Carl Grunfeld

..Thus, VAT and upper trunk SAT are independently associated with insulin resistance in controls and in HIV-infected persons...

..Distal coronary artery disease (CAD) is less amenable to surgery or stenting compared with proximal disease. However, little is known about the epidemiology of distal versus proximal CAD...

..However, it is controversial whether HIV infection contributes to accelerated atherosclerosis independent of traditional CVD risk factors...

..controls. Therefore, we determined change in regional adipose tissue from baseline examination to 5 years later among participants in the study of Fat Redistribution and Metabolic Change in HIV Infection...

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..Some HIV protease inhibitors (PIs) have been shown to induce insulin resistance in vitro but the degree to which specific PIs affect insulin sensitivity in humans is less well understood...

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..We studied the effects of the protease inhibitor combination lopinavir and ritonavir on insulin secretion, insulin sensitivity, and lipid metabolism in HIV-negative persons...

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..Thus, there are multiple cytokine pathways by which inflammation inhibits PEPCK expression in adipose tissue which could contribute to the increased mobilization of fatty acids during inflammation...

..Our study provides a possible mechanism by which infection and inflammation are associated with altered steroid metabolism and cholestasis...

..To determine the relationship of HIV infection, demographic, and cardiovascular disease (CVD) risk factors with mortality in the recent highly active antiretroviral therapy era...

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..Unintentional loss of weight and muscle due to aging and disease has been associated with increased mortality. Wasting and weight loss occur in HIV infection even in the modern era of effective antiretroviral therapy...

..Treatment with GH decreases visceral adiposity but worsens glucose metabolism. IGF-I, which mediates many of the effects of GH, improves insulin sensitivity in HIV-negative individuals...

..Boosting dose ritonavir (100-200 mg) is the most commonly prescribed PI, yet its effects on glucose metabolism have not been described in the absence of another PI...

..Studies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects...

..However, the kidney requires energy to support its transport functions, and the inability to generate energy via FA oxidation might contribute to the renal failure seen in severe sepsis...

..Leptin deficiency is associated with dyslipidemia and insulin resistance in animals and humans with lipoatrophy; leptin replacement ameliorates these abnormalities...

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..These data provide evidence that PLSCR1 is a positive intracellular acute phase protein with a tissue-specific mechanism for up-regulation...

..These alterations could contribute to the myocardial dysfunction that occurs during sepsis...

..The effects of different HIV protease inhibitors (PIs) on peripheral insulin resistance have been described, but less is known about their effects on insulin suppression of endogenous glucose production (EGP)...

..Insulin resistance from protease inhibitors may decrease with prolonged use; an increase in adiponectin levels may mediate this effect...

..Thus, ChREBP joins a growing list of transcription factors that are regulated during the acute phase response...

..To determine the association of inflammatory markers, fibrinogen, and C-reactive protein (CRP), with 5-year mortality risk...

..These studies demonstrate that ANGPTL4 is a positive acute phase protein and the increase in ANGPTL4 could contribute to the hypertriglyceridemia that characteristically occurs during the acute phase response by inhibiting LPL activity...

..FGF21 also protected from the toxic effects of cecal ligation and puncture-induced sepsis. Thus, FGF21 is a positive APR protein that protects animals from the toxic effects of LPS and sepsis...

..The decrease in FA oxidation in the diaphragm may be detrimental, leading to decreased diaphragm contraction and an increased risk of respiratory failure during sepsis...

..We aimed to describe the evolving incidence of AKI among HIV-infected individuals and to identify important AKI risk factors...

..These results are consistent with the finding that infections and inflammatory disorders accompanied by systemic inflammation are associated with an increased risk of atherosclerosis...

..HIV infection is associated with an increased risk of coronary artery disease, but the contribution of inflammation versus antiretroviral drugs is not well understood. Fibrinogen is an inflammatory factor associated with atherosclerosis...

