Paula Freitas

Fat Mass Ratio: An Objective Tool to Define Lipodystrophy in HIV-Infected Patients Under Antiretroviral Therapy

Human immunodeficiency virus (HIV) infection and its treatment with antiretroviral therapy (ART) have been associated with lipodystrophy. Different clinical methodologies have been used to define the syndrome. The aim of this study was to propose gender-specific reference values using objective measurements for defining lipodystrophy in HIV-infected patients. Using dual-energy X-ray absorptiometry (DXA), total body composition was analyzed in 221 HIV-infected patients under ART (146 men). We used fat mass ratio (FMR) as the ratio between the percent of the trunk fat mass and the percent of the lower-limb fat mass. One hundred forty patients (63.6%) presented clinically defined lipodystrophy. In men, the optimal cutoff value for the FMR was 1.961 (area under the receiver operating characteristic curve [AUC]: 0.74 [95% confidence interval (CI): 0.66-0.82], p<0.001), with a sensitivity 58.3%, a specificity 83.7%, a positive predictive value (PPV) of 89.6% and a negative predictive value (NPV) of 45.5%. In women, the optimal cutoff value for the FMR was 1.329 (AUC: 0.74 [95% CI: 0.63-0.86], p<0.001), with a sensitivity 51.4%, a specificity 94.6%, a PPV of 90.5%, and an NPV of 66.0%. The FMR evaluated by DXA with the gender-specific cutoffs defined here is an objective way to define HIV-related lipodystrophy.

Impact of Lipodystrophy on the prevalence and components of metabolic syndrome in HIV-infected patients.

BackgroundIn HIV-infected patients, combination antiretroviral therapy (cART) is associated with clinical lipodystrophy (CL) and metabolic abnormalities (MA). This study aimed to evaluate the prevalence of the metabolic syndrome (MS) and its components, and to determine whether patients with or without CL had a different prevalence of MA.MethodsWe evaluated 345 HIV-infected patients on cART using two different MS definitions (NCEP-ATPIII-2005 and IDF-2005) and the Framingham risk score.ResultsCL was present in 58.7% of the patients. The prevalence of the MS was 52.2% (ATPIII) and 43.2% (IDF), and it was not significantly different between patients with (W) or without (WT) CL, regardless of the definition used (ATPIII WCL 52.9% vs WT CL 51.1%; p = 0.738; IDF WCL 41.3% vs WTCL 46.0%; p = 0.379). Moderate concordance was observed between the 2 definitions (kappa = 0.484; p < 0.001) and after gender stratification there was good concordance in women (kappa = 0.759; p < 0.001). Patients with CL had lower waist circumference and HDL-C and higher triglycerides levels. In women, CL was significantly associated with MS, hypertriglyceridemia and low HDL cholesterol independently of age, cART and BMI. Patients with CL had a significantly higher risk of coronary heart disease at 10 years, measured by the Framingham risk score, than patients without CL. Those with CL and with MS had higher frequencies of moderate and high risk categories than those without MS.ConclusionsThe prevalence of the MS was high in these HIV-infected patients with an age average of 40 years and this finding could explain why HIV patients have an increased risk for cardiovascular disease (CVD).

Gut Microbiota: Association with NAFLD and Metabolic Disturbances.

Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, being frequently associated with obesity, insulin resistance, and dyslipidemia. Recent lines of evidence have demonstrated a role of gut microbiota in insulin resistance, obesity, and associated metabolic disturbances, raising the interest in its relationship with NAFLD pathogenesis. Therefore, intestinal microbiota has emerged as a potential factor involved in NAFLD, through different pathways, including its influence in energy storage, lipid and choline metabolism, ethanol production, immune balance, and inflammation. The main objective of this review is to address the pathogenic association of gut microbiota to NAFLD. This comprehension may allow the development of integrated strategies to modulate intestinal microbiota in order to treat NAFLD.

Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome

BackgroundLipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution.MethodsAnthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient’s fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation.ResultsLeptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than controls despite BMI-matching.ConclusionThe overall body fat reduction in HIV lipoatrophy was associated with low leptin plasma levels, and visceral fat accumulation was mainly associated with decreased plasma levels of adiponectin.

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.

Assessment of body fat composition disturbances by bioimpedance analysis in HIV-infected adults

HIV-lipodystrophy syndrome is characterized by different patterns of body fat distribution (BFD) which are identified by clinical and body composition (BC) assessment, including bioimpedance analysis (BIA). Our aim was to compare BC in HIV-infected patients on combination antiretroviral therapy (cART) according to 4 distinct phenotypes of BFD (G1-no lipodystrophy, G2-isolated central fat accumulation, G3-lipoatrophy, G4-mixed forms of lipodystrophy) and assessed factors associated with them. Anthropometry and BIA were performed in 344 HIV-1 patients. G2 and G4 phenotype patients had significantly higher fat mass (FM) but no differences were observed in fat-free mass (FFM) and total body water among the 4 phenotypes. Significant negative associations were found between the presence of lipoatrophy and female gender, body mass index (BMI), waist (WC), hip (HC) and thigh circumferences, and total body FM estimated by BIA. After adjustment for gender, cART duration and BMI, G3 had significant lower WC [odds ratio (OR)=0.84; 0.78–0.90] and HC (OR=0.88; 0.81–0.96) mean. Independently of gender, cART duration and BMI, G2 remained significantly associated with higher WC (OR=1.11; 1.05–1.18) and HC (OR=1.15; 1.07–1.23) mean, and with FM estimated by BIA [FM as %, OR=1.17 (1.09–1.26); and FM as kg, OR=1.15 (1.06–1.25)]. There was a significant positive association between G4 and female gender (OR=1.66; 1.01–2.75), BMI (OR=1.10; 1.04–1.17) and WC (OR=1.15; 1.09–1.21). The similar FFM along the BFD spectrum describes the actual BC of these patients without sarcopenia. In a clinical setting, BIA is an easy and useful tool to evaluate fat mass and FFM and gives us a picture of BC that was not possible with anthropometry.

