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1.
Asia Pac J Clin Nutr ; 31(3): 378-393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36173210

RESUMO

BACKGROUND AND OBJECTIVES: Maternal nutrition is important for healthy pregnancy, but it has not been well studied among pregnant women in Hong Kong. This study aims to examine the dietary pattern and nutritional intake of women in early pregnancy, and the associations between dietary patterns, dietary quality, and other health parameters. METHODS AND STUDY DESIGN: This is a prospective cohort study of healthy Chinese pregnant women, recruited at their first antenatal appointment. Dietary intakes were assessed by a locally validated food frequency questionnaire (FFQ) and dietary patterns were derived by principal component analysis. RESULTS: Of 160 women recruited, the mean age was 32.7±3.9 years and body mass index (BMI) before pregnancy was 22.6±3.8 kg/m2. The dietary analyses were restricted to 156 women who had completed the FFQ. 99% of women had excessive sodium intake and only 2.6% of women met the recommended fibre intake. Three dietary patterns identified were 'sweet and fast-food pattern', 'prudent pattern' and 'meat pattern', which altogether accounted for 23.5% of the total variation. The 'prudent pattern' was positively associated with dietary quality indices [Dietary Approaches to Stop Hypertension score, ρ=0.323, p<0.01; Dietary Quality Index-International, ρ=0.400, p<0.01; Mediterranean Diet Score, ρ=0.243, p=0.02]; and was inversely associated systolic (B=-3.71, 95% CI -7.06, -0.36) and diastolic blood pressure (B=-2.69, 95% CI -5.12, -0.26), suggesting this pattern represented a relatively healthier dietary option. CONCLUSIONS: Suboptimal dietary intake is a common issue among pregnant women in Hong Kong. Early dietary assessment and attention are warranted in this population.


Assuntos
Dieta Mediterrânea , Sódio na Dieta , Adulto , Dieta , Feminino , Hong Kong/epidemiologia , Humanos , Gravidez , Gestantes , Estudos Prospectivos
2.
Nutrients ; 13(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34371826

RESUMO

BACKGROUND: Sarcopenia is a major health problem in older adults. Exercise and nutrient supplementation have been shown to be effective interventions but there are limited studies to investigate their effects on the management of sarcopenia and its possible underlying mechanisms. Here, we studied T cell gene expression responses to interventions in sarcopenia. METHODS: The results of this study were part of a completed trial examining the effectiveness of a 12-week intervention with exercise and nutrition supplementation in community-dwelling Chinese older adults with sarcopenia, based on the available blood samples at baseline and 12 weeks from 46 randomized participants from three study groups, namely: exercise program alone (n = 11), combined-exercise program and nutrition supplement (n = 23), and waitlist control group (n = 12). T cell gene expression was evaluated, with emphasis on inflammation-related genes. Real-time PCR (RT-PCR) was performed on CD3 T cells in 38 selected genes. Correlation analysis was performed to relate the results of gene expression analysis with lower limb muscle strength performance, measured using leg extension tests. RESULTS: Our results showed a significant improvement in leg extension for both the exercise program alone and the combined groups (p < 0.001). Nine genes showed significant pre- and post-difference in gene expression over 12 weeks of intervention in the combined group. Seven genes (RASGRP1, BIN1, LEF1, ANXA6, IL-7R, LRRN3, and PRKCQ) showed an interaction effect between intervention and gene expression levels on leg extension in the confirmatory analysis, with confounder variables controlled and FDR correction. CONCLUSIONS: Our findings showed that T cell-specific inflammatory gene expression was changed significantly after 12 weeks of intervention with combined exercise and HMB supplementation in sarcopenia, and that this was associated with lower limb muscle strength performance.


Assuntos
Suplementos Nutricionais , Exercício Físico/fisiologia , Expressão Gênica/genética , Sarcopenia/terapia , Linfócitos T/metabolismo , Valeratos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Análise Fatorial , Feminino , Humanos , Vida Independente , Extremidade Inferior/fisiopatologia , Masculino , Força Muscular/genética , Músculo Esquelético/fisiopatologia , Treinamento Resistido/métodos , Sarcopenia/genética , Resultado do Tratamento
3.
Nutr Res Pract ; 13(5): 415-424, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31583061

