Uso de treprostinil sistémico en una paciente con hipertensión pulmonar grave, sin respuesta a la máxima terapia disponible / Use of treprostinil in a patient with a severe pulmonary arterial hypertension no responding to the maximal therapy available

En los pacientes con Hipertensión Arterial Pulmonar (HAP) de alto riesgo, en clase funcional (CF)IV, la terapia específica debe ser combinada y debe incluir una prostaciclina (PGI2) de uso sistémico en espera de trasplante bipulmonar (TBP). En el sistema público la única PGI2 disponible para asociar a Sildenafil y algún inhibidor de endotelina (Ambrisentan o Bosentan) es Iloprost nebulizado, que si bien es efectiva, no logra estabilizar los casos graves con severa disfunción del ventrículo derecho (VD). Se presenta el primer caso en el Instituto del Tórax, centro de referencia nacional de HAP, del uso de treprostinil en una paciente de 24 años con HAP grave e indicación de TBP. Treprostinil es un análogo sintético de PGI2 de uso subcutáneo en dosis desde 1 a 40 ng/kg/min. La paciente presentaba una situación de extrema gravedad: CF IV, distancia recorrida en el test de caminata de 6 min (DRTC 6 min) < 300 m,derrame pericárdico y severa disfunción del VD con TAPSE (índice de disfunción del VD) de 13 cm/s asociado a ProBNP >2.500 pg/ml. Luego de 6 meses de hospitalización en intermedio, terapia triple (Sildenafil, Ambrisentan e Iloprost nebulizado) asociado a O2,diuréticos y milrinona, logró ser dada de alta a las 3 semanas del inicio de treprostinil, regresando al trabajo a los 2 meses y estabilizando su condición en CF III, con DRTC 6 min > 440 m, mejoría de la función del VD(TAPSE 19). El ProBNP persistió elevado, 1.491 pg/ml, indicando que su enfermedad es grave y progresiva; sin embargo, ha logrado un nivel de estabilidad clínica que le permite una adecuada vida de relación familiar y laboral.

In high risk Pulmonary Arterial Hypertension (PAH) patients with functional class (FC) IV, specific therapy must be combined and must include systemic prostacyclin (PGI2), meanwhile they are enlisted for double lung transplant (DLT). In Chilean Public Health System, nebulized Iloprost is the only PGI2 available to combine with Sildenafil and either Ambrisentan or Bosentan as endothelin receptor antagonist. This association is not enough for severe cases with right ventricular (RV) dysfunction. The first case from the National Institute of Thorax as a referral center is presented now in a 24 years-old lady treated with treprostinil. She has severe PAH with DLT indication. Treprostinil is a PGI2 analog, for subcutaneous use in a dose from 1 to 40 ng/kg/min. She was extremely sick, with FC IV, she walked < 300 m at 6 min walking test (6 MWT), presented pericardial effusion and severe RV dysfunction, with TAPSE (echocardiography index for RV dysfunction)=13 cm/s, ProBNP > 2,500 pg/ml. Six months after being at intensive care unit with triple therapy (Sildenafil, ambrisentan and nebulized Iloprost) plus oxygen, diuretics and milrinone, she was finally discharged after receiving a 3 weeks treprostinil course. She came back to work two months later and her condition was more stable: FC III, she walked > 440 m at 6MWT, with a significant improvement in RV function with TAPSE = 19. Although ProBNP decreased to 1,491pg/ml, it was still high, pointing out the progressive nature of her disease. However, she met a better clinical condition which allows her to reach a much better quality of life from a personal, familial and social point of view.

The association of the rs670 variant of APOA1 gene with insulin resistance and lipid profile in morbid obese patients after a biliopancreatic diversion surgery.

OBJECTIVE: A common G-to-A transition (rs670) of the Apoprotein subtype 1 APOA1 gene has been evaluated. The presence of the A allele has been related with increased activity. We investigated the role of this genetic variant (rs670) on lipoprotein levels and anthropometric parameters after biliopancreatic diversion (BPD) surgery in morbid obese patients. PATIENTS AND METHODS: Sixty-three patients with morbid obesity without diabetes mellitus type 2 were enrolled. Biochemical and anthropometric evaluation were registered before and after one, two and three years follow-up. RESULTS: Genotype distribution was 73% (n=46) GG, 25.6% (n=16) GA and 1.4% (n=1) AA for the rs670 polymorphism. Percent excess weight loss, anthropometric and biochemical parameters improved in both groups (GG vs. GA±AA). The decrease of fasting insulin levels at 1 years (delta: -3.7±1.4 mUI/L vs. -2.9±1.2 mUI/L; p=0.02), 2 years (delta: -4.8±0.3 mUI/L vs. -4.0±0.2 mUI/L; p=0.01) and 3 years (delta: -6.7±3.1 mUI/L vs. -3.9±2.1 mUI/L; p=0.03) was higher in A allele carriers than in non carriers. The improvement of HOMA-IR levels at 1 years (delta: -3.7±1.4 mUI/L vs. -2.9±1.2 mUI/L; p=0.02), 2 years (delta: -4.8±0.3 mUI/L vs. -4.0±0.2 mUI/L; p=0.01) and 3 years (delta: -6.7±3.1 mUI/L vs. -3.9±2.1 mUI/L; p=0.03) was also higher in A allele carriers than non-carriers. Finally, the increase of HDL-cholesterol levels at 1 years (delta: 2.2±0.6 mg/dl vs. -1.2±0.2 mg/dl; p=0.001), 2 years (delta: 2.5±0.4 mg/dl vs. 0.3±0.1 mg/dl; p=0.01) and 3 years (delta: 2.4±0.6 mg/dl vs. 0.4±2.3 mg/dl; p=0.02) was higher in A allele carriers than non-carriers. CONCLUSIONS: This variant of the APOA1 gene showed important effects on HDL-cholesterol, HOMA-IR and insulin resistance after DBP for 3 years.

