Prevalencia familiar de patologías metabólicas en paciente con síndrome de ovario poliquístico / Prevalence of metabolic disorders among family members of patients with polycystic ovary syndrome

Background: About 60 percent 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 ñ 6.3; control group: 24.8 ñ 6.2 years). The prevalence of metabolic disorders was 62 percent in the relatives of the PCOS patients and 27.8 percent 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

Asociación obesidad y leptina en tres poblaciones aborígenes de Chile / Body mass index and leptin levels in 3 Chilean aborigin populations

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

Prevalencia de obesidad, hipertensión arterial y dislipidemia en grupos aborígenes rurales de Chile / Prevalence of obesity, hypertension and serum lipid profiles in chilean rural aboriginal communities

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 percent of mapuche men, 39.7 percent of the aymara women and 27.0 percent of aymara men had a body mass index over 27 kg/m2. Twenty percent of mapuche men, 18.0 percent of mapuche women, 9.0 percent of aymara men and 4.8 percent of the aymara women had high blood pressure values. Serum HDL cholesterol was below 35 mg/dl in 16 percent of mapuche women, 14 percent of mapuche men, 25 percent of the aymara women and 27 percent 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

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

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

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

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 byperandrogenic women. Patients and methods: Eight obese and eight obese and eight 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 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

Polimorfismos del gen de lipoproteína lipasa en diabéticos no insulino-dependientes: estudio preliminar / Lipoprotein gene polymorphism in non dependent diabetics: preliminary study

Background: Lipoprotein lipase plays a crucial role in plasma lipoprotein metabolism. Several lipoprotein lipase gene polymorphisms have been found associated with lipid levels, premature atherosclerosis and cardiovascular disease. Aim: To investigate, in the Chilean population, the genotype distribution of lipoprotein lipase polymorphism and its possible association with lipid levels and obesity. Patients and methods: Hind III and Pvu II polymorphism was determined in 45 non-insulin-dependent diabetic patients and in 52 non diabetic controls from Santiago, Chile. Results: Hind III (+/+) polymorphism had a higher frequency in diabetics as compared to controls (0.6 and 0.29 respectively, p= 0.009). The frequency of heterozygous distribution was higher in non diabetic subjects. Controls and diabetics had comparable gene frequencies for the Pvu II genotype distribution. Analyzing the impact of these polymorphisms on plasma lipid levels, Hind III (+/+) genotype was associated with high Levels of total cholesterol and triglycerides in both groups. The hterozygote (+/-) or homozygote (-/-) state for Hind III was effectively associated with high levels of HDL cholesterol levels, as compared to the (+/+) genotype. There was no relationship between these genotypes and body mass index and waist to hip ratio. Conclusions: An association between genetic variation at the lipoprotein lipase locus with high levels of triglycerides and total cholesterol was confirmed. However, no association of these genetic markers with anthropometric measurements was found

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

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. Insulin sensitivity, measure 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 0.09). 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). ITT is a sample and reliable method to asses insulin sensitivity. SHBG discriminates subjects with different levels of insulin sensitivity

Diabetes mellitus insulino-dependiente en Santiago de Chile: rol patogénico de factores inmunogenéticos y ambientales / Insulin-dependent diabetes mellitus in Santiago, Chile: pathogenic role of immunogenetic and environmental factors

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 hab year. The homozygosis for both markers (no Asp57+Arg52) had an AR of 7.56/100.000 hab 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, 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

Prueba de tolerancia a la insulina: un método útil para determinar resistencia insulínica en mujeres hiperandrogénicas obesas / Insulin tolerance test: a useful method for insulinic resistance determination in obese hyperandrogenic women