RESUMO

BACKGROUND/OBJECTIVES: Existing evidence on lifestyle modification programs for weight loss is limited by the high attrition rate of such programs. Identifying predictors of adherence to a lifestyle modification program could result in program improvement. However, little is known about behavior-specific adherence and its psychological predictors. This study aimed to examine the psychological predictors of adherence after one-month participation in a community-based lifestyle modification program among Chinese overweight and obese adults in Hong Kong. SUBJECTS/METHODS: A total of 205 Chinese overweight and obese adults aged 38.9 ± 10.5 years completed the study. Data were collected at baseline and after one month using self-reported questionnaires, which assessed knowledge (self-developed scale), motivation (Treatment Self-Regulation Questionnaire), stage of change (Stage of Exercise Scale) and self-efficacy (Self-Rated Abilities for Health Practices Scale). At one month, a 4-day dietary recall and the International Physical Activity Questionnaire-Short Form were used to assess dietary and physical activity (PA) adherence. Food and PA diaries were examined to indicate self-monitoring. Program attendance was tracked between baseline and one-month follow-up. RESULTS: After one month, participants reported high dietary adherence, attendance, and adherence to self-monitoring but low PA adherence. Multiple regression analyses suggested that diet self-efficacy (baseline) and nutrition knowledge (one-month change) were independent predictors of dietary adherence score at one month, whereas autonomous PA motivation (baseline) and PA self-efficacy (both baseline and one-month change) were independent predictors of PA adherence score at one month. No significant psychological predictor was identified for attendance or self-monitoring. CONCLUSIONS: The results suggest that the effect of psychological factors on adherence differs between diet and PA adherence outcomes. To promote adherence, practitioners should assess self-efficacy, knowledge, and motivation at the beginning of a weight-loss program and explore behavior-specific strategies to improve knowledge and self-efficacy. The results of this study have direct implications for program improvements.

4.
Sci Rep ; 8(1): 13849, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-30218012

RESUMO

Gestational diabetes mellitus (GDM) is of public health concern. This trial examined whether a clinically proven lifestyle modification program (LMP) in early pregnancy was superior to routine antenatal care in improving GDM, maternal and infant outcomes. Chinese pregnant women at risk of GDM (n = 220) were recruited at or before 12-week gestation and randomized to either a LMP group or a routine care control group. Eighty subjects completed a dietitian-led LMP including dietary and exercise components from early pregnancy till 24-week gestation. Data were compared with those of 86 control subjects. Twenty three (26.7%) control subjects and 20 (25.0%) LMP subjects developed GDM (p = 0.798). The proportion of infants born large for gestational age and macrosomia was similar between groups. The LMP group showed a lower proportion of excessive gestational weight gain (GWG). Subgroup analysis suggested that those with higher LMP adherence showed more desirable dietary composition and energy intake, and lower proportion of excessive GWG compared with the low LMP adherence group and the control group. The potential effect of LMP on GDM and other maternal and infant outcomes, in particular GWG, as well as barriers for making lifestyle changes warrant further investigations (ClinicalTrials.gov NCT02368600).


Assuntos
Diabetes Gestacional/prevenção & controle , Estilo de Vida , Adulto , Feminino , Hong Kong , Humanos , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Risco
5.
J Hepatol ; 69(6): 1349-1356, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30142427

RESUMO

BACKGROUND & AIMS: Around 10-20% of patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The benefit of weight reduction in such patients is unclear. We aim to study the efficacy of lifestyle intervention in non-obese patients with NAFLD and to identify factors that predict treatment response. METHODS: A total of 154 community NAFLD patients were randomised to a 12-month lifestyle intervention programme involving regular exercise, or to standard care. The primary outcome was remission of NAFLD at Month 12 by proton-magnetic resonance spectroscopy. After the programme, the patients were prospectively followed until Year 6. The Asian body mass index (BMI) cut-off of 25 kg/m2 was used to define non-obese NAFLD. RESULTS: Patients were assigned to the intervention (n = 77) and control (n = 77) groups (39 and 38 in each group had baseline BMI <25 and ≥25 kg/m2, respectively). More patients in the intervention group achieved the primary outcome than the control group regardless of baseline BMI (non-obese: 67% vs. 18%, p <0.001; obese: 61% vs. 21%, p <0.001). Lifestyle intervention, lower baseline intrahepatic triglyceride, and reduction in body weight and waist circumference were independent factors associated with remission of NAFLD in non-obese patients. Half of non-obese patients achieved remission of NAFLD with 3-5% weight reduction; the same could only be achieved in obese patients with 7-10% weight reduction. By Year 6, non-obese patients in the intervention group remained more likely to maintain weight reduction and alanine aminotransferase normalisation than the control group. CONCLUSIONS: Lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. Weight reduction predicts remission of NAFLD in non-obese patients, but a modest weight reduction may be sufficient in this population. LAY SUMMARY: Some patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The optimal management of such patients is unclear. In this long-term follow-up study of a clinical trial, we show that remission of NAFLD can be achieved in 67% of non-obese patients after lifestyle intervention. The majority of patients can achieve NAFLD remission with modest weight loss of 3-10%. Non-obese patients are also more likely than obese patients to maintain weight reduction and normal liver enzymes in the long run.