..Visceral adipose tissue (VAT) levels did not change significantly for the group as a whole, although a reduction in the VAT level was seen in patients with a greater VAT level at baseline...

..We investigated whether reduced estimated glomerular filtration rate (eGFR) and albuminuria are associated with subclinical vascular disease, as assessed by carotid intima-medial thickness (cIMT)...

..However, the clinical importance of increased cystatin C level and albuminuria in the HIV-infected population has not been studied...

..To determine the prevalence of illicit drug use and the impact on HIV treatment...

..Our study provides a potential mechanism by which the APR decreases fatty acid oxidation...

..Thus TLR agonists induce ADRP/ADFP and Mal1, which likely contributes to macrophage triglyceride and cholesterol ester storage leading to foam cell formation...

..We sought to identify traditional and HIV-related risk factors for ESRD in HIV-infected individuals and compare ESRD risk by estimated glomerular filtration rate (eGFR) and proteinuria levels...

..HIV infection and antiretroviral therapy are associated with dyslipidemia, but the association between regional body fat and lipid levels is not well described...

..Thus, inflammation stimulates PCSK9 expression leading to increased LDL receptor degradation and decreasing LDL receptors thereby increasing serum LDL, which could have beneficial effects on host defense...

..It remains to be determined whether CVD rates in HIV infection are higher than might be predicted from traditional risk factors, including smoking...

..Stavudine exposure is associated with both decreased IMAT and SAT, suggesting that IMAT shares cellular origins with SAT...

..We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women...

..Complaints of dry skin in HIV-infected individuals were reported after the advent of HAART. The objective of the study was to evaluate the prevalence of dry skin and associated factors in HIV-infected and control subjects...

..CONCLUSION: Both peripheral and central subcutaneous lipoatrophy was found in HIV infection. Lipoatrophy in HIV-positive men is not associated with reciprocally increased VAT...

..We propose that decreased RXR expression is limiting for RXR/TR DNA binding at 4 h, whereas the reduction in both TR and RXR levels results in further decreased binding at 16 h...

..During the euglycemic hyperinsulinemic clamp, indinavir blunted the ability of insulin to suppress glucose production. Therefore, indinavir worsens hepatic insulin sensitivity, increasing endogenous glucose production...

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..Cystatin C measurement may be more sensitive than creatinine for detecting impaired kidney function in persons with HIV...

..To evaluate the effect of HIV infection on longitudinal changes in kidney function and to identify independent predictors of kidney function changes in HIV-infected individuals...

..Recombinant PSP inhibits growth of Candida albicans in culture. In summary, our results showed that PSP is a novel anticandidal protein associated with HDL...

..The decreases in expression of RXRs, PPARs, LXRs, FXR, TRs, SREBPs, and PGC-1s could contribute to the alterations in lipid metabolism during late pregnancy...

..Microalbuminuria is associated with increased risk of cardiovascular disease and mortality. The objective of the study was to evaluate if HIV infection was an independent risk factor for microalbuminuria...

..HIV-associated adipose redistribution syndrome (HARS) is an HIV-associated disorder characterized by excess truncal fat, including visceral adipose tissue (VAT)...

..Peripheral lipoatrophy (as measured by leg SAT) is associated with striking increased CVD risk in HIV-infected patients even after controlling for VAT, whereas low leg SAT is associated with low CVD risk in controls...

..We hypothesized that muscle mass would be lower and decline faster in HIV-infected adults than in similar-aged controls...

..To identify changes in the protein composition of HDL during infection and inflammation, a proteomic approach was utilized...

..The aim of this study was to examine the expression of G protein-coupled receptor 81 (GPR81) in mouse adipose tissue in response to inflammatory stimuli. GPR81 is activated by lactate resulting in the inhibition of lipolysis...

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..The representativeness of the FRAM sample increases its value as a resource for studies on fat distribution, metabolic changes, and atherosclerosis in HIV infection...

