Retrospective national cohort study of pregnancy outcomes for women with type 1 and type 2 diabetes mellitus in Republic of Ireland.

AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.

The diagnostic utility of late night salivary cortisol (LNSF) and cortisone (LNSE) in Cushing's syndrome.

BACKGROUND: Measurement of late night salivary cortisol (LNSF) is useful in the identification of cyclical Cushing's syndrome (CS); the usefulness of its metabolite cortisone (late night salivary cortisone, LNSE) is less well described. AIM: The aim of this study was to determine the utility of measuring LNSE in patients with confirmed CS compared with other diagnostic tests and to analyse serial LNSF measurements for evidence of variable hormonogenesis. METHODS: This was a retrospective observational study including patients with confirmed CS in whom LNSF and LNSE were measured. RESULTS: Twenty-three patients with confirmed CS were included, 21 with Cushing's disease. LNSF had a sensitivity of 92%, LNSE 87% and combined LNSF/LNSE 94% per sample. Four patients had cyclical hormonogenesis, when the definition of one trough and two peaks was applied to LNSF measurements, and a fifth patient fell just outside the criteria. Six patients had evidence of variable hormonogenesis, defined as doubling of LNSF concentration on serial measurements. Sensitivity of 24-h urinary free cortisol (UFC) was 89% per collection. Sixteen patients had simultaneous measurements of LNSF and UFC; in three patients, they provided discordant results. CONCLUSION: LNSF appears more sensitive than LNSE and UFC in the diagnosis of CS, combining LNSF and LNSE results leads to superior sensitivity. Half of our cohort had evidence of cyclical or variable hormonogenesis. Fluctuations in LNSF did not always correlate with changes in UFC concentration, emphasising the importance of performing more than one screening test, particularly if pretest clinical suspicion is high.

Pregnancy outcomes in women with onset of type 1 diabetes mellitus less than 18 years of age.

BACKGROUND: Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with an increased risk of congenital malformations, obstetric complications and neonatal morbidity. This study aims to investigate maternal, perinatal and neonatal outcomes of pregnancies in women with onset of T1DM less than 18 years of age. METHODS: This retrospective cohort study extracted data regarding prenatal, intrapartum and postnatal outcomes of pregnancies in women with onset of T1DM<18 years identified from the diabetes in pregnancy register at University Maternity Hospital Limerick, treated from July 1, 2007 to July 1, 2017. RESULTS: Seventeen women with onset of T1DM <18 years gave birth to 23 live infants during the period studied. 73.9% of pregnancies were unplanned. Only 21.7% of pregnancies took preconceptual folic acid. 60.9% of infants required treatment for hypoglycemia. CONCLUSION: The high prevalence of unplanned pregnancy and poor uptake of prepregnancy care must be improved on in order to improve outcomes for this high-risk group.

Follow-up at 1 year and beyond of women with gestational diabetes treated with insulin and/or oral glucose-lowering agents: a core outcome set using a Delphi survey.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is linked with a higher lifetime risk for the development of impaired fasting glucose, impaired glucose tolerance, type 2 diabetes, the metabolic syndrome, cardiovascular disease, postpartum depression and tumours. Despite this, there is no consistency in the long-term follow-up of women with a previous diagnosis of GDM. Further, the outcomes selected and reported in the research involving this population are heterogeneous and lack standardisation. This amplifies the risk of reporting bias and diminishes the likelihood of significant comparisons between studies. The aim of this study is to develop a core outcome set (COS) for RCTs and other studies evaluating the long-term follow-up at 1 year and beyond of women with previous GDM treated with insulin and/oral glucose-lowering agents. METHODS: The study consisted of three work packages: (1) a systematic review of the outcomes reported in previous RCTs of the follow-up at 1 year and beyond of women with GDM treated with insulin and/or oral glucose-lowering agents; (2) a three-round online Delphi survey with key stakeholders to prioritise these outcomes; and (3) a consensus meeting where the final COS was decided. RESULTS: Of 3344 abstracts identified and evaluated, 62 papers were retrieved and 25/62 papers were included in this review. A total of 121 outcomes were identified and included in the Delphi survey. Delphi round 1 was emailed to 835 participants and 288 (34.5%) responded. In round 2, 190 of 288 (65.9%) participants responded and in round 3, 165 of 190 (86.8%) participants responded. In total, nine outcomes were selected and agreed for inclusion in the final COS: assessment of glycaemic status; diagnosis of type 2 diabetes since the index pregnancy; number of pregnancies since the index pregnancy; number of pregnancies with a diagnosis of GDM since the index pregnancy; diagnosis of prediabetes since the index pregnancy; BMI; post-pregnancy weight retention; resting blood pressure; and breastfeeding. CONCLUSIONS/INTERPRETATION: This study identified a COS that will help bring consistency and uniformity to outcome selection and reporting in clinical trials and other studies involving the follow-up at 1 year and beyond of women diagnosed with GDM treated with insulin and/or oral glucose-lowering agents during pregnancy.