Assuntos
Estilo de Vida , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/complicações , Indução de Remissão , Adulto , Idoso , Índice de Massa Corporal , Dieta , Exercício Físico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento , Triglicerídeos/análise , Circunferência da Cintura , Redução de Peso/fisiologia
6.
Am J Gastroenterol ; 110(9): 1306-14; quiz 1315, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26215532

RESUMO

OBJECTIVES: Some studies suggest that non-obese patients with nonalcoholic fatty liver disease (NAFLD) may have more severe disease. We aim to study the epidemiology and severity of non-obese NAFLD. METHODS: A total of 911 community subjects were randomly recruited from the census database of the Hong Kong Government. Intrahepatic triglycerides (IHTG) and liver fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. The Asian body mass index cutoff of 25 kg/m(2) was used to define non-obese NAFLD. RESULTS: The prevalence of NAFLD was 19.3% in non-obese subjects and 60.5% in obese subjects (P<0.001). Compared with obese NAFLD patients, non-obese NAFLD patients had similar IHTG content (median 9.8% vs. 9.9%; P=0.100) but lower cytokeratin-18 fragments (149 vs. 182 IU/l; P=0.019) and liver stiffness (4.6 vs. 5.6 kPa; P<0.001). The G allele at the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3 rs738409) was more common in non-obese than obese NAFLD patients (78.4% vs. 59.8%; P=0.001). Obesity, high hemoglobin A1c, insulin resistance, hyperferritinemia, and the PNPLA3 G allele were independent factors associated with NAFLD in non-obese subjects. Even among non-obese subjects with normoglycemia, those with NAFLD were more insulin resistant (mean homeostasis model assessment of insulin resistance: 2.0±1.0 vs. 1.1±1.1; P<0.001). CONCLUSIONS: One-fifth of the general non-obese Chinese population has NAFLD. Non-obese patients with NAFLD do not have a higher risk of steatohepatitis or advanced fibrosis. Patients with risk factors of advanced fibrosis such as metabolic syndrome and PNPLA3 G allele carriage should be assessed for severe NAFLD.


Assuntos
Fígado/patologia , Espectroscopia de Ressonância Magnética/métodos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Vigilância da População , Adolescente , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Seguimentos , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
7.
J Gastroenterol Hepatol ; 30(1): 139-46, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25040896

RESUMO

BACKGROUND AND AIM: Lifestyle modification is the cornerstone for the management of nonalcoholic fatty liver disease (NAFLD), and patatin-like phospholipase 3 (PNPLA3) is one of the most important genetic determinants of NAFLD. We aimed to investigate the effect of PNPLA3 gene polymorphism on the response to lifestyle modification in NAFLD patients. METHODS: This was a post-hoc analysis of a randomized controlled trial on a lifestyle modification program in community NAFLD patients. The PNPLA3 rs738409 gene polymorphism was correlated with changes in metabolic profile and intrahepatic triglyceride content (IHTG) as measured by proton magnetic resonance spectroscopy. RESULTS: One hundred and fifty-four patients were equally randomized into the intervention and control groups. The presence of G allele was associated with greater reduction in IHTG (CC: 3.7 ± 5.2%, CG: 6.5 ± 3.6%), and GG: 11.3 ± 8.8% (Spearman's correlation, 0.34; P = 0.002), body weight (P = 0.030), waist-to-hip ratio (P = 0.024), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.009) in the intervention group. In contrast, PNPLA3 polymorphism had no impact on IHTG changes in the control group. By multivariable analysis, PNPLA3 genotype and body mass index (BMI) change were independently associated with IHTG reduction in the intervention group. Only BMI change was associated with IHTG reduction in the control group. CONCLUSION: Although the PNPLA3 rs738409 GG genotype confers a higher risk of NAFLD, these patients are more sensitive to the beneficial effects of lifestyle modification and should be encouraged to do so.


