[Relationship between leptin and body mass and metabolic syndrome in an adult population]. / Relação entre a leptina, a massa corporal e a síndrome metabólica numa amostra da população adulta.

OBJECTIVE: To analyze the relationship between leptin and obesity expressed as body mass index (BMI) and certain components of the metabolic syndrome (MS) in an adult population. METHODS: The study included 103 subjects, 42 men and 61 women, aged over 30 years, clinically defined as non-diabetic but with personal or family history of cardiovascular disease. All subjects underwent fasting blood measurements of leptin, insulin, glucose, glucose after ingestion of 75g glucose, HDL cholesterol and triglycerides, and insulin resistance (IR) and BMI were calculated. RESULTS: BMI as an index of overall adiposity was strongly associated with serum leptin. BMI rose as serum leptin levels increased from the first to the third tertile; the correlation between leptin and BMI was strong, r=0.524 in men and r=0.603 in women, with high statistical significance (p<0.001); BMI was the best predictor of hyperleptinemia on ROC analysis, with area under the curve (AUC)=0.81 in men and 0.84 in women. The association between leptin and obesity (BMI ≥30kg/m(2)) showed high odds ratios (OR) in both sexes (10.11 in men, 6.00 in women) on univariate regression analysis and 9.30 in men and 8.21 in women on multivariate regression analysis. Hyperinsulinemia and IR strongly influenced hyperleptinemia. Leptin was the best predictor of IR in both sexes (AUC=0.89 in men and 0.85 in women), and IR in men (AUC=0.79) and hyperinsulinemia in women (AUC=0.78) were the best predictors of hyperleptinemia after BMI. The correlations between leptin and IR, and leptin and insulinemia, were strong in both sexes. With regard to MS components, increased serum levels of the study variables were observed as leptin concentrations rose from the first to the third tertile (with the exception of HDL cholesterol, which decreased). CONCLUSION: Elevated serum leptin, particularly in obese individuals, should be taken as a warning sign of energy imbalance, poor diet, hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are strongly associated with cardiovascular disease and type 2 diabetes.

[Association of gamma glutamyltransferase, metabolic syndrome and cardiovascular risk]. / Associação da gama glutamil transferase com a síndrome metabólica e o risco cardiovascular.

Serum gamma-glutamyl transferase (GGT) has been used as a marker of alcohol induced liver disease. Recent epidemiology and pathology studies have suggested its independent role in the pathogenesis and clinical evolution of cardiovascular diseases (CVD) promoting atherosclerosis through an oxidative process leading, within the atherosclerotic plaque, to LDL oxidation, metalloproteinase activation, cell proliferation and apoptosis. Besides it is known that GGT levels rise even in the normal range, with obesity and hepatic steatosis occurs, it is thought, which originates insulin resistance (IR). Being sure that IR is important in the development of type 2 diabetes and CVD, both very prevalent in Portugal, the authors considered as relevant to study the association of GGT with markers of multiple metabolic derangements: insulin-resistance (hyperinsulinemia, hyperglicemia, IR-HOMA = 3), obesity and dyslipidemia. So, a Portuguese sample population, consisted of 123 subjects (52 male and 71 female) was organized. As results were observed: elevation of GGT serum levels with the increasing risk of every marker and the same happened with metabolic syndrome and its components; compared with non obese the group of obese subjects exhibited elevated prevalence of risk factors, though in non obese subjects the percentages of insulin-resistance and dyslipidemias were high (hypercholesterolemia in both sexes, hypertriglyceridemia and low concentrations of HDL-c in men); association of serum GGT levels with every risk factor and metabolic syndrome. Though, as the association with the insulin-resistance state was particularly strong, it is thought that a high prevalence of non-alcoholic fatty liver disease (NAFLD) was present in the studied population. As serum determination of GGT activity is a low-cost, highly sensitive, accurate and frequently used laboratory test and there is association of this enzyme with the most important risk factors of diabetes type 2 and CVD, its serum levels should be considered as a marker of insulin-resistance when NAFLD is supposed to be present or there is obesity.