..We evaluated C-reactive protein (CRP) in HIV-infected and HIV/HCV-coinfected individuals in the era of effective antiretroviral (ARV) therapy...

..This article summarizes a presentation on insulin resistance in HIV infection made by Carl Grunfeld, MD, PhD, at the 10th Annual Ryan White HIV/AIDS Program Clinical Update in Phoenix in June 2007.

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..Some changes are antiretroviral drug (but not necessarily class)-specific, some represent the restoration to health, and others are due to effects of the host response to human immunodeficiency virus itself...

..This review examines the direct effects of PIs on glucose and lipid metabolism by assessing prospective studies of HIV-infected and healthy normal volunteers, and in vitro studies...

..Therefore, we tested the effects of the PI combination lopinavir and ritonavir on glucose and lipid metabolism in HIV-negative subjects...

..These recommendations were developed to guide physicians actively involved in HIV care in the management of metabolic complications that occur primarily within the context of potent antiretroviral therapy...

..We examined the association between longitudinal measures of kidney function and albuminuria with risk of atherosclerotic CVD and heart failure in a contemporary cohort of HIV-infected individuals...

..To estimate the incidence of lipoatrophy and lipohypertrophy among HIV-infected and HIV-uninfected women from the Women's Interagency HIV Study...

..We compared circulating fibrinogen levels in patients with RA with healthy controls and evaluated the relationship with measures of disease activity...

..This study within persons with known coronary artery disease (CAD) evaluated whether uromodulin concentrations could distinguish CKD risk...

..We investigated aP2 expression in RAW 264.7 cells treated with lipopolysaccharide (LPS) and other TLR agonists and assessed lipid accumulation in these activated murine macrophages...

..We report the first death associated with rhabdomyolysis in a patient treated with a statin and a protease inhibitor, which produced a significant drug-drug interaction...

..These findings represent one possible molecular mechanism underlying sepsis-induced repression of Cyp enzymes...

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..To evaluate the efficacy and safety of oxandrolone in promoting body weight and body cell mass (BCM) gain in HIV-associated weight loss...

..The conditions under which some patients rapidly progress to hepatic failure and/or cirrhosis need to be defined. This is a US government work. There are no restrictions on its use...

..Our data are compatible with the hypothesis that an acute effect of indinavir on glucose disposal in humans is mediated by a direct blockade of GLUT-4 transporters...

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..HIV infection and antiretroviral therapy are associated with dyslipidemia, but the association between regional adipose tissue depots and lipid levels is not defined...

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..Early and sustained increases in insulin and insulin resistance were seen only for ddI+d4T. In this prospective study, metabolic and body composition changes varied according to whether subjects received ddI+d4T or ABC+3TC...

..APR-induced alterations initially protect the host from the harmful effects of bacteria, viruses, and parasites. However, if prolonged, these changes in the structure and function of lipoproteins will contribute to atherogenesis...

..CONCLUSIONS: These results suggest that r-hGH dosed at 4 mg daily for 12 weeks decreases VAT and cholesterol concentrations in HIV-infected patients with excess VAT. The optimal regimen to sustain these effects awaits determination...

..Data on associations of body composition with HIV disease characteristics are limited...

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..The combined implications of these positive and negative metabolic effects for cardiovascular disease risk remain unknown...

..The results from these studies will define the direct toxicities of ARV, which provide essential information for rationally evaluating treatment strategies and counseling patients.Carl Grunfeld, MD, PhD.

..Specific Aim 3b: To determine the mechanisms by which NRTI adversely affect glucose metabolism, we will assess their effects on insulin mediated glucose disposal, insulin secretion and/or hepatic glucose production. ..

..The results will provide essential information on the risk of atherosclerosis and its contributors to aid in patient care, policy and future research. ..

..The results from these studies will define the direct toxicities of ARV, which provide essential information for rationally evaluating treatment strategies and counseling patients.Carl Grunfeld, MD, PhD.