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Genetic Predisposition to Polycystic Ovary Syndrome, Postpartum Weight Reduction, and Glycemic Changes: A Longitudinal Study in Women With Prior Gestational Diabetes.

ABSTRACT: Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women and a major female-specific risk factor of obesity, impaired glucose tolerance, and diabetes.We examined whether the genetic variation predisposing to PCOS affected glycemic changes in women with prior gestational diabetes mellitus (GDM) and whether such an effect was modified by changes in body adiposity, especially during and after pregnancy.This is a longitudinal study in Tianjin, China. We genotyped 7 genome-wide association study-identified PCOS single nucleotide polymorphisms and assessed gestational weight gain and changes in glycemic traits and weight at 1 to 5 years postpartum in 1133 women with prior GDM.The main outcome measure was postpartum glycemic changes.The PCOS genetic risk score significantly interacted with postpartum weight reduction on changes in fasting glucose and 2-h glucose (P for interaction = .032 and .007; respectively) after multivariable adjustment. In women with postpartum weight reduction of ? 5 kg/y, the genetic risk score was associated with decreased fasting and 2-h glucose, whereas an opposite genetic effect was found in women who lost less weight. The association between postpartum weight reduction and glycemic improvement was more significant among women with a higher genetic risk score.In a large cohort of Chinese women with a history of GDM, our data for the first time indicate that the genetic predisposition to PCOS may interact with postpartum weight reduction on long-term glycemic changes, emphasizing the importance of postpartum weight management in prevention of diabetes in this subgroup of women.

SUBMITTER: Wang T

PROVIDER: S-EPMC4667164 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Genetic Predisposition to Polycystic Ovary Syndrome, Postpartum Weight Reduction, and Glycemic Changes: A Longitudinal Study in Women With Prior Gestational Diabetes.

Wang Tiange T Leng Junhong J Li Nan N Martins de Carvalho Aline A Huang Tao T Zheng Yan Y Li Weiqin W Liu Huikun H Wang Leishen L Hu Gang G Qi Lu L

The Journal of clinical endocrinology and metabolism 20151002 12

<h4>Context</h4>Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women and a major female-specific risk factor of obesity, impaired glucose tolerance, and diabetes.<h4>Objective</h4>We examined whether the genetic variation predisposing to PCOS affected glycemic changes in women with prior gestational diabetes mellitus (GDM) and whether such an effect was modified by changes in body adiposity, especially during and after pregnancy.<h4>Design, setting, and participants< ...[more]

PMID: 26431507

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Project description:BackgroundWomen with polycystic ovary syndrome are more likely to experience several pregnancy complications including hypertensive disorders, gestational diabetes mellitus, and preterm births than women without polycystic ovary syndrome. However, at present, there is limited research on whether polycystic ovary syndrome is associated with both anxiety and depression during pregnancy and whether this augments a woman's risk of postpartum depression, particularly among high-risk populations who have limited access to care.ObjectiveOur primary objective was to assess the association between prepregnancy polycystic ovary syndrome and postpartum depression, considering important baseline confounding factors. Our secondary objective was to evaluate the mediating role of prenatal depression and anxiety on the association between polycystic ovary syndrome and postpartum depression.Study designThis study involved a population-based sample of 3906 postpartum (2-6 months) women who completed the Utah Pregnancy Risk Assessment Monitoring System Phase 8 questionnaire (2016-2018). Weighted adjusted prevalence ratios were used to assess the association between polycystic ovary syndrome and postpartum depression, considering potential confounding factors and assessing mediating effects of depression and anxiety experienced during pregnancy.ResultsFollowing the exclusion criteria, 8.2% of women reported clinical polycystic ovary syndrome and 19.1%, 6.2%, and 4.4% reported irregular periods and acne, irregular periods and hirsutism, and all 3 symptoms, respectively. Moreover, 17.7% and 23.5% reported experiencing prenatal depression and anxiety and 9.5% and 10.2% reported experiencing postpartum depressed mood and anhedonia, respectively. Clinical polycystic ovary syndrome was associated with a 1.76 higher adjusted prevalence ratio (95% confidence interval, 1.03-3.00) for postpartum depressed mood or anhedonia after taking into consideration age, prepregnancy body mass index, race/ethnicity, education, and marital status. A similar higher prevalence was seen for irregular periods and acne (adjusted prevalence ratio, 1.65; 95% confidence interval, 1.13-2.41), irregular periods and hirsutism (adjusted prevalence ratio, 1.40; 95% confidence interval, 0.82-2.40), and all 3 symptoms (adjusted prevalence ratio, 1.75; 95% confidence interval, 0.96-3.19) and postpartum depressed mood or anhedonia. Prenatal depression and anxiety mediated 20% and 32% of the effect of clinical polycystic ovary syndrome on postpartum depressed mood and anhedonia, respectively.ConclusionClinical polycystic ovary syndrome is associated with postpartum depressed mood and symptoms among this population-based sample inclusive of high-risk mothers. Prenatal depression and anxiety mediate this association, emphasizing the importance of prenatal psychological screening among women with polycystic ovary syndrome. An additional important clinical and public health implication of this study lies in the finding that nearly 20% of women in this population-based sample who reported at least 2 polycystic ovary syndrome symptoms (including at-risk women who may not have access to care) had not received a clinical diagnosis for polycystic ovary syndrome.

