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INTRODUCTION: Irisin activates the thermogenic function in adipose tissues. However, little is known on the association between human irisin and different cardiometabolic risk factors. We analyse the influence of morbid obesity on irisin levels and its relation with leptin and different cardiovascular risk factors. MATERIAL AND METHODS: We measured the serum irisin level and the fibronectin type III domain containing 5 (FNDC5) expression in adipose tissue from 33 morbidly obese subjects and 12 nonobese subjects. We also studied the effect of leptin on FNDC5 expression. RESULTS: Serum irisin was higher in the nonobese subjects than in morbidly obese subjects, both before (P = 0·043) and after bariatric surgery (P = 0·042). The variable that best explained the serum irisin levels in a multiple linear regression model was the waist-to-hip ratio (WHR) (R(2) = 0·201) (Beta = -0·357, P = 0·046). Those morbidly obese subjects with android-type obesity had lower serum irisin levels than those with gynecoid-type obesity, both before (P = 0·027) and after bariatric surgery (P = 0·006). Only the percentage change in WHR was associated with serum irisin levels after bariatric surgery (r = -0·529, P = 0·005). FNDC5 expression levels in subcutaneous adipose tissue (SAT) were higher in the nonobese than in the morbidly obese subjects (P = 0·042). In SAT explants from nonobese subjects, leptin (20 and 150 ng/mL) produced a decrease in FNDC5 expression (P = 0·009 and P = 0·037, respectively). CONCLUSIONS: We showed decreased serum irisin levels in morbidly obese subjects, related mainly to WHR. FNDC5 expression could be regulated by leptin.
Assuntos
Fibronectinas/metabolismo , Gordura Intra-Abdominal/química , Leptina/fisiologia , Obesidade Mórbida/sangue , Gordura Subcutânea/química , Adulto , Regulação para Baixo , Feminino , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Humanos , Masculino , RNA Mensageiro/metabolismo , Relação Cintura-QuadrilRESUMO
INTRODUCTION: Low maternal vitamin B12 status is a risk factor for various adverse pregnancy outcomes. Although vitamin B12 deficiency is not a primary target of newborn screening (NBS) programs, measurements of propionylcarnitine (C3) and its ratios with acetylcarnitine (C3/C2) and palmitoylcarnitine (C3/C16) may incidentally identify vitamin B12-deficient newborns. The objective of this study was to measure vitamin B12 levels in women during the first trimester of pregnancy, evaluate predictors of these concentrations, and study their relationship with newborn screening results. DESIGN: Vitamin B12 concentrations were evaluated in 204 women during the first trimester of pregnancy and possible confounding factors were analyzed. After giving birth, data of their newborns (189) were collected (sex, gestational age, birthweight) and the acylcarnitine profile obtained by tandem mass spectrometry during NBS was analyzed. To assess the effects of the variables on vitamin B12 serum concentrations and newborn screening markers, stepwise multiple linear regression models were used. RESULTS: The mean serum concentration of vitamin B12 was 370.8 pmol/L (502.4 pg/mL) (SD 142.81). Vitamin B12 concentrations were significantly lower in smokers (p=0.027), and in women with low meat consumption (p=0.040). There was a significant inverse correlation between mothers' vitamin B12 concentrations and their children's C3 (r=-0.24; p=0.001), C3/C2 (r=-0.23; p=0.002) and C3/C16 levels (r=-0.20; p=0.006). CONCLUSIONS: Newborn screening markers (C3, C3/C2, and C3/C16) present an inverse correlation with maternal vitamin B12 status in the first trimester of pregnancy. Regarding factors that may influence maternal serum vitamin B12 levels during the first trimester, smoking seems to have a negative effect, and meat consumption a positive effect.
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Biomarcadores/sangue , Triagem Neonatal , Deficiência de Vitamina B 12/sangue , Vitamina B 12/sangue , Acetilcarnitina/sangue , Adolescente , Adulto , Carnitina/análogos & derivados , Carnitina/sangue , Dieta , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Bem-Estar Materno , Carne , Estado Nutricional , Gravidez , Complicações na Gravidez/sangue , Terceiro Trimestre da Gravidez , Fumar/efeitos adversos , Fumar/sangue , Adulto JovemRESUMO
Enhancement of adiponectin level has been shown to have beneficial effects, including antiobesity, antidiabetic, and hepatoprotective effects. This evidence supports the therapeutic utility of adiponectin in complicated obesity. The present study characterized the in vivo effects of sustained adiponectin release by NP-1, a new class of thiazol derivative that increases adiponectin levels. Acute administration of NP-1 reduced feeding, increased plasma adiponectin, and improved insulin sensitivity without inducing malaise, as revealed by conditioned taste aversion studies. Short-term (7 days) treatment with NP-1 also reduced feeding and body weight gain and increased phosphorylation of AMPK in muscle, a main intracellular effector of adiponectin. NP-1 was also evaluated in diet-induced obesity, and adult male Wistar rats were fed two different types of diet: a standard high-carbohydrate/low-fat diet (SD) and a high-fat diet (HFD). Once obesity was established, animals were treated daily with NP-1 (5 mg/kg) for 14 consecutive days. Chronic NP-1 induced body weight loss and reduction of food intake and resulted in both a marked decrease in liver steatosis and an improvement of biochemical indexes of liver damage in HFD-fed rats. However, a marked induction of tolerance in adiponectin gene transcription and release was observed after chronic NP-1 with respect to the acute actions of this drug. The present results support the role of adiponectin signaling in diet-induced obesity and set in place a potential use of compounds able to induce adiponectin release for the treatment of obesity and nonalcoholic fatty liver, with the limits imposed by the induction of pharmacological tolerance.
