Michael Conall Dennedy

Atlantic DIP: high prevalence of abnormal glucose tolerance post partum is reduced by breast-feeding in women with prior gestational diabetes mellitus

OBJECTIVE Gestational diabetes (GDM) is associated with adverse fetal and maternal outcomes, and identifies women at risk of future type 2 diabetes mellitus (T2DM). Breast-feeding may improve post partum maternal glucose tolerance. Our objective was to identify the prevalence of post partum dysglycemia after GDM, to delineate associated factors and to examine the effect of lactation on post partum glucose tolerance. DESIGN We compared post partum 75 g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT) in five regional centers. Breast-feeding data was collected at time of OGTT. Methods Post partum OGTT results were classified as normal (fasting plasma glucose (FPG) <5.6 mmol/l, 2 h <7.8 mmol/l) and abnormal (impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2 h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPG ≥7 mmol/l±2 h glucose ≥11.1 mmol/l). Binary logistic regression was used to identify factors predictive of persistent hyperglycemia. RESULTS Five hundred and twenty women were tested; six (2.7%) with NGT in pregnancy had post partum dysglycemia compared with 57 (19%) with GDM in index pregnancy (P<0.001). Non-European ethnicity (odds ratio (OR) 3.40; 95% confidence interval (CI) 1.45-8.02, P=0.005), family history of T2DM (OR 2.14; 95% CI 1.06-4.32, P=0.034), and gestational insulin use (OR 2.62; 95% CI 1.17-5.87, P=0.019) were associated with persistent dysglycemia. The prevalence of persistent hyperglycemia was significantly lower in women who breast-fed vs bottle-fed post partum (8.2 vs 18.4%, P<0.001). CONCLUSIONS Non-European ethnicity, gestational insulin use, family history of T2DM, and elevated body mass index were associated with persistent dysglycemia after GDM. Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged.

ATLANTIC-DIP: excessive gestational weight gain and pregnancy outcomes in women with gestational or pregestational diabetes mellitus.

CONTEXT Women who have diabetes mellitus during pregnancy are at higher risk of adverse outcomes. Excessive gestational weight gain (GWG) is also emerging as a risk factor for maternofetal complications, and in 2009, the Institute of Medicine published recommendations for appropriate GWG. It is unclear whether excessive GWG confers additional risk to women with diabetes in pregnancy and whether Institute of Medicine recommendations are applicable to this population. OBJECTIVE The objective of this study was to examine whether excessive GWG in pregnancies complicated by diabetes mellitus is associated with higher adverse obstetric outcomes. DESIGN This was an observational study. SETTING The study was conducted at five antenatal centers along the Irish Atlantic seaboard. PARTICIPANTS 802 women with diabetes in pregnancy participated in the study. MAIN OUTCOME MEASURE Maternal outcomes examined included preeclampsia, gestational hypertension, and cesarean delivery. Fetal outcomes included large for gestational age (LGA), macrosomia, and small for gestational age. RESULTS Excessive GWG was noted in 59% of women. In all women, excessive GWG resulted in higher odds for LGA [adjusted odds ratio (aOR) 2.01, 95% confidence intervals 1.24-3.25 in GDM; aOR 3.97, CI 1.85-8.53 in pregestational diabetes mellitus (PGDM)] and macrosomia (aOR 2.17, CI 1.32-3.55 in GDM; aOR 3.58, CI 1.77-7.24 in PGDM). Excessive GWG was also associated with an increased odds for gestational hypertension (aOR 1.72, CI 1.04-2.85) in women with GDM, and treatment with insulin further increased the odds for LGA (aOR 2.80, CI 1.23-6.38) and macrosomia (aOR 5.63, CI 2.16-14.69) in this group. CONCLUSION We show that in the already high-risk settings of both GDM and PGDM, excessive GWG confers an additive risk for LGA birth weight, macrosomia, and gestational hypertension.

The maternal and fetal impacts of obesity and gestational diabetes on pregnancy outcome

Obesity has reached pandemic proportions and is of growing concern worldwide. Adverse health outcomes associated with a raised body mass index present the greatest challenge currently facing clinicians across all disciplines. Obesity is a chronic illness which is associated with metabolic disease, nutritional deficiency, musculoskeletal complications and cancer. These obesity-related health issues extend to pregnancy where they are responsible for producing a variety of medical and obstetric complications resulting in an increased incidence of maternal and fetal adverse outcomes. Management of diet, gestational diabetes and gestational and inter-gestational weight may improve outcomes in women who are obese during pregnancy. Specific recommendations for the management of obesity in pregnancy have recently been published.