Effect of the rs1862513 variant of resistin gene on insulin resistance and resistin levels after two hypocaloric diets with different fat distribution in subjects with obesity.

OBJECTIVE: Polymorphisms of a single nucleotide in resistin gene (RETN) have been associated with insulin resistance. We decide to investigate the role of this polymorphism on insulin resistance and resistin levels after two hypocaloric diets. PATIENTS AND METHODS: A sample of 361 obese non-diabetic Caucasian was enrolled. Biochemical evaluation and anthropometric data were measured at the start of the trial and repeated after 3 months of both diets (Diet P, Polyunsaturated vs. diet M, Monounsaturated). RESULTS: With both diets and in both genotype groups, BMI, weight, fat mass, waist circumference, systolic blood pressure, and diastolic blood pressure decreased. After diet P, insulin levels (GG vs. GC+CC genotypes) (-1.2±3.8 UI/L vs. -0.7±2.1 UI/L; p<0.05), HOMA-IR (-0.6±1.0 units vs. -0.4±0.9 units; p<0.05), total cholesterol (-10.5±20.1 mg/dl vs. -6.1±15.1 mg/dl; p<0.05) and LDL-total cholesterol (-8.6±10.1 mg/dl vs. -2.2±9.1 mg/dl; p<0.05) decreased in subjects with GG genotype. After diet M, insulin levels (-1.8±2.1 UI/L vs. -0.6±3.0 UI/L: p>0.05), HOMA-IR (-0.5±1.0 units vs. -0.3±1.1 units: p>0.05), total cholesterol (-9.5±13.1 mg/dl vs. -4.4±8.1 mg/dl; p<0.05) and LDL-total cholesterol (-8.1±6.1 mg/dl vs. -2.9±9.1 mg/dl; p<0.05) decreased, too. CONCLUSIONS: We suggest that GG genotype of RETN rs1862513 could be a predictor of the reduction of HOMA-IR, insulin, and LDL cholesterol secondary to two hypocaloric diet in obese subjects.

The Association of SNP276G>T at Adiponectin Gene with Insulin Resistance and Circulating Adiponectin in Morbid Obese Patients After a Biliopancreatic Diversion Surgery.

BACKGROUND: The effects of rs1501299 variant of ADIPO gene on weight loss after bariatric surgery have not been evaluated. We decided to investigate the role of this genetic variant on anthropometric and biochemical outcomes such as serum adiponectin levels after biliopancreatic diversion (BPD) surgery in morbidly obese patients during 3 years. MATERIAL AND METHODS: A sample of 64 patients with morbid obesity without diabetes mellitus was operated. Biochemical and anthropometric evaluation were realized at basal visit and at each visit during 3 years (1, 2, and 3 years). RESULTS: Percent excess weight loss, body mass index, weight, waist circumference, fat mass, blood pressure, fasting glucose, LDL cholesterol, total cholesterol, and triglycerides levels improved in both genotype groups. Fasting insulin levels and HOMA-IR decreased significantly only in non-T allele carriers. The decrease of fasting insulin levels at 3 years (delta -9.2 ± 3.4 vs -2.9 ± 2.2 mUI/L; p = 0.01) and HOMA-IR (delta -1.3 ± 0.3 vs -0.8 ± 0.4 units; p = 0.03) were higher in non-T allele carriers than T carriers. Adiponectin levels increased in all times after surgery in non-T allele carriers, too. The increase of adiponectin levels at 3 years (delta 12.2 ± 3.6 vs 1.8 ± 1.2 ng/mL; p = 0.01) was higher in non-T allele carriers than T carriers. CONCLUSION: Non-T allele of ADIPOQ gene variant (rs1501299) is associated with increases in adiponectin levels and better improvements of insulin and HOMA-IR after BPD massive weight loss. These parameters remained unchanged in T allele carriers.

