Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.

BACKGROUND: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. METHODS: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. RESULTS: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). CONCLUSIONS: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.).

Clinical management and outcome of head and neck paragangliomas (HNPGLs): A single centre retrospective study.

CONTEXT: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined. OBJECTIVE: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities. METHODS: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023. RESULTS: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04). CONCLUSION: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes.

The effect of increased fruit and vegetable consumption on blood pressure and lipids: a pooled analysis of six randomised controlled fruit and vegetable intervention trials.

BACKGROUND: Increasing fruit and vegetable (FV) consumption is associated with reduced cardiovascular disease risk in observational studies but with little evidence from randomised controlled trials (RCTs). The impact of concurrent pharmacological therapy is unknown. OBJECTIVE: To pool data from six RCTs to examine the effect of increasing FV intake on blood pressure (BP) and lipid profile, also exploring whether effects differed by medication use. DESIGN: Across trials, dietary intake was assessed by diet diaries or histories, lipids by routine biochemical methods and BP by automated monitors. Linear regression provided an estimate of the change in lipid profile or BP associated with a one portion increase in self-reported daily FV intake, with interaction terms fitted for medication use. RESULTS: The pooled sample included a total of 554 participants (308 males and 246 females). Meta-analysis of regression coefficients revealed no significant change in either systolic or diastolic BP per portion FV increase, although there was significant heterogeneity across trials for systolic BP (I2 = 73%). Neither adjusting for change in body mass index, nor analysis according to use of anti-hypertensive medication altered the relationship. There was no significant change in lipid profile per portion FV increase, although there was a significant reduction in total cholesterol among those not on lipid-lowering therapy (P < 0.05 after Bonferroni correction). CONCLUSION: Pooled analysis of six individual FV trials showed no impact of increasing intake on BP or lipids, but there was a total cholesterol-lowering effect in those not on lipid-lowering therapy.

First-trimester glycaemic markers as predictors of gestational diabetes and its associated adverse outcomes: A prospective cohort study.

OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with excessive fetal growth in later gestation. Recent data suggest accelerated growth may begin before 28 weeks' gestation when GDM is typically diagnosed. The identification of pregnancies at risk of early fetal growth would enable early intervention. We assessed the use of early pregnancy HbA1c in predicting excessive fetal growth. RESEARCH DESIGN AND METHODS: Women were recruited at antenatal booking from a major maternity unit in the UK. HbA1c was measured at <14 weeks gestation in 1243 women at risk of GDM as defined by UK NICE risk factors of whom 1115 underwent OGTT. Women with previous GDM were excluded. Comprehensive fetal ultrasound was performed at 28 weeks' gestation alongside 75 g OGTT in 976 of these women. GDM was defined using WHO criteria. Pregnancy outcomes were extracted from the regional maternity care database. RESULTS: Two hundred and thirty-six women screened positive for GDM. At diagnosis, GDM pregnancies demonstrated higher adjusted fetal weight percentile than non-GDM pregnancies: (51.8 vs. 46.3, p = 0.008). This was driven by increases in the fetal abdominal circumference percentile in GDM compared with non-GDM pregnancies (55.3 vs. 46.2, p = <0.001). Early pregnancy HbA1c was higher in the GDM versus non-GDM group: (35.7 mmol/mol vs. 32.9 mmol/mol p = <0.01). A threshold for predicting excessive fetal growth was not identified in this cohort. CONCLUSIONS: Accelerated fetal growth is evident prior to the diagnosis of GDM. There remains a need for suitable methods of early identification of pregnancies at high risk for early accelerated fetal growth due to GDM. First-trimester HbA1c was not useful in identifying these pregnancies. NOVELTY STATEMENT: WHAT IS ALREADY KNOWN?: Recent research suggests excessive growth associated with GDM may begin prior to 28 weeks' gestation, when GDM is typically tested for WHAT THIS STUDY HAS FOUND?: Pregnancies affected by GDM are already subject to accelerated fetal growth in comparison to non-GDM pregnancies by way of higher estimated fetal weight and fetal abdominal circumference Neither first-trimester HbA1c nor plasma glucose was useful predictors of these outcomes WHAT ARE THE IMPLICATIONS OF THIS STUDY?: Highlights the emergence of excessive growth prior to detection of GDM Reinforces need for suitable methods of identifying such pregnancies in earlier gestation.