Assuntos
Adiponectina/metabolismo , Peso Corporal/efeitos dos fármacos , Gorduras na Dieta/efeitos adversos , Fígado Gorduroso/tratamento farmacológico , Tiazóis/farmacologia , Adiponectina/sangue , Análise de Variância , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Western Blotting , Linhagem Celular , Dieta Hiperlipídica , Ingestão de Alimentos/efeitos dos fármacos , Teste de Tolerância a Glucose , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mioblastos/metabolismo , Hepatopatia Gordurosa não Alcoólica , RNA/biossíntese , RNA/genética , RNA/isolamento & purificação , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Paladar/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacosRESUMO
UV radiation has been consistently reported to cause folate photodegradation in vitro and in human skin. Seasonal variations in UV radiation might explain seasonal changes in folate levels in blood. Yet, few studies have addressed this phenomenon. The main objective of this study was to investigate whether a relationship exists between seasonal variations in serum folate levels in a population of Spain (Latitude: 36° 41' 6.88â³; Longitude: 4° 30' 0.64â³) and the annual variations of solar ultraviolet reached in the localization. From a sample of 118,831 serum folate determinations, two studies were performed. The first one, which included all subjects, showed a decreased in mean folate concentrations in all seasons with respect to winter with lower values in summer. The risk of folate deficiency was 1.37 times greater in summer than in winter (95%CI: 1.29-1.46). In the second study, subjects with a first folate determination in winter and a second one in summer were 3.32 more likely to develop folate deficiency than those with a first folate determination in summer and a second one in winter (95%CI: 1.55 to 7.11). Folate levels showed a seasonal variation inversely related to solar total UV radiation reached in our location, with maximum daily doses of 5000â¯Jâ¯m-2 reached in June. A gradual increase in percentage of folate deficiency is observed since spring. So, patients with folate levels close to deficiency are at a higher risk of having folate deficiency in summer.
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Ácido Fólico/efeitos da radiação , Estações do Ano , Raios Ultravioleta/efeitos adversos , Adulto , Feminino , Ácido Fólico/sangue , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Ácido Fólico/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fotólise , EspanhaRESUMO
Anandamide and oleoylethanolamide (OEA) are lipid mediators that regulate feeding and lipid metabolism. While anandamide, a cannabinoid CB1 receptor agonist, promotes feeding and lipogenesis, oleoylethanolamide, an endogenous agonist of peroxisome proliferator activated receptor alpha (PPAR-alpha), decreases food intake and activates lipid mobilization and oxidation. The treatment with a cannabinoid CB1 receptor antagonist results in reduction of body weight gain and cholesterol in obese humans and rodents. In the present study, we show the benefits of the treatment of obese Zucker rats with a combination of a cannabinoid CB1 receptor antagonist (Rimonabant) and oleoylethanolamide. This combinational therapy improved the separate effects of Rimonabant and OEA, and resulted in marked decreases on feeding, body weight gain, and plasma cholesterol levels. Additionally, the treatment with both drugs reduced the hepatic steatosis observed in Zucker rats, decreasing liver fat deposits and damage, as revealed by the levels of alanine aminotransferase activity in serum. The combined treatment inhibits the expression of stearoyl coenzyme-A desaturase-1 (SCD-1), a pivotal enzyme in lipid biosynthesis and triglyceride mobilization that is linked to obesity phenotypes. These results support the use of combined therapies with cannabinoid CB1 receptor antagonists and PPAR-alpha agonists for the treatment of obesity associated with dyslipemia.
