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Association of type 2 diabetes mellitus genes in polycystic ovary syndrome aetiology among women from southern India.

ABSTRACT: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder of premenopausal women. Given the phenotypic overlap between PCOS and type 2 diabetes mellitus (T2DM), this study was carried out to investigate whether genes implicated in T2DM were also involved in the susceptibility to PCOS among women from southern India.A total of 248 women with PCOS and 210 healthy women as controls were genotyped for a panel of 15 single nucleotide polymorphisms (SNPs) from the nine T2DM genes, such as TCF7L2, IGF2BP2, SLC30A8, HHEX, CDKAL1, CDKN2A, IRS1, CAPN10 and PPARG, on Sequenom MassARRAY platform.None of the 15 SNPs were found to be significantly associated with PCOS after Bonferroni correction for multiple testing, either in the univariate or multivariate context. The cumulative effect of risk alleles observed with reference to T2DM was also not seen with reference to PCOS.The nine T2DM genes considered in this exploratory study might not be the primary susceptibility factors for PCOS among Indian women. Our results supplement the lack of evidence of the association of T2DM genes with PCOS among the Chinese and Caucasians hinting at the possible universality of this pattern. Specifically designed comprehensive studies that include women with T2DM and PCOS are required to explore the precise role of the diabetes genes.

SUBMITTER: Reddy BM

PROVIDER: S-EPMC5320846 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Association of type 2 diabetes mellitus genes in polycystic ovary syndrome aetiology among women from southern India.

Reddy Battini Mohan BM Kommoju Uma Jyothi UJ Dasgupta Shilpi S Rayabarapu Pranavchand P

The Indian journal of medical research 20160901 3

<h4>Background & objectives</h4>Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder of premenopausal women. Given the phenotypic overlap between PCOS and type 2 diabetes mellitus (T2DM), this study was carried out to investigate whether genes implicated in T2DM were also involved in the susceptibility to PCOS among women from southern India.<h4>Methods</h4>A total of 248 women with PCOS and 210 healthy women as controls were genotyped for a panel of 15 single nucl ...[more]

PMID: 28139539

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Project description:BackgroundGestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes such as preeclampsia and macrosomia. Women with polycystic ovary syndrome (PCOS) are at increased risk of developing GDM. Today, GDM is diagnosed by oral glucose tolerance test (OGTT), a rather cumbersome test for the women and health care system. The objectives of this study were to investigate whether HbA1c in first trimester of pregnancy could be used as a screening test for GDM in first trimester and throughout pregnancy in order to reduce the number of OGTTs, and whether it could predict preeclampsia and macrosomia in women with PCOS.MethodsPost hoc analyses of data from 228 women from a prospective, randomised, multicenter study comparing metformin to placebo from first trimester to delivery. Fasting and 2-h plasma glucose were measured during a 75 g OGTT in first trimester, gestational week 19 and 32 as well as fasting plasma glucose in gestational week 36. GDM was diagnosed by WHO criteria from 1999 in first trimester and throughout pregnancy and by modified IADPSG criteria (i.e. lacking the 1-h plasma glucose value) in first trimester. The diagnostic accuracy was assessed by logistic regression and ROC curve analysis.ResultsThe area under the ROC curve for first trimester HbA1c for screening of GDM diagnosed by WHO criteria in first trimester was 0.60 (95 % CI 0.44-0.75) and 0.56 (95 % CI 0.47-0.65) for GDM diagnosed throughout pregnancy. Only 2.2 % (95 % CI 0.7-5.1 %) of the participants could have avoided OGTT. HbA1c was not statistically significantly associated with GDM diagnosed by modified IADPSG criteria in first trimester. However, first trimester HbA1c was statistically significantly associated with preeclampsia. Both HbA1c and GDM by WHO criteria in first trimester, but not by IADPSG, were negatively associated with birth weight.ConclusionFirst trimester HbA1c can not be used to exclude or predict GDM in women with PCOS, but it might be better to predict preeclampsia than the GDM diagnosis.

Project description:Aims:Despite the very clear association between polycystic ovary syndrome (PCOS) and dysglycemia, few studies have explored the continuum of glycemic alterations leading from minor glucose abnormalities to overt diabetes. The purpose of this review is to trace the natural history of glycemic alteration in women with PCOS. Methods:We performed a literature review without time limit until August 2019. Inclusion criteria were studies addressing the association between impaired glucose tolerance or impaired fasting glucose or type 2 diabetes (T2D) and PCOS with at least an English abstract. The exclusion criteria were no PCOS or impaired glucose tolerance or impaired fasting glucose or T2D as outcome. The outcomes of interest were the onset of impaired glucose tolerance, impaired fasting glucose, T2D, and the progression from impaired glucose tolerance or impaired fasting glucose to T2D. Results:Healthy diet and physical activity are the first-line therapy for PCOS. Treatment with metformin was associated with significant lower 2-hour postload glucose levels and with reduction in fasting glucose when compared to placebo. Thiazolidinediones were more effective in reducing fasting glucose levels compared to placebo. Metformin and pioglitazone treatments showed similar effects on fasting glucose levels. The sodium-glucose cotransporter-2 inhibitor empagliflozin did not show differences in metabolic parameters when compared to metformin. The combination therapy with metformin plus the glucagon-like peptide-1 receptor agonist liraglutide was associated with significant improvements in basal and postload glucose levels compared with only liraglutide. Likewise, a combination therapy with the dipeptidyl peptidase-4 inhibitor saxagliptin and metformin demonstrated superiority versus metformin in fasting glucose and oral glucose tolerance test normalization. Myo-inositol supplementation was associated with lower insulin levels, glucose levels, and insulin resistance when compared with placebo, metformin, or estrogen treatments. Conclusions:The use of insulin-sensitizing agents, such as metformin and inositols, along with lifestyle interventions may improve the metabolic profile in PCOS women.