A core outcome set for studies evaluating the effectiveness of prepregnancy care for women with pregestational diabetes.

AIMS/HYPOTHESIS: The aim of this study was to develop a core outcome set (COS) for trials and other studies evaluating the effectiveness of prepregnancy care for women with pregestational (pre-existing) diabetes mellitus. METHODS: A systematic literature review was completed to identify all outcomes reported in prior studies in this area. Key stakeholders then prioritised these outcomes using a Delphi study. The list of outcomes included in the final COS were finalised at a face-to-face consensus meeting. RESULTS: In total, 17 outcomes were selected and agreed on for inclusion in the final COS. These outcomes were grouped under three domains: measures of pregnancy preparation (n = 9), neonatal outcomes (n = 6) and maternal outcomes (n = 2). CONCLUSIONS/INTERPRETATION: This study identified a COS essential for studies evaluating prepregnancy care for women with pregestational diabetes. It is advocated that all trials and other non-randomised studies and audits in this area use this COS with the aim of improving transparency and the ability to compare and combine future studies with greater ease.

Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria.

OBJECTIVE: An increase in gestational diabetes mellitus (GDM) prevalence has been demonstrated across many countries with adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. Here, we determine the cumulative incidence of abnormal glucose tolerance among women with previous GDM, and identify clinical risk factors predicting this. DESIGN: Two hundred and seventy women with previous IADPSG-defined GDM were prospectively followed up for 5years (mean 2.6) post-index pregnancy, and compared with 388 women with normal glucose tolerance (NGT) in pregnancy. METHODS: Cumulative incidence of abnormal glucose tolerance (using American Diabetes Association criteria for impaired fasting glucose, impaired glucose tolerance and diabetes) was determined using the Kaplan-Meier method of survival analysis. Cox regression models were constructed to test for factors predicting abnormal glucose tolerance. RESULTS: Twenty-six percent of women with previous GDM had abnormal glucose tolerance vs 4% with NGT, with the log-rank test demonstrating significantly different survival curves (P<0.001). Women meeting IADPSG, but not the World Health Organization (WHO) 1999 criteria, had a lower cumulative incidence than women meeting both sets of criteria, both in the early post-partum period (4.2% vs 21.7%, P<0.001) and at longer-term follow-up (13.7% vs 32.6%, P<0.001). Predictive factors were glucose levels on the pregnancy oral glucose tolerance test, family history of diabetes, gestational week at testing, and BMI at follow-up. CONCLUSIONS: The proportion of women developing abnormal glucose tolerance remains high among those with IADPSG-defined GDM. This demonstrates the need for continued close follow-up, although the optimal frequency and method needs further study.

Health related quality of life two to five years after gestational diabetes mellitus: cross-sectional comparative study in the ATLANTIC DIP cohort.

