Body Fat Abnormalities Research Articles

Evaluation of the hypothalamic\u2013pituitary\u2013adrenal axis in a case series of familial partial lipodystrophy

BackgroundFamilial partial lipodystrophy (FPL) is a rare genetic disease characterized by body fat abnormalities that lead to insulin resistance (IR). Clinical conditions linked to milder IR, such as type 2 diabetes (T2D) and metabolic syndrome, are associated with abnormalities of the hypothalamic–pituitary–adrenal (HPA) axis, but little is known about its activity in FPL.MethodsPatients meeting the clinical criteria for FPL were subjected to anthropometric, biochemical and hormone analyses. A genetic study to identify mutations in the genes encoding peroxisome proliferator-activated receptor gamma (PPARγ) was performed. Polycystic ovary syndrome and hepatic steatosis were investigated, and the patient body compositions were analyzed via dual X-ray energy absorptiometry (DXA). The HPA axis was assessed via basal [cortisol, adrenocorticotrophic hormone (ACTH), cortisol binding globulin, nocturnal salivary cortisol and urinary free cortisol (UFC)] as well as dynamic suppression tests (cortisol post 0.5 mg and post 1 mg dexamethasone).ResultsSix patients (five female and one male) aged 17 to 42 years were included. In DXA analyses, the fat mass ratio between the trunk and lower limbs (FMR) was > 1.2 in all phenotypes. One patient had a confirmed mutation in the PPARγ gene: a novel heterozygous substitution of p. Arg 212 Trp (c.634C>T) at exon 5. HPA sensitivity to glucocorticoid feedback was preserved in all six patients, and a trend towards lower basal serum cortisol, serum ACTH and UFC values was observed.ConclusionsOur findings suggest that FPL is not associated with overt abnormalities in the HPA axis, despite a trend towards low-normal basal cortisol and ACTH values and lower UFC levels. These findings suggest that the extreme insulin resistance occurring in FPL may lead to a decrease in HPA axis activity without changing its sensitivity to glucocorticoid feedback, in contrast to the abnormalities in HPA axis function in T2D and common metabolic syndrome.

Body fat measurements using bioelectrical impedance in pediatric patientstreated with hematopoietic cell transplantation

In patients who have undergone hematopoietic cell transplantation (HCT), the metabolic syndrome may develop without obesity defined by Body Mass Index (BMI). The aim of the study was to compare body fat parameters measured using bioelectrical impedance (BIA) and using standard parameters of obesity in patients treated with HCT and healthy controls. We compared body fat (BF) and body fat percentage (BF%) measured using BIA in 44 patients before HCT and 28 patients after HCT, versus 26 controls. We also compared BMI and other BIA parameters in these groups of patients. The differences in BF and BF% between the patients before HCT and controls were not significant, while both BF and BF% were significantly lower in patients after HCT than in the control group. No significant differences in standard clinical obesity parameters were found in the patients before HCT, and in the patients after HCT, compared with the controls. The differences in other BIA parameters between the patients before HCT and the controls were not significant, while in the patients after HCT some parameters were significantly lower. Significant differences in BF and BF% in the patients after HCT compared with healthy controls suggest that BIA may be useful in screening for body fat abnormalities in patients after HCT.

Carotid intima media thickness is associated with body fat abnormalities in HIV-infected patients.