[Influence of the APOE genotypes in some atherosclerotic risk factors]. / Influência dos polimorfismos da APOE em alguns factores de risco de aterosclerose.

The aim of this work was to study the distribution of apolipoprotein E (APOE) genotypes and their association with some atherosclerotic risk factors, all of them modifiable: total, HDL and LDL cholesterol, triglycerides, systolic and diastolic blood pressure, BMI, waist circumference and smoking. The sample population was constituted of 672 healthy subjects recruited in the Lisbon area. Lipids were quantified by usual automatic enzymatic methods and the APOE genotypes performed in accordance with Hixson and Vernier. Blood pressure measurement and hypertension classification followed international specifications. The frequency distribution of APOE alleles was: epsilon2 = 6.4%, epsilon3 = 83.6% and epsilon4 = 10.0% and the more prevalent genotypes were epsilon2/epsilon3, epsilon3/epsilon3 and epsilon3/epsilon4 respectively 11.0%, 70.1% and 16.1%. We could only observe associations among the most prevalent genotypes and lipids, always statistically significant, specially when the epsilon4 allele was present which was even proved by an higher prevalence of epsilon4 in dyslipidemic subjects with the only exception of those with low HDL-c values. A stronger intervention in the epsilon4 carriers is so recommended through appropriate intervention measures on the connected modifiable risk factors.

APOE genotypes and dyslipidemias in a sample of the Portuguese population.

The objective of this work was to study the distribution of apolipoprotein E (APOE) genotypes in a sample of the Portuguese population, and its association with the dyslipidemias observed. Study participants were healthy users of local Public Health Laboratories in six regions of mainland Portugal (Porto, Vila Real, Viseu, Lisboa, Portalegre and Faro). A total of 779 men and 1153 women aged 15-74 years agreed to participate. Fasting lipid levels and APOE genotypes were determined centrally at the National Institute of Health in Lisboa. The frequency distribution of APOE alleles was: epsilon2=5.3%, epsilon3=84.9% and epsilon4=9.8%. Dyslipidemias were present in 66.6% of men and 60.7% of women. Comparison of APOE genotypes and relative allele frequencies showed that in dyslipidemic compared to normolipidemic subjects, the epsilon4 allele was more frequent in both sexes, although in a more pronounced way in men than in women due to higher frequencies of epsilon3/epsilon4 and epsilon4/epsilon4 genotypes. The known association of the epsilon4 allele with high cholesterol levels, the association of the epsilon2 allele with low cholesterol levels, and the association of the epsilon2 allele with high levels of triglycerides and low levels of high-density lipoprotein-cholesterol were confirmed in this study.

The role of HFE mutations on iron metabolism in beta-thalassemia carriers.

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and progressive storage resulting in organ damage. HFE gene mutations C282Y and H63D are responsible for the majority of HH cases. A third HFE mutation, S65C, has been associated with the development of a mild form of hemochromatosis. The beta-thalassemia trait is characterized by mild, ineffective erythropoiesis that can induce excess iron absorption and ultimately lead to iron overload. The aim of this study was to evaluate the effect of genetic markers (HFE mutations C282Y, H63D, and S65C) on the iron status of beta-thalassemia carriers. A total of 101 individuals heterozygous for beta-thalassemia and 101 normal control individuals were studied. The allelic frequencies of C282Y (1.5 versus 3.5%), H63D (15.3 versus 18.3%), and S65C (1.0 versus 1.5%) did not differ significantly between beta-thalassemia carriers and normal controls. Serum iron (P=0.029) and transferrin saturation (P=0.009) were increased in beta-thalassemia carriers heterozygous for H63D mutation. The number of subjects carrying C282Y or S65C mutations was too low to conclude their effect on the iron status. These results suggest that the beta-thalassemia trait tends to be aggravated with the coinheritance of H63D mutation, even when present in heterozygosity.