ATLANTIC-DIP: Raised Maternal Body Mass Index (BMI) Adversely Affects Maternal and Fetal Outcomes in Glucose-Tolerant Women According to International Association of Diabetes and Pregnancy Study Groups (IADPSG) Criteria

CONTEXT Raised maternal body mass index (BMI) in association with hyperglycemia is associated with adverse pregnancy outcome. The contribution of raised BMI as an independent risk factor for adverse pregnancy outcome is of growing concern and increasing prevalence. OBJECTIVE The aim of this study was to investigate the effects of raised maternal BMI on pregnancy outcome in glucose-tolerant women using the International Association of Diabetes and Pregnancy Study Groups criteria. PARTICIPANTS AND SETTING We studied a cohort of glucose-tolerant, pregnant women (n = 3656) who were attending antenatal obstetric clinics and were recruited to a universal screening program for gestational diabetes under the ATLANTIC-DIP partnership. DESIGN We conducted a prospective observational study of pregnancy outcome. Maternal outcomes include glucose, delivery mode, pregnancy-induced hypertension, preeclampsia, antepartum hemorrhage, and postpartum hemorrhage. Fetal outcomes included birthweight, congenital malformation, fetal death, neonatal jaundice, hypoglycemia, and respiratory distress. RESULTS Increasing maternal BMI was associated with adverse pregnancy outcomes: higher cesarean section rates, preeclampsia, pregnancy-induced hypertension, increased birth weight, and congenital malformation. The association of glucose with adverse pregnancy outcome was weak and did not interact with raised BMI. A BMI threshold of 28 kg/m(2) was associated with a significant rise in adverse pregnancy outcome. CONCLUSIONS Raised maternal BMI, within the overweight range, is associated with adverse pregnancy outcomes. These adverse effects of BMI occur independently of maternal glucose. It is apparent that pregnancy unmasks an underlying unhealthy metabolic milieu in obese and overweight women.

Corticosteroids and fetal vasculature: effects of hydrocortisone, dexamethasone and betamethasone on human umbilical artery

Objective To investigate the direct effects of corticosteroids on human umbilical artery resistance, in vitro.

Beta‐3 versus beta‐2 adrenergic agonists and preterm labour: in vitro uterine relaxation effects

Objective 1. To investigate the effects of the selective beta‐3 adrenoreceptor agonist, BRL 37344, on human pregnant myometrial contractility in vitro. 2. to compare these effects with those of the beta‐2 adrenoreceptor agonist, ritodrine.

Methylenedioxymethamphetamine-induced suppression of interleukin-1β and tumour necrosis factor-α is not mediated by serotonin

Abstract The purpose of the present study was to examine the role of serotonin release in methylenedioxymethamphetamine (MDMA)-induced immunosuppression in rats. We examined the effect of pretreatment with the selective serotonin reuptake inhibitor paroxetine, and the tryptophan hydroxylase inhibitor para-chlorophenylalanine on MDMA-induced suppression of interleukin-1β and tumour necrosis factor (TNF)-α secretion following an in vivo lipopolysaccharide challenge. Although paroxetine blocked MDMA-induced serotonin depletion in the cortex and hypothalamus, it failed to alter the suppressive effect of MDMA on lipopolysaccharide-induced TNF-α secretion. Similarly, although para-chlorophenylalanine caused a 90% depletion in cortical and hypothalamic serotonin content, it failed to alter the suppressive effect of MDMA on lipopolysaccharide-induced interleukin-1β or TNF-α secretion. In conclusion, although MDMA is a potent releaser of serotonin, the suppressive effects of MDMA on lipopolysaccharide-induced proinflammatory cytokine secretion cannot be attributed to its serotonin-releasing properties.

Investigation of patients with atypical or severe hyperandrogenaemia including androgen-secreting ovarian teratoma.

