Reported prevalence of gestational diabetes in Scotland: the relationship with obesity, age, socioeconomic status, smoking and macrosomia, and how many are we missing?

Aims/Introduction: Gestational diabetes mellitus (GDM) is defined as ‘carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy,’ and is associated with increased fetal and maternal risks. The aims of the present study were to investigate the prevalence of GDM in Scotland over 32 years (1981–2012), and using the data from 2012, to assess how GDM related to maternal body mass index, maternal age, parity, smoking, Scottish Index of Multiple Deprivation, infant gender and macrosomia status. Materials and Methods: GDM prevalence along with anthropometric, obstetric and demographic data were collected on a total of 1,891,097 women with a delivery episode between 1 January 1981 and 31 December 2012 using data extracted from the Scottish Morbidity Record 02. Univariate and multivariate logistic regression analysis was undertaken to investigate their association with GDM. Results: A ninefold increase in GDM prevalence was observed from 1981 to 2012 (P < 0.001). GDM prevalence in 2012 was 1.9%. Maternal body mass index, age, parity status, Scottish index of multiple deprivation and fetal macrosomia were positively associated with GDM. Reported smoking status at booking was inversely associated with GDM. Multivariable analysis showed that fetal macrosomia was not associated with GDM status. Conclusions: The present study confirmed that the reporting of GDM is low in Scotland, and that GDM is associated with maternal body mass index, maternal age, multiparity and social deprivation. GDM was negatively associated with smoking and requires further investigation. The lack of association between GDM and macrosomia (following multivariate analysis) might reflect the screening processes undertaken in Scotland

Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21) ratios and placental FGF21 production in gestational diabetes

Objectives: Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants. Design: CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m2) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m2)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA. Results: Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05). Conclusions: The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points

Scientific Evidence for Different Options for GDM Screening and Management: Controversies and Review of the Literature.

Background. Gestational diabetes (GDM) affects up to 7% of pregnant women and is associated with several maternal and perinatal morbidities. International organizations suggest several different recommendations regarding how to screen and to manage GDM. Objective. We aimed to analyze the most important and employed guidelines about screening and management of GDM and we investigated existing related literature. Results. We found several different criteria for screening for GDM, for monitoring GDM, and for starting pharmacological therapy. When using IADPSG criteria, GDM rate increased, perinatal outcomes improved, and screening became cost-effective. Compared to no treatment, treatment of women meeting criteria for GDM by IADPSG criteria but not by other less strict criteria has limited evidence for an effect on adverse pregnancy outcomes

Visceral Adipose Tissue Inflammatory Factors (TNF-Alpha, SOCS3) in Gestational Diabetes (GDM): Epigenetics as a Clue in GDM Pathophysiology

Gestational diabetes (GDM) is among the most challenging diseases in westernized countries, affecting mother and child, immediately and in later life. Obesity is a major risk factor for GDM. However, the impact visceral obesity and related epigenetics play for GDM etiopathogenesis have hardly been considered so far. Our recent findings within the prospective 'EaCH' cohort study of women with GDM or normal glucose tolerance (NGT), showed the role, critical factors of insulin resistance (i.e., adiponectin, insulin receptor) may have for GDM pathophysiology with epigenetically modified expression in subcutaneous (SAT) and visceral (VAT) adipose tissues. Here we investigated the expression and promoter methylation of key inflammatory candidates, tumor necrosis factor-alpha (TNF-α) and suppressor of cytokine signaling 3 (SOCS3) in maternal adipose tissues collected during caesarian section (GDM, n = 19; NGT, n = 22). The mRNA expression of TNF-α and SOCS3 was significantly increased in VAT, but not in SAT, of GDM patients vs. NGT, accompanied by specific alterations of respective promoter methylation patterns. In conclusion, we propose a critical role of VAT and visceral obesity for the pathogenesis of GDM, with epigenetic alterations of the expression of inflammatory factors as a potential factor

The prevalence of gestational diabetes mellitus and its related risk factors in Gorgan, north of Iran. Selective or universal screening test is cost-effective?

Gestational diabetes mellitus (GDM) is the most prevalent metabolic disorder in pregnancy. GDM is defined in <1 % to 28 % of pregnancies, depending on the diagnostic criteria, the ethnic and racial characteristics. This study was performed to determine the prevalence of GDM and related risk factors among pregnant women in Gorgan, north of Iran. In a cross sectional study, 1276 pregnant women were recruited. All of women screened with glucose challenge test (GCT) in 24–28th wks of gestational age. Women with positive GCT underwent 100 g glucose tolerance test (OGTT). Diagnosis of GDM was according to Carpenter and Coustan’s criteria. GCT was positive in 200 women (15.8 % with CI: 13.8 %–17.8 %) and GDM was diagnosed in 62 case (4.9 % with CI:3.7 %–6.8 %). In a multiple logistic regression, risk factors such as age, BMI, history of macrosomia, familial history of diabetes and impaired fasting glucose (IFG) were identified as independent risk factors for GDM (p < 0.05). Among GDM cases, 3.2 %(2 women) had no risk factor. These results show moderate prevalence of GDM in north of Iran. It seems that a selective GDM screening method for women with some risk factors is more appropriate than general screening. © 2015, Research Society for Study of Diabetes in India

Breastfeeding after Gestational Diabetes: Does Perceived Benefits Mediate the Relationship?