Five healthy women aged 27ñ7 years old with a body mass index of 21ñ2 kg/m² and 6 hyperandrogenic women aged 25ñ4 years old with a body mass index of 40ñ5 kg/m² were studied after a 10 hours fast. For the insulin tolerance test, 0.1 U/Kg of crystalline insulin were injected intravenously and blood samples were drawn to measure glucose at -5,0,3,5,10 and 15 min. after the injection. Insulin resistance was calculated using the slope of descending blood glucose levels (SIû). For the intravenous glucose tolerance test, 29 blood glucose samples were obtained after an intravenous injection of 0,3 g glucose/kg followed by an injection of 0.02 U/kg of crystalline insulin. Insulin sensitivity (SI²) was calculated using Bergman's minimal model. Healthy women had a SIû of 0.58 (range 0.53-0.63) and a SI² of 7.9x10-4x min-û/uU/ml (range 4.15-9.11). For hyperandrogenic women were 0.18 (range 0.06-0.29) and 0.9x10-4xmin-û/uU/ml (range 0.46-1.79) respectively. Both methods had a positive correlation coefficient of 0.859 (p<0.001). In conclusion, insulin tolerance test is a good method to measure insulin resistance and has a good correlation with the frequently sampled intravenous glucose tolerance test

Incidencia de diabetes mellitus insulino dependiente en Santiago, Chile, 1990-1993 / Incidence of insuline dependent diabetes mellitus in Santiago, Chile, 1990-1993

The aim of this study was to determine IDDM incidence in the Metropolitan Region of Chile, during the period 1990-1993 as part of the Multinational Project for Childhood Diabetes (WHO DIAMOND project group). The studied population was 1.499.784 inhabitants. All children in whom the diagnosis was made between january 1, 1990 and dec. 31, 1993 were included. We used a retrospective and prospective search and confirmation method, using as data sources public and private hospitals and medical records of pediatricians. The juvenile Diabetes Foundation was used as a secondary data source. All cases had at least two confirmation sources. A total of 176 new cases (90 males) were diagnosed in the study period, with an annual incidence of 2.92/100,000 for females and 2.95 for males. The group of children from 10 to 14 years old had the highest incidence rate (4.9/100.000), specially in women (5.25/100.000). The yearly incidence was 1.31 in 1990, 2.71 in 1991, 2.93 in 1992 and 3.7/1000,000 in 1993). It is concluded that the Metropolitan Region has one of the lowest incidences of IDDM in Latin America, although it increased along the study years

Predisposición genética para desarrollar diabetes mellitus insulino-dependiente: estudio en población de Santiago y Temuco, Chile / Genetic predisposition for developing insulin-dependent diabetes mellitus: study in population from Santiago and Temuco, Chile

Insulin dependent diabetes mellitus (IDDM) is strongly associated with particular HLA-DQ alpha/beta markers in white population. The heterodimers confirmation composed of a DQ alpha chain with an arginine at residue 52 (Arg52) combined to a DQ beta chain lacking an aspartic acid at residue 57 (non asp57) increase markedly the risk to develop IDDM. To confirm this association, 63 IDDM patients from Santiago de Chile registry, 20 IDDM patients from Temuco registry and 74 unrelated helathy non diabetic control subjects were studied. With polymerase chain reaction (PCR) and sequence specific oligonucleotide probes the individuals were typed for their HLA-DQA1 and DQB1 alleles, their DQA1/DQB1 genotype and heterodimers conformation were compared. In diabetic population both markers Arg52 homocygote and non Asp57 homocygote were increased regard to control subjects (R/R: 0.76 and 0.85 vs 0.33; ND/ND: 0.78 and 0.75 vs 0.50, p<0.05). A high relative risk (RR) was determined for both homocygote markers in IDDM groups.compared. Arg52 DQ alpha (R)/non Asp57 DQ beta (ND) heterodimers were strongly associated with susceptibility to IDDM. A high RR was observed in patients with four susceptibility DQ heterodimers (RR1: 13.7 in IDDM-Santiago and RR2: 18.6 in IDDM-Temuco, p<0.00003). The HLA-DQ alpha/beta markers and their risk heterodimers are increased in our diabetic population and could be considered as susceptibility markers to develop IDDM

HLA y diabetes mellitus insulino-dependiente / HLA and insulin-dependent diabetes mellitus