Trial to Encourage Adoption and Maintenance of a MEditerranean Diet (TEAM-MED): a randomised pilot trial of a peer support intervention for dietary behaviour change in adults from a Northern European population at high CVD risk.

Adhering to a Mediterranean diet (MD) is associated with reduced CVD risk. This study aimed to explore methods of increasing MD adoption in a non-Mediterranean population at high risk of CVD, including assessing the feasibility of a developed peer support intervention. The Trial to Encourage Adoption and Maintenance of a MEditerranean Diet was a 12-month pilot parallel group RCT involving individuals aged ≥ 40 year, with low MD adherence, who were overweight, and had an estimated CVD risk ≥ 20 % over ten years. It explored three interventions, a peer support group, a dietician-led support group and a minimal support group to encourage dietary behaviour change and monitored variability in Mediterranean Diet Score (MDS) over time and between the intervention groups, alongside measurement of markers of nutritional status and cardiovascular risk. 118 individuals were assessed for eligibility, and 75 (64 %) were eligible. After 12 months, there was a retention rate of 69 % (peer support group 59 %; DSG 88 %; MSG 63 %). For all participants, increases in MDS were observed over 12 months (P < 0·001), both in original MDS data and when imputed data were used. Improvements in BMI, HbA1c levels, systolic and diastolic blood pressure in the population as a whole. This pilot study has demonstrated that a non-Mediterranean adult population at high CVD risk can make dietary behaviour change over a 12-month period towards an MD. The study also highlights the feasibility of a peer support intervention to encourage MD behaviour change amongst this population group and will inform a definitive trial.

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial - study protocol.

BACKGROUND: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes. METHODS/DESIGN: A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events. DISCUSSION: This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy. TRIAL REGISTRATION: ISRCTN 56898625 Registration Date: 10 April, 2018.

Maternal vitamin D and neonatal anthropometrics and markers of neonatal glycaemia: Belfast Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Vitamin D deficiency is a common occurrence globally, and particularly so in pregnancy. There is conflicting evidence regarding the role of vitamin D during pregnancy in non-skeletal health outcomes for both the mother and the neonate. The aim of this study was to investigate the associations of maternal total 25-hydroxy vitamin D (25OHD) with neonatal anthropometrics and markers of neonatal glycaemia in the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Serological samples (n 1585) were obtained from pregnant women in the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, between 24 and 32 weeks' gestation as part of the HAPO study. 25OHD concentrations were measured by liquid chromatography tandem-MS. Cord blood and neonatal anthropometric measurements were obtained within 72 h of birth. Statistical analysis was performed. After adjustment for confounders, birth weight standard deviation scores (SDS) and birth length SDS were significantly associated with maternal total 25OHD. A doubling of maternal 25OHD at 28 weeks' gestation was associated with mean birth weight SDS and mean birth length SDS higher by 0·05 and 0·07, respectively (both, P=0·03). There were no significant associations with maternal 25OHD and other measures of neonatal anthropometrics or markers of neonatal glycaemia. In conclusion, maternal total 25OHD during pregnancy was independently associated with several neonatal anthropometric measurements; however, this association was relatively weak.

Mortality in type 1 diabetes diagnosed in childhood in Northern Ireland during 1989-2012: A population-based cohort study.

OBJECTIVE: To investigate long-term mortality rates and causes of death in individuals diagnosed with type 1 diabetes before the age of 15 years during the period 1989-2012 or known to paediatric diabetes teams in 1989, in Northern Ireland. METHODS: A cohort of 3129 patients from the Northern Ireland Childhood Diabetes Register was linked to death registrations and underlying causes, coded according to ICD-9 or ICD-10. Standardized mortality ratios (SMRs) were calculated as the ratio of observed to expected deaths by sex, attained age, time since diagnosis, calendar period, and cause of death. RESULTS: Subjects were followed to December 31, 2012 giving 39 764 person-years of follow-up (median 12.1 years). In total, 59 subjects had died (1.5 per 1000 person-years) compared with 19.9 deaths expected, an SMR of 296 (95% confidence interval (CI) 229-382). Women had a significantly higher excess risk of mortality than men with SMRs of 535 (95% CI 361-764) and 203 (95% CI 136-291), respectively. Over half of the deaths (56%) were judged to be related or possibly related to diabetes with most of these due to acute (n = 24) or late (n = 6) complications. CONCLUSIONS: Subjects with type 1 diabetes diagnosed less than 15 years of age had 3 times the mortality risk of the general population. Over half of the deaths were related to acute or chronic complications of diabetes.

