People living with human immunodeficiency virus infection (HIV) are at increased risk for developing cardiovascular disease (CVD). Safe and effective interventions for lowering CVD risk in HIV are high priorities.Objective-We conducted a prospective, randomized, controlled study to evaluate whether a yoga lifestyle intervention improves CVD risk factors, virologic or immunologic status, or quality of life in HIV-infected adults more than in a matched control group.Methods-Sixty HIV-infected adults with mild-moderate CVD risk were assigned to 20 wks of supervised yoga practice or standard of care treatment. Baseline and week 20 measures were; 2hr-oral glucose tolerance test with insulin monitoring, body composition, fasting serum lipid/lipoprotein profile, resting blood pressures, CD4+ T-cell number and plasma HIV RNA, and the Medical Outcomes Study SF-36 health-related quality of life inventory.Results-Resting systolic and diastolic blood pressures were reduced more (p=0.04) in the yoga group (−5±2 and −3±1 mmHg) than in the standard of care group (+1±2 and +2±2 mmHg), despite no greater reduction in body weight, fat mass, proatherogenic lipids, or improvements in glucose tolerance or overall quality of life after yoga. Immune and virologic status was not adversely affected.Conclusion-Among traditional lifestyle modifications, yoga is a low cost, simple to administer, non-pharmacological, popular behavioral intervention that can lower blood pressure in prehypertensive HIV-infected adults with mild-moderate CVD risk factors.

The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. We evaluated whether the peroxisome proliferator-activated receptor-␥ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Forty-four HIV-infected adults with baseline insulin resistance and central adiposity were randomly assigned to 4 mo of pioglitazone (30 mg/day) with or without supervised, progressive aerobic, and resistance exercise training (1.5-2 h/day, 3 days/wk). The hyperinsulinemic euglycemic clamp was used to evaluate alterations in central and peripheral insulin sensitivity. Thirty-nine participants completed the study. Hepatic insulin sensitivity improved similarly in both groups. Exercise training augmented the beneficial effects of pioglitazone on peripheral insulin sensitivity. Greater improvements in peripheral insulin sensitivity were associated with reductions in total body and limb adipose content rather than increases in limb adiposity or pioglitazone-induced increases in adiponectin concentration. We conclude that supplementing pioglitazone with increased physical activity improved insulin sensitivity more effectively than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Pioglitazone alone did not significantly increase limb adipose content. Potential cardiovascular benefits of these interventions in HIV need investigation.human immunodeficiency virus-1; cardiovascular disease risk factors; diabetes; chronic inflammation; metabolic complications; physical activity DESPITE ADVANCES IN COMBINATION antiretroviral therapy (cART) that reduce morbidity and mortality, insulin resistance and type 2 diabetes mellitus (DM) are common cardiovascular disease (CVD) risk factors among people living with human immunodeficiency virus-1 (HIV). In cross-sectional comparisons adjusted for age and body mass index, DM prevalence was 4.6 times higher and DM incidence was 4.1 times higher in HIV-infected men than in HIV-seronegative men (6). In agestratified analyses, DM prevalence was 11% in HIV-infected men Ͻ40 yr old and 18% in those Ն40 yr old, whereas corresponding DM prevalence rates in HIV-seronegative men were 3 and 13%, respectively (27). In HIV, insulin resistance and DM are common and important CVD risk factors for which few safe and effective treatments exist.CVD is a leading cause of death in HIV-infected adults (11). HIV-infected adults have a twofold higher prevalence of cardiovascular events than the general population (56). Recent estimates suggest that the risk of death from DM is 6.4-fold higher in AIDS patients than in the general population. Clearly, safe and effective prevention and treatment strategies for insulin resistance and DM are a high priority a...

