Transmission of high-risk HLA-DQB1 alleles in Chilean type 1 diabetic patients and their parents: stratification by the presence of ICA or GAD65 autoantibodies.

AIM: The purpose of this study was to assess whether the transmission of DQB1*0201 and DQB1*0302 alleles from heterozygous parents to Chilean type 1 diabetic patients depends on the presence of antibodies such as glutamic acid decarboxilase (GAD65) or Islet Cell (ICA) autoantibodies in the affected case. MATERIAL AND METHODS: A study of incident type 1 diabetic cases and parents was carried out in Santiago, Chile during 1997-98. The use of the case-parental design eliminates the possibility that case-controls differences are due to selection of controls whose genetic backgrounds differ systematically from those of cases. HLA-DQB1 polymorphisms were determined in cases and parents from n = 83 families using polymerase chain reaction and oligonucleotide dot-blot analysis. Detection of GAD65 antibodies was performed using a simple radio-binding asssay. Conventional ICA were detected by indirect immunofluorescence. RESULTS: Transmission disequilibrium test indicate a strong association between DQB1*0201 and DQB1*0302 and type I diabetes. When comparing the two subsets of families defined by having an affected child tested negative or positive for GAD65 antibodies (39 and 44 case-parent trios respectively) the probability of transmission of DQB1*0201 significantly differed between such strata (p-value=0.025). The pattern of transmission of DQB1*201 allele was also significantly different in the two subsets of families defined by ICA-or ICA+ cases (23 and 60 trios respectively) (p-value = 0.028). No differences were found in the transmission of DQB1*0302 allele in the different strata defined by the autoimmunity status of the proband. CONCLUSION: Our results reveal that DQB1*0201 allele may display distinct associations with type I diabetes depending on the autoimmunity to ICA and GAD65 autoantibodies.

[Prevalence of metabolic disorders among family members of patients with polycystic ovary syndrome]. / 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.

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.

Association between HLA-DQB1 alleles and type 1 diabetes in a case-parents study conducted in Santiago, Chile.

The human leukocyte antigen (HLA) system plays a crucial role in the autoimmune process leading to childhood diabetes. The purpose of this study was to evaluate the association between type 1 diabetes and the polymorphism encoded by the HLA-DQB1 gene by using case-parents trios. The study area was the metropolitan region of Santiago, Chile, and cases were ascertained from March 1997 to August 1998. Genotyping was performed in 94 trios comprising incident cases less than 17 years of age at the time of diagnosis and their parents. The transmission/disequilibrium test was used to detect differential transmission in the HLA-DQB1 locus. The authors found that alleles DQB1(*)0302 and DQB1(*)0201 were strongly associated with the disease. By using 1:3 matched sets of cases-pseudosibs and conditional logistic regression models, allelic relative risks were estimated for DQB1(*)0302 (r = 7.2, 95% confidence interval: 2.8, 18.5) and DQB1(*)0201 (r = 4.7, 95% confidence interval: 1.9, 11.6); DQB1(*)0301 was considered the baseline allele. When case-parents trios were used, alleles DQB1(*)0302 and DQB1(*)0201 were strongly associated with a higher risk of type 1 diabetes in the population of SANTIAGO:

[Obesity and leptin association in three Chilean aboriginal populations]. / Asociación obesidad y leptina en tres poblaciones aborígenes de Chile.

BACKGROUND: Although there is a clear relationship between body mass index and leptin levels, few authors have addressed the possible influence of ethnic factors on these levels. AIM: To measure serum leptin in three different Chilean aboriginal populations. SUBJECTS AND METHODS: Fasting serum leptin and insulin levels were measured by radioimmunoassay in 345 rural mapuche individuals, 247 rural aymara subjects and 162 urban mapuche subjects. A body mass index of 27.5 kg/m2 was used as cutoff point to classify study subjects. RESULTS: Among the three ethnic groups, women had serum leptin levels three times higher than men. In all three ethnic groups, there was a significant association between leptin levels, body mass index and gender (r2 = 0.32 and 0.5 p < 0.001, in rural mapuche, r2 = 0.32 and 0.5 p < 0.001, in aymara and r2 = 0.24 and 0.49, p < 0.001 in urban mapuche populations). No differences in leptin levels were observed for the interaction between age and insulin. The increments per quartile in leptin levels were lower among mapuche than aymara individuals. CONCLUSIONS: Rural mapuche individuals have a high frequency of obesity. However their leptin levels are lower than those of aymara or urban mapuche populations. The higher leptin levels observed in urban mapuche subjects could be due to environmental influences.