Assuntos
Metabolismo/efeitos dos fármacos , Obesidade/tratamento farmacológico , Ácidos Oleicos/administração & dosagem , Piperidinas/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Água Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Ingestão de Alimentos/efeitos dos fármacos , Endocanabinoides , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Ratos Zucker , Rimonabanto , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Fatores de TempoRESUMO
OBJECTIVES: We determined zinc (Zn) dialyzability as an indicator of Zn bioavailability in the in vitro gastrointestinal digests of 108 duplicate meals. The interaction exerted by levels of 51 nutrients and energy on total and dialyzable Zn fractions and on Zn dialyzability was also assessed. METHODS: Total and dialyzable Zn levels were measured by flame atomic absorption spectrometry. The Zn dialyzability is expressed as the percentage of dialyzed Zn in relation to the total Zn content in duplicate meals (dialysis Zn percentages). RESULTS: The mean total and dialyzable Zn fractions and Zn dialyzability were 2.180 +/- 1.806 mg, 0.478 +/- 0.556 mg, and 25.23 +/- 15.05%, respectively. The dialysis Zn levels increased significantly with total Zn content in duplicate meals (P < 0.001, r = 0.690). Total and dialyzable Zn fractions found in breakfasts were significantly lower (P < 0.001). The Zn dialyzability was significantly correlated only with total chromium contents, dialyzable copper (Cu) and manganese (Mn) fractions, and Cu and Mn dialyzabilities (P < 0.05). Zn dialyzabilities decreased significantly with increased daily Zn intakes (P = 0.010, r = 0.423). The total Zn supply by meals was directly and significantly (P < 0.001) correlated with their macronutrient contents (carbohydrates, protein, and fiber). The mean daily Zn intake determined was 6.541 mg. CONCLUSION: Duplicate diets studied are moderately low Zn-bioavailability diets. The protein and derivate amino acids act as formers of soluble complexes with Zn in the gastrointestinal tract. Daily Zn levels supplied by hospital meals are low.
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Análise de Alimentos , Serviço Hospitalar de Nutrição/normas , Zinco/farmacocinética , Disponibilidade Biológica , Cobre/análise , Cobre/farmacologia , Digestão , Humanos , Absorção Intestinal , Manganês/análise , Manganês/farmacologia , Valor Nutritivo , Espectrofotometria Atômica , Zinco/análiseRESUMO
Both total and dialyzable Mn levels were determined in 108 duplicate meals during 36 consecutive days. Both mineral fractions were measured by a graphite furnace atomic absorption spectrometry (GFAAS) method previously optimized. A total mean Mn fraction of 1.03±0.49mg was found in the meals. The Mn supplied by the meals is directly and significantly (p<0.001) correlated with macronutrient content (carbohydrates, fibre and protein). The mean Mn fraction dialyzed through the dialysis membrane was 0.23±0.17mg (22.0±8.93% as bioaccessible fraction). The total and dialyzable Mn fractions found for breakfasts were significantly lower (p<0.001). Nevertheless, the Mn bioavailabilities expressed as the percentage of dialyzable element, were not significantly different among the three primary meals (breakfast, lunch and dinner). A significant correlation between the total and the dialyzable fraction of Mn in meals was found (p<0.001, r=0.78, r(2)=0.61). The dialyzed element fractions present in meals were significantly correlated mainly with carbohydrates, protein and several amino acid levels (p <0.01). Foods with higher carbohydrate and therefore energy contents, e.g. cereals, legumes, vegetables and fruits, would be primary sources of bioaccessible Mn in the diet. The bioaccessibility of Mn was only significant influenced by energy, carbohydrates and Se levels present in meals. The mean Mn daily dietary intake (DDI) was 3.05±0.61mgday(-1).
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Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30-100, 15-30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia (FT4 < 12.0 pmol/L p5): OR 1.5 [1.1-2.2] p = 0.024, and hypotriiodothyroninemia (FT3 < 3.9 pmol/L p5): OR 1.8 [1.3-2.6] p = 0.001 than the reference category with ferritin ≥30 µg/L. There was no significant heterogeneity of the results between men, pre-menopausal and post-menopausal women or according to the iodine nutrition status. Our results confirm an association between ID and hypothyroxinemia and hypotriiodothyroninemia in the general adult population without changes in TSH.
Assuntos
Anemia Ferropriva/complicações , Anemia Ferropriva/epidemiologia , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Tiroxina/sangue , Tri-Iodotironina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População , Prevalência , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to investigate the national prevalence of thyroid dysfunction in Spain and its association with various clinical, environmental, and demographic variables. METHODS: The study included 4554 subjects (42.4% men) with a mean age of 50 years (range 18-93 years), who were participants in a national, cross-sectional, population-based survey conducted in 2009-2010. Data gathered included clinical and demographic characteristics, physical examination, and blood sampling. Thyrotropin, free thyroxine, free triiodothyronine, and thyroid peroxidase antibody (TPOAb) concentrations were analyzed by electrochemiluminescence. Urinary iodine (UI) levels were measured in an isolated urine sample. RESULTS: The prevalence of treated hypothyroidism, untreated subclinical hypothyroidism, and untreated clinical hypothyroidism was 4.2% [confidence interval (CI) 3.6-4.9%], 4.6% [CI 4.0-5.2%], and 0.3% [CI 0.1-0.5%], respectively. The prevalence of total hypothyroidism (including all fractions) was 9.1% [CI 8.2-10.0%]. The prevalence of total hyperthyroidism was 0.8% [CI 0.6-1.1]. A total of 7.5% [CI 6.7-8.3%] of the population tested positive for TPOAbs (≥50 IU/mL). In multivariate logistic regression models, TPOAbs were strongly associated with both hypothyroidism (p < 0.001) and hyperthyroidism (p = 0.005), whereas high UI levels (>200 µg/g creatinine) were associated with hypothyroidism (p < 0.001). The positive association between UI and hypothyroidism remained for both treated (p < 0.001) and untreated (p < 0.05) hypothyroidism, whereas it was especially significant for non-autoimmune (TPOAbs negative) forms (p < 0.001). At UI levels ≥200 µg/g, there was a positive correlation between UI and thyrotropin levels (ß = 0.152, p < 0.001) and a negative correlation between UI and free triiodothyronine levels (ß = -0.134, p = 0.001). CONCLUSION: According to the data, a large proportion (10%) of the Spanish population has some evidence of thyroid dysfunction. High TPOAb concentrations were associated with both hypo- and hyperthyroidism, whereas high UI concentrations were associated with hypothyroidism.