Assuntos
Fígado Gorduroso/genética , Fígado Gorduroso/terapia , Estilo de Vida , Lipase/genética , Proteínas de Membrana/genética , Polimorfismo Genético , Adulto , Alelos , Índice de Massa Corporal , Fígado Gorduroso/metabolismo , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/metabolismo
8.
J Hepatol ; 62(1): 182-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25195550

RESUMO

BACKGROUND & AIMS: Because abdominal ultrasonography cannot reliably quantify hepatic steatosis, accurate data on the incidence of non-alcoholic fatty liver disease (NAFLD) are lacking. We aimed to study the population incidence of NAFLD with state-of-the-art non-invasive tests. METHODS: This was a prospective cohort study. The intrahepatic triglyceride (IHTG) content was measured serially with proton-magnetic resonance spectroscopy in community subjects. Transient elastography was performed to assess liver fibrosis. RESULTS: 565 subjects (mean age 48 years, 62.7% women) without NAFLD at baseline underwent follow-up assessment after a median interval of 47 months (range 34-60 months). 78 (13.8%) subjects developed incident fatty liver with a mean IHTG content of 8.9% (SD 5.3%). 16 (20.5%) subjects had an IHTG content ⩾ 11.0% suggestive of moderate to severe steatosis. After excluding 2 men with significant alcohol consumption, the population incidence of NAFLD at 3-5 years was 13.5% (95% CI 10.6-16.3%; 3.4% per year). Only 1 subject with incident NAFLD had high liver stiffness (11.1 kPa) suggestive of advanced fibrosis. Metabolic syndrome at baseline was the strongest predictor of incident fatty liver. Incident central obesity developed in 31.0% of subjects with incident fatty liver and 5.6% of those without (p<0.001). No subject with incident fatty liver had regression of impaired fasting glucose, which occurred in 51.1% of those without incident fatty liver (p=0.001). CONCLUSIONS: 13.5% of the Hong Kong Chinese adult population develop NAFLD in 3-5 years, but few have severe steatosis or advanced fibrosis. Metabolic syndrome is the most important risk factor of incident NAFLD.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Vigilância da População , Estudos Transversais , Feminino , Seguimentos , Hong Kong/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estudos Prospectivos
9.
Am J Gastroenterol ; 109(4): 589-97, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24492753

RESUMO

OBJECTIVES: Nonalcoholic fatty liver disease is the most common chronic liver disease. Fatty pancreas has also been described but is difficult to assess. It is now possible to measure pancreatic and liver fat accurately with magnetic resonance imaging (MRI). We aimed to define the normal range of pancreatic fat and identify factors associated with fatty pancreas. In addition, the effect of fatty liver and fatty pancreas on insulin resistance (IR) and pancreatic ß-cell function was studied. METHODS: Fat-water MRI and proton-magnetic resonance spectroscopy were performed on 685 healthy volunteers from the general population to measure pancreatic and liver fat, respectively. On the basis of fasting plasma glucose and insulin levels, the IR and ß-cell function were assessed using the homeostasis model assessment (HOMA). RESULTS: Among subjects without significant alcohol consumption or any component of metabolic syndrome, 90% had pancreatic fat between 1.8 and 10.4%. Using the upper limit of normal of 10.4%, 110 (16.1%; 95% confidence interval 13.3-18.8%) subjects had fatty pancreas. On multivariable analysis, high serum ferritin, central obesity, and hypertriglyceridemia were independent factors associated with fatty pancreas. Subjects with both fatty pancreas and fatty liver had higher HOMA-IR than did those with either condition alone. Fatty pancreas was not associated with HOMA-ß after adjusting for liver fat and body mass index. CONCLUSIONS: In all, 16.1% of this community cohort of adult Hong Kong Chinese volunteers had a fatty pancreas by our definition. Central obesity, hypertriglyceridemia, and hyperferritinemia are associated with fatty pancreas. Individuals with fatty pancreas have increased IR.