Plasma leptin and insulin levels in Aymara natives from Chile.

The purpose of this study was to examine the relationship of plasma leptin levels with respect to obesity, gender, age and insulin levels in the native Aymara population. The Aymara natives live at high altitudes in isolated regions in the north of Chile, and they maintain distinctive genetic and cultural characteristics. Plasma leptin and insulin levels were correlated with body mass index (BMI), sex and age in a sample of 147 adult Aymara subjects who participated in a cross-sectional study. Multivariate analysis showed significant differences in leptin levels (dependent variable: natural log of leptin) by gender (p < 0.0001), and by BMI (p < 0.001), without significant statistical interaction between gender and BMI. The effect of age achieved statistical significance in the multivariate analysis (p = 0.02). Gender, BMI and insulin are independently associated with plasma leptin levels. On the other hand, the multivariate analysis of the plasma insulin concentration (dependent variable: natural log of insulin levels) shows that insulin is strongly associated with BMI (p < 0.0001), although non-statistically significant differences of insulin levels by sex (p = 0.07) or age (p = 0.9) were detected at alpha 0.05 level. Thus, in the special ecosystem where the Aymara population live, a strong and independent association between sex, obesity and insulin levels with plasma leptin levels has been detected.

Associations between HLA-DQB1 high-risk alleles and type I diabetes do not depend on cytomegalovirus antibody status at onset: a case-parent study conducted in Chile.

The purpose of the present study is to ascertain whether the associations between HLA-DQB1*0201 and DQB1*0302 alleles and childhood diabetes depend on the presence of antibodies to human cytomegalovirus (CMV). A study of incident type I diabetes cases and parents was conducted in Santiago, Chile. HLA-DQB1 polymorphisms were determined in 85 case-parent trios (255 subjects), while the detection of CMV was carried out only in the incident cases. As expected, HLA-DQB1 polymorphisms are strongly associated with type I diabetes, with crude odds ratios of 3.7 (95% confidence interval (CI) 1.8-7.7) for the DQB1*0201 allele and 10.3 (95% CI 5.0-21.4) for the DQB1*0302 allele. In the subset of families with CMV+ cases, the odds ratios were estimated as 3.7 (95% CI 1.6-8.6) for the DQB1*0201 allele and 11.1 (95% CI 4.8-25.8) for the DQB1*0302 allele. In families with patients who tested negative for CMV antibodies, the odds ratios were calculated as 3.5 (95% CI 0.7-16.8) for the DQB1*0201 allele, and 8.0 (95% CI 1.8-34.7) for the DQB1*0302 allele. There was no evidence of statistical interaction between CMV antibodies and the DQB1*0201 allele (P value = 0.9) or the DQB1*0302 allele (P value = 0.7). In conclusion, alleles DQB1*0302 and DQB1*0201 do not display distinct associations with type I diabetes depending on the presence of antibodies for CMV.

[Relationship between leptin and insulin sensitivity in patients with polycystic ovary syndrome]. / Relación entre leptina y sensibilidad a la insulina en mujeres con síndrome de ovario poliquístico.

BACKGROUND: The relationship between leptin and insulin sensitivity, sexual steroids and insulin concentrations in women with polycystic ovary syndrome is still controversial. The objective of this study was to assess the relationship between insulin levels, insulin resistance parameters and serum leptin concentrations in healthy and polycystic ovary syndrome women. PATIENTS AND METHODS: 33 hyperandrogenic polycystic ovary syndrome women (GHA) and 27 healthy women (GS) were included in this study. Leptin, insulin, sex-hormone binding globulin (SHBG), testosterone and estradiol concentrations were determined in a basal sample. Body mass index, waist diameter and waist to hip ratio were recorded. Insulin sensitivity was calculated by means of insulin tolerance test and glycemia/insulinemia ratio. RESULTS: The leptin concentration was not different between GHA and GS. Insulin levels and free testosterona index (FTI) were higher in GHA than GS (p < 0.01). The glycemia/insulinemia ratio, SHBG levels, and insulin sensitivity were lower in GHA (p < 0.01). In both groups positive correlations between leptin concentration and body mass index (p < 0.01), waist diameter (p < 0.01), insulin levels (p < 0.01) and glycemia/insulinemia ratio (p < 0.01) were observed. Only GHA showed correlation between insulin sensitivity and leptin concentration (p < 0.02). SHBG and leptin levels were not correlated. CONCLUSIONS: The leptin concentration was not different between GHA and healthy women, although they are metabolically different. This phenomenon could be due to the fact that in hyperandrogenic women the effects of insulin resistance and hyperandrogenemia counteract each other.

