Madhu N Rao

Publications (6)11.55 Total impact

• Article: Assessing the Association between Leptin and Bone Mineral Density in HIV-Infected Men.

  Madhu N Rao, Morris Schambelan, Viva W Tai, Donald I Abrams, Hootan Khatami, Peter J Havel, Giorgos Sakkas, Kathleen Mulligan
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  ABSTRACT: HIV-infected individuals are at risk for decreased bone mineral density (BMD). The known risk factors for bone loss do not fully explain the increased risk in this population. There is emerging evidence that leptin, a hormone secreted by adipocytes, plays an important role in bone metabolism. Several studies have assessed the relationship between leptin and bone density in healthy adults, but there are few such studies in HIV-infected individuals. Furthermore, HIV infected individuals on antiretroviral therapy are at increased risk for altered fat distribution, which may impact the relationship between leptin and BMD. In a cross-sectional analysis of data in 107 HIV-infected men, we determined whether serum leptin levels were associated with whole-body BMD and bone mineral content measured by dual-energy X-ray absorptiometry (DEXA), after adjusting for confounders including body fat distribution. We found an inverse association between leptin and bone density in those with peripheral lipoatrophy, defined objectively as <3 kg appendicular fat by DEXA, but no such relationship was seen in those with >3 kg appendicular fat. This result suggests that fat distribution may modify the relationship between leptin and bone density.
  AIDS research and treatment 01/2012; 2012:103072.
• Article: Effects of insulin-like growth factor (IGF)-I/IGF-binding protein-3 treatment on glucose metabolism and fat distribution in human immunodeficiency virus-infected patients with abdominal obesity and insulin resistance.

  Madhu N Rao, Kathleen Mulligan, Viva Tai, Michael J Wen, Artem Dyachenko, Melissa Weinberg, Xiaojuan Li, Thomas Lang, Carl Grunfeld, Jean-Marc Schwarz, Morris Schambelan
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  ABSTRACT: HIV-infected patients on antiretroviral therapy are at increased risk for excess visceral adiposity and insulin resistance. 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. Our objective was to determine whether IGF-I, complexed to its major binding protein, IGF-binding protein-3 (IGFBP-3), improves glucose metabolism and alters body fat distribution in HIV-infected patients with abdominal obesity and insulin resistance. We conducted a pilot, open-label study in 13 HIV-infected men with excess abdominal adiposity and insulin resistance to assess the effect of 3 months of treatment with IGF-I/IGFBP-3 on glucose metabolism and fat distribution. Glucose metabolism was assessed by oral glucose tolerance test and hyperinsulinemic-euglycemic clamp. Endogenous glucose production (EGP), gluconeogenesis, whole-body lipolysis, and de novo lipogenesis (DNL) were measured with stable isotope infusions. Body composition was assessed by dual-energy x-ray absorptiometry and abdominal computed tomography scan. Glucose tolerance improved and insulin-mediated glucose uptake increased significantly during treatment. EGP increased under fasting conditions, and suppression of EGP by insulin was blunted. Fasting triglycerides decreased significantly in association with a decrease in hepatic DNL. Lean body mass increased and total body fat decreased, whereas visceral adipose tissue did not change. Treatment with IGF-I/IGFBP-3 improved whole-body glucose uptake and glucose tolerance, while increasing hepatic glucose production. Fasting triglycerides improved, reflecting decreased DNL, and visceral adiposity was unchanged.
  The Journal of clinical endocrinology and metabolism 09/2010; 95(9):4361-6. · 6.50 Impact Factor
• Chapter: HIV Infection and Diabetes