BackgroundHIV-infected patients may be at increased risk of cardiovascular (CV) events, and lipodystrophy is generally associated with proatherogenic metabolic disturbances. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis and it has been shown to be an independent risk factor for CV disease. Our objective was to evaluate cIMT in HIV-infected patients on combined anti-retroviral therapy (cART) with and without lipodystrophy defined by fat mass ratio (L-FMR), and to determine the association of lipodystrophy and visceral obesity [(visceral (VAT), subcutaneous adipose tissue (SAT) volume and VAT/SAT ratio, objectively evaluated by CT scan] with cIMT.MethodsCross-sectional study of 199 HIV-infected patients. Body composition by DXA and abdominal CT, lipids, blood pressure, inflammatory markers, and cIMT by ultrasonography were performed. L-FMR was defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared using the chi-square or Fisher’s exact test. Spearman correlation coefficients were estimated to study the association between cIMT and clinical and metabolic characteristics. Means of cIMT, adjusted for age, were calculated, using generalized linear models.ResultsL-FMR was present in 41.2% of patients and cIMT was higher in these patients [0.81 (0.24) vs. 0.76 (0.25); p = 0.037)]. Lipodystrophic patients had higher VAT and VAT/SAT ratio and lower SAT. cIMT was associated with lipodystrophy evaluated by FMR, trunk fat, total abdominal fat, VAT and VAT/SAT ratio. No association was observed between cIMT and leg fat mass. Using generalized linear models, cIMT means were adjusted for age and no significant differences remained after this adjustment. The adjusted mean of cIMT was 0.787 (95% CI: 0.751-0.823) in patients without lipodystrophy, and 0.775 (95% CI: 0.732-0.817) in those with lipodystrophy (p = 0.671).ConclusionsHIV-infected patients on cART with lipodystrophy defined by FMR, had a significantly higher cIMT. Carotid IMT was also associated with classical cardiovascular risk factors. In these patients, visceral adipose tissue had a significant impact on cIMT, although age was the strongest associated factor.

Prolonged and Shorter Aerobic Exercise Training in HIV

The purpose of this review was to determine whether prolonged aerobic exercise training was as safe and effective as shorter aerobic exercise training. Shorter time period studies up to and including four months were summarized for aerobic exercise training parameters and results. Similarly, aerobic exercise training studies that were six and more months were also summarized. Predicted or measured maximum oxygen uptake (VO2max) results for the shorter term studies generally ranged from 10-29%. All the studies used 3x/wk. as a training frequency. Aerobic exercise training intensity averaged 75% of predicted heart rate (PHR) maximum and exercise duration ranged from 20-60 minutes. Since many of the subjects were on highly active antiretroviral therapy (HAART), blood lipids and body fat abnormalities were prevalent. In the few shorter aerobic exercise training studies to measure lipids and body fat, there appeared to be a favorable effect. Prolonged aerobic exercise training results were sparse. Studies indicated similar training parameters with the exception of using a higher aerobic training intensity for one study. VO2max results for the higher intensity study demonstrated a higher aerobic fitness than other studies. All the prolonged aerobic exercise regimes increased VO2max similar to the shorter term studies or maintained higher levels of aerobic fitness. Triglyceride levels were elevated and unfavorably increased during prolonged aerobic training. Body fat was favorably modified in another prolonged study in spite of HAART. Considering the paucity of studies it appears that prolonged aerobic exercise training is equally safe and effective as compared to shorter aerobic exercise training.

Mitochondrial Impact of Human Immunodeficiency Virus and Antiretrovirals on Infected Pediatric Patients With or Without Lipodystrophy

We determined the mitochondrial status of a group of HIV-infected children, some with body fat abnormalities (BFA). We included 24 controls, 16 HIV-infected untreated, 26 HIV-infected treated, 6 BFA-untreated, and 21 BFA-treated patients. Genetic, translational, and functional mitochondrial values were measured. As compared with controls, mitochondrial DNA depletion and a reduction in functionality were found in BFA groups.

A Comparison of Sonographic Assessments and Clinical Questionnaire in the Diagnosis of HIV-Associated Lipodystrophy

The study evaluated the use of sonographic measurements as an alternative to assessments based on clinical or other imaging techniques for the diagnosis of body-fat abnormalities. The study enrolled 179 HIV-infected patients, 81 (45.3%) of them diagnosed as lipodystrophy (LD)-positive based on a clinical standard questionnaire. Association between clinical LD and sonographic measurements of face, right upper limb, subcutaneous abdomen, and visceral compartments was evaluated by multiple logistic regression. The predicted probability of the logistic model was 0.64, corresponding to a maximum sensitivity of 69.1% (58%-79%), a specificity of 94.9% (88%-98%), and to positive and negative predictive values of 92% (82%-97%) and 79% (70%-86%), respectively. Kappa measure of concordance was 65% (54%-77%). Low sensitivity poses a problem for the use of sonography to detect LD in the clinical routine as a single exam, speaking in favor of the combined use of clinical and sonographic measurements over time.

