Early loss of bone mineral density is correlated with a gain of fat mass in patients starting a protease inhibitor containing regimen: the prospective Lipotrip study.

BACKGROUND: HIV-infected patients starting antiretroviral treatment (ART) experience deep and early disorders in fat and bone metabolism, leading to concomitant changes in fat mass and bone mineral density. METHODS: We conducted a prospective study in treatment-naive HIV-infected patients randomized to receive two nucleoside reverse transcriptase inhibitors in combination with either a protease inhibitor (PI) or a non-nucleosidic reverse transcriptase inhibitor (NNRTI), to evaluate early changes in body composition, bone mineral density and metabolic markers as differentially induced by antiretroviral therapies. We measured changes in markers of carbohydrate, of fat and bone metabolism, and, using dual-emission X-ray absorptiometry (DXA), body composition and bone mineral density (BMD). Complete data on changes between baseline and after 21 months treatment were available for 35 patients (16 in the PI group and 19 in the NNRTI group). RESULTS: A significant gain in BMI and in total and lower limb fat mass was recorded only in patients receiving PI. A loss of lumbar BMD was observed in both groups, being higher with PI. Plasma markers of bone metabolism (alkaline phosphatase, osteocalcin, collagen crosslaps) and levels of parathormone and of 1,25diOH-vitamin D3 significantly increased in both groups, concomitant with a decline in 25OH-vitamin D3. Lipids and glucose levels increased in both groups but rise in triglyceride was more pronounced with PI. A correlation between loss of BMD and gain of fat mass is observed in patients starting PI. CONCLUSIONS: We evidenced an early effect of ART on lipid and bone metabolisms. PI lead to a significant gain in fat mass correlated with a sharp drop in BMD but active bone remodelling is evident with all antiretroviral treatments, associated with low vitamin D levels and hyperparathyroidism. In parallel, signs of metabolic restoration are evident. However, early increases in lean and fat mass, triglycerides, waist circumference and leptin are much more pronounced with PI.

Longitudinal study of body composition of 101 HIV men with lipodystrophy: dual-energy X-ray criteria for lipodystrophy evolution.

The aim of this study was to define evolution profiles of body composition among human immunodeficiency virus (HIV)-infected men with lipodystrophy. The design is a retrospective analysis using observational data collected longitudinally. We included 101 HIV-infected men with lipodystrophy managed in routine practice and who had 2 dual energy X-ray absorptiometry scans within a minimum interval of 18 mo. Lipodystrophy was defined as a fat mass ratio (FMR, defined as the ratio of the percentage of the trunk fat mass over the percentage of the lower limbs fat mass) equal or superior to 1.5. Patients were classified in "improved" group (IG: increase of lower limbs fat mass >/= 10%) or "nonimproved" group (NIG). Body composition, immunovirological and epidemiological data were collected and compared between the 2 groups. In the whole population, over a 4-yr period, a significant increase was observed for total fat mass, trunk fat mass, and lower limbs fat mass, whereas total lean mass was stable. Total body mineral density decreased. Fifty-nine patients (IG), less exposed to zidovudine than the NIG, had an increase of lower limbs fat mass higher than 10%. But only 13 (22%) regained a normal distribution of fat mass (FMR < 1.5), showing that lipodystrophy was slowly reversible. Among the NIG, 5 patients (11.9%), less exposed to zidovudine and with a higher mean of viral load, reached an FMR below 1.5. It was mainly because of a loss of trunk fat mass, which could be the sign of a lipodystrophy worsening. Lipodystrophy improved for 58.4% of men. The improvement was very slow. Recovery was observed only in patients with an earlier intervention. No correlation was observed between lipodystrophy and total body bone mineral density. The loss of trunk fat mass without gain of lower limbs fat mass may indicate a worsening of HIV disease.

Effects of discontinuing stavudine or protease inhibitor therapy on human immunodeficiency virus-related fat redistribution evaluated by dual-energy x-ray absorptiometry.