Applicability of the case-parent design in the etiological research of Type 1 diabetes in Chile and other genetically mixed populations.

In case-control studies, spurious associations between Human Leukocyte Antigen (HLA) alleles and Type 1 diabetes could arise as a result of population stratification, if there are ethnic differences between cases and non-related controls. The Chilean population has several unique features which make it ideal for the study of the effect of stratification by ethnicity on genetic epidemiological research. The incidence rates of Type 1 diabetes in Chilean Aboriginal populations are very low compared to Caucasian populations, while the frequency of the alleles in HLA loci also vary across ethnic groups. In order to avoid the confounding effect of ethnicity, one possible remedy would be the use of cases and their parents in place of non-related controls. The case-parent design offers an adequate framework for the study of the association between HLA polymorphisms and Type 1 diabetes in the Chilean population and can also be applicable to other genetically mixed populations especially in the Americas.

[Prevalence of obesity, hypertension and dyslipidemia in rural aboriginal groups in Chile]. / 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.

Naltrexone effects on insulin sensitivity and insulin secretion in hyperandrogenic women.

A total of 12 women (24.2 +/- 1.6 years old, BMI 36.7 +/- 1.5 Kg/m2) with hyperandrogenism (HA) and with normal glucose tolerance test were studied to evaluate the involvement of endogenous opioids in the pathophysiology of insulin secretion and insulin sensitivity in HA by administering naltrexone, an oral opioid receptor antagonist. Six patients received naltrexone orally (75 mg daily) and another six received placebo for 12 weeks (double-blind study). Before and after therapy a frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed. The insulin sensitivity index (SI) was determined by Bergman's program. SHBG, DHEAS, testosterone, free androgen index (FAI) and plasma concentrations of IGF-I and IGFBP-1 were determined in 3 basal samples, before and after therapy. Treatment with naltrexone in hyperandrogenic patients resulted in a decrease in fasting insulin concentrations of 40% and C-peptide concentrations of 50% (p < 0.05). Insulin and C-peptide from the FSIVGTT displayed a similar pattern with a fall in the area under the curve under naltrexone treatment of 34% for insulin and 35% for C-peptide. Insulin sensitivity did not change under naltrexone (1.26 +/- 0.19 vs 1.32 +/- 0.32 10(-4) x min(-1)/(uU/ml)) or placebo (0.95 +/- 0.19 vs 1.12 +/- 0.28 10(-4) x min(-1)/(uU/ml)) administration. However, glucose effectiveness increased significantly with naltrexone (2.231 +/- 0.002 vs 3.354 +/- 0.006 x 10(-2) min(-1)). Glucose (fasting and area under the curve) was not modified significantly after naltrexone administration. Baseline hormone levels were similar in the two groups, and they did not change after long-term treatment with naltrexone or placebo. In conclusion, these results support the hypothesis of elevated opioid tonus and increased insulin secretion as a possible mechanism of hyperinsulinism in a group of hyperandrogenic women of ovarian origin. This alteration could act as an additional factor in the pathogenesis of insulin resistance found in an important proportion of these patients.

[Polycystic ovary syndrome: relationship of insulin tissular sensitivity, LH secretion and ovarian morphophysiologic changes]. / Síndrome de ovario poliquístico: relación entre sensibilidad tisular a la insulina, secreción de LH y cambios morfofuncionales ováricos.