Assuntos
Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Autoantígenos/imunologia , Feminino , Humanos , Hipertireoidismo/imunologia , Hipertireoidismo/metabolismo , Hipotireoidismo/imunologia , Hipotireoidismo/metabolismo , Iodeto Peroxidase/imunologia , Iodo/urina , Proteínas de Ligação ao Ferro/imunologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de Risco , Espanha/epidemiologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto JovemRESUMO
OBJECTIVE: To analyze the reference range of thyroid-stimulating hormone (TSH) in different BMI categories and its impact on the classification of hypothyroidism. METHODS: The study included 3,928 individuals free of thyroid disease (without previous thyroid disease, no interfering medications, TSH <10 µUI/mL and thyroid peroxidase antibodies [TPO Abs] <50 IU/mL) who participated in a national, cross-sectional, population-based study and were representative of the adult population of Spain. Data gathered included clinical and demographic characteristics, physical examination, and blood and urine sampling. TSH, free thyroxine, free triiodothyronine, and TPO Ab were analyzed by electrochemiluminescence (E170, Roche Diagnostics, Basel, Switzerland). RESULTS: The reference range (p2.5-97.5) for TSH was estimated as 0.6 to 4.8 µUI/mL in the underweight category (BMI<20 kg/m2 ), 0.6 to 5.5 µUI/mL in the normal-weight category (BMI 20-24.9 kg/m2 ), 0.6 to 5.5 µUI/mL in the overweight category (BMI 25-29.9 kg/m2 ), 0.5 to 5.9 µUI/mL in the obesity category (BMI 30-39.9 kg/m2 ), and 0.7 to 7.5 µUI/mL in the morbid obesity category (BMI ≥40). By using the reference criteria for the normal-weight population, the prevalence of high TSH levels increased threefold in the morbid obesity category (P < 0.01). CONCLUSIONS: Persons with morbid obesity might be inappropriately classified if the standard ranges of normality of TSH for the normal-weight population are applied to them.
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Hipotireoidismo/diagnóstico , Obesidade Mórbida/sangue , Variações Dependentes do Observador , Tireotropina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Estudos Transversais , Feminino , Humanos , Hipotireoidismo/sangue , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Sobrepeso/sangue , Sobrepeso/complicações , Prevalência , Valores de Referência , Espanha , Magreza/sangue , Magreza/complicações , Testes de Função Tireóidea , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto JovemRESUMO
OBJECTIVE: The effects of C-peptide on adipose tissue, an organ involved in the development of obesity and insulin resistance, are not yet well known. The aim of this study was to determine whether C-peptide could be involved in the regulation of the adipocytokine synthesis in human visceral adipose tissue. METHODS: The association between C-peptide and different serum adipocytokines, with an intravenous glucose tolerance test (IVGTT), and in an in vitro study in subjects without obesity and in subjects with morbid obesity were analyzed. RESULTS: In different multiple regression analysis models, C-peptide and C-peptide increase above basal levels during total IVGTT and between 0 and 10 min were associated positively with leptin and negatively with visfatin. Rhodamine-labeled C-peptide binds to human adipocytes, and this binding was blocked with excess of unlabeled C-peptide. Exposure of human visceral explants and adipocytes from subjects with morbid obesity to C-peptide at 1 and 10 nM induced a significant increase in leptin and a decrease in visfatin secretion. In subjects without obesity, these C-peptide effects were found mainly at 10 nM. These effects can be inhibited by phosphatidylinositol 3-kinase (PI3K) or protein kinase B (PKB) inhibitors. CONCLUSIONS: C-peptide may be involved in the regulation of leptin and visfatin secretion, molecules intimately involved in energy homeostasis processes, through PI3K or PKB pathways.