Effect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease. A randomized clinical pilot study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized health problem. Various treatment strategies such as thiazolidinediones, metformin, lipid-lowering agents and antioxidants have been evaluated. So far, no single intervention has convincingly improved liver histology. Experience of using silymarin alone or in combination with other agents in patients with NAFLD is limited in the medical literature. The present study was conducted to evaluate the efficacy of silymarin plus vitamin E in the treatment of NAFLD. PATIENTS AND METHODS: A sample of 36 patients was enrolled. The diagnosis of NAFLD was confirmed by percutaneous liver biopsy. All patients were randomized to one of the following intervention groups: group I: treated with 2 tablets per day of silymarin plus vitamin E (Eurosil 85®, MEDAS SL) and a lifestyle modification program consisting of hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of lipids and 23% of proteins) and exercise for 3 months and group II (only with the hypocaloric diet). Anthropometric variables as waist circumference, weight, body mass index (BMI) were measured. Biochemical parameters: Glucose, triglycerides, AST, ALT, GGt levels and insulin resistance (HOMA-IR) were determined under fasting conditions. Non-invasive NAFLD-index were applied before and after the treatments: Fatty liver index (FLI), liver accumulation product (LAP) and NAFLD-Fibrosis score (FS). RESULTS: The mean age was 47.4 ± 11.2 years old (range 18-67); 22 men and 14 women. In group I, 11 patients (61%) have a NAS-score > 5 and 10 (55.5%) in the group II (NS). Anthropometric parameters decreased after treatment in both groups. Patients in both groups showed a decrease in GGt levels after treatment (group I: 68 IU/L vs. 46.2 ± 27 IU/L; p < 0.05 and group II 80.5 ± 46 IU/L vs. 50.3 ± 27 IU/L; p < 0.05). Only in group II we observed a significant decrease in AST and ALT levels. In both groups, we observed a decrease in: FLI index (group I: 86.2 ± 19 vs. 76.9 + 20; p < 0.05 and in group II: 85.2 ± 18 vs. 77.5 ± 23; p < 0.05), and NAFLD-FS index (group I: -1.6 ± 1.8 vs. -2.1 ± 1.5; p < 0.05 and in group II -1 ± 1.9 vs. -1.5 ± 2.1; p < 0.05). Patients in group I who did not get a 5% loss of weight also displayed decreased GGt levels, and in the FLI and NAFLD-FS indexes; whereas patients in group II without decrease of 5% by weight showed no improvement in any of the analyzed parameters. CONCLUSIONS: Treatment with silymarin plus vitamin E and a hypocaloric diet ameliorate function hepatic test, and non-invasive NAFLD index. Silymarin can be an alternative valid therapeutic option particularly when other drugs are not indicated or have failed or as a complementary treatment associated with other therapeutic programs.

Effect of L-arginine supplementation on insulin resistance and adipocitokines levels in head and neck cancer non diabetic patients after surgery.

INTRODUCTION: Previous studies have found that L-arginine induced beneficial effects over insulin resistance both in type 2 diabetes mellitus patients and healthy individuals. The aim of our study was to investigate whether an L-arginine enteral supplementation (20 g per day) in head and neck cancer patients could modify insulin resistance, leptin and adiponectin levels after surgery. MATERIAL AND METHODS: At surgery 82 patients were randomly allocated to two groups: group I received an enteral diet supplements with a high dose of arginine (20g per day) and group II received an enteral formula without arginine. At basal time and on postoperative day 10, the following parameters were recorded: glucose, c-reactive protein, insulin, HOMA (homeostasis model assessment), leptin and adiponectin. RESULTS: Values of weight, body mass index, fat mass and fat free mass remained unchaged during the acute nutritional intervention in both groups. Insulin levels UI/L (-0.21+/-0.18) and HOMA units (-0.07+/-0.13) decreased in the arginine group. Adiponectin levels (+1.8+/-2.3ng/ml) increased in the arginine group. CONCLUSION: Short-term enteral L-arginine therapy addeded to usual enteral nutrition of patients affected by head and neck cancer and surgery without diabetes mellitus type 2 is able to improve insulin resistance and adiponectin levels.

Introducción: Alguntos trabajos han encontrado que la L-arginina induce efectos beneficiosos sobre la resistencia a la insulina, tanto en pacientes con diabetes tipo 2 como en individuos sanos. El objetivo de nuestro estudio fue investigar si la suplementación enteral de L-arginina (20 g por día) en pacientes con cáncer de cabeza y cuello puede modificar la resistencia a la insulina, los niveles de leptina y adiponectina después de la cirugía. Material y métodos: Tras la cirugía 82 pacientes fueron asignados aleatoriamente a dos grupos: grupo I recibió un enterales suplementos de dieta con una dosis alta de arginina (20 g por día) y el grupo II recibió una fórmula enteral sin arginina. En el momento basal y el día 10 tras la cirugia, se registraron los siguientes parámetros: glucosa, proteína C reactiva, insulina, HOMA (Homeostasis Model Assessment), leptina y adiponectina. Resultados: Los valores de peso, índice de masa corporal, la masa grasa y la masa libre de grasa se mantuvieron sin cambios durante la intervención nutricional aguda en ambos grupos. Los niveles de insulina UI/L (-0,21 + / -0,18) y HOMA (-0,07 + / -0,13) disminuyeron en el grupo de arginina. Los niveles de adiponectina (1,8 + / -2.3ng/ml) aumentaron en el grupo de arginina. Conclusión: La nutrición enteral con L-arginina a corto plazo en los pacientes afectados por cáncer de cabeza y cuello y tras cirugía es capaz de mejorar la resistencia a la insulina y los niveles de adiponectina.

