with the placebo group (−2.4 ± 0.4 vs 0.5 ± 0.7 mg/L; P<.001). Adiponectin levels rose significantly in the etanercept group compared with the placebo group (0.8 ± 0.4 vs −0.3 ± 0.3 µg/mL; P=.03). Fibrinogen levels decreased (−68 ± 16 vs −2 ± 31 mg/dL [−2.0 ± 0.47 vs −0.06 ± 0.91 µmol/L]; P=.04) and interleukin 6 levels tended to decrease (−1.2 ± 0.8 vs 0.5 ± 0.5 ng/L; P=.07) in the etanercept-treated subjects compared with placebo, respectively. No changes occurred in body composition parameters or insulin sensitivity, but high-density lipoprotein levels tended to decrease in the etanercept group (−1 ± 1 vs 2 ± 1 mg/dL [−0.03 ± 0.03 vs 0.05 ± 0.03 mmol/L]; P=.06) compared with the placebo group.
Conclusions
Etanercept reduces C-reactive protein levels and tends to improve other inflammatory cardiovascular risk indexes in patients with the metabolic syndrome. Etanercept may interrupt the inflammatory cascade that occurs with abdominal obesity. Further, longer-term studies are needed to determine the effects of tumor necrosis factor α inhibition on cardiovascular disease in patients with the metabolic syndrome.
doi:10.1001/archinte.166.8.902
PMCID: PMC3196549  PMID: 16636217
3.  Relationship of peak growth hormone to cardiovascular parameters, waist circumference, lipids and glucose in HIV-infected patients and healthy adults 
Clinical endocrinology  2009;71(6):815-822.
SUMMARY
Objective:
Relative growth hormone (GH) deficiency is highly prevalent in patients with HIV. The purpose of this study was to investigate relationships of GH to metabolic and anthropometric parameters in HIV patients and non-HIV controls.
Design:
Peak GH and metabolic parameters were assessed in a cross-sectional study of 191 HIV patients and 62 age and BMI-matched healthy controls.
Methods:
Peak GH was assessed by GHRH/arginine stimulation testing.
Results:
HIV patients demonstrated similar BMI, but increased waist circumference (WC) and reduced peak GH to GHRH/arginine compared with control subjects (12.4 [6.3, 24.8] vs. 21.3 [8.8, 34.5] μg/l, P=0.006, HIV vs. control). Among HIV and non-HIV groups, peak GH was inversely associated with WC (rho=−0.44, p<0.0001; rho=−0.63, p<0.0001)(HIV patients and controls, respectively), blood pressure (rho=−0.17, p=0.02; rho=−0.36, p=0.004), triglycerides (rho=−0.37, p<0.0001; rho=−0.43, p=0.001), glucose (rho=−0.34, p<0.0001; rho=−0.30, p=0.02), insulin (rho=−0.43, p<0.0001; rho=−0.60, p<0.0001) and CRP (rho=−0.29, p<0.0001; rho=−0.59, p<0.0001). Among HIV patients, the inverse association between peak GH and fasting glucose remained significant (β=−0.006mmol/l change in glucose per μg/l change in GH, p=0.004) controlling for age, gender, race, BMI, WC, protease inhibitor(PI) and nucleoside reverse transcriptase inhibitors(NRTI). Similarly, the inverse association between peak GH and triglycerides remained significant (β=−0.01mmol/l change in triglycerides per μg/l change in GH, p=0.02) controlling for age, gender, race, BMI, WC, PI and lipid-lowering medications. HIV men with peak GH<7.5μg/l demonstrated higher BMI, WC, SBP, triglycerides, glucose and CRP.
Conclusions:
Reduced GH secretion is independently associated with dyslipidemia and higher glucose, among HIV patients with abdominal fat accumulation.
doi:10.1111/j.1365-2265.2009.03603.x
PMCID: PMC2889024  PMID: 19508594
4.  Low-Dose Physiological Growth Hormone in Patients With HIV and Abdominal Fat Accumulation 
Context
Antiretroviral therapy can be associated with visceral adiposity and metabolic complications, increasing cardiovascular risk, and reduced growth hormone (GH) secretion may be a contributing factor.
Objective
To investigate the effects of low-dose physiological GH administration on body composition, glucose, and cardiovascular parameters in patients with human immunodeficiency virus (HIV) having abdominal fat accumulation and relative GH deficiency.
Design, Setting, and Patients
A randomized, double-blind, placebo-controlled trial of 56 patients with HIV, abdominal fat accumulation, and reduced GH secretion (peak GH <7.5 ng/mL) conducted at a US academic medical center between November 2003 and October 2007.
Intervention
Patients were randomly assigned to receive either subcutaneous GH or matching placebo titrated to the upper quartile of normal insulinlike growth factor 1 (IGF-1) range for 18 months. Starting dose was 2 μg/kg/d and increased to maximum dose of 6 μg/kg/d (average dose, 0.33 mg/d).
Main Outcome Measures
Change in body composition assessed by computed tomographic scan and dual-energy x-ray absorptiometry. Secondary outcomes included glucose, IGF-1, blood pressure (BP), and lipids. Treatment effect was the difference in the change between GH and placebo groups, using all available data.
Results
Fifty-five patients (26 with GH and 29 with placebo) were included in the safety analyses and 52 patients (25 with GH and 27 with placebo) were included in the efficacy analyses. Visceral adipose tissue area (treatment effect [last-value-carried-forward analysis {n=56}, -19 cm2; 95% confidence interval {CI}, -37 to -0.3 cm2], -19 cm2; 95% CI, -38 to -0.5 cm2; P=.049); trunk fat (-0.8 kg; 95% CI, -1.5 to -0.04 kg; P=.04); diastolic BP (-7 mm Hg; 95% CI, -11 to -2 mm Hg; P=.006); and triglycerides (-7 mg/dL, P=.002) improved but 2-hour glucose levels on glucose tolerance testing increased in the GH group vs the placebo group (treatment effect, 22 mg/dL; 95% CI, 6-37 mg/dL; P=.009). The IGF-1 levels increased (treatment effect, 129 ng/mL; 95% CI, 95-164 ng/mL; P<.001). Adverse events were not increased for GH vs placebo (23%; 95% CI, 9%-44% vs 28%; 95% CI, 13%-47%; P=.70).
Conclusions
In HIV-associated abdominal fat accumulation and relative GH deficiency, low-dose GH received for 18 months resulted in significantly reduced visceral fat and truncal obesity, triglycerides, and diastolic BP, but 2-hour glucose levels on glucose tolerance testing were increased.
doi:10.1001/jama.300.5.509
PMCID: PMC2532757  PMID: 18677023

Results 1-4 (4)