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Adipocinas/química , Tecido Adiposo/efeitos dos fármacos , Peptídeo C/sangue , Peptídeo C/química , Teste de Tolerância a Glucose/métodos , Leptina/sangue , Leptina/química , Nicotinamida Fosforribosiltransferase/química , Adulto , Feminino , Humanos , Masculino , Nicotinamida Fosforribosiltransferase/sangue , Fosfatidilinositol 3-QuinasesRESUMO
BACKGROUND AND OBJECTIVE: Vitamin D deficiency and metabolic syndrome are 2 very common health problems in the Spanish population. It has been suggested that patients with metabolic syndrome may be vitamin D deficient more often than subjects without it and that low vitamin D levels may predispose to metabolic syndrome development. However, the results of prospective and intervention studies have been different and such relationship remains unclear. We assessed the relationship between 25-hydroxyvitamin D levels and the prevalence and incidence of metabolic syndrome. PATIENTS AND METHODS: We undertook a population-based cohort study in Spain. At baseline (1996-1998), 1,226 subjects were evaluated. Follow-up visits were performed in 2002-2004 and 2005-2007.At baseline and follow-up, participants underwent an interview and a standardized clinical examination with an oral glucose tolerance test in those subjects without known diabetes. At the second visit, 25-hydroxyvitamin D levels and intact parathyroid hormone levels were measured. RESULTS: The prevalence of metabolic syndrome at the second and third visit was 29.4 and 42.5%, respectively. Mean levels of 25-hydroxyvitamin D were lower in subjects with metabolic syndrome: 21.7 (6.21) vs 23.35 (6.29) ng/ml, P<.001.The prevalence of vitamin D deficiency (25-hydroxyvitamin D<20 ng/ml) at the second evaluation was 34.7%, with significant differences between subjects with and without metabolic syndrome(34.6 vs 26.5%, P<.01). Men with vitamin D deficiency had more frequently hypertension and metabolic syndrome than men with normal levels. Women with vitamin D deficiency had more frequently hyperglycemia, hypertension, increased waist circumference and hypertriglyceridemia. In a prospective study, 25-hydroxyvitamin D values<20 ng/ml were not significantly associated with an increased risk of developing metabolic syndrome in the next 5 years (odds ratio 0,99, 95% confidence interval 0.57-1.7, P=.97) after adjusting by sex and age. CONCLUSIONS: Vitamin D deficiency is associated with an increased prevalence but not with an increased incidence of metabolic syndrome.
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Síndrome Metabólica/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adiponectina/sangue , Adulto , Índice de Massa Corporal , Comorbidade , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Hipertensão/epidemiologia , Hipertrigliceridemia/epidemiologia , Interleucina-6/sangue , Leptina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Resistina/sangue , Fatores de Risco , Fatores Sexuais , Fator de Necrose Tumoral alfa/análise , Vitamina D/análogos & derivados , Vitamina D/sangue , Circunferência da CinturaRESUMO
BACKGROUND AND PURPOSE: Peripheral blockade of cannabinoid CB(1) receptors has been proposed as a safe and effective therapy against obesity, putatively devoid of the adverse psychiatric side effects of centrally acting CB(1) receptor antagonists. In this study we analysed the effects of LH-21, a peripherally acting neutral cannabinoid receptor antagonist with poor brain penetration, in an animal model of diet-induced obesity. EXPERIMENTAL APPROACH: To induce obesity, male Wistar rats were fed a high-fat diet (HFD; 60 kcal% fat) whereas controls received a standard diet (SD; 10 kcal% fat). Following 10 weeks of feeding, animals received a daily i.p. injection of vehicle or 3 mg·kg(-1) LH-21 for 10 days. Plasma and liver samples were used for biochemical analyses whereas visceral fat-pad samples were analysed for lipid metabolism gene expression using real-time RT-PCR. In addition, the potential of LH-21 to interact with hepatic cytochrome P450 isoforms and cardiac human Ether-à-go-go Related Gene (hERG) channels was evaluated. KEY RESULTS: LH-21 reduced feeding and body weight gain in HFD-fed animals compared with the control group fed SD. In adipose tissue, this effect was associated with decreased gene expression of: (i) leptin; (ii) lipogenic enzymes, including SCD-1; (iii) CB(1) receptors; and (iv) both PPARα and PPARγ. Although there were no significant differences in plasma parameters between HFD- and SD-fed rats, LH-21 did not seem to induce hepatic, cardiac or renal toxicity. CONCLUSIONS AND IMPLICATIONS: These results support the hypothesis that treatment with the peripherally neutral acting CB(1) receptor antagonist, LH-21, may promote weight loss through modulation of visceral adipose tissue.