Clinical effects of a w3 enhanced powdered nutritional formula in postsurgical ambulatory head and neck cancer patients.

BACKGROUND: Patients with head and neck cancer undergoing surgery have a high risk of nutritional complications. OBJECTIVE: The aim of our study was to investigate the influence of an oral w3 enriched immunoenhanced powdered formula in nutritional and biochemical parameters in postsurgical ambulatory patients with head and neck tumor. DESIGN: A population of 33 ambulatory postsurgical patients with oral and laryngeal cancer was enrolled. At Hospital discharge postsurgical head and neck cancer patients were asked to consume two units per day of a w3 enriched immunoenhanced powdered formula for a twelve week period. RESULTS: The mean age was 61.3 ± 9.1 years (6 female/27 males). Duration of supplementation was 95.9 ± 21.1 days. A significant increase of albumin and transferrin levels was observed, in total group and in patients undergoing radiotherapy and without it. No differences were detected in weight and other anthropometric parameters in total group and in patients with radiotherapy during the protocol. Nevertheless, patients without radiotherapy showed a significant improvement of BMI; weight, fat free mass and fat mass. CONCLUSIONS: At dose used, an omega 3 enriched powdered formula improved seric protein levels in ambulatory postoperative head and neck cancer patients. Improvement of weight, fat mass and fat free mass was observed in patients whom not received radiotherapy during the follow up.

Antecedentes: Los pacientes con tumores de cabeza y cuello sometidos a cirugía presentan un alto riesgo de complicaciones nutricionales. Objetivo: El principal objetivo de nuestro trabajo fue evaluar la influencia de un suplemento oral en polvo inmunoenriquecido con ácidos grasos omega 3 en pacientes postquirúrgicos ambulatorios con tumores de cabeza y cuello. Diseño: Una muestra de 33 pacientes postquirúrgicos ambulatorios con tumores de cabeza y cuello fue evaluada. Tras el alta hospitalaria, los pacientes recibieron dos envases al día de un suplemento inmunoenriquecido con omega 3 en polvo durante 12 semanas. Resultados: La edad media fue de 61,3 ± 9,1 años (6 mujeres/27 varones). La duración media de la suplementación fue de 95,9 ± 21,1 días. Se detectó un aumento significativo en los niveles de albúmina y transferrina en los pacientes del grupo global, en los que recibieron radioterapia y en los que no al recibieron. El peso y los parámetros antropométricos no mejoraron en el grupo global ni en los que recibieron radioterapia. Sin embargo los pacientes que no recibieron radioterapia tuvieron un aumento de la masa magra, peso y masa grasa Conclusiones: A la dosis usada, la formula en polvo enriquecida en omega 3 mejoró lo niveles de proteínas séricas. Por otra parte los pacientes que no recibieron radioterapia durante el seguimiento presentaron un aumento del peso, masa grasa y masa magra.

Effect of a commercial hypocaloric diet in weight loss and post surgical morbidities in obese patients with chronic arthropathy, a randomized clinical trial.

INTRODUCTION: The aim of our study was to evaluate in patients with obesity and surgical indication of orthopaedic surgery for chronic osteoarthritis (hip or knee), the impact on weight loss, metabolic control and post surgical co morbidities of a hypocaloric commercial formula (Optisource®) versus conventional nutritional advice before orthopaedic surgery. MATERIALS AND METHODS: 40 patients were randomized in both branches: diet I with lunch and dinner substituted by two Optisource® (1109.3 kcal/day, 166.4 g of carbohydrates (60%), 63 g of proteins (23%), 21.3 g of lipids 17%) and intervention II with nutritional counselling that decreases 500 cal/day of the previous dietary intake. Previous and after 3 months of the treatment, a nutritional and biochemical study was realized. Postsurgical co-morbities have been recorded. RESULTS: 20 patients finished in each group. The improvement in weight (-7.56 ± 5.2 kg vs -5.18 ± 5.1 kg: p < 0.05), body mass index (-3.15 ± 2.2 vs -2.1 ± 1.9 kg/m2: p < 0.05), fat mass (-5.5 ± 5.9 kg vs -3.0 ± 2.6 kg: p < 0.05), insulin (-3.6 ± 3.8 mUI/L vs -3.0 ± 2.6) p < 0.05) and HOMA (-0.5 4 ± 1.2 vs -0.33 ± 1.14): p < 0.05) was higher in group I than in group II. All post surgical recorded parameters such as minutes of orthopaedic surgery, length of stay, vein thrombosis episodes, general infections complications, haemoglobin levels and days till independence of walking were similar in both groups. CONCLUSIONS: Obese patients with chronic osteoarthritis subsidiary of surgery, lose more weight, fat mass and improve more resistance to insulin treated with a mixed diet with a commercial formula hypocaloric that patients treated only with dietary advice.