The effect of increased fruit and vegetable consumption on selected macronutrient and micronutrient intakes in four randomised-controlled trials.

Fruit and vegetable (FV) intake is associated with reduced risk of a number of non-communicable diseases. Research tends to focus on antioxidants, flavonoids and polyphenols contained in FV as the main beneficial components to health; however, increasing FV may also alter overall diet profile. Extra FV may be substituted for foods thought to be less healthy, therefore altering the overall macronutrient and/or micronutrient content in the diet. This analysis merged dietary data from four intervention studies in participants with varying health conditions and examined the effect of increased FV consumption on diet profile. Dietary intake was assessed by either diet diaries or diet histories used in four FV randomised intervention studies. All food and drink intake recorded was analysed using WISP version 3.0, and FV portions were manually counted using household measures. Regression analysis revealed significant increases in intakes of energy (172 kJ (+41 kcal)), carbohydrate (+3·9 g/4184 kJ (1000 kcal)), total sugars (+6·0 g/4184 kJ (1000 kcal)) and fibre (+0·8 g/4184 kJ (1000 kcal)) and significant decreases in intakes of total fat (-1·4 g/4184 kJ (1000 kcal)), SFA (-0·6 g/4184 kJ (1000 kcal)), MUFA (-0·6 g/4184 kJ (1000 kcal)), PUFA (-0·1 g/4184 kJ (1000 kcal)) and starch (-2·1 g/4184 kJ (1000 kcal)) per one portion increase in FV. Significant percentage increases were also observed in vitamin C (+24 %) and -carotene (+20 %) intake, per one portion increase in FV. In conclusion, pooled analysis of four FV intervention studies, that used similar approaches to achieving dietary change, in participants with varying health conditions, demonstrated an increase in energy, total carbohydrate, sugars and fibre intake, and a decrease in fat intake alongside an expected increase in micronutrient intake.

Implementation of guidelines for multidisciplinary team management of pregnancy in women with pre-existing diabetes or cardiac conditions: results from a UK national survey.

BACKGROUND: Despite numerous publications stating the importance of multidisciplinary care for women with pre-existing medical conditions, there is a lack of evidence regarding structure or processes of multidisciplinary working, nor impact on maternal or infant outcomes. This study aimed to evaluate the implementation of guidelines for multidisciplinary team (MDT) management in pregnant women with pre-existing diabetes or cardiac conditions. These conditions were selected as exemplars of increasingly common medical conditions in pregnancy for which MDT management is recommended to prevent or reduce adverse maternal and fetal outcomes. METHODS: National on-line survey sent to clinicians responsible for management or referral of women with pre-existing diabetes or cardiac conditions in UK National Health Service (NHS) maternity units. The survey comprised questions regarding the organisation of MDT management for women with pre-existing diabetes or cardiac conditions. Content was informed by national guidance. RESULTS: One hundred seventy-nine responses were received, covering all health regions in England (162 responses) and 17 responses from Scotland, Wales and Northern Ireland. 132 (74%) related to women with diabetes and 123 (69%) to women with cardiac conditions. MDT referral was reportedly standard practice in most hospitals, particularly for women with pre-existing diabetes (88% of responses vs. 63% for cardiac) but there was wide variation in relation to MDT membership, timing of referral and working practices. These inconsistencies were evident within and between maternity units across the UK. Reported membership was medically dominated and often in the absence of midwifery/nursing and other allied health professionals. Less than half of MDTs for women with diabetes met the recommendations for membership in national guidance, and although two thirds of MDTs for women with cardiac disease met the core recommendations for membership, most did not report having the extended members: midwives, neonatologists or intensivists. CONCLUSIONS: The wide diversity of organisational management for women with pre-existing diabetes or cardiac conditions is of concern and merits more detailed inquiry. Evidence is also required to support and better define the recommendations for MDT care.

Management of pregnant and postnatal women with pre-existing diabetes or cardiac disease using multi-disciplinary team models of care: a systematic review.

