Physical Function, Quality of Life, and Energy Expenditure During Activities of Daily Living in Obese, Post-Bariatric Surgery, and Healthy Subjects.

OBJECTIVES: This study aimed to evaluate physical function (PF), quality of life (QOL), and energy expenditure (EE) during activities of daily living (ADL) in late outcome post-bariatric surgery (BS) patients and to compare them to severe obese individuals and matched controls. METHODS: Sixty-three subjects were included: 21 patients in post-operative (PO) of BS (3-4 years post-Roux-en-Y gastric bypass) with a stable weight for at least 6 months (16 women, 41 ± 11 years old, BMI = 28 ± 4 kg m-2) (group PO); 21 obese individuals with BS indication (16 women, 44 ± 9 years old, BMI = 44 ± 6 kg m-2) (group OB); and 21 controls matched to PO by gender, age, and BMI (16 women, 42 ± 12 years old, BMI = 27 ± 6 kg m-2) (group MC). PF was objectively assessed by the Glittre and modified Glittre ADL-tests. QOL (SF-36), EE (activity monitoring during ADL), and body composition (bioelectrical impedance) were also assessed. RESULTS: OB had worse PF (Glittre ADL-test) compared to PO and MC (OB = 224 ± 76 s; PO = 143 ± 39 s; and MC = 118 ± 17 s; p < 0.0001). The same was observed for QOL (p < 0.05 for all SF-36 domains). OB also had higher total EE in the Glittre ADL-test. However, 63% of the activity time was in low-intensity EE. In the Glittre modified protocol, OB had poorer performance than PO and MC when walking up/downstairs, rising/sitting in a chair, and moving objects on a shelf. CONCLUSIONS: Post-BS patients have better PF and QOL and perform activities under lower total EE than obese subjects, very similar to matched controls.

A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy.

Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy

SUMMARY Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

Lipoproteins and CETP levels as risk factors for severe sepsis in hospitalized patients.

BACKGROUND: The magnitude of lipoprotein level reduction during the acute-phase response may be associated with the severity and mortality of sepsis. However, it remains to be determined whether low lipoprotein levels can be considered a risk factor for developing sepsis. We aimed to investigate lipoprotein levels as risk factors for sepsis in hospitalized patients, and also describe sequential changes in lipoprotein and cholesterol ester transfer protein (CETP) levels during sepsis. DESIGN: This is a prospective cohort study and case-control analysis from selected hospitalized patients. Blood samples were collected at admission, and participants were monitored for severe sepsis. Total cholesterol, high density lipoprotein (HDL), low density lipoprotein, and triglyceride levels were compared between sepsis cases and controls. Cholesterol, apolipoprotein, phospholipid and CETP concentrations were monitored in the case group. RESULTS: Of 1719 enrolled patients, 51 developed severe sepsis and were paired with 71 controls by age, gender, presence of infection at admission and chronic disease. HDL cholesterol level at admission was a risk factor for severe sepsis (OR = 0.969; 95% CI: 0.944-0.995). Mean CETP levels diminished between hospital admission and day 3 of sepsis. The magnitude of this variation (Delta CETP) was more pronounced in non-survivors (0.78 +/- 1.08 microg mL(-1)) than that in survivors (0.02 +/- 0.58 microg mL(-1), P = 0.01). CONCLUSIONS: HDL cholesterol may have a protective effect against sepsis. Each 1 mg dL(-1) increase in HDL decreased the odds of severe sepsis by 3% during hospitalization. The reduction of plasma CETP was associated with mortality.

Metformin increases HDL3-cholesterol and decreases subcutaneous truncal fat in nondiabetic patients with HIV-associated lipodystrophy.

The purpose of this study was to assess metformin effects on high-density lipoprotein (HDL) composition of patients with HIV-associated lipodystrophy (LDHIV). Twenty-four adult outpatients were enrolled to receive metformin (1700 mg/d) during 6 months, but 2 were lost to follow-up and 6 stopped the drug due to adverse events (gastrointestinal in 5, and excessive weight loss in 1). From the 16 subjects who completed the study, 69% were female. At baseline, 3 and 6 months, we assessed: weight, waist and hip circumferences, blood pressure, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), lipids, and HDL subfractions by microultracentrifugation. At 0 and 6 months, body fat distribution was assessed by computed tomography (CT) scan (L4 and middle femur). Metformin use was associated with reduction of mean weight (-2.4Kg at 6 months; p < 0.001), body mass index, waist, waist-to-hip ratio and a marked decrease in blood pressure (p < 0.001). Subcutaneous (p = 0.01) and total abdominal fat (p = 0.002) were reduced, but no change was found in visceral or thigh fat. No difference was detected on plasma glucose, insulin, HOMA2-IR, cholesterol or triglycerides, except for an increase in HDL3-cholesterol (from 21 mg/dL to 24 mg/dL, p = 0.002) and a reduction of nascent HDL (the fraction of plasma HDL-cholesterol not associated to subfractions HDL2 or HDL3) (p = 0.008). Adverse effects were very common, but most were gastrointestinal and mild. Thus, metformin use in LDHIV increases HDL3-cholesterol (probably due to improved maturation of HDL) and decreases blood pressure, weight, waist, and subcutaneous truncal fat, making this an attractive option for preventing cardiovascular disease in this population.

