Elena Carrasco

Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes mellitus in Chilean children

This study was designed to examine the hypothesis that some environmental factors increase the risk for insulin-dependent diabetes mellitus. Data on dietary history was collected from 80 diabetic children from the Santiago de Chile Registry and from 85 nondiabetic control subjects who were comparable in terms of age, sex, and ethnic characteristics. Early exposure was defined as the ingestion of food sources other than maternal milk before 3 months of age. To define genetic susceptibility to insulin-dependent diabetes mellitus each subject was typed in terms of HLA DQA1 and DQB1, and the possible conformation of susceptible heterodimers was considered as a risk marker. Fewer children were exclusively breast fed in the diabetic group than in the control group (21.55±15.05 vs. 33.95±20.40 weeks, P<0.01). In addition, exposure to cows milk and solid foods occurred earlier in the diabetic group than in the control group (15.90±10.95 vs. 21.15 13.65 and 16.85±10.25 vs. 21.20±12.35 weeks, P<0.05). Our data show that a short duration of breast-feeding and early exposure to cows milk and solid foods may be important factors in the development of insulin-dependent diabetes mellitus. The high relative risk observed in individuals genetically predisposed indicates an interaction effect between genetic and environmental components.

MicroRNAs miR-21a and miR-93 are down regulated in peripheral blood mononuclear cells (PBMCs) from patients with type 1 diabetes

INTRODUCTION It is well established that type 1 diabetes (T1D) is an autoimmune disease. Controversial data exists regarding the differential control of the immune system in T1D patients compared to unaffected individuals. MicroRNAs (miRNAs) are involved in the control of gene expression (by negative regulation of gene expression at post-transcriptional level, by mediating translational repression or degradation of the mRNA targets). Their potential role in T cell activation and autoimmunity is controversial. AIM We investigated the expression profile of miR-21a and miR-93 in PMC samples of 20 T1D patients and 20 healthy controls by means of qPCR in different glucose concentrations (basal, 11 nM and 25 mM), and we analyzed the possible relationship of this expression pattern with autoimmunity. RESULTS MiR-21a was significantly underexpressed in T1D samples (media values expression 0.23 ± 0.05, p < 0.01) compared to controls (values less than 1 indicate a decrease in gene expression). When the PMCs were incubated with glucose 11 mM and 25 mM, miR-21a expression decreased in controls and increased in T1D samples (0.506 ± 0.05, p < 0.04). MiR-93 was underexpressed in T1D patients (0.331 ± 0.05, p < 0.02) compared to control samples. However, when the PBMCs were incubated with glucose, no changes were observed. No association with autoimmunity was observed. CONCLUSION We demonstrated that miRNAs have a differential expression in PBMCs from T1D patients compared to controls, suggesting that these miRNAs or others could be involved in T cell regulation.

Low prevalence of type 2 diabetes despite a high average body mass index in the aymara natives from chile

The aim of this study was to estimate the prevalence of type 2 diabetes mellitus (DM2), impaired glucose tolerance (IGT), and the frequency of dyslipidemia, obesity, and hypertension in the rural Aymara population from Northern Chile. In this cross-sectional study, 196 Aymara adult subjects were characterized with respect to their reported physical activity, fasting plasma glucose levels, insulin concentrations, blood pressures, body mass indexes, and plasma lipid profiles. The participants also underwent a 2-h oral glucose tolerance test. The diagnostic criteria for DM2 and IGT followed those of the World Health Organization. The overall prevalence of DM2 was estimated as 1.5% (95% confidence interval: 0.3--4.5). Overall prevalence of IGT was calculated as 3.6% (1.5--7.3). The occurrence of obesity and dyslipidemia was relatively high in the Aymara population, although the frequency of sedentary habits, and the prevalence of hypertension were low. In conclusion, the prevalence of DM2 in the rural Aymara population living at high altitudes in Northern Chile, was much lower than that of other Amerindian groups that adopted lifestyles from industrialized Western societies. Despite a relatively high prevalence of a body mass index of at least 30 kg/m(2), especially in women (23.5%), high physical activity levels and low plasma-insulin concentrations may have been responsible in part for the low prevalence of DM2 in the Aymara population.

Prevalence of Type 2 Diabetes and Obesity in Rural Mapuche Population From Chile

The aim of this study was to estimate the prevalence of Type 2 diabetes, impaired glucose tolerance (IGT), and obesity in the Mapuche natives from rural areas in Chile. This cross-sectional study involved men (n = 95) and women (n = 224) older than 20 y from an aboriginal ethnic group (Mapuches), residing in rural communities from the south of Chile. Prevalence of Type 2 diabetes and IGT was calculated according to the World Health Organization criteria. Data on age, degree of ancestral purity, obesity, and hypertension were also obtained. The prevalence of Type 2 diabetes in rural Mapuche natives was estimated as 3.2% (95% CI: 0.7--9.0) in men and 4.5% (95% CI: 2.2--8.1) in women. The overall prevalence of obesity was 56.1% (95% CI: 50.5--61.6): 40.0% (95% CI: 30.1--40.8) in men and 62.9% (95% CI: 56.3--69.3) in women (P value < 0.001). These data suggest that the prevalence of obesity and Type 2 diabetes has been increasing during recent years in the Mapuche communities. The prevalence estimated in this study is higher than that reported 15 y ago. This suggests an important role of lifestyle changes as a possible explanation for epidemiologic transition.