BACKGROUND: More women with an increased risk of poor pregnancy outcome due to pre-existing medical conditions are becoming pregnant. Although clinical care provided through multi-disciplinary team (MDT) working is recommended, little is known about the structure or working practices of different MDT models, their impact on maternal and infant outcomes or healthcare resources. The objectives of this review were to consider relevant international evidence to determine the most appropriate MDT models of care to manage complex medical conditions during and after pregnancy, with a specific focus on pre-existing diabetes or cardiac disease in high income country settings. METHODS: Quantitative and qualitative evidence of MDT models of care for the management of pregnant/postnatal women with pre-existing diabetes and cardiac disease was considered. A search of the literature published between January 2002 - January 2014 was undertaken. Methodological quality was assessed using checklists developed by the Joanna Briggs Institute. Given limited primary and secondary research evidence, guidelines and opinion papers were included. Two independent reviewers conducted critical appraisal of included papers. RESULTS: Nineteen papers were included from UK, Canada, USA, the Netherlands and Singapore. No studies were found which had compared MDT models for pregnant/postnatal women with pre-existing diabetes or cardiac disease. Two small retrospective studies reported better outcomes for women with cardiac disease if an MDT approach was used, although evidence to support this was limited. Due to study heterogeneity it was not possible to meta-analyse data. No evidence was identified of MDT management in the postnatal period or impacts of MDT working on healthcare resources. CONCLUSIONS: Despite widespread promotion of MDT models of care for pregnant and postnatal women with pre-existing diabetes or cardiac disease, there is a dearth of primary evidence to inform structure or working practices or beneficial impact on maternal and infant outcomes or healthcare resources. Primary research into if or how MDT models of care improve outcomes for women with complex pregnancies is urgently needed.

Mothers' experiences of a lifestyle intervention for weight reduction 12 months after gestational diabetes mellitus: Qualitative findings from the PAIGE2 study.

The standardised pooled prevalence of gestational diabetes mellitus (GDM) globally is approximately 14 %, a reflection of increasing rates of obesity in women of childbearing age. Lifestyle interventions to reduce GDM and subsequent type 2 diabetes (T2D) have been deemed a research priority but are challenging to perform and have variable success rates. The PAIGE2 study was a pragmatic lifestyle randomised controlled trial for women with GDM and body mass index ≥25 kg/m2, which began during pregnancy and continued for one year postnatally. The primary outcome was weight loss 12 months postnatally compared with mothers receiving standard maternity care. Qualitative results are presented from end of study focus groups conducted amongst intervention mothers to gather feedback and determine acceptability of the PAIGE2 intervention. In total, 19 mothers participated in five virtual focus groups. Content analysis explored general study experience, longer term changes to lifestyle and suggested improvements of intervention components including monthly phone calls, motivational text messages, Fitbit experience, Slimming World, and study contact timings. Overall, most mothers found the individual PAIGE2 intervention components enjoyable, although opinions differed as to which were the most effective. Several mothers claimed the intervention helped them make long-term changes to their behaviours. A common suggested improvement was the establishment of a local group where mothers could share their experiences. In conclusion, most mothers deemed the intervention acceptable, and felt that with minor enhancements, it could be utilised as an effective tool to support weight loss after pregnancy and reduce future risk of obesity and T2D.

Increased circulating CC chemokine levels in the metabolic syndrome are reduced by low-dose atorvastatin treatment: evidence from a randomized controlled trial.

OBJECTIVE: Central obesity and insulin resistance are key components of the metabolic syndrome, which is associated with an increased risk of cardiovascular disease. In obesity, CC chemokines, such as monocyte chemotactic protein-1 (MCP-1), macrophage inhibitory protein-1ß (MIP-1ß) and eotaxin-1 and their respective receptors, are critically involved in peripheral monocyte activation and adipose tissue infiltration. The aim of the current study was to examine whether low-dose atorvastatin (10 mg/d) treatment modulated serum levels of CC chemokines in metabolic syndrome subjects. MATERIALS AND METHODS: Serum levels of MCP-1, eotaxin-1, MIP-1ß, C reactive protein (CRP) and interleukin-6 (IL-6) were measured in lean control and metabolic syndrome subjects at baseline, and following a 6-week randomized placebo-controlled clinical trial of atorvastatin (10 mg/d). Peripheral CD14(+) monocytes were isolated and mRNA levels of MCP-1, MIP-1 ß and CCR5 determined. RESULTS: Serum MCP-1 (P = 0·02), eotaxin-1 (P = 0·02) and MIP-1ß (P = 0·03), CRP (P < 0·001) and IL-6 (P = 0·006) were significantly increased in metabolic syndrome in comparison with lean controls. Furthermore, CD14(+) peripheral monocyte mRNA expression of the chemokine receptor, CCR5, of which MIP-1ß and eotaxin-1 are ligands, was increased two-fold in the metabolic syndrome group (P = 0·03). In addition to the expected improvements in lipid profile, atorvastatin treatment significantly reduced circulating eotaxin-1 (P < 0·05), MIP-1ß (P < 0·05) levels and CD14(+) peripheral monocyte CCR5 mRNA expression (P = 0·02). CONCLUSION: These results support a model whereby atorvastatin treatment, by inhibiting CD14(+) monocyte CCR5 expression, may inhibit monocyte trafficking, reduce chronic inflammation and, thus, lower circulating levels of CC chemokines.