BACKGROUND: There is no consensus on the effect of gestational diabetes mellitus (GDM) on health-related quality of life (HRQOL) for the mother in the short or long term. In this study we examined HRQOL in a group of women who had GDM in the index pregnancy 2 to 5 years previously and compared it to a group of women with normal glucose tolerance (NGT) in the index pregnancy during the same time period. METHODS: The sample included 234 women who met International Association of Diabetes Study Groups (IADPSG) criteria for GDM in the index pregnancy and 108 who had NGT. The sample was drawn from the ATLATIC-DIP (Diabetes In Pregnancy) cohort - a network of antenatal centers along the Irish Atlantic seaboard serving a population of approximately 500,000 people. HRQOL was measured using the visual analogue component of the EQ-5D-3 L instrument in a cross-sectional survey. RESULTS: The difference in HRQOL between GDM and NGT groups was not significant when adjusted for the effects of the covariates. HRQOL was negatively affected by increased BMI and abnormal glucose tolerance post-partum in the NGT group. Moderate alcohol consumption was positively associated with HRQOL in the NGT group only. The negative association with smoking on HRQOL was substantially higher in the GDM group. CONCLUSIONS: A diagnosis of GDM does not appear to have an adverse effect on HRQOL, 2 to 5 years after the index pregnancy. On the contrary, its diagnosis might lead to the development of coping strategies, which, consequently attenuates the adverse effect of the subsequent acquisition of abnormal glucose tolerance post-partum on HRQOL. Women whose pregnancy was affected by GDM are more susceptible to the adverse effects on HRQOL of alcohol use and tobacco smoking.

Can the Onset of Type 2 Diabetes Be Delayed by a Group-Based Lifestyle Intervention in Women with Prediabetes following Gestational Diabetes Mellitus (GDM)? Findings from a Randomized Control Mixed Methods Trial.

OBJECTIVE: To evaluate a 12-week group-based lifestyle intervention programme for women with prediabetes following gestational diabetes (GDM). DESIGN: A two-group, mixed methods randomized controlled trial in which 50 women with a history of GDM and abnormal glucose tolerance postpartum were randomly assigned to intervention (n = 24) or wait control (n = 26) and postintervention qualitative interviews with participants. MAIN OUTCOME MEASURES: Modifiable biochemical, anthropometric, behavioural, and psychosocial risk factors associated with the development of type 2 diabetes. The primary outcome variable was the change in fasting plasma glucose (FPG) from study entry to one-year follow-up. RESULTS: At one-year follow-up, the intervention group showed significant improvements over the wait control group on stress, diet self-efficacy, and quality of life. There was no evidence of an effect of the intervention on measures of biochemistry or anthropometry; the effect on one health behaviour, diet adherence, was close to significance. CONCLUSIONS: Prevention programmes must tackle the barriers to participation faced by this population; home-based interventions should be investigated. Strategies for promoting long-term health self-management need to be developed and tested.

Type 2 diabetes after gestational diabetes: The influence of changing diagnostic criteria.

A previous diagnosis of gestational diabetes (GDM) carries a lifetime risk of progression to type 2 diabetes of up to 60%. Identification of those women at higher risk of progression to diabetes allows the timely introduction of measures to delay or prevent diabetes onset. However, there is a large degree of variability in the literature with regard to the proportion of women with a history of GDM who go on to develop diabetes. Heterogeneity between cohorts with regard to diagnostic criteria used, duration of follow-up, and the characteristics of the study population limit the ability to make meaningful comparisons across studies. As the new International Association for Diabetes in Pregnancy Study Group criteria are increasingly adopted worldwide, the prevalence of GDM is set to increase by two-to three-fold. Here, we review the literature to examine the evolution of diagnostic criteria for GDM, the implications of changing criteria on the proportion of women with previous GDM progressing to diabetes, and how the use of different diagnostic criteria may influence the development of appropriate follow-up strategies.

