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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.)

The aim of this study was to assess red blood cell glutathione from insulin-sensitive and insulin-resistant individuals before and after an oral glucose dose. Fifteen healthy, young (24 ± 5 years), nonobese (23 ± 2 kg·m⁻²), insulin-sensitive (ISI composite = 6.0 ± 1.2) individuals and 14 healthy, young (22 ± 2 years), nonobese (24 ± 2 kg·m⁻²), insulin-resistant (ISI composite = 2.7 ± 1.1) individuals received a 75 g oral glucose dose. Blood samples were drawn before and for 2 h after glucose ingestion for red blood cell glutathione and serum glucose and insulin concentrations. Glycemia before and after glucose ingestion was similar between groups (p = 0.17), which suggest that hyperinsulinemia compensated impaired insulin sensitivity. Red blood cell total (p = 0.81), reduced (p = 0.79), and oxidized (p = 0.88) glutathione concentrations were similar between groups under fasting and postprandial conditions. However, in response to glucose, increases in total and reduced glutathione concentrations were found at the end of the 2 h assessment period in both groups (p < 0.05). Direct associations between postprandial glucose response and red blood cell total (r = 0.52; p < 0.05) and oxidized (r = 0.61; p = 0.02) glutathione concentrations were observed only in insulin-sensitive subjects. In conclusion, healthy individuals differing in their degree of insulin resistance showed similar red blood cell glutathione concentrations under non-glucose- and glucose-stimulated conditions.

Objective: To evaluate in a cross-sectional study adiponectin and leptin levels in prepubertal and pubertal daughters of women with PCOS and their relationship to insulin sensitivity and reproductive features., Study Design: We studied 92 daughters of PCOS women (PCOSd) and 76 daughters of control women (Cd) matched by age and body mass index SD scores and distributed according to breast Tanner stage: prepuberty (Tanner 1), early puberty (Tanner 2-3) or late puberty (Tanner 4-5). In all girls an oral glucose tolerance test was performed. Leptin, adiponectin, sex steroids, SHBG, glucose, insulin and lipid profile were determined. Leptin-adiponectin ratio, free androgen index and insulin sensitivity (HOMA-IR and ISI composite) were then calculated., Results: Prepubertal PCOSd showed lower serum adiponectin compared to Cd (p=0.028), whereas during puberty no differences were observed between the groups. Leptin concentrations were similar in both groups in all Tanner stages. In addition, in PCOSd during early puberty, adiponectin showed a negative correlation with testosterone and leptin showed a negative correlation with ISI composite, which were independent of BMI SDS (r=-0.39; p=0.02 and r=-0.42; p=0.01)., Conclusion: These observations suggest that during the prepubertal period PCOSd exhibit abnormal adiponectin levels, independently of BMI. Moreover, leptin and adiponectin may be related to metabolic and reproductive abnormalities observed in PCOSd during the early stages of sexual development., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Imprecise measurement of physical activity variables might attenuate estimates of the beneficial effects of activity on health-related outcomes. We aimed to compare the cardiometabolic risk factor dose-response relationships for physical activity and sedentary behaviour between accelerometer- and questionnaire-based activity measures., Methods: Physical activity and sedentary behaviour were assessed in 317 adults by 7-day accelerometry and International Physical Activity Questionnaire (IPAQ). Fasting blood was taken to determine insulin, glucose, triglyceride and total, LDL and HDL cholesterol concentrations and homeostasis model-estimated insulin resistance (HOMA(IR)). Waist circumference, BMI, body fat percentage and blood pressure were also measured., Results: For both accelerometer-derived sedentary time (<100 counts.min(-1)) and IPAQ-reported sitting time significant positive (negative for HDL cholesterol) relationships were observed with all measured risk factors--i.e. increased sedentary behaviour was associated with increased risk (all p ≤ 0.01). However, for HOMA(IR) and insulin the regression coefficients were >50% lower for the IPAQ-reported compared to the accelerometer-derived measure (p<0.0001 for both interactions). The relationships for moderate-to-vigorous physical activity (MVPA) and risk factors were less strong than those observed for sedentary behaviours, but significant negative relationships were observed for both accelerometer and IPAQ MVPA measures with glucose, and insulin and HOMA(IR) values (all p<0.05). For accelerometer-derived MVPA only, additional negative relationships were seen with triglyceride, total cholesterol and LDL cholesterol concentrations, BMI, waist circumference and percentage body fat, and a positive relationship was evident with HDL cholesterol (p = 0.0002). Regression coefficients for HOMA(IR), insulin and triglyceride were 43-50% lower for the IPAQ-reported compared to the accelerometer-derived MVPA measure (all p≤0.01)., Conclusion: Using the IPAQ to determine sitting time and MVPA reveals some, but not all, relationships between these activity measures and metabolic and vascular disease risk factors. Using this self-report method to quantify activity can therefore underestimate the strength of some relationships with risk factors.

