ABSTRACT
Type 1 diabetes (T1D) is a multifactorial disease that has a strong genetic component. The HLA-G is a nonclassical HLA class I locus that is associated with immunomodulatory functions, including downregulation of innate and adaptive immune responses and induction of immune tolerance. However, there is currently limited information about the involvement of HLA-G in T1D susceptibility. This case-control study aims to investigate the T1D susceptibility association of alleles and genotypes of a widely investigated 14-bp insertion/deletion polymorphism in the HLA-G and to provide further evidence of the frequency distribution of class II HLA-DR-DQ-risk genotypes in T1D children and adolescents in the Brazilian population. The deletion allele and the homozygous deletion genotype are associated with susceptibility to T1D and the insertion allele and the heterozygous deletion/insertion genotype are associated with protection from T1D. We also confirm that genetic susceptibility to T1D is associated with the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04-DQA1*03:01-DQB1*03:02 haplotypes in Brazilian northeast region. The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D. Our results identify a novel association of the 14-bp deletion allele and the homozygous deletion genotype with T1D development and provide additional evidence of the importance of HLA class II heterozygous DR3-DQ2/DR4-DQ8 genotype in T1D susceptibility.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Genetic Predisposition to Disease , HLA-G Antigens/genetics , Adolescent , Brazil , Case-Control Studies , Child , Female , HLA-D Antigens/genetics , HLA-D Antigens/immunology , HLA-G Antigens/immunology , Haplotypes , Humans , Male , Polymorphism, GeneticABSTRACT
The dyslipidemia associated with excess weight is a risk profile global call for cardiovascular disease (CVD). The aim of this study was to investigate the association between dyslipidemias and other risk factors for cardiovascular diseases (CVD) in adolescents, considering sexual maturation. A cross-sectional study was carried out with 432 adolescents from public schools, aged 10-19 years. The correlations between the variables from the lipid profile and the Body Mass Index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), sexual maturation, familial history and maternal education were evaluated using Pearson's correlation coefficient. Low high-density lipoprotein cholesterol (HDL-C) was the most prevalent dyslipidemia (50.5%), regardless of gender. There were significant correlations between triglycerides and BMI (r = 0.30, p<0.01), WC (r = 0.32, p < 0.01) and WHtR (r = 0.33, p < 0.01). The linear model, which took into consideration sexual maturation, age and BMI, explain about 1 to 10.4% of the lipid profile variation. The low HDL-c was the most prevalent dyslipidemia in all adolescents and hypertriglyceridemia was most prevalent in overweight adolescents. Associations between dyslipidemias and anthropometric indicators (BMI and RCA) detected in this study can generate the hypothesis of the risk factors for CVD in adolescents.
Subject(s)
Dyslipidemias/blood , Dyslipidemias/epidemiology , Overweight/blood , Overweight/epidemiology , Adolescent , Anthropometry , Body Mass Index , Brazil/epidemiology , Cardiovascular Diseases/epidemiology , Child , Cross-Sectional Studies , Female , Humans , Lipids/blood , Male , Nutritional Status , Risk Factors , Sex Factors , Waist Circumference/physiology , Young AdultABSTRACT
The aim of this study was to assess erythrocyte and plasma copper concentrations and correlate them with the lipid profile of overweight and obese children and adolescents. The study was performed with 15 overweight and 30 obese children and adolescents, and the results were compared to the control group (21), aged 6-16 yr. Anthropometric assessment was carried out using body mass index (BMI). Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride serum levels were investigated. Erythrocyte and plasma copper levels were determined by atomic absorption spectrophotometry. Greater alterations in the lipid profile were observed in HDL-cholesterol, LDL-cholesterol, and triglyceride levels, with distinctions according to gender. The plasma copper concentrations in the overweight and obese male groups were significantly higher than those in the control group (p = 0.0006). Negative correlations between plasma copper and total cholesterol (r = -0.54) and LDL cholesterol (r = -0.59) were observed in the obese male group. There was no statistical difference in copper erythrocyte concentrations. The obesity associated to disorders in lipid metabolism predisposes to changes in copper plasma concentrations, but there was no alteration in intracellular reserves, which suggests an important homeostatic control to compensate for plasma oscillations and metabolic alterations of the disease.
Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , Copper/blood , Obesity/blood , Triglycerides/blood , Adolescent , Case-Control Studies , Child , Female , Humans , Male , OverweightABSTRACT
A high prevalence of menstrual cycle and fertility disturbances has long been associated with diabetes mellitus. However, rationalization of the intrinsic mechanisms of these alterations is controversial and even contradictory. This review considers (i) the relationship between diabetes mellitus, especially type 1 diabetes mellitus (T1DM), and the hypothalamus-pituitary-ovary (HPO) axis, (ii) the state of our knowledge concerning neuroendocrine control and its relationship with dopaminergic and opioid tonus, and (iii) the influence of the hypothalamus-pituitary-adrenal axis on ovarian function. Functional disturbances that occur as a consequence of diabetes are also discussed, but some T1DM-related diseases of autoimmune origin, such as oophoritis, are not further analysed. Although there are clear indications of a relationship between menstrual and fertility alterations and glycaemic control, in many instances the improvement of the latter is not sufficient to reverse such alterations. It appears that the oligoamenorrhoea and amenorrhoea associated with T1DM is mainly of hypothalamic origin (i.e. failure of the GnRH pulse generator) and may be reversible. The importance of the evaluation of the HPO axis in T1DM women with menstrual irregularities, even in the presence of adequate metabolic control, is emphasized.