Francisco Pérez B

Prevalencia de diabetes tipo 2 y obesidad en dos poblaciones aborígenes de Chile en ambiente urbano

Background: The prevalence of cardiovascular risk factors is increasing in aboriginal populations in Chile. Aim: To study the prevalence of obesity, type 2 diabetes and serum lipids in two aboriginal populations, Mapuche and Aymara, that were transferred from a rural to a urban environment. Subjects and Methods: Two groups of subjects over 20 years were analyzed, Mapuche and Aymara. The Mapuche group was formed by 42 men and 105 women, living in four urban communities of Santiago, and an Aymara group formed by 42 men and 118 women, living in Arica, in Northern Chile. Anthropometric measurements, blood pressure, lipid profile, oral glucose tolerance test, fasting insulin and serum leptin were determined. Results: The prevalence of type 2 diabetes was 6.9% in Aymara and 8.2% in Mapuche subjects. The frequency of glucose intolerance was similar in both groups, but greater among men. A total blood cholesterol over 200 mg/dl was observed in 43.1% of Aymara and 27.9% of Mapuche subjects (p <0.008). Serum triglycerides over 150 mg/dl were observed in 16.9 and 23.1% of Aymara and Mapuche individuals, respectively (p= NS). Conclusions: The prevalence of type 2 diabetes and dyslipidemia in urban aboriginal populations is higher than that of their rural counterparts. A possible explanation for these results are changes in lifestyles that come along with urbanization, characterized by a high consumption of saturated fat and refined sugars and a low level of physical activity (Rev Med Chile 2004; 132: 1189-97). (Key Words: Diabetes Mellitus, type II; Hypercholesterolemia; Hyperlipidemia; Indians, South American)

Prevalencia familiar de patologías metabólicas en pacientes con síndrome de ovario poliquístico

Background: About 60% of patients with polycystic ovary syndrome (PCOS) have insulin resistance, predisposing them to the premature coronary disease and type 2 -diabetes mellitus. However, the history of metabolic disorders in family members of patients with PCOS has been seldom documented in the literature. Aim: To evaluate the family profile of metabolic disorders of PCOS patients and to determine their relative risk of developing one of them in comparison to a control group. Patients and Methods: Sixty PCOS patients were evaluated. The control group were 60 normal women. The data were obtained from the clinical history and personal interview with the patients, the controls and their relatives (brothers, parents and grandparents). The metabolic disorders considered were: dyslipidemia, obesity, hypertension and diabetes. Results: The ages were similar between groups (PCOS: 24.0 ± 6.3; control group: 24.8 ± 6.2 years). The prevalence of metabolic disorders was 62% in the relatives of the PCOS patients and 27.8% in the relatives of the control group (p <0.005). The probability to develop a metabolic disorder within the family was 2.7 (2.2-3.3) fold higher in the PCOS group compared to the control group. The risk of developing hypertension, dyslipidemia, obesity and diabetes was 2.1 (1.5-2.9); 1.8 (1.5-2.7); 3.6 (2.6-4.9) and 2.7 (1.8-3.9), respectively, in the PCOS group compared to the control group. Conclusions: The probability of finding a metabolic disorder in the families of PCOS patients, is 2.7 fold higher than in the control group families. The metabolic disorders are more frequent in parents and grandparents of the PCOS patients than in those of normal women (Rev Med Chile 2001; 129: 707-12)

Prevalencia de obesidad , hipertensión arterial y dislipidemia en grupos aborígenes rurales de Chile

Background: Chilean aboriginal ethnic groups (mapuche and aymaras) have a very low prevalence rate of type 2 diabetes. The investigation of a possible relationship between this low prevalence of diabetes and obesity, hypertension and serum lipid profiles in both groups is worthwhile. Aim: To study the prevalence of obesity, hypertension and lipid profile in two Chilean aboriginal communities. Subjects and Methods: The prevalence of obesity, hypertension, fasting serum total cholesterol, HDL cholesterol, triglycerides, glucose, insulin, leptin and oral glucose tolerance test were measured in 345 mapuche (106 male) and 247 aymara (100 male) individuals. Results: Sixty three percent of mapuche women, 37.9% of mapuche men, 39.7% of the aymara women and 27.0% of aymara men had a body mass index over 27 kg/m2. Twenty percent of mapuche men, 18.0% of mapuche women, 9.0% of aymara men and 4.8% of the aymara women had high blood pressure values. Serum HDL cholesterol was below 35 mg/dl in 16% of mapuche women, 14% of mapuche men, 25% of the aymara women and 27% of aymara men. No differences in total cholesterol levels were observed between mapuches and aymaras. Conclusion: Mapuche women have higher prevalence of obesity and high blood pressure than aymara women. Low serum HDL cholesterol has a higher prevalence among aymara individuals.

