HIV Fat Redistribution and the Evaluation of Brown Fat
The specific aims of this study are to determine whether HIV-infected patients with significant fat redistribution and ectopic fat accumulation have increased brown adipose tissue using 18F-FDG Positron Emission Tomography techniques.
Recent studies suggest down regulation of Dicer, a major component of miRNA has an important role in the differentiation and function of brown and white adipose tissue and may contribute to lipodystrophy. Therefore we will expand on recent research in this area by recruiting HIV-infected men with lipodystrophy. We will perform subcutaneous fat biopsies of the dorsocervical and abdominal fat in a subset of HIV-infected and non-HIV-infected men in order to explore further the question of down regulation of Dicer and its implication on metabolic abnormalities in this population.
|Study Design:||Observational Model: Case Control
Time Perspective: Cross-Sectional
|Official Title:||FDG/PET Imaging for the Assessment of Brown Adipose Tissue in HIV Lipodystrophy|
- Brown Fat [ Time Frame: Baseline ] [ Designated as safety issue: No ]Brown Fat will be assessed by PET FDG
- UCP-1 [ Time Frame: Baseline ] [ Designated as safety issue: No ]UCP-1 will be analyzed from tissue collected from a fat biopsy of dorsocervical spine fat accumulation.
- Indirect Calorimetry [ Time Frame: Baseline ] [ Designated as safety issue: No ]Indirect Calorimetry will be performed to measure resting energy expenditure
- Anthropometrics [ Time Frame: Baseline ] [ Designated as safety issue: No ]Anthropometric measurements of waist to hip ratio, leg circumference, arm circumference and neck circumference will be performed using a standardized technique.
- Glucose tolerance [ Time Frame: Baseline ] [ Designated as safety issue: No ]A baseline glucose level will be obtained and then patients will consume a 75g glucose beverage. Subjects must complete the beverage within 5-10 minutes. Subsequently, blood glucose at +30, +60, +90, and +120 minutes, insulin levels will be assessed at baseline and +120 minutes. Glucose tolerance will be calculated by insulin area under the curve in response to OGTT.
Biospecimen Retention: Samples With DNA
Blood tests will include a complete blood count, creatinine, SGPT TSH and Free T4, triglyceride, total, HDL and LDL cholesterol, HIV test, CD4 count (for HIV+ subjects only), HIV viral load (for HIV+ subjects only), fasting glucose, 2 hour OGTT, as well as tissue samples from fat biopsy.
|Study Start Date:||March 2010|
|Estimated Study Completion Date:||August 2016|
|Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
HIV-infection with fat redistribution (lipoatrophy)
HIV-infected with fat redistribution (lipohypertrophy)
30 men [HV-infected with fat redistribution (n = 10), HIV-infected without fat redistribution (n=10), and healthy controls (n= 10)] will be recruited for this group.
Among individuals infected with HIV, highly active antiretroviral therapy has reduced the incidence of morbidity and mortality however, despite recent improvements in newer antiretrovirals patients continue to exhibit secondary effects related to body composition such as lipoatrophy of the periphery, increased adiposity of the trunk and lipomatosis, especially of the dorsocervical spine. Changes in body composition have been reported in 40-50% of HIV-infected patients. Several studies have shown that antiretroviral therapy contributes to changes in body composition and is coupled with increased dyslipidemia, insulin resistance and diabetes.
Accumulation of fat over the dorsocervical spine, or "buffalo" has been reported in 2% to 13% of HIV-infected patients. Enlargement of adipose tissue in the dorsocervical region involves subcutaneous fat and is therefore unique to fat accumulation of the abdominal area. Guallar et al. examined dorsocervical adipose tissue after surgical removal and found that adipose tissue in this area showed substantial levels of the marker gene of brown fat, uncoupling protein 1 (UCP-1) suggesting there may be brown adipose tissue (BAT) in HIV infected individuals with lipomatosis of the dorsocervical spine. Until recently, BAT was known to be present in rodents throughout their lifetime and was thought to be present in humans only during infancy and early childhood. However, recent studies using 18F-FDG PET-CT have confirmed the presence of BAT in adults. Brown adipose tissue is known to affect whole-body metabolism and may be related to insulin sensitivity as well as susceptibility to weight gain.
Using 18F-FDG PET techniques, our group has evaluated HIV-infected subjects with lipoatrophy and noted there was significantly increased glucose uptake into subcutaneous tissue which may suggest presence of BAT in HIV-infected patients. However our previous study did not specifically examine areas of BAT in the subjects. Therefore, using 18F-FDG PET-CT in addition to fat biopsies we propose to explore the presence of BAT in fat depots among HIV-infected patients with fat redistribution, focusing specifically in the cervical area.
Also, as recent studies suggest down regulation of Dicer, a major component of miRNA has an important role in the differentiation and function of brown and white adipose tissue and may contribute to lipodystrophy. We will perform subcutaneous fat biopsies of the dorsocervical and abdominal fat in a subset of HIV-infected and non-HIV-infected men in order to explore further the question of down regulation of Dicer and its implication on metabolic abnormalities in this population.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01098045
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Steven Grinspoon, MD||Massachusetts General Hospital|
|Study Director:||Martin Torriani, MD||Massachusetts General Hopsital|