Randomized controlled trial assessing the effect of simvastatin in primary biliary cirrhosis.

BACKGROUND: This study evaluated the effect of statins in Primary biliary cirrhosis (PBC) on endothelial function, anti-oxidant status and vascular compliance. METHODS: Primary biliary cirrhosis patients with hypercholesterolaemia were randomized to receive 20 mg simvastatin or placebo in a single blind, randomized controlled trial. Body mass index, blood pressure, glucose, liver function, lipid profile, immunoglobulin levels, serological markers of endothelial function and anti-oxidant status were measured as well as vascular compliance, calculated from pulse wave analysis and velocity, at recruitment and again at 3, 6, 9 and 12 months. RESULTS: Twenty-one PBC patients (F = 20, mean age = 55) were randomized to simvastatin 20 mg (n = 11) or matched placebo (n = 10). At completion of the trial, serum cholesterol levels in the simvastatin group were significantly lower compared with the placebo group (4.91 mmol/L vs. 6.15 mmol/L, P = 0.01). Low-density lipoprotein (LDL) levels after 12 months were also significantly lower in the simvastatin group (2.33 mmol/L vs. 3.53 mmol/L, P = 0.01). After 12 months of treatment, lipid hydroperoxides were lower (0.49 µmol/L vs. 0.59 µmol/L, P = 0.10) while vitamin C levels were higher (80.54 µmol/L vs. 77.40 µmol/L, P = 0.95) in the simvastatin group. Pulse wave velocity remained similar between treatment groups at 12 months (8.45 m/s vs. 8.80 m/s, P = 0.66). Only one patient discontinued medication owing to side effects. No deterioration in liver transaminases was noted in the simvastatin group. CONCLUSIONS: Statin therapy in patients with PBC appears safe and effective towards overall reductions in total cholesterol and LDL levels. Our initial study suggests that simvastatin may also confer advantageous effects on endothelial function and antioxidant status.

The influence of diet and physical activity on bone density of children aged 5-7 years: The Belfast HAPO family study.

OBJECTIVE: Osteoporosis is a global health issue, and modifiable behavioural factors need to be identified in childhood to reduce the risk of osteoporosis in later life. The aim of this study was to investigate the influence of diet and physical activity on bone density of children aged 5-7 years participating in the Belfast Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Family study. DESIGN AND METHODS: Pregnant women were recruited to the Belfast centre of the HAPO study at 24-32 weeks gestation. Offspring were followed up at 5-7 years as part of the Belfast HAPO Family Study. Heel bone mineral density (BMD) and bone mineral apparent density (BMAD) were measured and calculated, respectively. Physical activity in the offspring was measured by accelerometery and dietary intakes were measured using a 4-day food diary. RESULTS: Results from 793 offspring were analysed. Mean age of the offspring ± standard deviation was 6.4 ± 0.5 years. A mean of 48.3 ± 22.4 min each day was spent in moderate to vigorous physical activity (MVPA). Median (interquartile range) dietary calcium and vitamin D intakes were 844 (662-1073) mg/day and 1.7 (1.1-2.5) µg/day, respectively. Neither dietary vitamin D nor calcium intakes were significantly associated with offspring heel BMD or BMAD in multiple regression. However, controlling for confounders, a 30-min greater MVPA was associated with significantly larger heel BMD (0.018 g/cm2 in boys and 0.010 g/cm2 in girls) and BMAD (0.005 g/cm3 in boys and 0.003 g/cm3 in girls). CONCLUSION: Physical activity was associated with better BMD and BMAD in 5-7-year-old children. Dietary calcium and vitamin D were not predictive of BMD and BMAD.

