Recombinant Human Growth Hormone and Rosiglitazone for Abdominal Fat Accumulation in HIV- Infected Patients with Insulin Resistance: A Randomized, Double-Blind, Placebo-Controlled, Factorial Trial

Background: Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Methodology/Principal Findings: Randomized, double-blind, placebo-controlled, multicenter trial using a 262 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2- hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (217.5% in rhGH/rosiglitazone and 222.7% in rhGH) but not in the rosiglitazone alone (22.5%) or control arms (21.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. Conclusions/Significance: The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT

Validation of an elliptical anthropometric model to estimate visceral compartment area

The visceral compartment is a surrogate for visceral adipose tissue. Cross-sectional visceral compartment area (VCA) has been approximated from waist circumference using a circular model. However, the two-dimensional shape of the abdomen is rarely circular. This study validated an elliptical model of cross-sectional total abdominal area (TAA), subcutaneous adipose tissue (SAT) area, and VCA at the L(4)-L(5) level. We analyzed magnetic resonance images (MRIs) at the level of the L(4)-L(5) intervertebral space from 35 subjects with a wide range of abdominal adiposity. Waist circumference, abdominal thickness (midline sagittal diameter), abdominal width (coronal diameter at one-half of abdominal thickness), and abdominal SAT thickness at four sites (front, back, right, and left) were measured from MRI images using an image analysis software. The same anatomical regions were also estimated from anthropometrics purely by geometric formulae of circular and elliptical models. A simple linear regression model was used to interpret the association strength between anthropometric estimates and MRI measures. Estimated TAA by either model was strongly related to MRI TAA (r(2) = 0.98, p < 0.0001). The SAT and VCA by MRI analysis showed a stronger association with calculation from an elliptical model (r(2) = 0.95 and 0.88, respectively; p < 0.001) than a circular model (r(2) = 0.69 and 0.25, respectively; p < 0.001). The absolute prediction residuals and variances were significantly smaller with an elliptical model than a circular model (p < 0.0001). An elliptical anthropometric model might be superior to a circular model to estimate abdominal SAT and VCA

The Rationale, Feasibility, and Optimal Training of the Non-Physician Medical Nutrition Scientist

Dietary components have potential to arrest or modify chronic disease processes including obesity, cancer, and comorbidities. However, clinical research to translate mechanistic nutrition data into clinical interventions is needed. We have developed a one-year transitional postdoctoral curriculum to prepare nutrition scientists in the language and practice of medicine and in clinical research methodology before undertaking independent research. Candidates with an earned doctorate in nutrition science receive intensive, didactic training at the interface of nutrition and medicine, participate in supervised medical observerships, and join ongoing clinical research. To date, we have trained four postdoctoral fellows. Formative evaluation revealed several learning barriers to this training, including deficits in prior medical science knowledge and diverse perceptions of the role of the translational nutrition scientist. Several innovative techniques to address these barriers are discussed. We propose the fact that this “train the trainer” approach has potential to create a new translational nutrition researcher competent to identify clinical problems, collaborate with clinicians and researchers, and incorporate nutrition science across disciplines from “bench to bedside.” We also expect the translational nutrition scientist to serve as an expert resource to the medical team in use of nutrition as adjuvant therapy for the prevention and management of chronic disease

Body composition and metabolic effects of a diet and exercise weight loss regimen on obese, HIV-infected women

HIV has classically been a wasting disease. However, in the United States, obesity is increasingly common among HIV-infected individuals receiving effective antiviral treatment. The risks of obesity are unclear in HIV, although the increased prevalence of diabetes and cardiovascular disease in the presence or absence of obesity causes growing concern. This study aimed to assess the effects of weight loss (through energy restriction combined with aerobic and resistance exercise) on body composition, body fat distribution, resting energy expenditure, quality of life (QOL), strength and fitness, and metabolic risk factors in obese, HIV-infected women. Eighteen HIV-infected women with a body mass index of 30 or more completed a 12-week weight loss program. Before and after the intervention, body composition and fat distribution by dual energy x-ray absorptiometry and whole-body magnetic resonance imaging, resting energy expenditure by indirect calorimetry, QOL, strength, and fitness were measured. Insulin sensitivity by intravenous glucose tolerance test and circulating cardiovascular risk factors (including lipids, tissue plasminogen activator, and plasminogen activator inhibitor 1) were measured in a subset (n = 9). Daily food intake and total body weight decreased (mean ± SD) by 3195 ± 477 kJ and 6.7 ± 4.2 kg, respectively. Weight lost was 95.5% fat by dual energy x-ray absorptiometry or 6.2 L of subcutaneous adipose tissue, 0.7 L visceral adipose tissue, and 0.8 L skeletal muscle by magnetic resonance imaging. Resting energy expenditure fell approximately 419 kJ, strength and fitness increased by 28.9% ± 18.5% and 36.8% ± 41.6%, respectively, and QOL improved in 11 of 13 dimensions. There was significant insulin resistance in the subset with metabolic measurements at baseline, and at follow-up there was no improvement in fasting glucose, insulin, or insulin sensitivity, nor was there any change in fasting lipids, tissue plasminogen activator, or plasminogen activator inhibitor 1. There was no significant change in CD4 count or HIV viral load. In conclusion, moderate weight loss achieved by a short-term program of diet and exercise in obese HIV-positive women appears safe and induces loss of adiposity in both the subcutaneous adipose tissue and visceral adipose tissue regions. Despite reduced food intake, weight and fat loss, as well as improvements in strength, fitness, and QOL, the lack of improvement in metabolic parameters suggests that additional interventions may be necessary to reduce the risk of diabetes and cardiovascular disease in this population