[Relation of -55CT polymorphism of UCP3 gene with weight loss and metabolic changes after a high polyunsaturated fat diet in obese patients]. / Relación del polimorfismo -55CT del gen UCP3 con la pérdida de peso y los cambios metabólicos tras una dieta hipocalórica rica en ácidos grasos poliinsaturados en pacientes obesos.

BACKGROUND AND OBJECTIVES: The alteration in the protein expression of UCP3 could reduce energy consumption and increase energy storage as fat. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene in the metabolic response, weight loss and serum levels of adipokines following a hypocaloric diet rich in polyunsaturated fat in obese patients. DESIGN: A sample of 133 obese patients were analyzed prospectively for 3 months. The hypocaloric diet was 1459 kcal, 45.7% carbohydrate, 34.4% from 19.9% lipids and proteins. The fat distribution was, a 21.8% saturated fat, 55.5% monounsaturated and 22.7% of polyunsaturated fat (7 g per day of fatty acids w6, 2 g per day of w -3 and a ratio w6/w3 of 3.5). RESULTS: A total of 100 patients (28 males/72 females) (75.2%) had genotype - 55CC (wild genotype group) and 33 patients (8 males/25 females) (24.8%) -55CT genotype (group mutant genotype). In the wild genotype, body mass index (-2.5 ± 5.3 kg/m²), weight (-4.2 ± 3.7 kg), fat mass (-3,7 ± 3.3 kg), waist circumference (-4.1 ± 2.9 cm), systolic blood pressure (-4.9 ± 10.1 mmHg), total cholesterol levels (- 16.1 ± 23.6 mg / dl), LDL cholesterol (-11.1 ± 26.8 mg/dl), triglycerides (-12.0 ± 46.8 mg/dl), insulin (-1.8 ± 4.5 IU/L), HOMA-R (-0.6 ± 1.5) and leptin (-6.2 ± 8.4 ng/ml) decreased. In the mutant genotype anthropometric parameters were significantly decreased without significant changes in biochemical parameters. CONCLUSION: The T allele carriers of -55CT UCP3 polymorphism exhibit no metabolic response to weight loss induced by a hypocaloric diet rich in polyunsaturated fatty acids.

[Relation of the rs9939609 gene variant in FTO with cardiovascular risk factor and serum adipokine levels in morbid obese patients]. / Relación del polimorfismo rs9939609 del gen FTO con factores de riesgo cardiovascular y niveles de adipocitoquinas en pacientes con obesidad mórbida.

BACKGROUND: Common polymorphisms of the fat mass and obesity associated gene (FTO) have been linked to obesity in some populations. The aim of our study was to analyze the relationship of the rs9939609 FTO gene polymorphism on body weight, cardiovascular risk factors and serum adipokine levels in morbid obese patients. MATERIAL AND METHODS: A sample of 129 patients with obesity was analyzed in a cross sectional design. Weight, blood pressure, basal glucose, c-reactive protein (CRP), insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides blood and adipocytokines (leptin, adiponectin, resistin, TNF alpha, and interleukin 6) levels were measured. A tetrapolar bioimpedance and a prospective serial assessment of nutritional intake with 3 days written food records were realized. Genotype of FTO gene polymorphism (rs9939609) was studied. RESULTS: Forty three patients (31.8%) had TT genotype, 55 patients (42.6%) TA genotype and 33 patients (25.6%) AA genotype. Body mass index (43.6 (2.6) kg/m² vs. 44.1 (2.9) kg/m²; p < 0.05), fat mass (52.0 (12.5) kg vs. 56.3 (11.7) kg: p < 0.05), weight (111.6 (16.2) kg vs. 114.9 (18.9) kg; p < 0.05), levels of C reactive protein (6.1 (4.3) mg/dl vs. 9.8 (7.1) mg/dl; p < 0.05) and levels of leptin (65.9 (52.2) ng/ml vs. 110.9 (74.1); < 0.05) were higher in mutant type group (A allele) than wild genotype group (TT). CONCLUSION: The FTO gene polymorphism, rs9939609, was found to be associated with weight, fat mass, C reactive protein and leptin levels in morbid obese patients with A allele.

Lys656Asn polymorphism of leptin receptor, leptin levels and insulin resistance in patients with non alcoholic fatty liver disease.