The propensity of an individual to develop type I (insulin dependent) diabetes mellitus is directly related to specipic HLA clase II proteins, specially those from DR and DQ regions. Genetic susceptibility to insulin dependent diabetes arises from a preestablished conformation of alpha and ß chains of DQ and ß chain of DR. Since the classic demonstration by McDevitt and colleagues that DQ ß chain aspartate at position 57 was protective against the development of the disease, many populations have been surveyed to study the association between the incidence Type I diabetes and determined frequencies of DR and DQ haplotypes. The assocation between these markers and susceptibility to Type I diabetes is well established in caucasians at the present time. However, little information is available for Latin American populations, that share a mixture of european, african and native genes. Our group is studying genetic markers of three Latin American populations (Argentina, Perú and Chile) and their possible association to the different incidence of Type I diabetes mellitus in each country

Lipoproteína (a) y otros factores de riesgo en niños chilenos con diabetes mellitus tipo I / Lipoprotein (a) and other risk factors in chilean children with diabetes mellitus type I

Aims- To study serum Lp(a) levels and other metabolic cardiovascular risk factors in children with type I diabetes mellitus (DM) in comparison with sex and age matched nondiabetic children. To determine the influence of diabetes control on serum lipoprotein (a) concentrations. Design- Transversal observational study. Target population: diabetic group: 70 type I DM children with microalbuminuria and no macro-microvascular nor neurological complications, aged from 8 to 15 years; 30 boys, 40 girls. Mean duration of type I DM was 8 ñ 4 years. Non diabetic group: composed by 123 healthy children with no family history of DM, aged from 8 to 15 years, 53 boys, 70 girls. Methods- The lipids profile include: total cholesterol (TC) and triglyceride (TG), cholesterol high-density lipoproteins (C-HDL) cholesterol very-low-density lipoproteins (C-LDL) and cholesterol low-density lipoproteins (C-LDL). ApoAI, APOAII and ApoB, Lp(a) and fructosamine. Results- Fructosamine concentration in diabetic children was 340 ñ 108 uM/1 in 240 ñ 25 uM/I nondiabetic children. Lp(a) serum levels did not significantly differ among both groups 17 ñ 16 mg/dl in diabetics 19 ñ 18 mg/dl in controls. Multivariate analysis showed that in the diabetic children the worsening of metabolic control as reflected by fructosamine, was positively correlated with the increase in total Lp(a) serum concentration. Conclusions- In children aged 8-15 years with uncomplicated IDDM lasting less than 15 years duration (Lp(a) serum levels are positively correlated with the poorest metabolic control

Proteínas de la leche y su asociación con diabetes mellitus insulino-dependiente / Milk proteins and it association with insulin dependent diabetes mellitus

Cow`s milk has been implicated as a possible trigger of the autoinmune respose that destroys pancreatic beta cells in genetically susceptible host, thus causing diabetes mellitus. Studies in animals have suggested that bovine serum albumin, BSA, is the milk protein responsible, and an albumin peptide containing 17 amino acids, ABBOS, may be the reactive epitope. Antibodies to this peptide react with p69 a beta cell surface protein that may represent the target antigen for milk-induced beta-cell specific inmunity. The consumption of cow`s milk in Europe may support the hypothesis that cow`s milk may be a triggering factor for the development of type I diabetes. However, several epidemiological studies has not found significance correlation between the observed the importance of several enviromental factors in the devepment of type I diabetes with the objetive to establish a good prevention in susceptible subjects

Autoanticuerpos y diabetes mellitus insulinodependientes / Autoantibodies and insulin-dependent diabetes mellitus

La diabetes insulinodependiente es el producto de la destrucción autoinmune de las células beta. Los autoanticuerpos se pueden detectar incluso en la etapa preclínica, entre ellos los antiislotes citoplasmáticos (ICA) y los anti 64K. El antígeno de este último, sería una proteína de 64KD con actividad de decarboxilasa del ácido glutámico (GAD). Se han encontrado dos formas de esta enzima (GAD 65K y GAD 67K), determinadas genéticamente. En caucásicos, los diabéticos insulinodependientes que poseen HLA DR3 y DR4 tienen altos niveles de anti 64K. El anticuerpo anti 64K sería un marcador más específico de diabetes mellitus insulinodependiente