Abnormal Glucose Tolerance in Women Diagnosed With Gestational Diabetes (WHO 2013) 10 Years After Index Pregnancy.

Context: It is not clear if the risk of abnormal glucose tolerance (AGT) is attenuated in the long-term in women diagnosed with gestational diabetes (GDM) using the World Health Organization (WHO) 2013 criteria and who have received appropriate treatment during pregnancy. Objective: We aimed to assess the long-term prevalence of AGT and other cardiovascular disease (CVD) risk factors in this cohort. Methods: A retrospective cohort follow-up study was conducted of 37 and 107 women diagnosed with and without GDM respectively using the WHO 2013 criteria between June 2010 and December 2010. Women were invited to attend our center, where they underwent a 75-g oral glucose tolerance test, blood and urine collection, body measurements, and electrocardiography. Main outcome measure included the development of AGT using the American Diabetes Association criteria. Results: Sixteen (43.2%) women with GDM compared to 5 (4.7%) women with normal glucose tolerance (NGT) at index pregnancy had AGT (P < .001). In the GDM group, 10 (27.0%), 7 (18.9%), and 4 (10.8%) women had impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM), respectively. In the NGT group, 2 (1.9%), 3 (2.8%), and 1 (0.9%) woman had IFG, IGT, and T2DM, respectively. Women with AGT also had an unfavorable metabolic profile including obesity, hypertension, insulin resistance, and dyslipidemia. Conclusion: Women treated for GDM (WHO 2013 criteria) remain at increased risk for developing AGT and adverse CVD risk factors as early as a decade after diagnosis. Continued efforts are needed to accurately follow this population to address modifiable risk factors.

Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

Abnormal glucose tolerance in women with prior gestational diabetes mellitus: a 4-year follow-up study.

BACKGROUND: Adoption of the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for diagnosis of gestational diabetes mellitus (GDM) varies worldwide. Early detection of women at increased risk of developing type 2 diabetes mellitus (T2DM) following GDM enables initiation of measures to delay disease onset. OBJECTIVES: To determine the 4-year cumulative incidence and risk factors for developing abnormal glucose tolerance (AGT) among women with previous GDM using modified IADPSG criteria. Additionally, to review post-natal attendance at diabetes screening and the impact of post-partum lifestyle modifications and breastfeeding on the risk of T2DM development. METHODS: Four hundred twenty-six women with a prior history of GDM were invited to participate in the study, 4 years after the index pregnancy. The following were completed: body measurements, oral glucose tolerance test (OGTT), glycated haemoglobin (HbA1c), vitamin D, and other biochemistry measurements. Participants also completed a lifestyle questionnaire. RESULTS: Of the 74 women who participated, 15 (20%) had AGT. Predictive factors for AGT development were as follows: fasting glucose levels (p = 0.004), HbA1c (p = 0.008) at GDM diagnosis, and early pregnancy BMI (p = 0.001). Thirty-three (45%) women had not attended their postnatal screening. The odds ratio of the association between breastfeeding and AGT development was 0.16 (95% CI: 0.05 to 0.53). CONCLUSION: The proportion of women who develop AGT after a diagnosis of GDM remains high. The factors associated with progression to AGT are available at GDM diagnosis. Preventing AGT in this group is possible by supporting breastfeeding. Attendance at post-natal screening should also be encouraged.

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.

Is repeat fine needle aspiration required in thyroid nodules with initial benign cytology? Results from a large Irish series.

BACKGROUND : Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2). METHODS: We retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria. RESULTS: The mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%). CONCLUSIONS: With a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making.

International comparison of glycaemic control in people with type 1 diabetes: an update and extension.

AIMS: To update and extend a previous cross-sectional international comparison of glycaemic control in people with type 1 diabetes. METHODS: Data were obtained for 520,392 children and adults with type 1 diabetes from 17 population and five clinic-based data sources in countries or regions between 2016 and 2020. Median HbA1c (IQR) and proportions of individuals with HbA1c < 58 mmol/mol (<7.5%), 58-74 mmol/mol (7.5-8.9%) and ≥75 mmol/mol (≥9.0%) were compared between populations for individuals aged <15, 15-24 and ≥25 years. Logistic regression was used to estimate the odds ratio (OR) of HbA1c < 58 mmol/mol (<7.5%) relative to ≥58 mmol/mol (≥7.5%), stratified and adjusted for sex, age and data source. Where possible, changes in the proportion of individuals in each HbA1c category compared to previous estimates were calculated. RESULTS: Median HbA1c varied from 55 to 79 mmol/mol (7.2 to 9.4%) across data sources and age groups so a pooled estimate was deemed inappropriate. OR (95% CI) for HbA1c < 58 mmol/mol (<7.5%) were 0.91 (0.90-0.92) for women compared to men, 1.68 (1.65-1.71) for people aged <15 years and 0.81 (0.79-0.82) aged15-24 years compared to those aged ≥25 years. Differences between populations persisted after adjusting for sex, age and data source. In general, compared to our previous analysis, the proportion of people with an HbA1c  < 58 mmol/l (<7.5%) increased and proportions of people with HbA1c ≥ 75 mmol/mol (≥9.0%) decreased. CONCLUSIONS: Glycaemic control of type 1 diabetes continues to vary substantially between age groups and data sources. While some improvement over time has been observed, glycaemic control remains sub-optimal for most people with Type 1 diabetes.