W(h)ither Metreleptin for Lipodystrophy and the Metabolic Syndrome?

Lipodystrophy, congenital or acquired, partial or generalized, is a disorder characterized by pathologic deposition of adipose tissue (lipoatrophy, lipohypertrophy, or both) accompanied by metabolic abnormalities ( 1 Gao C Mantzoros CS Lipodystrophy syndromes. in: Jameson JL De Groot LJ Endocrinology.6th ed. Elsevier, Mosby, Saunders, Philadelphia, PA2010 Crossref Google Scholar ). Lipodystrophy is extremely rare among human immunodeficiency virus (HIV)-negative subjects; it is estimated that worldwide there are only several hundred subjects with either congenital lipodystrophy or non-HIV-associated acquired lipodystrophy ( 1 Gao C Mantzoros CS Lipodystrophy syndromes. in: Jameson JL De Groot LJ Endocrinology.6th ed. Elsevier, Mosby, Saunders, Philadelphia, PA2010 Crossref Google Scholar , 2 Grinspoon S Carr A Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005; 352: 48-62 Crossref PubMed Scopus (878) Google Scholar , 3 Leow MK Addy CL Mantzoros CS Clinical review 159: human immunodeficiency virus/highly active antiretroviral therapy-associated metabolic syndrome; clinical presentation, pathophysiology, and therapeutic strategies. J Clin Endocrinol Metab. 2003; 88: 1961-1976 Crossref PubMed Scopus (104) Google Scholar ). The widespread use of combinations of antiretroviral agents for the treatment of HIVpositive patients since the 1990s, however, has resulted in the development of a new syndrome, the HIV/hightly active antiretroviral therapy (HAART)-associated lipodystrophy and metabolic syndrome (HALS) ( 3 Leow MK Addy CL Mantzoros CS Clinical review 159: human immunodeficiency virus/highly active antiretroviral therapy-associated metabolic syndrome; clinical presentation, pathophysiology, and therapeutic strategies. J Clin Endocrinol Metab. 2003; 88: 1961-1976 Crossref PubMed Scopus (104) Google Scholar ). In contrast to the extremely low prevalence of non-HIV-associated lipodystrophy worldwide, there are several hundreds of thousands of HIV-positive patients who have HALS, with approximately 200,000 of them having lipoatrophy (adipose tissue deficiency) and hypoleptinemia ( 1 Gao C Mantzoros CS Lipodystrophy syndromes. in: Jameson JL De Groot LJ Endocrinology.6th ed. Elsevier, Mosby, Saunders, Philadelphia, PA2010 Crossref Google Scholar , 2 Grinspoon S Carr A Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005; 352: 48-62 Crossref PubMed Scopus (878) Google Scholar , 3 Leow MK Addy CL Mantzoros CS Clinical review 159: human immunodeficiency virus/highly active antiretroviral therapy-associated metabolic syndrome; clinical presentation, pathophysiology, and therapeutic strategies. J Clin Endocrinol Metab. 2003; 88: 1961-1976 Crossref PubMed Scopus (104) Google Scholar ).

Body-Fat Abnormalities in Patients With HIV: Progress and Challenges

The introduction of newer antiretroviral drugs has provided greater levels of HIV suppression with fewer of the metabolic effects, lipoatrophy, and body habitus changes associated with earlier therapies. Previously classified under the collective term, lipodystrophy, lipoatrophy and body-fat changes are now known to occur independently in some HIV-infected patients, depending on the type and duration of antiretroviral therapy and a myriad of factors including HIV infection alone that contribute significantly to these changes. This article reviews the current scientific literature and recent clinical trial results that distinguish lipoatrophy or dyslipidemia pathophysiologically from body-fat changes seen as central and peripheral lipohypertrophy and fat redistribution, as well as the nature and extent of changes associated with HIV infection alone and newer antiretroviral therapies. This information may assist physicians in identifying individual risk factors and choosing the type of antiretroviral therapy that may minimize these changes without loss of virologic suppression.

