Effect of Leptin Therapy on Survival in Generalized and Partial Lipodystrophy: A Matched Cohort Analysis.

CONTEXT: Data quantifying the impact of metreleptin therapy on survival in non-human immunodeficiency virus (HIV)-related generalized lipodystrophy (GL) and partial lipodystrophy (PL) are unavailable. OBJECTIVE: This study aimed to estimate the treatment effect of metreleptin on survival in patients with GL and PL. DESIGN/SETTING/PATIENTS: Demographic and clinical characteristics were used to match metreleptin-treated and metreleptin-naïve patients with GL and PL. Differences in mortality risk were estimated between matched cohorts of metreleptin-treated and metreleptin-naïve patient cohorts using Cox proportional hazard models. Sensitivity analyses assessed the impact of study assumptions and the robustness of results. OUTCOME MEASURES: This study assessed time-to-mortality and risk of mortality. RESULTS: The analysis evaluated 103 metreleptin-naïve patients with characteristics matched to 103 metreleptin-treated patients at treatment initiation. Even after matching, some metabolic and organ abnormalities were more prevalent in the metreleptin-treated cohort due to bias toward treating more severely affected patients. A Cox proportional hazards model associated metreleptin therapy with an estimated 65% decrease in mortality risk (hazard ratio [HR] 0.348, 95% confidence interval (CI): 0.134-0.900; P = 0.029) even though the actual number of events were relatively small. Results were robust across a broad range of alternate methodological assumptions. Kaplan-Meier estimates of time-to-mortality for the metreleptin-treated and the matched metreleptin-naïve cohorts were comparable. CONCLUSIONS: Metreleptin therapy was associated with a reduction in mortality risk in patients with lipodystrophy syndromes despite greater disease severity in treated patients, supporting the view that metreleptin can have a positive disease-modifying impact. Confirmatory studies in additional real-world and clinical datasets are warranted.

Association between creatine kinase activity, oxidative stress and selenoproteins mRNA expression changes after Brazil nut consumption of patients using statins.

BACKGROUND & AIMS: Although the mechanisms by which statins promote muscle disorders remain unclear, supplementation with dietary antioxidants may mitigate statins' side effects. This study aimed to investigate whether the consumption of Brazil nuts modulates serum creatine kinase (CK) activity in patients regularly using statins. METHODS: The study was performed in the Ribeirão Preto Medical School University Hospital. Thirty-two patients in regular use of statins were divided according to CK activity levels (G1: increased or G2: normal) and received one unit of Brazil nut daily for 3 months. Body composition, blood selenium (Se) concentrations, erythrocyte glutathione peroxidase (GPX) activity, oxidative stress parameters, and CK activity were evaluated before and after supplementation. RESULTS: In both groups, supplementation with one Brazil nut daily for 3 months contributed to achieve decreased levels of CK activity in serum, with positive changes in plasma and erythrocyte Se concentrations (p < 0.0001), and increased levels of GPX activity. Among the parameters related to curbing of oxidative stress, we observed reduced levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in both groups after supplementation. We also found a moderately negative association between CK and GPX activity (r = -41; p < 0.02). Expression of selenoproteins GPX1, SELENOP, and SELENON after Brazil nut supplementation was unchanged. CONCLUSION: Brazil nut consumption enhanced the control of CK activity by improving oxidative stress biomarkers in patients using statins but did not modulate mRNA expression of selenoproteins.

Comorbidities and Survival in Patients With Lipodystrophy: An International Chart Review Study.