BACKGROUND: Some studies have pointed to a role of leptin and insulin resistance in pathogenesis of non alcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the influence of Lys656Asn polymorphism LEPR gene on the histological changes, insulin resistance and leptin levels in overweight patients. MATERIAL AND METHODS: A population of 76 patients with NAFLD was recruited in a cross sectional study. A biochemical analysis of serum was measured. Genotype of LEPR gene Lys656Asn was studied. RESULTS: Nineteen patients (25%) had the genotype Lys656Asn and 4 patients genotype Asn656Asn (mutant type group) and 53 patients (69.7%) Lys656Lys (wild type group). Body mass index, weight, fat mass, waist circumference, waist to hip ratio, glucose levels and HOMA-IR were higher in mutant than wild type group. LEPR polymorphism is in any way related with liver lesions. The multivariate analysis adjusted by age, sex, BMI and genotype showed an independently association of lobular inflammation 4.19 (CI95%: 1.37-12.77), portal inflammation 1.97 (CI95%: 1.05-3.74) and steatosis 9.23 (CI95%: 1.47-57.83) with HOMA. Liver steatosis was associated with leptin levels (1.09 (CI95%: 1.06-1.18)), too. CONCLUSION: Lys656Asn polymorphism of LEPR gene is associated with obesity parameters, insulin resistance and glucose levels in patients with NAFLD. In logistic regression analysis, only insulin resistance was associated with portal inflammation), lobular inflammation and steatosis; liver steatosis was related with leptin levels, too.

Influence of G1359A polimorphysm of the cannabinoid receptor gene (CNR1) on insulin resistance and adipokines in patients with non alcoholic fatty liver disease.

BACKGROUND: Considering the evidence that endogenous cannabinoid system plays a role in metabolic aspects of body weight and metabolic syndrome components such as non alcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the influence of this polymorphism on insulin resistance, liver histological changes, anthropometric parameters and adipocytokines in patients with NAFLD. MATERIAL AND METHODS: A population of 71 patients with NAFLD was recruited in a cross sectional study. A biochemical analysis of serum was measured. Genotype of G1359A polymorphism of CB1 receptor gene CB1 receptor was studied. Forty one patients (36.9%) had the genotype G1359G (wild type group) and twenty nine (26.1%) patients G1359A or A1359A (mutant type group). RESULTS: Twenty four 24 patients (32,3%) had a Brunt grade > 4 and 12 patients (17%) had a significative fibrosis (F > = 2). HOMA values were higher in wild type group than mutant type group. Adiponectin and visfatin levels were higher in mutant type group. Moreover, TNF-alpha and resistin levels were higher in wild type group than mutant type group. Patients with mutant genotype showed less frequently elevated levels of AST. AST > 40 UI/L was detected in 28.5% of patients in the mutant vs. 53% of patients with wild genotype, p < 0.05. Patients with mutant type group presented a percentage of Brunt grade > = 4 less frequently than patients with wild type group (28.5%vs 7.1%). CONCLUSION: A variant of the polymorphism G1359A CBR1 is associated with lower levels of HOMA, TNF-alpha, resistin and higher levels of adiponectin than patients with the wild variant of this polymorphism. Besides, patients with A allele variant shown lower Brunt grade in liver biopsy.

The serum profile of adipokines in naïve patients with diabetes mellitus type 2 and obesity.

BACKGROUND: The aim of this study was to explore the relationship of serum profile of adipokines with cardiovascular risk factors and anthropometric parameters in patients with diabetes mellitus type 2. SUBJECTS: A population of 108 obese patients with DM2 was analyzed. A complete biochemical anthropometric and nutritional evaluation was performed. RESULTS: In the analysis with leptin as a dependent variable, the IL-6 and glucose levels remained in the model (F = 6.2; P<0.05), with an increase of 5.8 (CI 95%:2.7-7.6) ng/ml with each 1 pg/ml of IL-6 and of 5.2 (CI95%:2.5-5.8) ng/ml with each 1 mg/dl of glucose. In a second model with adiponectin as a dependent variable, the BMI remained in the model (F = 3.77;P<0.05), with an decrease of -3.77 (CI 95%:0.53-7.1) ng/ml with each 1 point of BMI. In the third multivariate analysis with IL-6 as a dependent variable, the glucose level remained in the model (F = 10.1; P<0.01), with an increase of 0.09 (CI95%:0.06-0.12) pg/ml with each 1 mg/dl of glucose. In the fourth multivariate analysis with resistin as a dependent variable, the CRP remained in the model (F = 2.51; P<0.05), with an increase of 0.28 (CI 95%:0.08-0.48) pg/ml with each 1 mg/dl of CRP. CONCLUSION: Serum profile of adipokines is associated with different risk factors in diabetic obese patients.

Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: a double blind randomized clinical trial.

OBJECTIVE: The present pilot trial was carried out to evaluate the effects of an acute treatment with a mixture containing 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus per day in patients with non alcoholic fatty liver disease (NAFLD). RESEARCH METHODS: A sample of 30 patients with NAFLD (diagnosed by liver biopsy) was enrolled and 28 patients were analyzed in a double blind randomized clinical trial. Patients were randomized to one of the following treatments during 3 months: group I, treated with one tablet per day with 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus and group II, treated with one placebo tablet (120 mg of starch). RESULTS: In group I, alanine amino transferase (ALT: 67.7 +/- 25.1 vs. 60.4 +/- 30.4 UI/L; p < 0.05), aspartate aminotransferase activity (AST: 41.3 +/- 15.5 vs. 35.6 +/- 10.4 UI/L; p < 0.05) and gammaglutamine transferase levels (gammaGT: 118.2 +/- 63.1 vs. 107.7 +/- 60.8 UI/L; p < 0.05) decreased. In group II, all liver function parameters remained unchanged (ALT: 60.7 +/- 32.1 vs. 64.8 +/- 35.5 UI/L; p < 0.05), aspartate aminotransferase activity (AST: 31.7 +/- 13.1 vs. 36.4 +/- 13.8 UI/L; ns) and gammaglutamine transferase levels (gammaGT: 82.1 +/- 55.1 vs. 83.6 +/- 65.3 UI/L; ns). Anthropometric parameters and cardiovascular risk factors remained unchanged after treatment in both groups. CONCLUSION: A tablet of 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus, with a randomized clinical design, improved liver aminotransferases levels in patients with NAFLD.