Patient-reported outcomes (PROs) in randomised controlled trials in diabetes and pregnancy: protocol for a systematic review.

INTRODUCTION: Diabetes mellitus is the most common metabolic complication of pregnancy and its prevalence worldwide is rising. The number of randomised controlled trials (RCTs) being conducted in people with diabetes is also increasing. Many studies preferentially publish findings on clinical endpoints and do not report patient-reported outcomes (PROs). In studies that do include PROs, PRO reporting is often of poor quality. METHODS: We will conduct this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using a combination of medical subject headings and keywords (combined using Boolean operators), we will search web-based databases (PubMed, Cochrane and EMBASE) for RCTs published in English between 2013 and 2021. Two reviewers will review titles and abstracts. We will review the full texts of any relevant abstracts and extract the following data: date of publication or recruitment period, journal of publication, country of study, multicentre or single centre, population and number of participants, type of intervention, frequency of PRO assessment and type of PRO (or PRO measurement) used. We will also record if the PRO was a primary, secondary or exploratory outcome. We will exclude reviews, observational studies, unpublished data for example, conference abstracts and trial protocols. Any published RCT that includes data on a PRO as a primary or secondary outcome will then be compared against the Consolidated Standards of Reporting Trials-Patient-Reported Outcome extension checklist, a structured and approved framework for the publication of results of PROs. ETHICS AND DISSEMINATION: Ethical approval to conduct this study was obtained from the ethics committee at Galway University Hospitals on 24 March 2021 (CA 2592). We aim to publish our findings in a peer-reviewed journal and present our findings at national and international conferences. SYSTEMATIC REVIEW REGISTRATION: This systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO). Registration number CRD42021234917.

Developing a core outcome set for the treatment of pregnant women with pregestational diabetes-a study protocol.

BACKGROUND: Pregestational diabetes mellitus (PGDM) is associated with adverse pregnancy outcomes including increased rates of caesarean section birth, macrosomia, congenital malformation, prematurity, admission to the neonatal intensive care unit and stillbirth. As a result, there has been an increase in interventions to improve outcomes in both mother and infant. To date, meaningful comparisons between these studies are limited due to heterogeneity in outcome selection and reporting. The aim of this study is to develop a core outcome set (COS) for randomised controlled trials evaluating the effectiveness of interventions for the treatment of pregnant women with PGDM. METHODS: The study consists of three steps. The first step is a systematic review of the literature to assess outcomes reported in randomised controlled trials assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. The second step is a three round, online Delphi survey to prioritise these outcomes. In this step, stakeholders (including women with PGDM, healthcare workers, researchers and policymakers) will be asked to rank the importance of outcomes for inclusion in the COS using a 9-point Likert type scale. Outcomes that meet the inclusion criteria after completion of the Delphi surveys will be brought to the consensus meeting. The consensus meeting will be the third and final step, where the COS will be finalised. The consensus meeting will include members from each stakeholder group. DISCUSSION: This paper describes the process used to develop a COS for the reporting of studies evaluating the effectiveness of interventions in pregnant women with PGDM. The COS will enable greater comparison between and information synthesis across RCTs in the treatment of PGDM. In addition, this COS will also help improve trial reporting and minimise research waste by prioritising the collection and reporting of outcomes that matter to all relevant stakeholder groups. TRIAL REGISTRATION: This COS has been registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative ( http://www.comet-initiative.org/studies/details/1425 ) on the 4th of November 2019. The systematic review component of this study has also been registered with the International Prospective Register of Systematic Reviews (PROSPERO) ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020173549 ).

Core Outcome Sets for Studies of Diabetes in Pregnancy: A Review.

Core Outcome Sets (COS) contain an agreed minimum set of outcomes to be measured and reported in all studies in a specific area, with the objective of standardizing outcome reporting. COS may minimize research waste by identifying outcomes important to key stakeholders, allowing for improved evidence synthesis, and facilitating translation of research findings to clinical practice. Over the past 5 years, there has been significant progress in developing COS relevant to studies of diabetes in pregnancy. This review summarizes work in this area, reviews the role of patient and public involvement in COS development, and suggests areas for future research.