Background: Effects of urbanisation on diabetes risk appear to be greater in indigenous populations worldwide than in populations of European origin, but the reasons are unclear. This cross-sectional study aimed to determine whether the effects of environment (Rural vs. Urban), adiposity, fitness and lifestyle variables on insulin resistance differed between individuals of indigenous Mapuche origin compared to those of European origin in Chile., Methodology/principal Findings: 123 Rural Mapuche, 124 Urban Mapuche, 91 Rural European and 134 Urban European Chilean adults had blood taken for determination of HOMA-estimated insulin resistance (HOMA(IR)) and underwent assessment of physical activity/sedentary behaviour (using accelerometry), cardiorespiratory fitness, dietary intake and body composition. General linear models were used to determine interactions with ethnicity for key variables. There was a significant "ethnicity x environment" interaction for HOMA(IR) (Mean±SD; Rural Mapuche: 1.65±2.03, Urban Mapuche: 4.90±3.05, Rural European: 0.82±0.61, Urban European: 1.55±1.34, p((interaction)) = 0.0003), such that the effect of urbanisation on HOMA(IR) was greater in Mapuches than Europeans. In addition, there were significant interactions (all p<0.004) with ethnicity for effects of adiposity, sedentary time and physical activity on HOMA(IR,) with greater effects seen in Mapuches compared to Europeans, an observation that persisted after adjustment for potential confounders., Conclusions/significance: Urbanisation, adiposity, physical activity and sedentary behaviour influence insulin resistance to a greater extent in Chilean Mapuches than Chileans of European descent. These findings have implications for the design and implementation of lifestyle strategies to reduce metabolic risk in different ethnic groups, and for understanding of the mechanisms underpinning human insulin resistance.

The aim of this study was to establish the frequency of gene CYP17 promoter polymorphism in women with polycystic ovary syndrome (PCOS) from a Chilean population and to examine the association of this polymorphism with body weight and estimate of insulin resistance in PCOS patient carriers and noncarriers of the A2 allelic variant. A total of 159 women with clinical and hormonal evidence of PCOS and 93 healthy women (HW) were evaluated. Diagnosis of PCOS was made according to the National Institutes of Health consensus criteria. In PCOS and HW, an oral glucose tolerance test was performed; and serum glucose and insulin were measured before the glucose load and 30, 60, 90, and 120 minutes after. Lipid profile and free fatty acid concentrations were determined in the basal sample. Insulin resistance was evaluated by homeostatic model assessment and insulin sensitivity index composite. A polymerase chain reaction-restriction fragment length polymorphism analysis was performed in all women to determine the A2 allele of the gene CYP17 promoter. The genotype frequency was similar between HW and PCOS women. No differences in anthropometric measurements and metabolic parameters were observed in HW carrier and noncarrier of the A2 variant. In PCOS women, an increase in body mass index, waist circumference, homeostatic model assessment of insulin resistance, and fasting insulin according to the A2 allele dosage was observed (P = .008, P = .016, P = .012, and P = .006, respectively). Polycystic ovary syndrome patient carriers of the A2 allele with a body mass index greater than 29.9 kg/m(2) showed an odds ratio of 9.1 (confidence interval, 3.0-27.4; P < .0001) for developing insulin resistance. These data suggest that the frequency of the A2 allele is similar between PCOS patients and HW; however, the presence of this gene defect in PCOS patients seems to be associated with increase in body weight, abdominal adiposity, and metabolic components.

Introduction: Associations between FABP2 Ala54Thr polymorphism and increased fasting insulin concentration, fasting fatty acid oxidation and reduced glucose uptake have been identified in several populations. The aim of this study was to evaluate the association of Ala54 Thr polymorphism of the FABP2 gene with insulin sensitivity in pubertal girls born small for gestational age (SGA)., Results: The frequency of the Thr54 allele did not differ between AGA and SGA girls (0.52 vs 0.43). Girls born SGA positive for the Ala/Thr polymorphism were older at the beginning of puberty compared to girls born AGA with the Thr54 allele (p < 0.01). These girls had lower whole body insulin sensitivity index (WBISI) (4.1 +/- 1.7 vs 9.2+/-7.4, p < 0.05), higher leptin (17.3 +/- 5.9 vs 12.1 +/- 13.7, p < 0.02), insulin area under the curve (AUC) (64,272 +/- 9,209 vs 27,981 +/- 15,637, p < 0.001), proinsulin (17.3 +/- 5.4 vs 10.9 +/- 3.6, p < 0.01) and insulinogenic index (4.6 +/- 3.0 vs 2.9 +/- 5.9, p < 0.01). Conversely, girls born SGA positive for the Ala/Thr polymorphism were older at the beginning of puberty (ns) compared to girls born SGA positive for the Ala/Ala polymorphism. These girls had higher insulin AUC (64,272 +/- 9,209 vs 33,322 +/-7,533, p < 0.01), insulinogenic index (4.6 +/- 3.0 vs 2.5 +/- 3.6, p < 0.01) and lower WBISI (4.1 +/- 1.7 vs 6.3 +/- 1.8, p < 0.05)., Discussion: Our results suggest that the Thr54 variant of the FABP2 gene could be associated with a synergic effect in the SGA group regarding higher leptin levels (p < 0.05), lower insulin sensitivity by WBISI (p < 0.05) and higher insulin secretion determined by higher insulinogenic index (p < 0.01), insulin AUC (p < 0.01) and beta-cell stress measured by higher proinsulin (p < 0.05). Our data suggest an involvement of genetic factors in the insulin resistance associated with reduced fetal growth and strengthen the hypothesis that this association could be the consequence of interactions between detrimental factors during fetal life and genetic susceptibility.