Lack of association of serum resistin levels with metabolic syndrome criteria in obese female patients.

BACKGROUND: As unclear data of resistin relation with metabolic syndrome has been published, we decide to investigate the association between metabolic syndrome and resistin levels in female obese subjects. SUBJECTS: A sample of 551 female obese subjects was analyzed. A complete nutritional and biochemical evaluation was performed. RESULTS: Levels of C reactive protein, weight, fat mass and waist circumference were higher in patients in the highest tertile group of resistin than the lowest and middle tertiles of resistin. In the multivariate analysis with metabolic syndrome presence/absence-, only fat mass remained as an independent predictor in the model. Resistin concentration increases 0.020 ng/ml (CI95%:0.006-0.038) for each kg of fat mass in female obese subjects. CONCLUSION: Only fat mass was associated in an independent way. Serum resistin was not associated with the accumulation of MetS factors or the diagnosis of MetS in obese female subjects.

Roles of G1359A polymorphism of the cannabinoid receptor gene (CNR1) on weight loss and adipocytokines after a hypocaloric diet.

BACKGROUND: A intragenic biallelic polymorphism (1359 G/A) of the CB1 gene resulting in the substitution of the G to A at nucleotide position 1359 in codon 435 (Thr), was reported as a common polymorphism in Caucasian populations. Intervention studies with this polymorphism have not been realized. OBJECTIVE: We decided to investigate the role of the polymorphism (G1359A) of CB1 receptor gene on adipocytokines response and weight loss secondary to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients. DESIGN: A population of 94 patients with obesity was analyzed. Before and after 3 months on a hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for the combined G1359A and A1359A as a group and wild type G1359G as second group, with a dominant model. RESULTS: Forty seven patients (50%) had the genotype G1359G (wild type group) and 47 (50%) patients G1359A (41 patients, 43.6%) or A1359A (6 patients, 6.4%) (mutant type group) had the genotype. In wild and mutant type groups, weight, body mass index, fat mass, waist circumference and systolic blood pressure decreased. In mutant type group, resistin (4.15 ± 1.7 ng/ml vs. 3.90 ± 2.1 ng/ml: P < 0.05), leptin (78.4 ± 69 ng/ml vs 66.2 ± 32 ng/ml: P < 0.05) and IL-6 (1.40 ± 1.9 pg/ml vs 0.81 ± 1.5 pg/ml: P < 0.05) levels decreased after dietary treatment. CONCLUSION: The novel finding of this study is the association of the mutant allele (A1359) with a decrease of resistin, leptin and interleukin-6 secondary to weight loss.

Resistin levels in morbid obese patients following the biliopancreatic diversion surgery.

Previous studies addressing the changes of resistin concentrations in morbidly obese patients after bariatric surgery have yielded conflicting results. The purpose of the present study was to investigate the changes in serum resistin levels 1 year after biliopancreatic diversion in morbidly obese patients without diabetes mellitus. A cohort of 39 morbidly obese patients without diabetes mellitus was operated. Biochemical and anthropometric evaluation were realized at basal visit and at each visit. The frequency of patients with hypertension and hyperlipidemia was recorded at each visit. Overall the mean patient age was 44.8 ± 14.1, and the mean preoperative BMI was 47.3 ± 6.5 kg/m². After one year of surgery, a significant decrease was observed in BMI, weight, waist circumference, fat mass, blood pressure, total cholesterol, LDL cholesterol, and triglyceride levels. Resistin levels did not change after surgery (5.61 ± 1.93 ng/ml vs. 6.41 ± 3.58 ng/ml; ns). Correlation analysis showed a positive association between basal resistin and weight (r = 0.68, p < 0.01) and fat mass (r = 0.65, p < 0.05). Resistin concentrations did not change after massive weight loss with biliopancreatic diversion in morbid obese patients without diabetes mellitus.

Allelic frequency of G380A polymorphism of tumor necrosis factor alpha gene and relation with cardiovascular risk factors and adipocytokines in obese patients.