Pathogenesis and management of lipoatrophy

Despite impressive decreases in mortality and morbidity, significant adverse events have surfaced as a result of combination antiretroviral therapy (ART). They include lipoatrophy, or subcutaneous fat wasting of the face, arms, buttocks, or legs, which can be associated with central fat accumulation. Although the underlying mechanism of ART-related body fat abnormalities has not been definitively established, mitochondrial toxicity is increasingly implicated in the lipoatrophy component of these fat abnormalities. Several studies evaluating switches off of nucleoside analogues have showed modest but statistically significant increases in limb fat. Because ART switches result in slow and small improvements and are not an option in many patients, other therapeutic interventions are needed. Although peroxisome proliferator-activated receptor chi agonist thiazolidinediones would be expected to have positive effects on lipoatrophy, initial clinical studies are conflicting. Other interventions of uridine, pravastatin, and facial fillers have been evaluated in small studies.

Abnormal Glucose Regulation and Treatment Strategies for Insulin Resistance HIV-Infected Patients

HIV-infected patients receiving highly active antiretroviral therapy often demonstrate abnormalities in glucose regulation, in association with changes in fat distribution[1,2]. In the majority of cases, these abnormalities are best characterized by insulin resistance and impaired glucose tolerance, rather than overt diabetes mellitus and fasting hyperglycemia. Insulin resistance may result from direct effects of antiretroviral therapy, changes in fat distribution or abnormal regulation of fat metabolism and adipocytokines. Use of insulin sensitizing agents may be rationale to reduce cardiovascular risk and improve related metabolic and body fat abnormalities in HIV-infected patients.

Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine

To evaluate the 24-month metabolic and morphological benefits obtained from replacing the protease inhibitor (PI) in a regimen with nevirapine, efavirenz or abacavir. NEFA was a randomized study designed to compare the efficacy of nevirapine, efavirenz or abacavir as substitutes for PI. A subset of 90 patients [abacavir (n = 29), efavirenz (n = 32), nevirapine (n = 29)] formed the metabolic study. Fasting total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and triglycerides levels were determined. Glucose homeostasis parameters were also collected. Lipodystrophy was evaluated by clinical examination and morphological measurements. Treatment simplification led to overall lipid profile improvements. At 24 months, the two non-nucleoside reverse transcriptase inhibitors produced similar lipid benefits: HDL-c levels increased [efavirenz, 15% (P = 0.001); nevirapine, 21% (P < 0.001)] and TC to HDL-c ratios decreased [efavirenz, 14% (P < 0.001); nevirapine, 19% (P < 0.01)], an effect not observed in the abacavir arm. Non-HDL-c levels decreased by 10% in both the abacavir (P = 0.001) and efavirenz (P < 0.05) arms. Significant decreases in the levels of triglycerides occurred for the first year in all treatments; however, at 24 months most of the initial loss had been regained. Patients with baseline moderate or severe lipodystrophy obtained less-pronounced lipid benefits. Several insulin resistance markers showed a trend towards improvement. Conversely, no improvements in morphological abnormalities were observed. Replacing PI with efavirenz, nevirapine or abacavir improved the lipid profile, with more marked results in non-lipodystrophic patients. In contrast, this strategy does not seem to be effective for reversing body fat abnormalities.

Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults

Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults

Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults

Metabolic complications such as dyslipidemia, insulin resistance, and altered fat distribution (loss of subcutaneous fat and relatively increased central fat) are common in adults infected with the human immunodeficiency virus who are receiving highly active antiretroviral therapy and may increase their risk of cardiovascular disease. This review discusses progress in understanding the pathogenetic mechanisms and treatment strategies for addressing cardiovascular risk in this population.

Evidence of human immunodeficiency virus-associated lipodystrophy syndrome in children treated with protease inhibitors

We conducted a prospective evaluation for evidence of the HIV-associated lipodystrophy syndrome of 26 children infected with HIV-1. Six children had evidence of body fat redistribution. Nine children showed laboratory evidence of insulin resistance. All children with body fat distribution or insulin resistance had been treated with protease inhibitors. Children treated with protease inhibitors had higher total cholesterol, higher low density lipoprotein-cholesterol and higher triglycerides than untreated children.