  Madhu N. Rao, Kathleen Mulligan, Morris Schambelan
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  ABSTRACT: Since the introduction of highly active antiretroviral therapy (HAART) more than a decade ago, there has been a dramatic improvement in the morbidity and mortality associated with human immunodeficiency virus (HIV) infection and AIDS. As survival has improved, a constellation of metabolic and morphologic abnormalities, often referred to as the HIV-associated lipodystrophy syndrome, has become increasingly evident. Features of this syndrome include abnormal glucose metabolism, dyslipidemia, and alterations in body fat distribution including peripheral lipoatrophy and central adiposity. In this chapter, we will focus primarily on the abnormalities of glucose metabolism in patients with HIV/AIDS, including insulin resistance, impaired glucose tolerance, and frank diabetes mellitus. After first considering the effects of HIV infection per se, we will examine the mechanisms by which antiretroviral (ARV) medications are purported to disrupt glucose metabolism.
  12/2009: pages 617-642;
• Article: Association between sleep architecture and measures of body composition.

  Madhu N Rao, Terri Blackwell, Susan Redline, Marcia L Stefanick, Sonia Ancoli-Israel, Katie L Stone
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  ABSTRACT: To determine whether slow wave sleep (SWS) is inversely associated with body mass index (BMI) and other measures of body composition. Cross-sectional, observational study. Community-based. 2745 older men from the MrOS Sleep Study who completed polysomnography. Interventions: N/A. SWS as a percentage of total sleep duration was obtained from in-home, overnight polysomnography. Measures of body composition including BMI, weight, waist circumference and total body fat mass were determined by standard techniques. Other covariates in the analysis were age, race/ethnicity, clinic site, physical activity, respiratory disturbance index (RDI), total sleep time, and sleep efficiency. In the multivariate analysis, there was a significant inverse association between quartiles of SWS and BMI (P-trend = 0.0095). Older men in the lowest quartile of SWS had an average BMI of 27.4 kg/m2, compared to 26.8 for those in the highest quartile of SWS. This association was attenuated in men with RDI > or = 15. Furthermore, participants in the lowest quartile of SWS had a 1.4-fold increased odds for obesity (P = 0.03, 95% CI 1.0, 1.8) compared to those in the highest quartile. A similar inverse association between SWS and waist circumference as well as weight was observed. REM sleep was not associated with measures of body composition. Independent of sleep duration, percentage time in SWS is inversely associated with BMI and other measures of body composition in this population of older men. Participants in the lowest quartile of SWS (compared to those in the highest quartile) are at increased risk for obesity.
  Sleep 05/2009; 32(4):483-90. · 5.05 Impact Factor
• Article: Metabolic Abnormalities Associated with the Use of Protease Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors.

  Madhu N Rao, Grace A Lee, Carl Grunfeld
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  ABSTRACT: The use of protease inhibitors and non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection and AIDS has been associated with multiple abnormalities in glucose and lipid metabolism. Specifically, these abnormalities include insulin resistance, increased triglycerides and increased LDL cholesterol levels. The metabolic disturbances are due to a combination of factors, including the direct effect of medications, restoration to health and HIV disease, as well as individual genetic predisposition. Of the available anti-retroviral medications, indinavir has been associated with causing the most insulin resistance and ritonavir with causing the most hypertriglyceridemia.
  American journal of infectious diseases 09/2006; 2(3):159-166.
• Article: The effects of HIV protease inhibitors on carbohydrate and lipid metabolism.

  Grace A Lee, Madhu N Rao, Carl Grunfeld
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  ABSTRACT: Since the introduction of HIV protease inhibitors (PIs), disorders of glucose and lipid metabolism have emerged. In dissecting out the direct effect on lipid and glucose metabolism, it has become apparent that individual PIs have different effects on metabolism. Some PIs such as indinavir acutely induce insulin resistance. PIs have also been shown to cause other disorders of glucose metabolism, including impairment of insulin secretion and increased endogenous glucose production. Individual PIs also have different effects on lipid metabolism. Ritonavir predominantly increases triglyceride and very low-density lipoprotein cholesterol levels. Limited studies in HIV-negative volunteers suggest that several of the PIs do not increase low-density lipoprotein cholesterol levels. 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.
  Current HIV/AIDS Reports 03/2005; 2(1):39-50.