Niveles plasmáticos de citoquinas IL-1ß, IL2 e IL-4 en niños diabéticos tipo 1 de diagnóstico reciente y su asociación con anticuerpos ß pancreáticos

9.1 pg/ml respectively, p=0,01). No differences in serum IL-4 were observed between diabetics and con-trol. Diabetic children with one or two positive autoantibodies (IA-2 and/or GAD65) had significantly higherlevels of IL-1s and IL-2 and lower levels of IL-4 than diabetic children without positive autoantibodies. Highconcentrations of IL-1s were associated with an early onset of the disease.

Polimorfismos del gen del receptor de muerte celular programada 1 (PDCD1) y diabetes tipo 1 en población Chilena

BACKGROUND Programmed cell death 1 (PDCD-1) immune-receptor is a key element in the negative regulation of peripheral tolerance in T cells. Several polymorphisms of this gene have been described and it is linked with susceptibility to autoimmune diseases like Lupus and Multiple Sclerosis. AIM To analyze four gene polymorphisms of PDCD-1 gene and explore its possible contribution as a susceptibility gene for type 1 diabetes (T1D). PATIENTS AND METHODS We analyzed 160 cases with T1D of recent diagnosis aged 9.5 +/- 3.3 years and 160 control children aged 10.7 +/- 3.1 years. Four genetic variants of PDCD-1 gene were studied (PD1.2; PD1.5; PD1.6 and PD1.9) by polymerase chain reaction and restriction enzymes. Autoantibodies GAD65 and anti-IA-2 were also measured in all studied children. The comparison of allelic and genotypic frequency and consistency with respect to Hardy-Weinberg equilibrium test were analyzed using Chi-square and Fisher exact test. RESULTS No differences between cases and controls were observed for PDCD1.2; PDCD1.5 and PDCD1.9 polymorphisms. PDCD1.6 polymorphism (carriers of allele A) had a higher frequency in the control group (0.794 versus 0.644, p < 0.017). There was no particular association of these polymorphisms with anti- GAD65 and anti-IA-2 antibodies among patients with T1D. CONCLUSIONS Only PDCD1.6 polymorphism showed differences between T1D cases and controls. Possibly, none of these genetic variants of PDCD1 has a relevant role as a marker for T1D in the Chilean population.

Incidencia de diabetes mellitus tipo 1 en Santiago de Chile: análisis por comunas de la Región Metropolitana en el período 2000-2004

BACKGROUND There are great geographical differences in the incidence of type I diabetes mellitus. AIM To determine the incidence rate of type 1 diabetes mellitus (DM1) in the Metropolitan Region of Santiago, Chile from January 1, 2000 to December 31, 2004 and to observe the distribution of cases in the different counties of Santiago. MATERIAL AND METHODS All the cases diagnosed with DM1 in the Metropolitan Region who fulfilled the following requirements were included in the study: age of onset <15 years, insulin treatment from onset, permanent residency in the area, and a diagnosis made between January, 2000 and December, 2004. RESULTS The incidence of DM1 was 6.58/100,000 inhabitants/year, and showed a significant increase from 2001 to 2004 (5.44 and 8.33 inhabitants/year, respectively, p <0.04). The incidence of DM1 also increased significantly in children younger than 4 years old. The incidence by counties exhibited large differences, ranging from 1.5 to 26.6/100,000 inhabitants. Counties with higher income, urbanization and low aborigine component showed a high incidence rate of type 1 diabetes. CONCLUSIONS In the Metropolitan Region of Santiago, an increase of the incidence of DM1 has occurred in the period 2000-2004, especially in children younger than 4 years old. Large differences among counties were observed.

Frecuencia del polimorfismo C677T de la 5, 10-metilentetrahidrofolato reductasa (MTHFR) en mujeres chilenas madres de afectados con espina bífida y en controles normales

Background: Several population studies have shown that patients with neural tube defects (NTD), have a higher frequency of a genetic mutation related with thermolability of the enzyme 5,10-metylentetrahydrofolate reductase (MTHFR). There are regional and ethnic variations in the genotypic or allelic frequency of this mutation and its possible relationship with NTD and others congenital anomalies. Aim: To estimate the frequency of the C677T polymorphism of MTHFR in control women and mothers of spina bifida cases. Patients and Methods: We analyzed 58 blood samples from mothers who had a child diagnosed with spina bifida. A group of 184 healthy mothers matched by age and with no NTD offspring served as controls. We determined the C677T polymorphism on the MTHFR gene by means of PCR and the analysis of the digestion pattern of HinfI restriction enzyme. Results: The genotypic frequencies showed concordance with Hardy-Weinberg equilibrium, in controls (p=0.35), and in mothers of the cases (p=0.95). The odds ratio to the TT genotype compared with the CC genotype (reference category) was estimated as 1.54 (IC 95%: 0,66-3,61), while the odds ratio for the TC genotype compared with CC genotype was 1.06 (IC 95%: 0,48-2,33). Conclusion: No differences in the C677T polymorphism of the MTHFR were observed between mothers who had a child diagnosed with spina bifida and control mothers (Rev Med Chile 2003; 131: 1399-404).