BACKGROUND: Insulin resistance to LH hypersecretion are recognized features of polycystic ovary syndrome. Previous studies have suggested that both defects are independent from each other. AIM: To examine the relationship between insulin sensitivity and LH secretion in women with polycystic ovary syndrome. PATIENTS AND METHODS: Eighteen women with clinical and biochemical evidence of hyperandrogenism, normal oral glucose tolerance test and polycystic ovaries on ultrasonography, were studied. Insulin sensitivity was assessed using the insulin tolerance test. LH secretion was studied integrating LH values of blood samples taken every 10 minutes for 6 h. Testosterone, testosterone index, SHBG and IGFBP-1 were measured in three selected samples and ovarian volume was assessed by ultrasound. RESULTS: Insulin sensitivity ranged from 0.06 to 0.75 and the area under the curve for LH, from 532 to 8.517 IU/L/6 h. No correlation was found between these two parameters and between each parameter and ovarian volume or androgen concentration. Positive correlations were observed between insulin sensitivity and SHBG concentrations (r = 0.612 p < 0.01) and IGFBP-1 concentrations (r = 0.588 p < 0.001). When compared to patients body mass index of less than 30 kg/m2, patients with body mass index over 30 kg/m2 had significantly lower insulin sensitivity and higher LH levels. In the latter a positive correlation between insulin sensitivity and the area under the curve for LH was observed (r = 0.683 p < 0.02). CONCLUSIONS: Obese polycystic ovary syndrome patients exhibited an inverse correlation between insulin resistance and LH hypersecretion, suggesting a relationship between both defects.

[HLA haplotypes in families with type 1 diabetes]. / Haplotipos HLA en familias chilenas con diabetes tipo 1.

BACKGROUND: Inherited susceptibility to type 1 diabetes is partially determined by HLA genes. HLA-DQA1 and DQB1 alleles have been chosen as the most sensitive susceptibility markers. Family studies are a good method to establish specific relationship between type 1 diabetes and specific haplotypes as risk markers for the disease. AIM: To analyse the role of class II HLA molecules and the distribution of haplotypes in the genetic predisposition to type 1 diabetes in Chilean families. MATERIAL AND METHODS: Twelve family groups constituted by 58 individuals were studied. Fourteen children (10 male) less than 15 years old with diabetes and their family members were included. The allele and haplotype frequency of the population was determined in 74 unrelated healthy children. RESULTS: Risk haplotypes such as HLA-DR3/DQB1*0201/DQA1*0501 and HLA-DQB10302/DQA1*0501 were more common among diabetic patients and comparable to the haplotypes described in other Caucasian populations. Meanwhile, protective haplotypes found in relatives without diabetes, such as HLA-DR2/DQB1*0301/DQA1*0301 and HLA-DR8/DQB1*0402/DQA1*0301, were absent in children with diabetes. CONCLUSIONS: The general pattern of neutral or protective haplotypes, found with higher frequency in non diabetic individuals, indicates that their presence could confer protection against the disease, with a higher effect over those haplotypes associated to the disease.

Different statistical models used in the calculation of the prevalence of insulin-dependent diabetes mellitus according to the polymorphism of the HLA-DQ region.

The use of three statistical models yielded different estimates of the odds ratio relative to the association between the polymorphism in the HLA-DQ region and insulin-dependent diabetes mellitus (IDDM). The models used were: (1) the allele-dosage model which assumes that the number of susceptibility alleles has a linear effect on the logarithm of the odds; (2) the reference cell coding method used with alleles of susceptibility as a risk factor; or (3) a model that uses a classification of alpha/beta heterodimers as a susceptibility factor. We suggest that models which imply a log-linear relationship between a susceptibility marker and disease such as the first model are not appropriate in the assessment of the HLA-IDDM association. In contrast, although both latter models are valid, the third model is more compatible with current hypotheses of the pathological process of the disease. Once an estimation of the odds ratio is chosen, we use such an estimation to calculate an approximation of the prevalence of IDDM according to the polymorphism in HLA-DQ region using the iterative procedure of Newton-Raphson. These approaches are illustrated with data from a case-control study previously conducted in the city of Santiago, Chile.

[Biochemical markers and methods to assess insulin resistance in normal, obese and hyperandrogenic women]. / Marcadores bioquímicos y métodos de cuantificación de insulinorresistencia en mujeres normales, obesas e hiperandrogénicas.