Project description:BackgroundPrevious studies have shown that polycystic ovary syndrome is a predictor of gestational diabetes mellitus, but we do not know exactly how many polycystic ovary syndrome patients may develop gestational diabetes mellitus. Currently, the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome varies greatly across studies, ranged from 4.12% to 59.50%. Besides, many factors have been found to be related to the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, but the results among different studies are not consistent. The possible causes of inconsistencies between the current estimates were unclear. This review aimed at exploring the pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, summarizing possible causes of the inconsistencies in the current estimates, try to provide a reference for prevention of gestational diabetes mellitus and polycystic ovary syndrome in the future.MethodsSystematic searches of different databases (including EMBASE, Web of Science, MEDLINE, The Cochrane Library, CNKI and PubMed) were conducted for studies published until 31 May 2021. Statistical analyses were performed using R software, the pooled incidence of gestational diabetes mellitus among polycystic ovary syndrome patients was combined using random effects model. Cochrane's "Tool to Assess Risk of Bias in Cohort Studies" was used for quality assessment.ResultsTwenty-two longitudinal studies were included. A total of 24,574 women with polycystic ovary syndrome were identified in the 22 articles, of which 4478 were reported with gestational diabetes mellitus. The pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome was 20.64%, with a 95% CI of 14.64% to 28.30%. In the meta-regression model, several variables including age, area, quality score and sample size were suggested as significant sources of heterogeneity, accounted for 77.57% of the heterogeneity across studies.ConclusionsEvidence in this review suggests that gestational diabetes mellitus were common among women with polycystic ovary syndrome. More research is needed to found effective interventions for preventing gestational diabetes mellitus among women with polycystic ovary syndrome.

Project description:Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation to be of uncertain cause: obesity, insulin resistance, or PCOS itself. The aim of the study was to investigate the WBC (white blood cell) count and CRP (C-reactive protein) concentration in women with PCOS and to determine the factors that affect their concentration. The study included 200 women aged 18-40 with PCOS and 105 healthy women as the control group, recruited in the Department of Gynaecological Endocrinology of Medical University in Warsaw from 2016 to 2018. Each patient underwent clinical, biochemical, and ultrasonographic assessments. WBC and CRP were significantly higher in the PCOS group (Z = -2,353, p = 0,019 and Z = -2,453, p = 0,014). WBC positively correlated with serum insulin at 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,221, p = 0,001; INS1: r = 0,194, p = 0,003; INS2: r = 0,022, p = 0,001), testosterone (r = 0,130, p = 0,046), androstenedione (r = 0,212, p = 0,001), and DHEAS (r = 0,178, p = 0,006) and negatively correlated with progesterone (r = -0,204, p = 0,002), estradiol (r = -0,140, p = 0,032), and SHBG (r = -0,308, p < 0,001). CRP positively correlated with insulin concentration in 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,343, p < 0,001; INS1: r = 0,276, p = 0,001; INS2: r = 0,320, p < 001) and negatively correlated with progesterone (r = -0,194, p = 0,030) and SHBG (-0,244, p = 0,005). We also estimated positive correlation between BMI and serum CRP and WBC concentration. Multiple linear regression analysis showed that CRP values are positively associated with BMI (beta = 0,374, p < 0,001) and insulin level (INS1) (beta = 0,282, p = 0,004); and WBC results are negatively associated with SHGB (beta = -0,284, p < 0,001) but positively associated with testosterone (beta = 0,163, p = 0,024) and BMI (beta = 0,157, p = 0,047). PCOS is associated with increased WBC and CRP concentrations. The main predicting factors of increased CRP are BMI and insulin resistance, but there is also a relationship between WBC count in PCOS and androgen concentration itself so that inflammation may be mediated not only through adiposity but also through increased androgen concentration.

Project description:BackgroundPolycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions.ObjectivesTo assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS.Search methodsWe searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL and AMED (date of last search March 2018). We also searched controlled trials registries, conference abstracts, relevant journals, reference lists of relevant papers and reviews, and grey literature databases, with no language restrictions applied.Selection criteriaRandomised controlled trials (RCTs) comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS.Data collection and analysisTwo authors independently selected trials, assessed evidence quality and risk of bias, and extracted data. Our primary outcomes were live birth, miscarriage and pregnancy. We used inverse variance and fixed-effect models in the meta-analyses. We reported dichotomous outcomes as an odds ratio and continuous outcomes as a mean difference (MD) or standardised mean difference (SMD).Main resultsWe included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review.Lifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I2 = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I2 = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m2) (-0.34 kg/m2, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I2= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I2 = 0%, low-quality evidence).Authors' conclusionsLifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.

Dataset Information

Association of type 2 diabetes mellitus genes in polycystic ovary syndrome aetiology among women from southern India.

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Association of type 2 diabetes mellitus genes in polycystic ovary syndrome aetiology among women from southern India.

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