Assuntos
Fígado Gorduroso/complicações , Resistência à Insulina , Células Secretoras de Insulina/fisiologia , Gordura Intra-Abdominal/patologia , Imageamento por Ressonância Magnética/métodos , Pâncreas/patologia , Pancreatopatias/diagnóstico , Adulto , Idoso , Estudos de Coortes , Fígado Gorduroso/patologia , Feminino , Hong Kong/epidemiologia , Humanos , Gordura Intra-Abdominal/anatomia & histologia , Modelos Lineares , Modelos Logísticos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica , Pâncreas/anatomia & histologia , Pancreatopatias/epidemiologia , Pancreatopatias/etiologia , Pancreatopatias/fisiopatologia , Prevalência , Valores de Referência , Fatores de Risco
10.
J Hepatol ; 59(3): 536-42, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23623998

RESUMO

BACKGROUND & AIMS: Healthy lifestyle is the most important management of non-alcoholic fatty liver disease (NAFLD). This study aimed at assessing the efficacy of a community-based lifestyle modification programme in the remission of NAFLD. METHODS: This was a parallel group, superiority, randomized controlled trial. 154 adults with NAFLD identified during population screening were randomized to participate in a dietitian-led lifestyle modification programme at 2 community centres or receive usual care for 12 months. The primary outcome was remission of NAFLD at month 12 as evidenced by intrahepatic triglyceride content (IHTG) of less than 5% by proton-magnetic resonance spectroscopy. RESULTS: 74 patients in the intervention group and 71 patients in the control group completed all study assessments. In an intention-to-treat analysis of all 154 patients, 64% of the patients in the intervention group and 20% in the control group achieved remission of NAFLD (difference between groups 44%; 95% CI 30-58%; p<0.001). The mean (SD) changes in IHTG from baseline to month 12 were -6.7% (6.1%) in the intervention group and -2.1% (6.4%) in the control group (p<0.001). Body weight decreased by 5.6 (4.4) kg and 0.6 (2.5) kg in the two groups, respectively (p<0.001). While 97% of patients with weight loss of more than 10% had remission of NAFLD, 41% of those with weight loss of 3.0-4.9% could also achieve the primary outcome. CONCLUSIONS: The community-based lifestyle modification programme is effective in reducing and normalizing liver fat in NAFLD patients.


Assuntos
Fígado Gorduroso/terapia , Adulto , Centros Comunitários de Saúde , Terapia por Exercício , Fígado Gorduroso/dietoterapia , Fígado Gorduroso/metabolismo , Feminino , Humanos , Estilo de Vida , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Indução de Remissão/métodos , Método Simples-Cego , Triglicerídeos/metabolismo
11.
Gut ; 61(3): 409-15, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21846782

RESUMO

OBJECTIVE: Knowledge of the epidemiology of non-alcoholic fatty liver disease (NAFLD) is incomplete because liver biopsy cannot be performed on the general population to assess disease severity. New non-invasive tests allow accurate and safe assessment in healthy individuals. The aim of this study was to examine the prevalence of NAFLD and advanced fibrosis in the general Hong Kong Chinese population. METHODS: Subjects were recruited from the community by random selection from the government census database. Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. RESULTS: Overall, 264 of 922 (28.6%) subjects had intrahepatic triglyceride content ≥5%. Excluding 12 subjects with significant alcohol consumption, the population prevalence of NAFLD was 27.3% (95% CI 24.5% to 30.2%). Each component of the metabolic syndrome increased the risk of fatty liver in a dose-dependent manner (prevalence of 4.5% in subjects without any component and 80.0% in those with all five components). 8 (3.7%) patients with fatty liver had liver stiffness ≥9.6 kPa, a level suggestive of advanced fibrosis. Body mass index and alanine aminotransferase level were independent factors associated with liver stiffness. Together with other clinical prediction scores, the estimated prevalence of advanced fibrosis in patients with fatty liver in the community was <10%. Compared with non-drinkers, modest drinkers (<10 g per day) did not have higher risk of fatty liver after adjustment for demographic and metabolic factors. The liver stiffness was 4.7±1.9 kPa in modest drinkers and 4.6±1.7 kPa in non-drinkers (p=0.54). CONCLUSION: NAFLD is found in over a quarter of the general adult Chinese population, but the proportion of patients with advanced fibrosis is low. Modest alcohol consumption does not increase the risk of fatty liver or liver fibrosis.


Assuntos
Fígado Gorduroso/epidemiologia , Cirrose Hepática/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Antropometria , Estudos Transversais , Técnicas de Imagem por Elasticidade/métodos , Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico , Feminino , Hong Kong/epidemiologia , Humanos , Fígado/química , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Prevalência , Distribuição por Sexo , Triglicerídeos/análise , Adulto Jovem
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