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Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Receptor CB1 de Canabinoide/antagonistas & inibidores , Triazóis/farmacologia , Animais , Fármacos Antiobesidade/farmacocinética , Fármacos Antiobesidade/toxicidade , Encéfalo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Canal de Potássio ERG1 , Ingestão de Alimentos/efeitos dos fármacos , Canais de Potássio Éter-A-Go-Go/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Leptina/genética , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Obesidade/etiologia , Obesidade/genética , Obesidade/metabolismo , PPAR alfa/deficiência , PPAR alfa/genética , PPAR gama/genética , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/genética , Triazóis/farmacocinética , Triazóis/toxicidade , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVES: To evaluate the association between high levels of glycemia and low serum uric acid levels in two independent population-based samples. PATIENTS AND METHODS: The first sample was taken from the Pizarra Study, a population-based prospective study of 1.226 persons classified according to their glycometabolic status, as measured from an oral glucose tolerance test. Variables recorded included anthropometric data, serum fasting insulin, uric acid (UA) and HOMA-IR. The second sample was obtained from the Central Laboratory Database, which includes 81,754 laboratory requests for HbA(1c) carried out over 30 months. We selected those that included measurements of UA, triglycerides and albuminuria. RESULTS: In the Pizarra Study, the fasting glucose levels showed a bell-shaped relation with serum UA levels in men and more especially in women (P<0.0001). In the second sample, the UA levels in women showed a bell-shaped relation with HbA(1c), increasing as the HbA(1c) rose to 7% and then falling with the further increase of HbA(1c) (P<0.0001). Men experienced a linear decrease in UA levels as the HbA(1c) rose (r=-0.19; P<0.0001), though only with effect from HbA(1c) values > 7%. The odds ratio for hyperuricemia (≥ 6mg/dL in women and ≥ 7mg/dL in men) fell continuously as the HbA(1c) levels rose. CONCLUSIONS: This study, undertaken in two different populations, showed that serum UA levels are non-linearly correlated with the levels of glucose, HbA(1c) and HOMA-IR, especially in women. The risk of hyperuricemia and gout may be higher in persons with prediabetic states or with better-controlled diabetes than in persons with poorly-controlled diabetes.
Assuntos
Hemoglobinas Glicadas/análise , Hiperuricemia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
Total and dialysable magnesium and calcium levels and corresponding dialysabilities were measured in duplicate meals (n = 108) during 36 consecutive days. The interaction exerted by other nutrients and energy on them was also performed. Total mean magnesium and calcium fractions of 113.9 +/- 98.3 and 337.2 +/- 278.9 mg/meal respectively, were found. The Mg and Ca levels supplied by meals are positively (p < 0.05) correlated with macronutrient contents (carbohydrates and proteins). The mean dialysable Mg and Ca fractions were 56.9 +/- 36.3 and 127.4 +/- 112.3 mg/meal (50.4 +/- 13.2 and 37.8 +/- 10.7% as dialysabilities, respectively). Total Mg and Ca levels are significantly correlated with corresponding element dialysabilities (p < 0.05). For both minerals, significant correlations between their total and dialysable fractions and between their dialysable level and dialysabilities were noted (p < 0.01). The mean Mg and Ca daily dietary intakes (DDI) were 341.7 +/- 68.0 and 1,011.6 +/- 424.4 mg/day, respectively. For Ca and Mg the existence of similarities in their behaviour in meals and absorptive processes has been found. Duplicate meals with raw vegetables are good sources of bioaccessible Mg. High Ca dialysability has been found in the analysed meals. The fish and products constitute a good source of bioaccessible Ca. Mg, Ca, zinc, and chromium levels enhanced significantly the Mg dialysability. The Ca dialysability rose significantly with dialysable Ca and chromium fractions (p < 0.05).
Assuntos
Cálcio/análise , Análise de Alimentos/métodos , Serviço Hospitalar de Nutrição/normas , Magnésio/análise , Animais , Disponibilidade Biológica , Cálcio da Dieta/análise , Cromo/análise , Peixes , Humanos , Absorção Intestinal , Necessidades Nutricionais , Ciências da Nutrição , Valor Nutritivo , Controle de QualidadeRESUMO
Both total and dialyzable iron levels and corresponding dialyzability were determined in 108 duplicate meals during 36 consecutive days. Total mean iron fraction of 5.90 +/- 4.97 mg was found in the meals. The iron supplied by the meals is directly and significantly (p < 0.05) correlated with macromicronutrient content (carbohydrates, fiber, and protein). The mean iron dialyzability (4.81 +/- 3.25%) was low and not significantly different among the three primary meals (breakfast, lunch, and dinner). Significant interactions of several minerals on iron levels were found (p < 0.05). Iron dialyzability was only statistically influenced by zinc dialyzability in meals (p < 0.05). The dialyzed iron fraction present in meals was significantly correlated with protein and ascorbic acid levels (p < 0.01). The mean iron daily dietary intake was 17.7 +/- 6.91 mg. The hospital meals provided enough iron. Foods of animal origin are primary sources of iron in diet.