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:AimsWomen with prior gestational diabetes mellitus (GDM) or high genetic susceptibility are prone to development of type 2 diabetes. We examined whether a lifestyle intervention modified the genetic effect on changes in glycemic markers among women with prior GDM.Research design and methodsThis study included 560 women with prior GDM from a randomized controlled trial, the Tianjin Gestational Diabetes Mellitus Prevention Program, who were assigned into an intervention arm (improved physical activity and healthy dietary intakes) or a control arm. We assessed associations of GDM related genetic variants in/near the CDKAL1 (rs7754840) and MTNR1B (rs10830962) genes with changes in fasting levels of glucose and insulin, β-cell function (HOMA-B) and insulin resistance (HOMA-IR) at 1 year and 2 years after the baseline.ResultsWe found significant interactions between CDKAL1 variant rs7754840 and lifestyle intervention on changes in fasting insulin and HOMA-IR at 1 year (P for interactions = 0.008 and 0.006, respectively). The GDM-increasing C allele was associated with a 0.07-unit greater increase in fasting insulin (P = 0.048) and HOMA-IR (P = 0.045) in the control group, while opposite-directional associations were observed in the intervention group; women with the C allele seemed to decrease more in these glycemic markers than the non-C-carriers (both P ≤ 0.06). The interactions between the CDKAL1 genetic variant and lifestyle intervention on changes in fasting insulin (P = 0.035) and HOMA-IR (P = 0.024) remained significant over the 2-year period, even though the effects of lifestyle intervention were attenuated at 2-year. The MTNR1B variant rs10830962 did not show interaction with lifestyle intervention on changes in the glycemic markers.ConclusionsHealthy lifestyle intervention may be beneficial for women with the GDM predisposing CDKAL1 genetic variant in improvement of insulin resistance.Trial registration numberClinicalTrials.gov NCT01554358. URL OF REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01554358.

Project description:ObjectiveTo assess patterns and predictors of postpartum diabetes screening in a commercially insured, geographically and sociodemographically diverse sample of women with gestational diabetes mellitus.MethodsUsing commercial insurance claims (2000-2012) from all 50 states, we conducted a retrospective cohort study in 447,556 women with at least one delivery and continuous enrollment 1 year before and after delivery. We identified women with a gestational diabetes mellitus pregnancy and examined postpartum diabetes screening type and timing and performed logistic regression to identify screening predictors.ResultsGestational diabetes mellitus was diagnosed in 32,253 (7.2%) women during the study timeframe. Three fourths received no screening within 1 year postpartum. Rates of recommended 75-g oral glucose tolerance testing within 6-12 weeks were low but increased over time (27 [2%] in 2001 compared with 249 [7%] in 2011, adjusted odds ratio [OR] 3.1, 95% confidence interval [CI] 2.0-47). Among women screened, those in the Northeast (19%) and South (18%) were least likely to receive a 75-g oral glucose tolerance test within 0-12 weeks (adjusted OR 0.4 for each, CI 0.4-0.5) compared with the West (36%). Asian women were most likely to receive any screening (18%; adjusted OR 1.5, CI 1.3-1.6) compared with white women (12%). Black women were most likely to receive hemoglobin A1c (21%; adjusted OR 2.0, CI 1.3-3.2) compared with white women (11%). Antepartum antiglycemic medication (21%; adjusted OR 2.1, CI 2.0-2.3) or visit to a nutritionist-diabetes educator (19%; adjusted OR 1.6, CI 1.4-1.7) or endocrinologist (23%; adjusted OR 1.7, CI 1.6-1.9) predicted screening within 12 weeks postpartum.ConclusionPostpartum diabetes screening remains widely underused among commercially insured women with gestational diabetes mellitus. Differences in screening by geography, race, and antepartum care can inform health system and public health interventions to increase diabetes detection in this high-risk population.

Dataset Information

Genetic Predisposition to Polycystic Ovary Syndrome, Postpartum Weight Reduction, and Glycemic Changes: A Longitudinal Study in Women With Prior Gestational Diabetes.

Publications

Genetic Predisposition to Polycystic Ovary Syndrome, Postpartum Weight Reduction, and Glycemic Changes: A Longitudinal Study in Women With Prior Gestational Diabetes.

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