Increasing incidence of type 1 diabetes in population from Santiago of Chile: trends in a period of 18 years (1986–2003)

The aim of this study is to determine the incidence rate of type 1 diabetes in the metropolitan region of Santiago, Chile from 1 January 1986 to 31 December 2003.

Leptin levels distribution and ethnic background in two populations from Chile: Caucasian and Mapuche groups.

OBJECTIVE: Leptin, the product of the human ob gene is increased in obese individuals, suggesting resistance to its effect. We examined the relationship of serum leptin levels with respect to obesity, gender and insulin levels in two populations with different ethnic compositions in Chile.METHODS: Leptin and insulin levels were determined by radioimmunoassay (RIA) and correlated with body mass index (BMI), gender and ethnic background. 79 Caucasian subjects from Santiago and 65 Mapuche natives from the Araucania region, Chile, were included in this study.RESULTS: Leptin concentrations in obese subjects were significantly increased in both ethnic groups in relation to lean status: Caucasian and Mapuche obese 19.3±11.6 and 10.1±5.8 (P<0.001), respectively vs Caucasian and Mapuche lean 10.4±5.8 and 4.7±2.9 (P<0.001, respectively). When we compared Mapuche and Caucasian groups, similar leptin levels were observed among the males of the two populations in both metabolic states (lean and obese). In contrast, the leptin level distributions between women showed a marked difference, having a minor value in the Mapuche women with a comparable value with the male group in this ethnic population.CONCLUSIONS: The leptin concentrations are associated with obesity in both ethnic groups in Chile. However, the leptin levels between the Mapuche natives were significantly decreased compared to the Caucasian group. The gender distribution does not seem to be important in the Mapuche natives. The ethnic composition seems to be important in the leptin distribution in the analysed populations.

Vitamin D receptor polymorphism and susceptibility to type 1 diabetes in chilean subjects: A case-parent study

Several reports have found a relation between polymorphisms of the vitamin D receptor gene (VDR) and the development of type 1 diabetes. We have examined the association of three VDR polymorphism with type 1 diabetes in 59 Chilean case-parents trios. Genotyping for Bsm1, Apa1 and Taq1 polymorphism were performed. Transmission/disequiibrium tests were used to assess gene-disease associations through the evaluation of allelic transmission to affected offspring. Non-significant increased transmissions of B allele (probability of transmission=52.5, p=0.69), A allele (probability of transmission=58.4, p=0.17) and T allele (probability of transmission=52.0, p=0.77) were estimated in Bsm1, Apa1 and Taq1 sites, respectively. Haplotype-based analyses showed non-significant preferential transmissions (global p=0.52). The present study does not support the hypothesis of a significant contribution of VDR alleles in the etiology of type 1 diabetes of Chilean cases.

One of the lowest validated incidence rates of insulin dependent diabetes mellitus in the Americas: Santiago, Chile

The goal of this study was to estimate the average annual incidence rate of insulin-dependent diabetes mellitus (IDDM) in Santiago as part of a Multinational Project in Childhood Diabetes (Diabetes Mondiale or DiaMond). Incidence was calculated among subjects under 15 years of age, through a retrospective search and confirmation method from 1 January 1986 to 31 December 1992. Hospitals and private offices of endocrinologists and specialists in diabetes were surveyed. A total of 252 registered cases, 118 boys and 134 girls, for an annual incidences of 2.36/100,000 hab.year. which is one of the lowest validated rates in the Americas.

Lack of association between the fatty acid binding protein 2 (FABP2) polymorphism with obesity and insulin resistance in two aboriginal populations from Chile

The aim of this study was to assess the frequency of fatty acid binding protein 2 (FABP2) Ala54Thr genetic polymorphism and to evaluate its association with obesity and insulin resistance in Chilean aboriginal populations. A sample of 96 urban Aymara and 111 urban Mapuche subjects aged 20–80 years were recruited for this cross-sectional study. Glucose, insulin and lipid profile were measured in fasting plasma samples. Insulin resistance was estimated through the HOMA-IR model. FABP2 Ala54Thr genotypes were determined by PCR followed by RFLP analysis. The allele frequency of Thr54 variant was estimated as 18.2% in Aymara subjects, which is one of the lowest reported to date. The corresponding frequency in Mapuche subjects was 31.9% (p<0.002). Regarding genotype–phenotype associations, no significant differences were found in any of the anthropometric or metabolic variables according to Ala54Thr genotypes. After adjustment by BMI and metabolic variables through a logistic regression analysis, the association of the FABP2 polymorphism with ethnic group persisted (Mapuche group: OR=2.37, 95% CI 1.319–4.277, p=0.004) It is unlikely that Ala54Thr polymorphism of the FABP2 gene plays a relevant role in obesity and insulin resistance in Chilean ethnic groups.

Duration of breast feeding and bovine serum albumin antibody levels in type 1 diabetes: a case-control study

To compare the levels of bovine serum albumin (BSA) antibodies and their relationship with duration of breast feeding, age of exposure to cows milk, and human leukocyte antigen (HLA‐DQ) genotype in children with and without type 1 diabetes.