Assuntos
Diálise/métodos , Análise de Alimentos , Serviço Hospitalar de Nutrição , Ferro da Dieta/análise , Digestão , Análise de Alimentos/métodos , Humanos , Ferro da Dieta/metabolismo , Política Nutricional , Espanha , Espectrofotometria Atômica , Estatísticas não ParamétricasRESUMO
Intake of chromium was estimated using a duplicate diet sampling method of 108 meals (36 breakfasts, 36 lunches and 36 dinners) from the restaurant of the Hospital of Motril (S.E. Spain), corresponding to 36 consecutive days. Total and dialyzable Cr levels were measured by a validated electro-thermal atomic absorption spectrometry (ETAAS) method. A mean Cr fraction of 26 +/- 12 microg meal (-1) was found. The Cr uptake from meals was directly and significantly (p < 0.001) correlated with their macronutrient (carbohydrates, fibre and protein) content. Cereals and cereal by-products, legumes, dry fruits, meat, potatoes, dairy products and seafood are the primary sources of Cr. The mean Cr fraction dialyzed through dialysis tubing was 1.2 +/- 1.1 microg meal(-1) (4.6 +/- 3.8% as mean Cr dialysability). Cr intake for breakfasts was significantly lower (p < 0.001). A correlation between the logarithmic data of total and dialyzable fraction of Cr in meals (p = 0.020) was found and dialysis ratio enhancement and, therefore, bioavailability increased with total Cr. The dialysed element content present in meals was significantly correlated with fibre, protein, Fe, Na, I, F, sodium, ascorbic acid and vitamin A levels (p < 0.05). At Fe contents in meals higher than congruent with7.5 mg meal(-1) the net absorption of Cr decreased significantly. The mean Cr daily dietary intake (DDI) was 77 +/- 17 microg day (-1) which indicates that no adverse effects in relation to Cr nutrition (deficiency or toxicity) should occur in individuals from the area.
Assuntos
Cromo/análise , Dieta , Análise de Alimentos/métodos , Espectrofotometria Atômica/métodos , Disponibilidade Biológica , Cromo/administração & dosagem , Digestão , Serviço Hospitalar de Nutrição , Humanos , Absorção Intestinal , Sensibilidade e EspecificidadeRESUMO
Fundamento y objetivo: El déficit de vitamina D y el síndrome metabólico son 2 entidades muy frecuentes en población española. Se ha sugerido que los pacientes con síndrome metabólico pueden tener déficit de vitamina D con mayor frecuencia que los sujetos sin e'l, y que unos valores bajos de vitamina D pueden predisponer al desarrollo de síndrome metabólico. No obstante, los resultados de estudios prospectivos y de intervención han sido diversos, sin que se haya aclarado por el momento si existe esta relación. El objetivo de este trabajo fue evaluar la relación entre los valores de 25-hidroxivitamina D y la prevalencia e incidencia del síndrome metabólico. Pacientes y método: Se realizó un estudio poblacional de cohortes. Al inicio del estudio (1996-1998), 1.226 pacientes fueron evaluados. Las visitas de seguimiento se llevaron a cabo en 2002-2004 y 2005-2007. Basalmente y durante el seguimiento, los participantes se sometieron a una entrevista y un examen clínico estandarizado con una prueba de tolerancia oral a la glucosa. En la segunda visita se midieron la 25-hidroxivitamina D y los valores de parathormona intacta. Resultados: La prevalencia de síndrome metabólico en la segunda y la tercera evaluación fue del 29,4 y del 42,5%, respectivamente. Los valores medios (DE) de 25-hidroxivitamina D fueron menores en los pacientes con síndrome metabólico, 21,7 (6,21) frente a 23,35 (6,29) ng/ml, p < 0,001. La prevalencia de deficiencia de vitamina D (25-hidroxivitamina D < 20 ng/ml) en la segunda evaluación fue del 34,7%, con diferencias significativas entre los sujetos con y sin síndrome metabólico (34,6 frente a 26,5%, p < 0,01). Los varones con deficiencia de vitamina D tuvieron con mayor frecuencia hipertensión y síndrome metabólico que aquellos con valores normales. Las mujeres con deficiencia de vitamina D tuvieron más frecuentemente hiperglucemia, hipertensión, aumento de la circunferencia de la cintura e hipertrigliceridemia. En el estudio prospectivo, los valores de 25-hidroxivitamina D < 20 ng/ml no se asociaron significativamente con un mayor riesgo de desarrollar el síndrome metabólico en los siguientes 5 años (odds ratio 0,99, intervalo de confianza del 95% 0,57-1,7, p < 0,97) después de ajustar por sexo y edad. Conclusiones: Los pacientes con síndrome metabólico tienen con mayor frecuencia déficit de vitamina D, pero este no predice el riesgo de desarrollar síndrome metabólico (AU)