Polimorfismo de la proteína ligante de ácidos grasos intestinal (FABP2), obesidad e insulina resistencia

The genetic components of insulin-resistance, diabetes and obesity have been largely studied. These conditions are determined by multiple polygenic and environmental factors. Certain candidate genes, that have common functional variants in the general population, may be important determinants of inter-individual differences in the response to dietary changes. This review focuses in one of the major candidate genes, the gene encoding for the FABP2, an intracellular protein expressed only in the intestine, involved in the absorption and intracellular transport of dietary long chain fatty acids. Carriers of the Thr54 allele in FABP2 have a 2-fold greater affinity for long chain fatty acids than Ala54 carriers. The increased flux of dietary fatty acids (FA) into the circulation, among carriers of FABP2 Ala54Thr, supports a role of the polymorphism of this allele in the etiology of metabolic disorders. The frequencies of the polymorphism in different populations fluctuate between 18% and 40%. FABP2 Ala54Thr variant has been associated with an increased fasting insulin concentration, fasting fatty acid oxidation and reduced glucose uptake. This evidence, although not conclusive, sustains an association between FABP-2 genotype and metabolic abnormalities.

Epidemiología genética de la obesidad: estudios familiares

This review focuses on methodological aspects and main results of different family studies that have been conducted to assess the existence of a genetic contribution in human obesity. A genetic component in the etiology of obesity has been elucidated through specific study designs answering different research questions such as: a) Do obesity aggregate in families? b) Is there a genetic contribution to familial clustering? c) Is it possible to localize chromosomal regions that contain susceptibility genes to obesity? d) Is it possible to estimate the risk for developing obesity depending on the genotype profile in candidate genes? There are sufficient evidences indicating the existence of a moderate familial clustering of obesity defined as body mass index ≥30 with a stronger aggregation with more extreme values of body mass index. Twin studies have demonstrated that the familial aggregation of obesity has a genetic component and is not only due to cultural or environmental factors clustered in families. Linkage studies have identified markers and genes related to obesity in virtually all human chromosomes. However, some of these linkage studies have produced conflicting results. Discordant results are even more pronounced in case-control studies that evaluate the association between alleles at candidate genes and obesity. Topics related to study design will acquire increasing importance in order to avoid methodological problems related to trait definition, sample sizes, population stratification by ethnicity and other confounding factors (Rev Med Chile 2005; 133: 349-61). (Key Words: Alleles; Body weight; Ethnicity; Genes; Obesity)

Estudio temporal de diabetes mellitus tipo 1 en Chile: asociación con factores ambientales durante el período 2000-2007

BACKGROUND Pollution and viral infections could be associated with the incidence of type 1 diabetes mellitus. AIM To look for associations between the temporal patterns of Type 1 Diabetes Mellitus (T1D) in infants younger than the age of 15 years, and environmental factors, such as air pollution and viruses. MATERIAL AND METHODS Data registries from hospitals, emergency services, and the Infantile Diabetes Foundation were reviewed, corresponding to children aged less than 15 years, who received their first insulin injection between 2000 and 2007. The incidence of type 1 diabetes was computed for each epidemiological week. Environmental ozone and particulate matter rates for each week were obtained from Environmental services. Rates of influenza and respiratory syncytial virus infections were obtained from the epidemiological department of the Ministry of Health. An ecological Bayesian Poisson regression model was fitted, introducing the covariates, lagged covariates and errors, to estimate the incidence by epidemiological week. RESULTS Three factors were significant by the proposed model: particulate matter PPM 2.5 (relative risk (RR): 1.003) lagged by two weeks, influenza (RR: 0.1808) and RSV (RR: 1.021). Trends and seasonality were clearly controlled by these covariates, considering the epidemiological week as a counting period. CONCLUSIONS These results show that environmental factors could be related to peaks of type 1 diabetes incidence.Background: Pollution and viral infections could be associated with the incidence of type 1 diabetes mellitus. Aim: To look for associations between the temporal patterns of Type 1 Diabetes Mellitus (T1D) in infants younger than the age of 15years, and environmental factors, such as air pollution and viruses. Material and Methods: Data registries from hospitals, emergency services, and the Infantile Diabetes Foundation were reviewed, corresponding to children aged less than 15years, who received their first insulin injection between 2000 and 2007. The incidence of type 1 diabetes was computed for each epidemiological week. Environmental ozone and particulate matter rates for each week were obtained from Environmental services. Rates of influenza and respiratory syncytial virus infections were obtained from the epidemiological department of the Ministry of Health. An ecological Bayesian Poisson regression model was fitted, introducing the covariates, lagged covariates and errors, to estimate the incidence by epidemiological week. Results: Three factors were significant by the proposed model: particulate matter PPM 2.5 (relative risk (RR): 1.003) lagged by two weeks, influenza (RR: 0.1808) and RSV (RR: 1.021). Trends and seasonality were clearly controlled by these covariates, considering the epidemiological week as a counting period. Conclusions: These results show that environmental factors could be related to peaks of type 1 diabetes incidence.