A peer support dietary change intervention for encouraging adoption and maintenance of the Mediterranean diet in a non-Mediterranean population (TEAM-MED): lessons learned and suggested improvements.

Peer support interventions for dietary change may offer cost-effective alternatives to interventions led by health professionals. This process evaluation of a trial to encourage the adoption and maintenance of a Mediterranean diet in a Northern European population at high CVD risk (TEAM-MED) aimed to investigate the feasibility of implementing a group-based peer support intervention for dietary change, positive elements of the intervention and aspects that could be improved. Data on training and support for the peer supporters; intervention fidelity and acceptability; acceptability of data collection processes for the trial and reasons for withdrawal from the trial were considered. Data were collected from observations, questionnaires and interviews, with both peer supporters and trial participants. Peer supporters were recruited and trained to result in successful implementation of the intervention; all intended sessions were run, with the majority of elements included. Peer supporters were complimentary of the training, and positive comments from participants centred around the peer supporters, the intervention materials and the supportive nature of the group sessions. Attendance at the group sessions, however, waned over the intervention, with suggested effects on intervention engagement, enthusiasm and group cohesion. Reduced attendance was reportedly a result of meeting (in)frequency and organisational concerns, but increased social activities and group-based activities may also increase engagement, group cohesion and attendance. The peer support intervention was successfully implemented and tested, but improvements can be suggested and may enhance the successful nature of these types of interventions. Some consideration of personal preferences may also improve outcomes.

A pragmatic lifestyle intervention for overweight and obese women with gestational diabetes mellitus (PAIGE2): A parallel arm, multicenter randomized controlled trial study protocol.

Background: The global epidemic of type 2 diabetes (T2D) and obesity has been translated into pregnancy, with approximately 18% of women being diagnosed worldwide with Gestational Diabetes Mellitus (GDM). Whilst preventive strategies have proven effective in the non-pregnant context, attrition rates are high and there is an urgent need to develop a customized, pragmatic lifestyle intervention for women both during and after pregnancy. Diet and exercise modification, behavioral support, and Commercial Weight Management Organizations have been strongly recommended to aid postpartum weight reduction for mothers with previous GDM, subsequently reducing their risk of developing obesity and T2D. This study, informed by a previous pilot study, aims to determine the effectiveness of a pragmatic pregnancy and postpartum lifestyle modification program for overweight women with previous GDM (PAIGE2) to reduce body weight at 12 months postpartum. Methods/design: This paper summarizes the protocol for the PAIGE2 study, which has been developed based on results from a pilot study (PAIGE). A six center, two parallel arm, 12-month, randomized controlled trial will be conducted across Northern Ireland and the Republic of Ireland (3 centers each), involving 340 women with GDM and body mass index ≥25 kg/m2 recruited during pregnancy. The lifestyle intervention involves a one-hour virtual educational program (to take place at 32-36 weeks gestation). Postpartum, the intervention will include monthly phone calls, weekly motivational text messages, weekly step counts, and referral for three months to a Commercial Weight Management Organization (Slimming World). The control arm will receive usual care as offered by the local maternity hospital. The primary outcome is weight loss at 12 months postpartum. Study visits for anthropometric and clinical measurements, fasting blood samples, questionnaires pertaining to health, wellbeing and physical activity will take place at 6 weeks, 6- and 12-months postpartum. Focus groups will be conducted with intervention mothers' post-intervention to determine the acceptability of the study design including utility of a Commercial Weight Management Organization, feasibility of remote patient contact, family involvement and patient satisfaction. Discussion: The PAIGE2 study will address the gaps in previously conducted research and, if positive, has the potential to have major public health implications for the prevention of future GDM and subsequent T2D. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04579016?term=NCT04579016&draw=2&rank=1, identifier NCT04579016.

Rollout of Closed-Loop Technology to Pregnant Women with Type 1 Diabetes: Healthcare Professionals' Views About Potential Challenges and Solutions.