BACKGROUND: The aim of our study was to investigate the allelic frequency of the G308A polymorphism in the TNF alpha gene and the influence of G308A this polymorphism on cardiovascular risk factors and adipokine levels in obese patients. DESIGN: A population of 834 obesity patients was analyzed. A nutritional evaluation and a blood analysis were performed. The statistical analysis was performed for the combined G308A and A308A as mutant group and type G308G as wild group. RESULTS: A total of 630 patients (181 males/449 females) (75.5%) had the genotype G308/G308 (wild genotype group) with an average age of 43.5 ± 14.8 years, 188 patients (61 males/127 females) (22.5%) had the genotype G308/A308 (mutant genotype group-heterozygote) and 16 patients (5 males/11 females) (1.9%) with an average age of 44.5 ± 14.2 years had the genotype A308/A308 (mutant group-homorozygote) with an average age of 44.3 ± 11.4 years, without statistical differences in the mean age or sex distribution. Genotypes G308/A308 and A308/A308 was designed (mutant genotype group) as a dominant model. Allelic frequency of the A substitucion -308 was 13.19%. Anthropometric, adipokines, insulin resistance, lipid levels ad dietary intake were similar in both genotypes. CONCLUSION: In conclusion, allelic frequency of G308A polymorphism is is in accordance with allelic frequencies observed in other populations. Carries of A308 allele have the same anthropometric and metabolic profile than wild type carriers.

Interaction between tumor necrosis factor-α gene -308G/A promoter and leptin receptor gene Lys656Asn single-nucleotide polymorphisms: effect on serum leptin concentrations.

BACKGROUND AND OBJECTIVE: The aim of our study was to investigate the interaction between the tumor necrosis factor-α (TNF-α) gene -308G/A promoter and the leptin receptor (LEPR) gene Lys656Asn polymorphisms and their effects on serum leptin levels in obese subjects. DESIGN: A population of 237 obese patients was analyzed prospectively. Bipolar electrical bioimpedance, a biochemical analysis and serum concentrations of leptin and TNF-α were assessed. RESULTS: The number of subjects with both mutations was 21 (8.86%). Subjects carrying the mutant LEPR genotype had higher concentrations of leptin than those with the wild-type LEPR genotype only when they also carried the mutant TNF-α genotype (G308A or A308A) (82.7 ± 63 vs. 147.6 ± 89 ng/ml; p < 0.05). In subjects with TNF-α G308G, multivariate analysis with leptin as a dependent variable revealed fat mass as an independent predictor in the model (F = 15.4; p < 0.05), with an increase of 4.1 ng/ml (95% CI 2.5-5.6) per kilogram of fat mass. The same was seen in subjects with TNF-α G308A and A308A genotypes, with an increase in leptin levels of 3.56 ng/ml (95% CI 1.8-5.3) per kilogram fat mass. CONCLUSION: There is an interaction between TNF-α gene G308A promoter and LEPR gene Lys656Asn polymorphisms, with higher concentrations of leptin in the G308A and A308A genotypes combined with the mutant LEPR genotype.

Relation of phase angle tertiles with blood adipocytokines levels, insulin resistance and cardiovascular risk factors in obese women patients.

BACKGROUND: Few studies have evaluated the relation between phase angle (PA) and metabolic syndrome. As long as we know, there are not studies of association between phase angle and adipocytokines. The aim of our study was to evaluate the association of adipocytokines levels and classical cardiovascular risk factors with tertiles of phase angle in obese women. MATERIAL AND METHODS: A cross-sectional study was designed to establish whether phase angle from 228 adult female patients with obesity are related with adipocitokynes and cardiovascular risk factors. These patients were studied in a Nutrition Clinic Unit after signed informed consent. All patients with a 2 weeks weight-stabilization period before recruitment were enrolled. Weight, blood pressure, basal glucose, C-reactive protein (CRP), insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides blood and adypocitokines (leptin, adiponectin, resistin Interleukin-6 and TNF-alpha) levels were measured. The phase angle alpha was determined by bioimpedance with the equation [PA degrees =(Xc/R)x(180 degrees/pi)]. RESULTS: Two hundred and twenty-eight females gave informed consent and were enrolled in the study. The mean age was 38.2 +/- 14.7 years and the mean BMI 35.27 +/- 6.5. Patients were divided by tertiles of phase angle. Fat mass was higher in first tertile than third tertile (43.6 +/- 12.6 vs 40.9 +/- 15 kg: p<0.05). HOMA (2.4 +/- 1.6 vs 1.46 +/- 1.6: p<0.05), insulin (14.4 +/- 8.5 vs 11.3 +/- 9.4 mUI/L: p<0.05) and glucose (102.1 +/- 20 vs 90 +/- 19.5 mg/dl: p<0.05) levels were higher in first tertile than second and third tertiles. Leptin (167.3 +/- 98 vs 104.5 +/- 80 ng/ml: p<0.05) and IL-6 (3.84 +/- 5.7 vs 1.8 +/- 2.9 pg/ml: p<0.05) levels were higher in first phase angle tertile than third tertile phase angle. CONCLUSION: Obese women with a low PA tertile have high fat mass with a secondary high level of glucose, HOMA, IL-6 and leptin. Perhaps, a low tertile of phase angle could be a new subrogate cardiovascular risk factor to categorize the obese patients.