A core outcome set for studies of gestational diabetes mellitus prevention and treatment.

AIMS/HYPOTHESIS: The aim of this systematic review was to develop core outcome sets (COSs) for trials evaluating interventions for the prevention or treatment of gestational diabetes mellitus (GDM). METHODS: We identified previously reported outcomes through a systematic review of the literature. These outcomes were presented to key stakeholders (including patient representatives, researchers and clinicians) for prioritisation using a three-round, e-Delphi study. A priori consensus criteria informed which outcomes were brought forward for discussion at a face-to-face consensus meeting where the COS was finalised. RESULTS: Our review identified 74 GDM prevention and 116 GDM treatment outcomes, which were presented to stakeholders in round 1 of the e-Delphi study. Round 1 was completed by 173 stakeholders, 70% (121/173) of whom went on to complete round 2; 84% (102/121) of round 2 responders completed round 3. Twenty-two GDM prevention outcomes and 30 GDM treatment outcomes were discussed at the consensus meeting. Owing to significant overlap between included prevention and treatment outcomes, consensus meeting stakeholders agreed to develop a single prevention/treatment COS. Fourteen outcomes were included in the final COS. These consisted of six maternal outcomes (GDM diagnosis, adherence to the intervention, hypertensive disorders of pregnancy, requirement and type of pharmacological therapy for hyperglycaemia, gestational weight gain and mode of birth) and eight neonatal outcomes (birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, neonatal hypoglycaemia, neonatal death and stillbirth). CONCLUSIONS/INTERPRETATION: This COS will enable future GDM prevention and treatment trials to measure similar outcomes that matter to stakeholders and facilitate comparison and combination of these studies. TRIAL REGISTRATION: This study was registered prospectively with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/studies/details/686/.

Post-transplant diabetes mellitus associated with heart and lung transplant.

BACKGROUND: The incidence of post-transplant diabetes (PTDM) is variable primarily due to a lack of standardised diagnostic criteria. AIM: This study aimed to assess the incidence of PTDM in heart and lung transplant (HLT) patients and to review if the management of these patients is in accordance with the 2014 American Society of Transplantation guidelines. METHODS: This was a retrospective study in the Mater Misericordiae University Hospital, Dublin, Ireland. Data was collected from the patients who had undergone HLT. RESULTS: All patients who had a heart and/or lung transplant between 2005 and 2017 were identified. The majority of our patients had lung 111 (53.9%), heart 94 (45.6%) and combined heart/lung 1(0.5%) transplants. A total of 174 (84.5%) patients were screened for diabetes pre-transplantation. Two hundred five (99.9%) patients were screened for PTDM post-surgery. The cumulative incidence for PTDM was 19.4% (40/206). All patients with PTDM were on prednisolone, 32 (80%) on tacrolimus and 4 (10%) on cyclosporine. CONCLUSIONS: The cumulative incidence of post-transplant diabetes in our cohort was 19.4%. The majority of the patients were screened before and after transplant for glucose abnormality. The authors recommend that all patients should be managed in a multidisciplinary setting including transplant physicians, endocrinlogist, diabetes nurse specialists, transplant nurses and dietitians.

Growth Hormone Deficiency Following Traumatic Brain Injury.

Traumatic brain injury (TBI) is fairly common and annually affects millions of people worldwide. Post traumatic hypopituitarism (PTHP) has been increasingly recognized as an important and prevalent clinical entity. Growth hormone deficiency (GHD) is the most common pituitary hormone deficit in long-term survivors of TBI. The pathophysiology of GHD post TBI is thought to be multifactorial including primary and secondary mechanisms. An interplay of ischemia, cytotoxicity, and inflammation post TBI have been suggested, resulting in pituitary hormone deficits. Signs and symptoms of GHD can overlap with those of TBI and may delay rehabilitation/recovery if not recognized and treated. Screening for GHD is recommended in the chronic phase, at least six months to a year after TBI as GH may recover in those with GHD in the acute phase; conversely, it may manifest in those with a previously intact GH axis. Dynamic testing is the standard method to diagnose GHD in this population. GHD is associated with long-term poor medical outcomes. Treatment with recombinant human growth hormone (rhGH) seems to ameliorate some of these features. This review will discuss the frequency and pathophysiology of GHD post TBI, its clinical consequences, and the outcomes of treatment with GH replacement.

Hypopituitarism post traumatic brain injury (TBI): review.