Beyond gut microbiota: understanding obesity and type 2 diabetes

Obesity and type 2 diabetes are metabolic diseases that have reached epidemic proportions worldwide. Although their etiology is complex, both result from interplay between behaviour, environment and genetic factors. Within ambient determinants, human overall gut bacteria have been identified as a crucial mediator of obesity and its consequences. Gut microbiota plays a crucial role in gastro-intestinal mucosa permeability and regulates the fermentation and absorption of dietary polyssacharides, which may explain its importance in the regulation of fat accumulation and the resultant development of obesity-related diseases. The main objective of this review is to address the pathogenic association between gut microbiota and obesity and to explore related innovative therapeutic targets. New insights into the role of the small bowel and gut microbiota in diabetes and obesity may make possible the development of integrated strategies to prevent and treat these metabolic disorders.

Prevalence of obesity and its relationship to clinical lipodystrophy in HIV-infected adults on anti-retroviral therapy.

Background: Combination antiretroviral therapy (cART) is associated with lipodystrophy (lipoatrophy and lipoaccumulation) and several metabolic abnormalities that together can contribute to an increased cardiovascular risk. The aim of this study was to evaluate the prevalence of obesity in patients on cART according to the presence of clinical lipodystrophy (CL) and to analyze factors associated with obesity. Methods: We evaluated 368 HIV-infected adults on cART. Results: CL was present in 59.0%. Independently of gender, patients with CL were more frequently underweight [5.7% (21/368)] and of normal weight [47.3% (174/368)], and less frequently overweight [33.2% (122/368)] or obese [13.9% (51/368)]. Mean body mass index was higher in patients with abdominal prominence regardless of the presence of clinical lipoatrophy. Patients with CL had lower waist circumference, higher waist/hip and fat mass ratio and lower total and subcutaneous fat, without significant difference in visceral fat but with a higher visceral/subcutaneous fat ratio, as evaluated by CT at abdominal level. CL was significantly less frequent in overweight [odds ratio (OR)=0.21, 95% confidence interval (CI): 0.05–0.92] and obese (OR=0.05, 95%CI: 0.01–0.26) patients, when compared to underweight ones, independent of age, gender, duration of infection, cART regimen, virological suppression, and HIV-infection risk factor. Conclusions: Being overweight or obese is highly prevalent in HIV-infected patients on cART. Patients with CL were more frequently under- or normal weight, and less frequently overweight or obese. Obesity is a condition that should be considered in HIV patients on cART.

Lipodystrophy defined by Fat Mass Ratio in HIV-infected patients is associated with a high prevalence of glucose disturbances and insulin resistance

IntroductionCombined antiretroviral therapy (cART) in the treatment of HIV-1 infection has been associated with complications, including lipodystrophy, hyperlipidaemia, insulin resistance (IR) and diabetes.AimsTo compare the prevalence of glucose homeostasis disturbances and IR in HIV patients on cART according to the presence of lipodystrophy (defined clinically and by Fat Mass Ratio) and different patterns of fat distribution and to establish their associations.DesignCross-sectional cohort study.MethodsWe evaluated body composition and IR and insulin sensitivity indexes in 345 HIV-infected adults.ResultsPatients with clinical lipodystrophy (CL) had higher plasma glucose levels than patients without CL, without significant differences in plasma insulin levels, A1c, HOMA-IR, HOMA-B, QUICKI, or MATSUDA index. Patients with lipodystrophy defined by FMR had higher plasma glucose and insulin levels, A1c, HOMA-IR, QUICKI and MATSUDA than patients without lipodystrophy, without differences in HOMA-B. Higher insulin resistance (HOMA-IR ≥ 4) was present in patients with FMR-defined lipodystrophy. Patients with FMR-defined lipodystrophy had a higher prevalence of IFG, IGT and DM than patients without lipodystrophy. Significant associations between HOMA-IR and total, central and central/peripheral fat evaluated by CT at abdominal level were found and no association between HOMA-IR and peripheral fat. Association between HOMA-IR and total and trunk fat but no association with leg and arm fat (evaluated by DXA) was found.ConclusionsIR and glucose disturbances were significantly increased in patients with FMR-defined lipodystrophy. FMR lipodystrophy definition seems to be a more sensitive determinant of insulin resistance and glucose disturbances than clinical definition.

Central⁄Peripheral Fat Mass Ratio Is Associated With Increased Risk of Hypertension in HIV-Infected Patients

J Clin Hypertens (Greenwich). 2012; 14:593–600.