[Prevalence of HIV-associated lipodystrophy in Brazilian outpatients: relation with metabolic syndrome and cardiovascular risk factors]. / Prevalência da lipodistrofia associada ao HIV em pacientes ambulatoriais brasileiros: relação com síndrome metabólica e fatores de risco cardiovascular.

Lipodystrophy in HIV-infected patients (LDHIV) affects 40-50% of HIV-infected patients, but there are no data on its prevalence in Brazil. The aim of this study was to assess the LDHIV prevalence among HIV-infected adult Brazilian individuals, as well as to evaluate LDHIV association with cardiovascular risk factors and the metabolic syndrome (MS). It was included 180 adult HIV-infected outpatients consecutively seen in the Infectology Clinic of Universidade Estadual de Londrina. Anthropometric and clinical data (blood pressure, family and personal comorbidities, duration of HIV infection/AIDS, antiretroviral drugs used, CD4+ cells, viral load, fasting glycemia and plasma lipids) were obtained both from a clinical interview as well as from medical charts. LDHIV was defined as the presence of body changes self-reported by the patients and confirmed by clinical exam. MS was defined using the NCEP-ATPIII criteria, reviewed and modified by AHA/NHLBI. A 55% prevalence of LDHIV was found. Individuals with LDHIV presented a longer infected period since HIV infection, longer AIDS duration and longer use of antiretroviral drugs. In multivariate analysis, women (p=0.006) and AIDS duration >8 years (p<0.001) were independently associated with LDHIV. Concerning MS diagnostic criteria, high blood pressure was found in 32%, low HDL-cholesterol in 68%, hypertriglyceridemia in 55%, altered waist circumference in 17% and altered glycemia and/or diabetes in 23% of individuals. Abnormal waist and hypertriglyceridemia were more common in LDHIV-affected individuals. MS was diagnosed in 36%. In multivariate analysis, the factors associated with MS were: BMI >25 kg/m(2) (p<0.001), family history of obesity (p=0.01), indinavir (p=0.001) and age >40 years on HIV first detection (p=0.002). There was a trend to higher frequency of LDHIV among patients with MS (65% versus 50%, p=0.051). LDHIV prevalence among our patients (55%) was similar to previous reports from other countries. MS prevalence in these HIV-infected individuals seems to be similar to the prevalence reported on Brazilian non-HIV-infected adults.

Prevalência da lipodistrofia associada ao HIV em pacientes ambulatoriais brasileiros: relação com síndrome metabólica e fatores de risco cardiovascular / Prevalence of HIV-associated lipodystrophy in Brazilian outpatients: relation with metabolic syndrome and cardiovascular risk factors

A lipodistrofia associada ao HIV (LAHIV) acomete 40 por cento a 50 por cento dos pacientes infectados pelo vírus, mas sua prevalência no Brasil é desconhecida. O objetivo deste trabalho foi avaliar a prevalência de LAHIV entre adultos brasileiros infectados, bem como sua relação com fatores de risco cardiovascular e síndrome metabólica (SM). Foram avaliados 180 pacientes maiores de 18 anos, infectados por HIV, atendidos no Ambulatório de Infectologia da Universidade Estadual de Londrina. Por meio de entrevista e revisão de prontuário, foram avaliados dados antropométricos, pressão arterial, antecedentes mórbidos pessoais e familiares, duração da infecção por HIV e da aids, drogas anti-retrovirais utilizadas, CD4+, carga viral, glicemia e perfil lipídico. A LAHIV foi definida como a presença de alterações corporais percebidas pelo próprio paciente e confirmadas ao exame clínico. A SM foi diagnosticada usando os critérios do Adult Treatment Panel III (NCEP-ATPIII), revistos e atualizados pela American Heart Association (AHA/NHLBI). A prevalência observada de LAHIV foi de 55 por cento. Os pacientes com LAHIV apresentaram maior duração da infecção por HIV, da aids e do uso de anti-retrovirais. Na análise multivariada, estiveram independentemente associados ao risco de LAHIV: sexo feminino (p = 0,006) e duração da aids > 8 anos (p < 0,001). Quanto aos critérios para SM, hipertensão foi detectada em 32 por cento, baixo HDL-colesterol em 68 por cento, hipertrigliceridemia em 55 por cento, cintura aumentada em 17 por cento e glicemia aumentada e/ou diabetes em 23 por cento dos indivíduos. A cintura aumentada e a hipertrigliceridemia foram mais comuns em portadores de LAHIV. A SM foi identificada em 36 por cento dos pacientes. Na análise multivariada, estiveram associados à SM: IMC > 25 kg/m² (p < 0,001), história familiar de obesidade (p = 0,01), uso de indinavir (p = 0,001) e idade > 40 anos no diagnóstico do HIV (p = 0,002). A LAHIV apresentou...

