[Show abstract][Hide abstract] ABSTRACT: HIV-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.
[Show abstract][Hide abstract] ABSTRACT: Lipodystrophies 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-alpha, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution.
[Show abstract][Hide abstract] ABSTRACT: Leptin is a hormone produced predominantly by adipocytes, essential in energy homeostasis regulation. It acts as a sensor of body fat mass stores, being involved in lipids control in non adipose tissues, food intake and thermogenesis with subsequent metabolic implications.
Leptin administration in replacement doses constitutes an important step forward in the understanding and treatment of various lipodystrophic syndromes, conditions characterized by a hypoleptinemic state. Particularly, recombinant methionyl leptin administration in patients with lipodystrophy exhibiting severe hypoleptinemia ameliorated hyperinsulinemia, insulin resistance, hyperglycemia, hypertriglyceridemia, and neuroendocrine abnormalities without significant adverse effects, providing the rationale for metreleptin treatment in these patients.
Revista Portuguesa de Endocrinologia, Diabetes e Metabolismo. 01/2014;
[Show abstract][Hide abstract] ABSTRACT: Genetic and acquired lipodystrophies are disorders of adipose tissue distribution. In this review we will emphasize its phenotype, metabolic and genetic particularities. Special stress will be given to the most prevalent lipodystrophy ‑that associated with HIV infection - describing the similarities with congenital lipodystrophies and its pathogenic mechanisms. It will be discussed the pathways involved in development, differentiation and death of adipocytes, emphasizing that both genetic and acquired, including that associated with HIV can induce changes in adipogenesis and how the two main adipose tissue dysfunctions - obesity and lipodystrophy - can cause a similar metabolic profile (diabetes, hypertension, dyslipidemia) with increased cardiovascular risk. Rare monogenic laminopathies and other genetic lipodystrophies could be relevant to understand common pathways - physiopathology of aging, atherosclerosis process, vascular endothelial cell dysfunction, frailty syndrome and common disorders such as type 2 diabetes, insulin resistance, dyslipidemia, hypertension and metabolic syndrome. Also, some lipodystrophies can be associated with premature aging and precocious cardiovascular disease. The authors aimed to give a focus on the particularities of each of the issues addressed.
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Combined antiretroviral therapy (cART) in the treatment of HIV-1 infection has been associated with complications, including lipodystrophy, hyperlipidaemia, insulin resistance (IR) and diabetes. AIMS: To 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. DESIGN: Cross-sectional cohort study. METHODS: We evaluated body composition and IR and insulin sensitivity indexes in 345 HIV-infected adults. RESULTS: Patients 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 [greater than or equal to] 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. CONCLUSIONS: IR 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.
[Show abstract][Hide abstract] ABSTRACT: The increased survival rates in childhood and young adulthood cancer have resulted in a parallel rise in survivors of reproductive age. Accordingly, fertility preservation is an increasingly valued issue by patients and the scientific community. Despite the recognized importance of timely discussion with the patient about the infertility risk associated with cancer and anticancer treatment, there are several barriers that may explain why more than half the oncologists do not routinely address these issues further. Embryo cryopreservation is a well established method to preserve fertility in cancer patients, but the need for prior stimulation with gonadotrophins and the use of male gametes are recognized limitations. Oocyte cryopreservation guarantees women's reproductive autonomy, since it does not imply a partner or a sperm donor. Important technical developments in this area, along with improvement in fertilization rates with intracytoplasmic injection (ICSI), contributed to the progress in its implementation. Ovarian tissue cryopreservation has the advantage of not requiring prior hormonal stimulation, without imposing delays to the beginning of anticancer treatment. It may be offered to selected women, ideally integrated in clinical research protocols. GnRH agonists are used in various centers during chemotherapy, but their effectiveness in the preservation of ovarian function and fertility is controversial. Data so far available show no increased incidence of congenital malformations in the offspring of cancer survivors. Particular attention should be given to women undergoing pelvic irradiation, as there is an increased risk of miscarriage, preterm delivery and low birth weight, as well as to women undergoing thoracic irradiation or anthracycline treatment, for the risk of cardiomyopathy. A multidisciplinary team consisting of oncologists and other clinicians involved in cancer treatment, reproductive medicine specialists (as gynecologists, geneticists, endocrinologists), psychologists, among others, will help women to preserve their fertility as efficiently and timely as possible, without jeopardizing the success of anticancer treatment.
Revista Portuguesa de Endocrinologia, Diabetes e Metabolismo. 01/2012; 7(2):44–51.
[Show abstract][Hide abstract] ABSTRACT: 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 analyse 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 BMI 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 (OR=0.21, 95%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 HIVinfection risk factor. Conclusions: Being overweight or obese is highly prevalent in HIV-infected patients on cART. Patients with clinical lipodystrophy were more frequently under- or normally weighted, and less frequently overweighed or obese. Obesity is a condition that should be considered in HIV patients on cART.
Journal of endocrinological investigation 12/2011; · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In 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.
We evaluated 345 HIV-infected patients on cART using two different MS definitions (NCEP-ATPIII-2005 and IDF-2005) and the Framingham risk score.
CL 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.
The 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).
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of endocrinological investigation 07/2011; 34(10):e321-9. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Clinical Densitometry 03/2010; 13(2):197-203. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is a common inherited disorder of adrenal hormone biosynthesis due to mutations in the 21-hydroxylase gene, CYP21A2. Genotyping for ten of the most frequent mutations was performed in 84 Portuguese CAH patients: 10 salt-wasters, 6 simple-virilizers and 68 non-classical patients. The patients were diagnosed by a level of 17-hydroxyprogesterone above 10 ng/ml either in basal conditions or after an ACTH 0,25 mg IV Test. A variety of genotyping techniques were used to detect these ten mutations. CYP21A2 mutations were detected in 91.7% (77/84) of the patients. The frequency of alleles carrying two or more CYP21A2 mutations (9.5% - 16/168) is higher than in other populations. The most frequent mutations identified in our population were V281L (41.7%) and deletions/conversions involving the promoter region of the CYP21A2 gene (28.3%). A decreased frequency of IVS2-12C/A>G mutation (5.6%) was the most characteristic feature of our population. This study allow the characterization of the mutational spectrum of CAH patients, mainly non-classical CAH, with 21-hydroxylase deficiency from Portugal showing specific genetic features of this population which reveals differences with worldwide countries.