CONTEXT: Limited natural history data are available in patients with non-HIV-related lipodystrophy syndromes who never received disease-specific therapies, making interpretation of benefits of therapies in lipodystrophy syndromes challenging. OBJECTIVE: We assessed the natural history of non-HIV-related generalized lipodystrophy (GL) and partial lipodystrophy (PL) in patients who have never received leptin or other lipodystrophy-specific therapies. DESIGN/SETTING/PATIENTS: We conducted an international chart review of 230 patients with confirmed GL or PL at five treatment centers who never received leptin or other lipodystrophy-specific therapies. Patients were observed from birth to loss to follow-up, death, or date of chart abstraction. OUTCOME MEASURES: Lifetime prevalence of diabetes/insulin resistance and select organ abnormalities, time to diabetes/insulin resistance, first organ abnormality, disease progression, and mortality were described. RESULTS: Diabetes/insulin resistance was identified in 58.3% of patients. Liver abnormalities were the most common organ abnormality (71.7%), followed by kidney (40.4%), heart (30.4%), and pancreatitis (13.0%). Kaplan-Meier estimates of mean (SE) time to first organ abnormality were 7.7 years (0.9) in GL and 16.1 years (1.5) in PL (P < 0.001). Mean time to diabetes/insulin resistance was 12.7 years (1.2) in GL and 19.1 years (1.7) in PL (P = 0.131). Mean time to disease progression was 7.6 years (0.8) and comparable between GL and PL subgroups (P = 0.393). Mean time to death was 51.2 years (3.5) in GL and 66.6 years (1.0) in PL (P < 0.001). CONCLUSIONS: This large-scale study provides comprehensive, long-term data across multiple countries on the natural history of non-HIV-related lipodystrophy.

Anthropometry and bioelectrical impedance analyis compared to dual-photon absorptiometry for the assessment of body composition of hiv-seropositive patients / Antropometría y análisis de impedancia bioeléctrica comparado con absorciometría fotónica dual para la evaluación de la composición corporal en pacientes infectados por vih

Introduction: HIV-seropositive patients have shown changes in body composition such as lipoatrophy in certain regions of the body and lipohypertrophy in others, representing characteristics of lipodystrophy syndrome. It is important to monitor the quantity of fat per body segment using practical and low-cost methods in order to optimize the treatment of this group. Objectives: To correlate the body composition per body segment obtained by anthropometric measurements and by segmental bioelectrical impedance with DXA in HIV-seropositive patients on antiretroviral treatment Methods: We measured circumferences (arm, waist, hip, thigh and calf) and skinfolds (biceps, triceps, subscapular, suprailiac) and performed segmental bioelectrical impedance (BIA) analysis and DXA. The Pearson test was used to determine correlations and the St. Laurent test was used to assess concordance between variables. Results: We evaluated 26 patients, 35% of whom were overweight. The triceps skinfold (TSF), waist circumference (WC) and thigh circumference (TC) were significantly correlated with the measurement obtained by the gold standard (p<0.01). There was no concordance between the values obtained by segmental BIA and by DXA. Conclusions: Anthropometric measurements such as TSF, WC and TC are importantfor the monitoring of changes in body composition among HIV-seropositive patients on antiretroviral treatment. Segmental BIA did not prove to be appropriate for the assessment of body composition in HIV-seropositive patients.

Introducción: Se ha descrito cambios en la composición corporal de pacientes infectados por VIH, tales como la lipoatrofia en ciertas regiones del cuerpo y lipohipertrofia en otros, en representación de las características del síndrome de lipodistrofia. Es importante controlar la cantidad de grasa corporal por segmento utilizando métodos prácticos y de bajo costo con el fin de optimizar el tratamiento de este grupo. Objetivos: correlacionar la composición corporal por segmento corporal obtenidos por las mediciones antropométricas y por impedancia bioeléctrica com DXA segmentaria en pacientes seropositivos al VIH en tratamiento antir-retroviral. Métodos: Se midieron las circunferencias de brazo, cintura, cadera, muslo y pantorrilla y los pliegues cutáneos: bíceps, tríceps, subescapular, suprailíaco) y se realizaron impedancia bioeléctrica segmentaria (BIA) el análisis y DXA. La prueba de Pearson se utilizó para determinar las correlaciones y la prueba de San Lorenzo se utilizó para evaluar la concordancia entre las variables. Resultados: Se evaluaron 26 pacientes, 35% de los cuales tenían sobrepeso. El pliegue del tríceps (PT), circunferencia de la cintura (CC) y la circunferencia del muslo (CM) se correlacionaron significativamente con la medida obtenida por el patrón de oro (p <0.01). No hubo concordancia entre los valores obtenidos por BIA y DXA segmentaria. Conclusiones: Las mediciones antropométricas como PT, CC y CM son importantes para el seguimiento de los cambios en la composición corporal de los pacientes infectados por VIH que reciben tratamiento antirretroviral. La BIA segmental no demostró ser adecuado para la evaluación de la composición corporal en pacientes infectados por VIH.