BACKGROUND: Euglycemic or hyperglycemic clamp and the frequently sampled i.v. glucose tolerance test are the most frequently used methods to assess insulin resistance. However, both are expensive and cumbersome. AIM: To evaluate the relative or discriminatory usefulness of sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS) and insulin like growth factor binding protein 1 (IGFBP-1) as markers of insulin resistance and to estimate the tissue sensitivity to insulin by means of the insulin tolerance test (ITT) and the frequently sampled i.v. glucose tolerance test (IVGTT) in normal, obese and hyperandrogenic women. SUBJECTS AND METHODS: Six normal, 6 obese and 12 hyperandrogenic women of similar ages, were studied. In two consecutive days, the ITT and the IVGTT were performed and a basal blood sample was obtained to measure SHBG, DHEAS and IGFBP-1. Insulin sensitivity was calculated as the blood glucose slope in the ITT and with the minimal model of Bergman in the IVGTT. RESULTS: Insulin sensitivity, measured with ITT was 0.58 (0.53-0.63) in normal, 0.38 (0.05-0.59) in obese and 0.20 (0.0-0.36) in hyperandrogenic women. The figures for the IVGTT were 7.97 (4.1-15.4), 2.41 (0.81-4.89) and 1.1 (0.46-1.88), respectively. Both methods had a positive correlation coefficient of 0.792 (p < 0.001). SHBG was 87.0 m 37.9 and 18.3 nmol/l in normal, obese and hyperandrogenic women, respectively (p < 0.09). IGFBP-1 values were 3.0, 2.1 and 1.6 ng/ml respectively (p < 0.05). DHEAS values were 132, 190 and 206 ug/dl, respectively (ND). CONCLUSIONS: ITT is a simple and reliable method to assess insulin sensitivity. SHBG discriminates subjects with different levels of insulin sensitivity. Since it is easy to measure, it could be used as a marker on insulin sensitivity.

[Effects of metformin on insulin resistance in obese and hyperandrogenic women]. / Efecto de la metformina sobre la resistencia insulínica en mujeres obesas y obesas hiperandrogénicas.

BACKGROUND: Metformin is a biguanide often used in obese diabetics that improves tissue sensitivity to insulin. AIM: To assess the effects of metformin on tissue insulin sensitivity in obese and hyperandrogenic women. PATIENTS AND METHODS: Eight obese and eight obese and hyperandrogenic women received metformin 850 mg orally during 12 weeks. Before and at the end of the treatment period, an insulin tolerance test to measure insulin sensitivity was performed and blood was drawn to measure sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), testosterone, triglycerides, total and HDL cholesterol. The free androgen index was calculated for each sample. RESULTS: After metformin treatment, the insulin sensitivity index improved from 0.38 (0.05-0.5) to 0.43 (0.25-0.59) in obese women and from 0.2 (0-0.36) to 0.3 (0.06-0.4) in obese and hyperandrogenic women. SHBG increased and total cholesterol and triglycerides decreased significantly in both groups. No other significant changes were observed. CONCLUSIONS: Metformin has a favorable effect on tissue sensitivity to insulin, SHBG and serum lipids in obese and hyperandrogenic women.

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.

[Insulin-dependent diabetes mellitus in Santiago, Chile: the role of immunogenetic and environmental factors]. / Diabetes mellitus insulino-dependiente en Santiago de Chile: rol patogenético de factores inmunogenéticos y ambientales.

The role of HLA class II alleles in the genetic susceptibility to develop insulin-dependent diabetes mellitus (IDDM) was examined by means of PCR and oligospecific probes in 63 IDDM children and 74 controls subjects. In diabetic patients we found a significant increase in the alleles frequency DR3, DR4, DQB1*0302 and DQA1*0301 compared to the control group, where the most prevalent alleles were DR2, DR14 (DRB1*1402), DQA1*0101 and DQA1*0201. All the risk genotypes in the diabetic group were similar than in other caucasian groups: DR3/DR4-DQB1*0201/0302-DQA1*0301/0501 and DR4/DR4-DQB1*0302/0302-DQA1*0301/0301. The homozygote character no asp57 conferred an absolute risk (AR) of 3.87 and the marker Arg52 an AR of 5.78/100.000 bab year. The homozygosis for both markers (no Asp57 + Arg52) had an AR of 7.56/100.000 bab year. Regarding environmental factors associated with IDDM, our population under study showed a low prevalence of infectious agents (mainly mumps and rubella, specifically associated with IDDM) and a high prevalence of effective breast-feeding (over 3 months). These factors could be exercising a protector role in the development of IDDM. The factors that appear to be important in the low incidence of IDDM in Santiago de Chile are: the low prevalence of infectious agents related to IDDM, the high percentage of breast-feeding children in the population, the reduced frequency of susceptible molecules as DR3, DQB1*0201 (compared to other caucasian groups) and the presence of protective genotypes related to DR13 and DR14 observed in the non diabetic children.