Search

Objective: To study the association of SLC16A11 gene variants with obesity and metabolic markers in nondiabetic Chilean adults., Methods: This cross-sectional study included 263 non-diabetic adults. The genotype of the rs75493593 polymorphism of SLC16A11 gene was performed by real-time PCR. It's association with adiposity markers (body weight, BMI, waist circumference and fat mass percentage), metabolic markers (glucose, insulin, HOMA IR , leptin, total cholesterol, LDLc, HDLc, triglycerides, ALT, GGT and hsCRP) and blood pressure was analyzed by linear regression., Results: The minor allele (T) of the SLC16A11 gene (rs75493593) has a frequency of 29.7% among Chileans. Risk genotypes (GT and TT) were associated with a significant 1.49 mU/l increase in plasmatic insulin for each copy of the minor allele (95% CI: 0.12, 2.87, p < 0.05). This association remained significant after adjusting for socio-demographic variables, physical activity and smoking (1.36 mU/l, 95% CI: 0.16, 2.58 p < 0.05), but was lost when BMI was included as a confounding factor. Higher BMI was also significantly associated with polymorphic genotypes in SLC16A11 , independent of socio-demographic variables., Conclusion: The minor allele of the SLC16A11 gene (T) is highly prevalent among Chileans and is associated with increased insulin and BMI in nondiabetic individuals. These findings suggest that the genetic variant in SLC16A11 is not only associated with type 2 diabetes as previously shown in Mexicans, but is also related to early metabolic alterations in healthy subjects that may lead to type 2 diabetes.

Glucagon dysregulation is an essential component in the pathophysiology of type 2 diabetes. Studies in vitro and in animal models have shown that zinc co-secreted with insulin suppresses glucagon secretion. Zinc supplementation improves blood glucose control in patients with type 2 diabetes, although there is little information about how zinc supplementation may affect glucagon secretion. The objective of this study was to evaluate the effect of 1-year zinc supplementation on fasting plasma glucagon concentration and in response to intravenous glucose and insulin infusion in patients with type 2 diabetes. A cross-sectional study was performed after 1-year of intervention with 30 mg/day zinc supplementation or a placebo on 28 patients with type 2 diabetes. Demographic, anthropometric, and biochemical parameters were determined. Fasting plasma glucagon and in response to intravenous glucose and insulin infusion were evaluated. Patients of both placebo and supplemented groups presented a well control of diabetes, with mean values of fasting blood glucose and glycated hemoglobin within the therapeutic goals established by ADA. No significant differences were observed in plasma glucagon concentration, glucagon/glucose ratio or glucagon/insulin ratio fasting, after glucose or after insulin infusions between placebo and supplemented groups. No significant effects of glucose or insulin infusions were observed on plasma glucagon concentration. One-year zinc supplementation did not affect fasting plasma glucagon nor response to intravenous glucose or insulin infusion in well-controlled type 2 diabetes patients with an adequate zinc status.

Objective: To assess insulin sensitivity, insulin secretion and metabolic profile in women with polycystic ovary syndrome (PCOS) in different stages of reproductive life., Materials and Methods: In a cross-sectional study, 190 PCOS women (PCOSw) and 99 controls (Cw) aged between 18 and 55years were included. PCOSw and Cw were distributed into 3 stages of reproductive life: early reproductive age (18-34years old), late reproductive age (35-40years old) and perimenopausal period (41-55years old). Waist circumference (WC), body mass index (BMI) and blood pressure (BP) were recorded. An oral glucose tolerance test (OGTT) with measurement of glucose and insulin was performed. Sex steroids and lipid profile were also determined in the fasting sample. Insulin sensitivity was assessed by HOMA-IR and ISI composite, and insulin secretion by HOMA-β and insulinogenic index. Visceral adiposity index (VAI) and lipid accumulation product (LAP) were also calculated. Metabolic syndrome (MS) was assessed by the IDF and ATPIII criteria., Results: At early reproductive age, PCOSw showed higher BMI, WC, and VAI and a higher prevalence of MS compared to Cw (p<0.05). In addition, at late reproductive age PCOSw also showed elevated total cholesterol, triglycerides, insulin secretion, LAP and BP. At perimenopausal period, these parameters were not different between Cw and PCOSw. Within the PCOSw group, HOMA-β was lower at late reproductive and perimenopausal periods compared to the early reproductive age. Regarding control women, a deterioration of anthropometric and metabolic parameters was observed in perimenopausal women compared to early and late reproductive women., Conclusions: Our results suggest that metabolic derangements associated with PCOS are more evident at the early and late reproductive ages. On the other hand, during perimenopause, there is no further deterioration of metabolic parameters. Nevertheless, a disruption in pancreatic β-cell function is evidenced at this stage., (Copyright © 2016. Published by Elsevier Inc.)