Lipodystrophy in HIV-infected patients (LDHIV) affects 40-50 percent of HIV-infected patients, but there are no data on its prevalence in Brazil. The aim of this study was to assess the LDHIV prevalence among HIV-infected adult Brazilian individuals, as well as to evaluate LDHIV association with cardiovascular risk factors and the metabolic syndrome (MS). It was included 180 adult HIV-infected outpatients consecutively seen in the Infectology Clinic of Universidade Estadual de Londrina. Anthropometric and clinical data (blood pressure, family and personal comorbidities, duration of HIV infection/AIDS, antiretroviral drugs used, CD4+ cells, viral load, fasting glycemia and plasma lipids) were obtained both from a clinical interview as well as from medical charts. LDHIV was defined as the presence of body changes self-reported by the patients and confirmed by clinical exam. MS was defined using the NCEP-ATPIII criteria, reviewed and modified by AHA/NHLBI. A 55 percent prevalence of LDHIV was found. Individuals with LDHIV presented a longer infected period since HIV infection, longer AIDS duration and longer use of antiretroviral drugs. In multivariate analysis, women (p=0.006) and AIDS duration >8 years (p<0.001) were independently associated with LDHIV. Concerning MS diagnostic criteria, high blood pressure was found in 32 percent, low HDL-cholesterol in 68 percent, hypertriglyceridemia in 55 percent, altered waist circumference in 17 percent and altered glycemia and/or diabetes in 23 percent of individuals. Abnormal waist and hypertriglyceridemia were more common in LDHIV-affected individuals. MS was diagnosed in 36 percent. In multivariate analysis, the factors associated with MS were: BMI >25Kg/m² (p<0.001), family history of obesity (p=0.01), indinavir (p=0.001) and age >40 years on HIV first detection (p=0.002). There was a trend to higher frequency of LDHIV among patients with MS (65 percent versus 50 percent, p=0.051). LDHIV prevalence...

Regulation of hepatic cholesterol metabolism in CETP/LDLr mice by cholesterol feeding and by drugs (cholestyramine and lovastatin) that lower plasma cholesterol.

1. The hepatic mechanisms involved in the simultaneous regulation of plasma cholesterol concentration and cholesteryl ester transfer protein (CETP) activity were investigated by sharply modifying the hepatic rates of cholesterol synthesis. This was accomplished by cholestyramine, lovastatin and cholesterol feeding in human CETP transgenic mice cross-bred with low-density lipoprotein receptor (LDLr)-knockout mice, generating CETP(+/-)/LDLr(+/-) mice, which present a plasma lipoprotein profile resembling that of humans. 2. Analyses of pooled data showed that the plasma CETP activity correlated positively with plasma total cholesterol concentration, hepatic CETP mRNA and the liver microsomal cholesterol content; a negative correlation was found between plasma CETP activity and the liver 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and LDLr mRNA levels. These coordinated events represent an efficient control system that stabilizes the cell cholesterol content. 3. Nonetheless, not all cholesterol metabolism regulatory systems seem to fit into a coherent pattern of responses, suggesting that other unknown cellular mechanisms play roles depending on the type of pharmacological intervention. 4. For example, microsomal cholesterol content was not affected by cholestyramine, but was increased on cholesterol feeding (as predicted), and, surprisingly, on lovastatin treatment. Furthermore, although both plasma cholesterol-lowering drugs increased CYP7A1 mRNA and had no effect on CYP27 mRNA, other metabolic components were differentially modified. Cholestyramine and lovastatin, respectively, did not modify and increased both HMG-CoA and sterol responsive element binding protein 1c mRNA, did not modify and lowered liver X receptor alpha mRNA, lowered and increased ATP binding cassette A1 mRNA and lowered and did not modify scavenger receptor B1 mRNA. 5. That is, different to unabsorbed cholestyramine, lovastatin, as an absorbed plasma cholesterol-lowering drug, may have modified the activity of other unknown genes that play roles in the interaction of CETP with the metabolism of hepatic cholesterol.