Approximately 7% of women of reproductive age manifest polycystic ovary syndrome (PCOS) and <0.5% have other causes of hyperandrogenism including congenital adrenal hyperplasia (CAH), androgen-secreting tumour of an ovary or an adrenal gland, Cushings syndrome or hyperthecosis. The presence of features atypical of PCOS should prompt more extensive evaluation than that usually undertaken. Features atypical of PCOS include the onset of symptoms outside the decade of 15-25 years, rapid progression of symptoms, the development of virilization and a serum testosterone concentration in excess of twice the upper limit of the reference range. Ethnic background, family history and specific clinical findings, e.g. Cushingoid appearance, may inform a focused investigation. Otherwise, patients should have measurement of 17-hydroxyprogesterone (17-OHP) under basal conditions ideally in the early morning, and if abnormal, they should have measurement of 17-OHP one hour after the administration of synthetic ACTH, 250 microg i.v., to screen for CAH, which is present in approximately 2% of hyperandrogenic patients. The overnight cortisol suppression test employing 1 mg dexamethasone at midnight is a sensitive test for Cushings syndrome. Coronal tomographic (CT) scanning of the adrenals and transvaginal ultrasonography of the ovaries are the investigations of choice when screening for tumours in these organs. Less frequently required is catheterization and sampling from both adrenal and ovarian veins, which is a technically demanding procedure with potential complications which may provide definitive diagnostic information not available from other investigations. Illustrative case reports highlight some complexities in the investigation of hyperandrogenic patients presenting with features atypical of PCOS and include only the ninth case report of an androgen-secreting ovarian teratoma.

Anti-hypertensive therapy and the feto-placental circulation: effects on umbilical artery resistance.

Abstract Objective: To investigate and compare the direct effects of compounds used in the treatment of hypertensive disease in pregnancy on human umbilical artery resistance in vitro. Methods: Isometric tension recordings were performed under physiological conditions on human umbilical arterial rings (n=30). The in vitro effects of labetolol, hydralazine, alpha-methyldopa, nifedepine and magnesium sulphate (at concentration ranges from 1 nanomolar to 1 millimolar), and their respective vehicle controls, were measured. Results were expressed as −logEC50 (pD2) and mean maximal inhibition values for each compound. Results: All compounds investigated, except alpha methyldopa, exerted a significant relaxant effect on umbilical arterial tone. Alpha-methyldopa was significantly less potent when compared to all other compounds (mean maximal inhibition value [20.89±7.99%] versus all other agents [range 63.15±8.70−84.12±3.84%] (P<0.01)). The dose response curve of nifedipine yielded a significantly greater pD2 value when compared to that of hydralazine, labetalol, and magnesium sulphate (pD2 value [5.82±0.34] versus the above groups [range 3.10±0.09−3.52±0.14] (P<0.01)). Conclusion: These findings demonstrate that agents commonly used for the treatment of hypertensive disease in pregnancy, excluding alpha-methyldopa, have significant direct effects on the feto-placental circulation. These results suggest that alpha-methyldopa administration during pregnancy is less likely to produce significant direct effects on fetal vasculature then other agents used.

The prevalence of diabetes, pre-diabetes and the metabolic syndrome in an Irish regional homeless population

BACKGROUND Diabetes is a major chronic health condition. Prevalence is rising, superseding public health estimates. Chronic diseases are more common among lower socioeconomic groups, for example, the homeless population. There is paucity of data on the health status of the homeless population in Ireland, and the prevalence of diabetes and associated cardiovascular risk factors is unknown. AIM We aimed to assess the prevalence of diabetes, pre-diabetes and the metabolic syndrome (MetS) in an Irish regional homeless population. DESIGN This study is a cross-sectional study of the homeless population living in a regional university city of Ireland. METHODS After informed consent and following an overnight fast, blood was drawn for fasting plasma glucose, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein and glycosylated haemoglobin (HbA1c). A 75 g glucose load was given orally and an oral glucose tolerance test completed. Anthropometric measurements and blood pressure were recorded. Smoking, alcohol and drug status were noted. RESULTS Of the 252 participants, 8% (n = 20), 10% (n = 24) and 21% (n = 54) were diagnosed with type 2 diabetes, pre-diabetes and MetS, respectively. Obesity (body mass index >30) was present in 22%, while 90% displayed abdominal obesity. Participants who screened positive for diabetes, pre-diabetes and MetS demonstrated an inferior cardiovascular risk profile. CONCLUSION The prevalence of diabetes, pre-diabetes and MetS in this homeless population is in keeping with national estimates. As this cohort is less likely to seek health care, this may result in later diagnosis and a greater risk of diabetic complications at presentation.