Background and objective: Vitamin D deficiency and metabolic syndrome are 2 very common health problems in the Spanish population. It has been suggested that patients with metabolic syndrome may be vitamin D deficient more often than subjects without it and that low vitamin D levels may predispose to metabolic syndrome development. However, the results of prospective and intervention studies have been different and such relationship remains unclear. We assessed the relationship between 25-hydroxyvitamin D levels and the prevalence and incidence of metabolic syndrome. Patients and methods: We undertook a population-based cohort study in Spain. At baseline (1996-1998), 1,226 subjects were evaluated. Follow-up visits were performed in 2002-2004 and 2005-2007.At baseline and follow-up, participants underwent an interview and a standardized clinical examination with an oral glucose tolerance test in those subjects without known diabetes. At the second visit, 25-hydroxyvitamin D levels and intact parathyroid hormone levels were measured. Results: The prevalence of metabolic syndrome at the second and third visit was 29.4 and 42.5%, respectively. Mean levels of 25-hydroxyvitamin D were lower in subjects with metabolic syndrome: 21.7 (6.21) vs 23.35 (6.29) ng/ml, P < .001.The prevalence of vitamin D deficiency (25-hydroxyvitamin D < 20 ng/ml) at the second evaluation was 34.7%, with significant differences between subjects with and without metabolic syndrome(34.6 vs 26.5%, P < .01). Men with vitamin D deficiency had more frequently hypertension and metabolic syndrome than men with normal levels. Women with vitamin D deficiency had more frequently hyperglycemia, hypertension, increased waist circumference and hypertriglyceridemia. In a prospective study, 25-hydroxyvitaminD values < 20 ng/ml were not significantly associated with an increased risk of developing metabolic syndrome in the next 5 years (odds ratio 0,99, 95% confidence interval 0.57-1.7, P = .97) after adjusting by sex and age. Conclusions: Vitamin D deficiency is associated with an increased prevalence but not with an increased incidence of metabolic syndrome (AU)
Assuntos
Humanos , Deficiência de Vitamina D/complicações , Síndrome Metabólica/epidemiologia , Diabetes Mellitus/epidemiologia , Estudos de Coortes , Teste de Tolerância a Glucose , Hormônio Paratireóideo/análiseRESUMO
Fundamento y objetivo: Evaluar la hipótesis de que valores elevados de glucemia se asocian con menores valores séricos de ácido úrico, en 2 poblaciones independientes. Pacientes y método:La primera población procede del Estudio Pizarra, estudio prospectivo con 1.226 sujetos que se clasificaron según su situación metabólica tras una sobrecarga oral de glucosa. Se midieron variables antropométricas, valores basales de insulina, ácido úrico y resistencia a la insulina según el Homeostasis Model Assessment (HOMA-IR). La segunda muestra procede de la base de datos del Hospital Universitario Carlos Haya (Málaga), que recoge 81.754 sucesivas peticiones analíticas de hemoglobina glucosilada (HbA1c) realizadas a lo largo de 30 meses.Resultados: En el Estudio Pizarra los valores de glucosa se relacionaron con los valores de ácido úrico en ambos sexos. En la segunda muestra los valores de ácido úrico de mujeres siguieron una relación en forma de campana con la HbA1c, incrementándose hasta valores de HbA1c del 7% y descendiendo a medida que la HbA1c aumentaba (p<0,0001). En varones se produjo un descenso lineal de los valores de ácido úrico con el incremento de la HbA1c (r=−0,19; p<0,0001), a partir de valores de HbA1c del 7%. El valor de odds ratio para hiperuricemia descendió de manera continua según aumentaban los valores de HbA1c. Conclusión: Este estudio muestra en ambas poblaciones una correlación no lineal entre los valores séricos de ácido úrico y los de glucosa, HbA1c y HOMA-IR, siendo esta tendencia especialmente marcada en mujeres. El riesgo de hiperuricemia y gota podría ser mayor en las personas con estados prediabéticos o con diabetes mejor controlados que en diabéticos mal controlados (AU)
Background and objectives: To evaluate the association between high levels of glycemia and low serum uric acid levels in two independent population-based samples. Patients and methods: The first sample was taken from the Pizarra Study, a population-based prospective study of 1.226 persons classified according to their glycometabolic status, as measured from an oral glucose tolerance test. Variables recorded included anthropometric data, serum fasting insulin, uric acid (UA) and HOMA-IR. The second sample was obtained from the Central Laboratory Database, which includes 81,754 laboratory requests for HbA1c carried out over 30 months. We selected those that included measurements of UA, triglycerides and albuminuria Results: In the Pizarra Study, the fasting glucose levels showed a bell-shaped relation with serum UA levels in men andmore especially in women (P < 0.0001). In the second sample, the UA levels in women showed a bell-shaped relation with HbA1c, increasing as the HbA1c rose to 7% and then falling with the further increase of HbA1c (P < 0.0001). Men experienced a linear decrease in UA levels as the HbA1c rose (r = 0.19; P < 0.0001), though only with effect from HbA1c values > 7%. The odds ratio for hyperuricemia ( 6 mg/dL in women and 7 mg/dL in men) fell continuously as the HbA1c levels rose. Conclusions: This study, undertaken in two different populations, showed that serum UA levels are nonlinearlycorrelated with the levels of glucose, HbA1c and HOMA-IR, especially in women. The risk ofhyperuricemia and gout may be higher in persons with prediabetic states or with better-controlleddiabetes than in persons with poorly-controlled diabetes (AU)