Post-traumatic hypopituitarism (PTHP) is an important and relatively common complication of TBI (traumatic brain injury). A number of studies have shown that this clinical phenomenon can occur soon after TBI (acute) or later in the chronic phase. Patients with moderate to severe TBI are at a particular risk of developing PTHP. In the acute setting, it is important to monitor patients for hypoadrenalism as this confers a high risk for morbidity and even mortality. The gonadotrophin, growth hormone and TSH deficiencies are better defined in the chronic phase. Untreated PTHP can lead to delayed recovery, impaired rehabilitation and persistent neuropsychiatric symptoms. This review will discuss the frequency and natural history of PTHP and its clinical implications and propose a pathway for investigation and management of this still under-recognised entity.

ATLANTIC DIP: Insulin Therapy for Women With IADPSG-Diagnosed Gestational Diabetes Mellitus. Does It Work?

INTRODUCTION: Approximately 40% of women with gestational diabetes mellitus (GDM) diagnosed using International Association of the Diabetes and Pregnancy Study Group (IADPSG) criteria require insulin therapy. OBJECTIVE: We assessed whether the outcomes for women with GDM treated with insulin are comparable to women with normal glucose tolerance (NGT). MATERIALS AND METHODS: This retrospective cohort study included 752 women with insulin-treated GDM and 2496 women with NGT during pregnancy. Maternal and fetal outcomes were examined. RESULTS: Infants of women with insulin-treated GDM had rates of macrosomia [adjusted odds ratio (aOR), 1.19; 95% confidence interval (CI), 0.87 to 1.63; P = 0.26], large for gestational age (LGA) (aOR, 1.07; 95% CI, 0.77 to 1.47; P = 0.67), and small for gestational age (SGA) (aOR, 0.70; 95% CI, 0.38 to 1.38; P = 0.26) similar to women with NGT. They were more likely to be hypoglycemic at birth (aOR, 6.85; 95% CI, 2.31 to 20.28; P < 0.01) and to require neonatal intensive care unit care (NICU) (aOR, 12.09; 95% CI, 8.72 to 16.76; P < 0.01), predominantly for nonmedical reasons. Maternal rates of hypertensive disorders (preeclampsia: aOR, 0.64; 95% CI, 0.34 to 1.12; P = 0.17; pregnancy-induced hypertension: aOR, 1.11; 95% CI, 0.74 to 1.66; P = 0.60) and hemorrhage (ante partum hemorrhage: aOR, 0.56; 95% CI, 0.19 to 1.58; P = 0.27; postpartum hemorrhage: aOR, 1.17; 95% CI, 0.68 to 2.03; P = 0.55) were similar between groups, but the risk of polyhydramnios was increased in the GDM cohort (aOR, 7.75; 95% CI, 3.96 to 15.16; P < 0.01). CONCLUSIONS: Insulin treatment of IADPSG-diagnosed GDM results in rates of macrosomia, LGA, SGA, and maternal hypertensive disorders similar to those of women with NGT. Although NICU admissions are greater in the GDM cohort, they are primarily for nonmedical reasons. Neonatal hypoglycemia and polyhydramnios remain greater among women with insulin-treated GDM.

Treatment With Diet and Exercise for Women With Gestational Diabetes Mellitus Diagnosed Using IADPSG Criteria.

CONTEXT: Prevalence of gestational diabetes mellitus (GDM) and obesity continue to increase. OBJECTIVE: This study aimed to ascertain whether diet and exercise is a successful intervention for women with GDM and whether a subset of these women have comparable outcomes to those with normal glucose tolerance (NGT). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of five antenatal centers along the Irish Atlantic seaboard of 567 women diagnosed with GDM and 2499 women with NGT during pregnancy. INTERVENTION: Diet and exercise therapy on diagnosis of GDM were prescribed and multiple maternal and neonatal outcomes were examined. RESULTS: Infants of women with GDM were more likely to be hypoglycemic (adjusted odds ratio [aOR], 7.25; 95% confidence interval [CI], 2.94-17.9) at birth. They were more likely to be admitted to the neonatal intensive care unit (aOR, 2.16; 95% CI, 1.60-2.91). Macrosomia and large-for-gestational-age rates were lower in the GDM group (aOR, 0.48; 95% CI, 0.37-0.64 and aOR, 0.61; 95% CI, 0.46-0.82, respectively). There was no increase in small for gestational age among offspring of women with GDM (aOR, 0.81; 95% CI, 0.49-1.34). Women with diet-treated GDM and body mass index (BMI) < 25 kg/m(2) had similar outcomes to those with NGT of the same BMI group. Obesity increased risk for poor pregnancy outcomes regardless of diabetes status. CONCLUSION: Medical nutritional therapy and exercise for women with GDM may be successful in lowering rates of large for gestational age and macrosomia without increasing small-for-gestational-age rates. Women with GDM and a BMI less than 25 kg/m(2) had outcomes similar to those with NGT suggesting that these women could potentially be treated in a less resource intensive setting.