Aims: To explore healthcare professionals' views about the training and support needed to rollout closed-loop technology to pregnant women with type 1 diabetes. Methods: We interviewed (n = 19) healthcare professionals who supported pregnant women using CamAPS FX closed-loop during the Automated insulin Delivery Amongst Pregnant women with Type 1 diabetes (AiDAPT) trial. Data were analyzed descriptively. An online workshop involving (n = 15) trial team members was used to inform recommendations. Ethics approvals were obtained in conjunction with those for the wider trial. Results: Interviewees expressed enthusiasm for a national rollout of closed-loop, but anticipated various challenges, some specific to use during pregnancy. These included variations in insulin pump and continuous glucose monitoring expertise and difficulties embedding and retaining key skills, due to the relatively small numbers of pregnant women using closed-loop. Inexperienced staff also highlighted difficulties interpreting data downloads. To support rollout, interviewees recommended providing expert initial advice training, delivered by device manufacturers together with online training resources and specific checklists for different systems. They also highlighted a need for 24 h technical support, especially when supporting technology naive women after first transitioning onto closed-loop in early pregnancy. They further recommended providing case-based meetings and mentorship for inexperienced colleagues, including support interpreting data downloads. Interviewees were optimistic that if healthcare professionals received training and support, their long-term workloads could be reduced because closed-loop lessened women's need for glycemic management input, especially in later pregnancy. Conclusions: Interviewees identified challenges and opportunities to rolling-out closed-loop and provided practical suggestions to upskill inexperienced staff supporting pregnant women using closed-loop. A key priority will be to determine how best to develop mentorship services to support inexperienced staff delivering closed-loop. Clinical Trials Registration: NCT04938557.

Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life in hypopituitary females: a double-blind, placebo-controlled study.

OBJECTIVE: Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism. DESIGN: Randomized, double-blind, placebo-controlled, crossover design was used. Patients received either DHEAS 50 mg daily or placebo for 12 weeks. PATIENTS: Fourteen hypopituitary females on stable standard replacement therapy and with low DHEAS were enrolled. MEASUREMENTS: Insulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of life parameters were assessed after each treatment. RESULTS: Serum DHEAS (DHEAS 5·4 ± 0·8 vs placebo <0·8 ± 0·0 µm; P < 0·001) and androstenedione (DHEAS 4·1 ± 0·8 vs placebo 1·3 ± 0·2 nm; P < 0·05) rose to within the normal range after DHEAS 50 mg daily. There were no differences between treatments in testosterone, sex hormone-binding globulin (SHBG) or IGF-1. Quality of life measures were unchanged after DHEAS. There were no differences between treatments in fasting glucose, serum insulin, HbA1c or in insulin action (glucose infusion rates required to maintain euglycaemia; DHEAS 21·9 ± 2·5 vs placebo 24·5 ± 2·1 µmol/kg/min; P = 0·4). Triglyceride concentrations were lower following DHEAS (DHEAS 1·24 ± 0·18 vs placebo 1·41 ± 0·19 mm; P < 0·05) but other lipid parameters remained unchanged. CONCLUSION: There were no differences compared with placebo in quality of life or insulin action after DHEAS replacement therapy for 12 weeks. These results do not provide evidence for the addition of DHEAS to standard hypopituitary replacement therapy.

Diversity in diabetes: the role of insulin aspart.

Diabetes management is changing not only with novel treatments but also in patient demography. This presents clinical challenges and influences our view of diabetes therapies. Insulin analogues have been developed to overcome some of the limitations of traditional human insulins, with the aim of providing a more physiological pharmacokinetic/pharmacodynamic profile. The rapid-acting insulin analogue insulin aspart has been investigated in many clinical trials over the past 10 years and the aim of this review is to present the insulin aspart clinical trial data from across the spectrum of patients with diabetes. Five studies have looked at insulin aspart use (including continuous subcutaneous insulin infusion) in children and adolescents, where the analogue was as effective and well tolerated as soluble human insulin. One large-scale, randomized, controlled trial in pregnant women with type 1 diabetes observed trends towards a reduction in major hypoglycaemia, fewer preterm deliveries and lower birthweight with insulin aspart compared with soluble human insulin. Two 6-month, randomized, controlled, multicentre, multinational, parallel-group, open-label trials reported significant reductions in haemoglobin A(1c) and major nocturnal hypoglycaemia with insulin aspart compared with soluble human insulins in patients with type 1 diabetes. There are fewer data involving insulin analogue use in hospitals and in elderly patients with diabetes, but some recent studies have investigated insulin aspart in the emergency department, intensive/non-intensive care setting and in a pharmacokinetic/pharmacodynamic study in patients aged ≥ 65 years. In summary, the evidence would suggest that insulin aspart is suitable for use in a variety of patients with diabetes.