Introduction. Breastfeeding is recognized as one of the best ways to decrease infant mortality and morbidity. However, women with gestational diabetes mellitus (GDM) may have breastfeeding barriers due to the increased risk of neonatal and pregnancy complications. While the prevalence of GDM is increasing worldwide, it is important to understand the full implications of GDM on breastfeeding outcomes.The current study aims to investigate the (1) direct effect of GDM on breastfeeding duration and (2) indirect effect of GDM on breastfeeding duration through perceived benefits of breastfeeding. Methods. Prospective cohort data from the Infant Feeding and Practices Study II was analyzed (=4,902). Structural equation modeling estimated direct and indirect effects. Results. Perceived benefits of breastfeeding directly influenced breastfeeding duration ( = 0.392, ≤ 0.001). GDM was not directly associated with breastfeeding duration or perceived benefits of breastfeeding. Similarly, GDM did not have an indirect effect on breastfeeding duration through perceived benefits of breastfeeding. Conclusions. Perceived benefits of breastfeeding are an important factor associated with breastfeeding duration. Maternal and child health care professionals should enhance breastfeeding education efforts

Epigenetic Down-Regulation of Sirt 1 via DNA Methylation and Oxidative Stress Signaling Contributes to the Gestational Diabetes Mellitus-Induced Fetal Programming of Heart Ischemia-Sensitive Phenotype in Late Life.

Rationale: The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. However, whether and how GDM exposure induces fetal programming of adult cardiac dysfunctional phenotype, especially the underlying epigenetic molecular mechanisms and theranostics remain unclear. To address this problem, we developed a late GDM rat model. Methods: Pregnant rats were made diabetic on day 12 of gestation by streptozotocin (STZ). Experiments were conducted in 6 weeks old offspring. Results: There were significant increases in ischemia-induced cardiac infarction and gender-dependent left ventricular (LV) dysfunction in male offspring in GDM group as compared to controls. Exposure to GDM enhanced ROS level and caused a global DNA methylation in offspring cardiomyocytes. GDM attenuated cardiac Sirt 1 protein and p-Akt/Akt levels, but enhanced autophagy-related proteins expression (Atg 5 and LC3 II/LC3 I) as compared to controls. Ex-vivo treatment of DNA methylation inhibitor, 5-Aza directly inhibited Dnmt3A and enhanced Sirt 1 protein expression in fetal hearts. Furthermore, treatment with antioxidant, N-acetyl-cysteine (NAC) in offspring reversed GDM-mediated DNA hypermethylation, Sirt1 repression and autophagy-related gene protein overexpression in the hearts, and rescued GDM-induced deterioration in heart ischemic injury and LV dysfunction. Conclusion: Our data indicated that exposure to GDM induced offspring cardiac oxidative stress and DNA hypermethylation, resulting in an epigenetic down-regulation of Sirt1 gene and aberrant development of heart ischemia-sensitive phenotype, which suggests that Sirt 1-mediated signaling is the potential therapeutic target for the heart ischemic disease in offspring

Implementation of the International Association of Diabetes and Pregnancy Study Groups criteria: Not always a cause for concern

Background: Controversy surrounds the decision to adopt the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for the diagnosis of gestational diabetes mellitus (GDM) as fears that disease prevalence rates will soar have been raised. Aims: To investigate the prevalence of pregnancy complicated with GDM before and after the introduction of the IADPSG 2010 diagnostic criteria. Materials and Methods: A prospective audit of all women who delivered from July 1, 2010, to June 30, 2014, in a predefined geographic region within the North Metropolitan Health Service of Western Australia. Women were diagnosed with GDM according to Australian Diabetes in Pregnancy Society (ADIPS 1991) criteria until December 31, 2011, and by the IADPSG 2010 criteria after this date. Incidence of GDM and predefined pregnancy outcomes were audited. Results: Of 10,296 women, antenatal oral glucose tolerance test (OGTT) results and follow-up data were obtained for 10,103 women (98%), of whom 349 (3.5%) were diagnosed with GDM. The rate of GDM utilising ADIPS criteria was 3.4% and the rate of utilising IADPSG criteria was 3.5% ( = 0.92). Conclusion: IADPSG diagnostic criteria did not significantly increase the incidence of GDM in this low prevalence region

Early antenatal prediction of gestational diabetes in obese women: development of prediction tools for targeted intervention

All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0–18+6 weeks’ gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68–0.74). This increased to 0.77 (95%CI 0.73–0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74–0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most