STUDY OBJECTIVE: To determine whether discontinuation of stavudine or protease inhibitor therapy improves human immunodeficiency virus (HIV)-related fat distribution in men. DESIGN: Observational, retrospective study consisting of a cross-sectional (part 1) and a longitudinal (part 2) study. DATA SOURCE: Medical records from Purpan University Hospital and La Grave University Hospital, Toulouse, France. Subjects. Eighty men with HIV infection treated with antiretrovirals and 151 healthy male controls matched for age. MEASUREMENTS AND MAIN RESULTS: In part 1, body composition and fat distribution of the HIV-infected men were compared by dual energy x-ray absorptiometry (DEXA) with those of the controls to determine whether body fat distribution is altered in HIV-infected men. In part 2, we analyzed modifications of body composition and fat distribution in 45 of the 80 patients. These 45 had been exposed to antiretroviral drugs, including stavudine and a protease inhibitor, for at least 5 months before the first of two DEXA assessments. They received three different treatment strategies for several months. In group 1, stavudine was withdrawn; in group 2, protease inhibitor was discontinued, and in group 3, stavudine plus protease inhibitor were continued. Group 1 showed a significant fat gain in the lower extremities 31.7 +/- 5.9 months after stavudine discontinuation (p<0.0001). Group 2 did not show any significant modification of total body, lower limb, or trunk fat despite protease inhibitor discontinuation for 35.2 +/- 6.6 months. Findings were similar for group 3, who continued receiving stavudine-protease inhibitor therapy for 21.2 +/- 12.8 months. CONCLUSION: These data suggest that long-term withdrawal of stavudine from the antiretroviral therapy regimen may be associated with significant improvement in lipoatrophy in the lower extremities, whereas long-term protease inhibitor withdrawal did not modify fat distribution.

Effect of macronutrient composition of the diet on the regulation of lipolysis in adipose tissue at rest and during exercise: microdialysis study.

The aim of the present study was to elucidate, using a microdialysis technique, whether modifications in the proportion of fat in the diet influence lipid mobilization from adipose tissue in situ. Nine healthy volunteers (age, 23.4 +/- 0.2 years; body mas index [BMI], 23.5 +/- 1.6 kg/m(2)) were fed, in random order, with a high-fat diet (HFD) (65% of energy content fat, 15% protein, 20% carbohydrate) or a high-carbohydrate diet (HCD) (70% carbohydrate, 15% protein, 15% fat) for 5 days, with a washout period of 10 days between the diets. Subjects were studied in the fasting state on the morning following days 4 and 5 of each diet. We measured the concentration of extracellular glycerol (EGC) in adipose tissue in response to (1) pharmacologic stimulation with isoprenaline (1 and 10 micromol/L) in situ, (2) stimulation with intravenous infusion of epinephrine (0.0375 microg/min/kg body weight), and (3) submaximal aerobic exercise (50% V*O2max, 60-minute duration). No effect of the diet composition was found in the increases of EGC in response to isoprenaline (area under the curve [AUC]: HFD, 1,534 +/- 370 micromol/90 min; HCD, 1,108 +/- 465 micromol/90 min; not significant [NS]) or epinephrine stimulations (AUC: HFD, 190 +/- 92 micromol/30 min; HCD, 251 +/- 298 micromol/30 min; NS). The exercise-induced increase in EGC was higher during the HFD (AUC: HFD, 1,641 +/- 181 micromol/60 min; HCD, 963 +/- 156 micromol/60 min; P <.05) and was associated with a higher exercise-induced response of norepinephrine (P <.05) and epinephrine (P =.056) and lower insulinemia during exercise. The results suggest that macronutrient composition of diet does not affect the beta-adrenergic responsiveness of adipose tissue to catecholamine action at rest. During exercise, the HFD promotes higher lipolysis in adipose tissue and this is associated with a higher catecholamine response and lower insulinemia.

Effects of a longitudinal training program on responses to exercise in overweight men.

OBJECTIVE: The aim of this study was to determine how training modifies metabolic responses and lipid oxidation in overweight young male subjects. RESEARCH METHODS AND PROCEDURES: Eleven overweight subjects were selected for a 4-month endurance training program. Before and after the training period, they cycled for 60 minutes at 50% of their VO(2)max after an overnight fast or 3 hours after eating a standardized meal. Various metabolic and endocrine parameters, and respiratory exchange ratio values were evaluated. RESULTS: Exercise-induced plasma norepinephrine concentration increases were similar before and after training in fasted or fed conditions. After food intake, exercise promoted a decrease in plasma glucose and a higher increase in epinephrine than in fasting conditions. The increase in epinephrine after the meal was more marked after training (264 +/- 32 vs. 195 +/- 35 pg/mL). Training lowered the resting plasma nonesterified fatty acids. During exercise, changes in glycerol were similar to those found before training. Lipid oxidation during exercise was higher in fasting than in fed conditions (15.5 +/- 1.4 vs. 22.3 +/- 1.7 g/h). Training did not significantly increase fat oxidation when exercise was performed in fed conditions, but it did in fasting conditions (18.6 +/- 1.4 vs. 27.2 +/- 1.8 g/h). DISCUSSION: Endurance training decreased plasma nonesterified fatty acids, cholesterol, and insulin concentrations. Training increased lipid oxidation during exercise, in fasting conditions, and not when exercise was performed after the meal. During exercise in overweight subjects, the fasting condition seems more suited to oxidizing fat and maintaining glucose homeostasis than a 3-hour wait after a standard meal.