Growth hormone may help to increase final height in patients with short stature, but its efficacy is variable. It has been recently reported that the isoform of the GH receptor (GHR) that lacks exon 3 (d3-GHR) is associated with a greater growth response to GH therapy. We hypothesized that nocturnal growth hormone concentrations, basal IGF-I and IGFBP-3 levels, and insulin sensitivity might show variations among individuals depending on their GHR allelic variant. To test this hypothesis, we studied 38 prepubertal LBW children with nocturnal GH concentrations, IGF-I and IGFBP-3 levels and insulin sensitivity during OGTT and Insulin test. The GHR allelic variant was analyzed through multiplex PCR analysis in DNA from peripheral leukocytes. Characteristics of the overnight GH secretion [(mean GH: 6.8 +/- 0.6 vs. 6.2 +/- 0.5 ng/ml), (AUC: 3,227 +/- 280 vs. 2,908 +/- 212 ng/ml.min), (peak number: 4.4 +/- 0.3 vs. 4.4 +/- 0.2), (amplitude: 12 +/- 1.1 vs. 10.8 +/- 1.1 ng/ml)] did not differ between groups (f1/f1 vs. f1/d3 plus d3/d3). In addition, we did not observe any significant differences in serum IGF-I SDS (-0.49 +/- 0.26 vs. -0.40 +/- 0.35) or IGFBP-3 SDS (-1.21 +/- 0.24 vs. -0.89 +/- 0.21) nor in insulin sensitivity (WIBSI: 12 +/- 1.2 vs. 10.8 +/- 1.1) in LBW children with full length GHR compared to children carrying at least one GHRd3 allele. The distribution of the f1/f1 allelic variant and fi/d3 or d3/d3 was similar in the LBW children with or without catch-up growth. These results suggest that the GHR allelic variant does not play a significant role in the regulation of GH-IGF-I/BP3 axis or in insulin sensitivity in prepubertal LBW children., (Copyright 2007 S. Karger AG, Basel.)

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.

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.

Objective: To assess the association between the Ala54Thr genetic polymorphism of the fatty acid-binding protein 2 (FABP2) gene with insulin resistance and obesity., Research Methods and Procedures: According to a sampling scheme based on BMI, 33 adult obese women (BMI > or = 30) and 30 adult normal-weight women (BMI > 18.5 and < 25 kg/m(2)) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor alpha (TNF alpha) were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment for insulin resistance method. The Ala54Thr allelic variant was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis., Results: The Thr54 allele was more frequent in obese than in nonobese women (47.0% vs. 31.7; p = 0.08). Among obese women, higher TNF alpha concentrations were found when comparing the Thr54/Thr54 genotype (30.0 +/- 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 +/- 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 +/- 7.0 pg/mL) (p < 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p < 0.05)., Discussion: Our results suggest that the Ala54Thr polymorphism of the FABP2 gene is associated with obesity and insulin resistance. The effect of this polymorphism might be mediated by elevated production of TNF alpha.

Aims/hypothesis: Insulin resistance with increased risk of Type II (non-insulin-dependent) diabetes is a common feature of polycystic ovary syndrome (PCOS). To investigate antecedents of metabolic disorders in family members of patients with PCOS, we evaluated glucose tolerance and insulin resistance in parents of patients with PCOS compared to parents of healthy women., Methods: A total of 200 parents of women with clinical and hormonal evidence of PCOS (PCOSp) and 120 parents of healthy normally cycling women (HWp) were studied. A 75-g OGGT was performed and subjects were classified according to the World Health Organization (WHO) criteria (1999). Serum glucose and insulin were measured before the glucose load and 30, 60 and 120 min after. C-peptide and sex hormone-binding globulin were also determined before the glucose load. Insulin resistance was assessed by HOMA model and ISI composite., Results: The prevalence of Type II diabetes was 1.89-(1.06-3.38)-fold higher in PCOSp compared to HWp. Insulin resistance, evaluated by HOMA(IR)and ISI composite was also significantly higher in the PCOSp group compared to the HWp group. After both study groups were distributed by sex, and adjusted by age and BMI, the metabolic parameters were still significantly different between PCOSp and HWp., Conclusions/interpretation: The data suggest that parents of PCOS women exhibit insulin resistance and Type II diabetes more frequently than those of healthy women, thus constituting a high-risk group but an ideal cohort to detect and prevent the development of Type II diabetes.

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.

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]