Context: We have previously described increased serum levels of anti-Müllerian hormone (AMH) and stimulated insulin in daughters of women with polycystic ovary syndrome (PCOS), suggesting that these girls may have an altered ovarian follicular development which may be modulated by insulin. However, the specific relationship between serum AMH and insulin levels during each Tanner stage of puberty in this cohort has not been established., Objective: The aim of our study was to establish the relationship between AMH and poststimulated insulin serum concentrations during each stage of puberty in daughters of women with PCOS (PCOSd), compared to daughters of control women (Cd)., Design: We studied 135 PCOSd and 93 Cd classified according to their Tanner stage. Gonadotrophins, sex steroids, sex hormone-binding globulin (SHBG), and AMH were determined in a fasting sample. Ovarian volume was measured by pelvic ultrasound. In addition, in both groups we performed an oral glucose tolerance test with measurements of glucose and insulin., Results: Anti-Müllerian hormone levels were significantly higher in PCOSd compared to Cd at all Tanner stages. Daughters of women with PCOS having AMH concentrations greater than 2 standard deviation (SD) above the mean AMH value for the Cd group showed decreased serum follicle-stimulating hormone (FSH) concentrations and increased stimulated levels of insulin during Tanner stages I, II, and III., Conclusions: Anti-Müllerian hormone levels are increased in PCOSd during all stages of puberty. We suggest that those PCOSd with the highest AMH levels probably represent a group of girls with more severe ovarian dysfunction and metabolic derangements.

Objective: We evaluated metabolic parameters in Chilean women with polycystic ovary syndrome (PCOS) who were carriers and non-carriers of the glycine-to-arginine substitution at codon 972 (Gly972Arg) variant of insulin receptor substrate-1 and to assess insulin response after oral high- and low-glycemic loads, Methods: In 146 women with PCOS and 97 healthy women (HW), Gly972Arg genotypes were obtained by polymerase chain reaction, and an oral glucose tolerance test was performed with glucose and insulin measurements. An insulinogenic index, a homeostasis model assessment for insulin resistance, and whole-body insulin sensitivity index (composite) were calculated. Eight carriers and eight non-carriers (four PCOS and four HW, respectively) underwent a 50-g glucose (high glycemic) or 50-g fructose (low glycemic) load with serum glucose and insulin measurements at 15-min intervals for 3 h., Results: The frequency of the Gly972Arg variant was higher in PCOS patients than in HW (P < 0.05). The insulinogenic index was lower in HW carriers than in non-carriers (P < 0.05). In PCOS carriers, 2-h insulin was higher than in those without the mutation. In overweight PCOS carriers, the homeostasis model assessment for insulin resistance was higher and the insulin sensitivity index was lower than in PCOS patients without the mutation. In HW carriers, a delay in the maximal response of insulin secretion was observed, with a decrease of 26.7% in insulin concentrations 30 to 60 min after the 50-g glucose load. Glucose concentrations increased by 19.7% between 60 and 120 min. Glucose concentrations between 0 and 120 min were 14.9% higher in PCOS carriers than in non-carriers after the 50-g glucose load., Conclusions: In HW, this polymorphism appears to be associated with a decrease in insulin secretion; in PCOS women, this polymorphism interacts with obesity to influence insulin resistance, thus contributing to the pathogenesis of the metabolic component of PCOS.

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.

Background: The aim of this study was to establish the effect of polycystic ovary syndrome (PCOS) adjusted for adiposity on proinsulin concentrations.Methods: Ninety-one women with PCOS and 72 normal cycling (NC) women were recruited. A 2 h, 75 g oral glucose tolerance test was performed. Glucose and insulin were measured in each sample. Proinsulin and C-peptide were determined at 0 and 30 min and the fasting proinsulin/insulin ratio (PI/I) was calculated. Insulin sensitivity was estimated by insulin sensitivity index (ISI) composite, and beta-cell function was estimated by insulinogenic index.Results: Insulin, proinsulin and C-peptide concentrations were higher in women with PCOS than in NC women (P < 0.05). PI/I and insulinogenic index were similar in both groups. Proinsulin concentrations increased with body mass index (P < 0.05) only in women with PCOS; therefore, proinsulin concentrations were higher in obese PCOS patients compared with obese control women (P < 0.05). Moreover, a positive association between proinsulin concentrations and waist diameter adjusted for C-peptide (P < 0.05) and a negative association between proinsulin concentrations and ISI composite values were observed in PCOS patients (P < 0.05).Conclusions: Data suggest that in PCOS patients an elevated proinsulin concentration could reflect insulin resistance more than beta-cell dysfunction. However, the elevated concentration of proinsulin in these patients could also result from impaired beta-cell function resulting from intra-abdominal obesity independently of insulin resistance. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the peripheral serum androgen concentrations in normal and polycystic ovarian syndrome (PCOS) women during pregnancy, in order to establish if PCOS may induce gestational hyperandrogenism and therefore constitute a potential source of androgen excess for the fetus.Methods: Twenty pregnant PCOS (PPCOS) women and 26 normal pregnant (NP) women of similar age with singleton pregnancies were selected for the study. During gestational weeks 10-16 and 22-28, a 2 h, 75 g oral glucose tolerance test (OGTT) was performed. For the OGTT, glucose and insulin were measured in each sample and testosterone, androstenedione, dehydroepiandrosterone sulphate (DHEAS), estradiol, progesterone and sex hormone-binding globulin were determined in the fasting sample.Results: In the first study period (gestational weeks 10-16), the levels of androstenedione, testosterone and DHEAS and the free androgen index tended to be higher in the PCOS group. These differences became significant in the second study period (gestational weeks 22-28). In this second period, 2 h insulin concentrations were also significantly higher in PPCOS than in NP women.Conclusions: The present study demonstrates a significant increase in androgen concentrations during pregnancy in PCOS women. We propose that these androgen concentrations could provide a potential source of androgen excess for the fetus, without leading to fetal virilization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The use of three statistical models yielded different estimates ofthe 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 α/β helerodimers 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. [ABSTRACT FROM AUTHOR]