In this study, a two-stage euglycemic hyperinsulinemic clamp, with infusion of stable isotopically labeled tracers, was used to evaluate insulin action in skeletal muscle, liver, and adipose tissue in HIV-infected men with dyslipidemia (HIV-DL; plasma triglyceride Ͼ250 mg/dl and HDL Ͻ45mg/dl; n ϭ 12), HIV-infected men without dyslipidemia (HIV w/o DL; n ϭ 12), and healthy men (n ϭ 6). Basal rates of glucose production (glucose R a), glucose disposal (glucose R d), and lipolysis (palmitate Ra) were similar between groups. The relative suppression of glucose R a (63 Ϯ 4, 77 Ϯ 2, and 78 Ϯ 3%, P ϭ 0.008) and palmitate R a (49 Ϯ 4, 63 Ϯ 3, and 68 Ϯ 3%, P ϭ 0.005) during low-dose insulin infusion (plasma insulin ϳ30 U/ml), and the relative stimulation of glucose R d (214 Ϯ 21, 390 Ϯ 25, and 393 Ϯ 46%, P ϭ 0.001) during high-dose insulin infusion (plasma insulin ϳ75 U/ml) were lower in HIV-DL than in HIV w/o DL and healthy volunteers, respectively. Suppression of basal glucose R a correlated with plasma adiponectin (r ϭ 0.44, P ϭ 0.02) and inversely with plasma IL-6 (r ϭ Ϫ0.49, P Ͻ 0.001). Stimulation of glucose R d correlated directly with adiponectin (r ϭ 0.48, P Ͻ 0.01) and inversely with IL-6 (r ϭ Ϫ0.49, P ϭ 0.02). We conclude that dyslipidemia in HIV-infected men is indicative of multiorgan insulin resistance, and circulating adipokines may be important in the pathogenesis of impaired insulin action. insulin resistance; adipokine; hepatic steatosis THE INTRODUCTION of highly active antiretroviral therapy (HAART) has led to a marked increase in survival of patients with human immunodeficiency virus (HIV) infection. The beneficial effect on survival has been tempered by the potential effect of treatment on increased risk of coronary heart disease (CHD) mortality (15) and by metabolic abnormalities that are risk factors for CHD, including hypertriglyceridemia, low plasma HDL-cholesterol concentration, impaired glucose tolerance, type 2 diabetes, and increased abdominal fat mass (6,8,9). Dyslipidemia (i.e., high plasma triglyceride and low HDLcholesterol concentrations) is a common complication of HIV infection and occurs in Ն50% of patients receiving HAART (2, 3). In patients who do not have HIV infection, dyslipidemia is often associated with insulin-resistant glucose metabolism (12,34). Therefore, the presence of dyslipidemia could identify patients with HIV infection, who are at particularly high risk for developing CHD because of concomitant risk factors. However, it is controversial whether dyslipidemia in patients with HIV infection is associated with abnormalities in insulin action (26,27,42).The purpose of the present study was to evaluate insulin action in liver [glucose rate of appearance (R a )], muscle [glucose rate of disposal (R d )] and adipose tissue (fatty acid R a ), and specific factors (i.e., plasma adipokine concentrations and fat distribution) that may be involved in the pathogenesis of insulin resistance in men who have HIV infection and dyslipidemia (HIV-DL). A two-stage euglycemic hyperinsuli...

Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In animals, Xen regulates gastrointestinal function and glucose homeostasis, typically by initiating neural relays. However, little is known about Xen action in humans. This study determines whether exogenously administered Xen modulates gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion. Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2 diabetes mellitus (T2DM; n = 10-14 per group) ingested a liquid mixed meal plus acetaminophen (ACM; to assess gastric emptying) at time zero. On separate occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen) or 12 (Hi-Xen) pmol · kg(-1) · min(-1) was administered from zero until 300 min. Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM, glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP-1) levels were measured and ISRs calculated. Areas under the curves were compared for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed gastric emptying and reduced postprandial glucose levels in all groups. Infusions for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma GLP-1, but not GIP, levels without altering the insulin secretory response to glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric emptying in humans with and without T2DM, probably via a neural relay. Moreover, endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy humans under physiological conditions.

BackgroundPersistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular 18Fluorodeoxyglucose (18FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. We hypothesized that 18FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk.MethodsWe studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52 yrs, median BMI 29 kg/m2, median CD4 count 655 cells/μL, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44 yrs, median BMI 25 kg/m2, no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p < 0.01). 18FDG (370 MBq) was administered intravenously. 3D-PET-CT images were obtained 3.5 hrs later. 18FDG uptake into both carotid arteries and the aorta was compared between the two groups.ResultsRight and left carotid 18FDG uptake was greater (P < 0.03) in the HIV group (1.77 ±0.26, 1.33 ±0.09 target to background ratio (TBR)) than the control group (1.05 ± 0.10, 1.03 ± 0.05 TBR). 18FDG uptake in the aorta was greater in HIV (1.50 ±0.16 TBR) vs control group (1.24 ± 0.05 TBR), but did not reach statistical significance (P = 0.18).ConclusionsCarotid artery 18FDG PET-CT imaging detected differences in vascular inflammation and early atherosclerosis between HIV-infected adults with CVD risk factors and healthy HIV-seronegative controls. These findings confirm the utility of this molecular level imaging approach for detecting and quantifying glucose uptake into inflammatory macrophages present in metabolically active, rupture-prone atherosclerotic plaques in HIV infected adults; a population with increased CVD risk.