ATLANTIC-DIP: prevalence of metabolic syndrome and insulin resistance in women with previous gestational diabetes mellitus by International Association of Diabetes in Pregnancy Study Groups criteria.

Women with previous gestational diabetes (GDM) are a high-risk group for future development of diabetes, metabolic syndrome, and cardiovascular disease. The new International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria significantly increase the number of women diagnosed with GDM. The long-term metabolic outcome in these women is unknown. We set out to determine the prevalence of metabolic syndrome, using adult treatment panel-III criteria; and insulin resistance, using HOMA2-IR, in white European women with previous GDM. Using a cohort design, we invited women meeting IADPSG GDM criteria across four Irish antenatal centres between 2007 and 2010 to participate. Two hundred and sixty-five women with previous values meeting IADPSG criteria for GDM participated (44 % of the population eligible for participation). Mean age was 36.7 years (SD 5.0). These women were compared with a randomly selected control group of 378 women (mean age 37.6 years, SD 5.1) known to have normal glucose tolerance (NGT) in pregnancy during the same period. A total of 25.3 % of women with previous IADPSG-defined GDM met metabolic syndrome criteria, compared to 6.6 % of women with NGT [at 2.6 (SD 1.0) vs. 3.3 years (SD 0.7) post-partum]. The prevalence of HOMA2-IR >1.8 was higher in women with previous IADPSG-defined GDM (33.6 vs. 9.1 % with NGT, p < 0.001). Women with previous GDM by IADPSG criteria demonstrate a greater than threefold prevalence of metabolic syndrome compared to women with NGT in pregnancy. Efforts to prevent projected long-term consequences of this should focus on interventions both in the preconception and post-partum periods.

An evaluation of Croí MyAction community lifestyle modification programme compared to standard care to reduce progression to diabetes/pre-diabetes in women with prior gestational diabetes mellitus (GDM): study protocol for a randomised controlled trial.

BACKGROUND: Universal screening using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria has identified a prevalence of gestational diabetes mellitus (GDM) of 12.4% in women living in Ireland. Women with prior GDM are at increased risk of developing type 2 diabetes later in life. A number of risk factors linked to the development of type 2 diabetes are potentially modifiable through lifestyle and behaviour changes, and medical management. No previous Irish studies have adequately investigated the efficacy of lifestyle intervention programmes in reducing these risk factors in women with prior GDM. Through a two-group, parallel randomised controlled trial (RCT), this study aims to assess the clinical impact, cost-effectiveness and psychological experience of the Croí MyAction intensive lifestyle modification programme for women with prior GDM. METHODS/DESIGN: A total of 54 women with a history of GDM and persistent post-partum glucose dysfunction (impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)), are randomly assigned to a control arm (n=27) or to the Croí MyAction intervention group (n=27). The control arm receives usual health care advice--written information on diet and lifestyle changes for reducing diabetes risks and visits with general practitioners as required. The intervention group receives usual health care as per the control group in addition to attending a 12-week intensive lifestyle modification programme known as Croí MyAction. Croí MyAction involves 2.5 hour sessions once per week (for 12 weeks) comprising a group exercise programme, group health promotion or education seminars, and one-to-one meetings with a multidisciplinary health care team to personalise risk factor reductions. Randomisation and allocation to the intervention arms is carried out by an independent researcher, ensuring that the allocation sequence is concealed from study researchers until the interventions are assigned. The primary analysis is based on glucose dysfunction, comparing a mean reduction in fasting plasma glucose (FPG) levels on a 75 gram oral glucose tolerance test (OGTT) in the two groups at a one-year, post-intervention follow-up. The trial is funded by the Irish Health Research Board (HRB). Ethics approval was obtained on 27 March 2012 from the Clinical Research Ethics Committee, Galway University Hospitals, Health Service Executive of Ireland (Ref: C.A.691). TRIAL REGISTRATION: Current Controlled Trials ISRCTN41202110.