Search

Mullan BA, Young IS, Fee H, McCance DR. Hypertension 2002;40:804-809. Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes. We [...]

Objective The phenotype of the antioxidant and pro-angiogenic protein haptoglobin ( Hp) predicts cardiovascular disease risk and treatment response to antioxidant vitamins in individuals with diabetes. Our objective was to determine whether Hp phenotype influences pre-eclampsia risk, or the efficacy of vitamins C and E in preventing pre-eclampsia, in women with type-1 diabetes. Design This is a secondary analysis of a randomised controlled trial in which women with diabetes received daily vitamins C and E, or placebo, from 8 to 22 weeks of gestation until delivery. Setting Twenty-five antenatal metabolic clinics across the UK (in north-west England, Scotland, and Northern Ireland). Population Pregnant women with type-1 diabetes. Methods Hp phenotype was determined in white women who completed the study and had plasma samples available ( n = 685). Main outcome measure Pre-eclampsia. Results Compared with Hp 2-1, Hp 1-1 ( OR 0.59, 95% CI 0.30-1.16) and Hp 2-2 ( OR 0.93, 95% CI 0.60-1.45) were not associated with significantly decreased pre-eclampsia risk after adjusting for treatment group and Hb A1c at randomisation. Our study was not powered to detect an interaction between Hp phenotype and treatment response; however, our preliminary analysis suggests that vitamins C and E did not prevent pre-eclampsia in women of any Hp phenotype ( Hp 1-1, OR 0.77, 95% CI 0.22-2.71; Hp 2-1, OR 0.81, 95% CI 0.46-1.43; Hp 2-2, 0.67, 95% CI 0.34-1.33), after adjusting for Hb A1c at randomisation. Conclusions The Hp phenotype did not significantly affect pre-eclampsia risk in women with type-1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes.Research Design and Methods: Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8-12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account.Results: A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8-12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, -0.06% [95% CI -0.21 to 0.08]; per protocol, -0.15% [-0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups.Conclusions: Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable. [ABSTRACT FROM AUTHOR]

Objective: To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.Research Design and Methods: Participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes.Results: Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m(2)), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93-2.47), for obesity alone 1.73 (1.50-2.00), and for both GDM and obesity 3.62 (3.04-4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women).Conclusions: Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone. [ABSTRACT FROM AUTHOR]

Objective: To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women.Research Design and Methods: Eligible pregnant women underwent a 75-g OGTT at 24-32 weeks' gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders.Results: Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ± SD A1C was 4.79 ± 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery.Conclusions: On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women. [ABSTRACT FROM AUTHOR]

Objective: Diabetes during pregnancy is a strong risk factor for obesity in the offspring, but the age at which this association becomes apparent is unknown. The purpose of this study was to examine the relation of glycemia during pregnancy with anthropometry in offspring of nondiabetic pregnant women from the Belfast U.K. center of the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.Research Design and Methods: Women from the HAPO Study were invited to participate in follow-up of their offspring aged 2 years. Measurements included height, weight, and thickness of triceps, subscapular, and suprailiac skinfolds.Results: A total of 1,165 offspring (73% of eligible children; 598 boys and 567 girls) were seen from ages 22-30 completed months. The only association that reached statistical significance was between categories of maternal 1-h glucose and BMI Z score >or=85th percentile at 2 years (P = 0.017). Overall the correlations between maternal glucose during pregnancy and BMI Z score at age 2 years were weak (fasting glucose r = 0.05, P = 0.08; 1-h glucose r = 0.04, P = 0.22; 2-h glucose r = 0.03, P = 0.36; and area under the curve for glucose r = 0.04, P = 0.18).Conclusions: This study found little association between maternal glucose during pregnancy and obesity in the offspring at this young age. These findings are not unexpected given that study results for young offspring whose mothers had diabetes during pregnancy were indistinguishable from those for normal offspring at this age. It will be interesting to see whether, as these children age, maternal glucose during pregnancy in the ranges included in the HAPO Study will be associated with obesity in their children. [ABSTRACT FROM AUTHOR]

Objective: Low-fat hypocaloric diets reduce insulin resistance and prevent type 2 diabetes in those at risk. Low-carbohydrate, high-fat diets are advocated as an alternative, but reciprocal increases in dietary fat may have detrimental effects on insulin resistance and offset the benefits of weight reduction.Research Design and Methods: We investigated a low-fat (20% fat, 60% carbohydrate) versus a low-carbohydrate (60% fat, 20% carbohydrate) weight reduction diet in 24 overweight/obese subjects ([mean +/- SD] BMI 33.6 +/- 3.7 kg/m(2), aged 39 +/- 10 years) in an 8-week randomized controlled trial. All food was weighed and distributed, and intake was calculated to produce a 500 kcal/day energy deficit. Insulin action was assessed by the euglycemic clamp and insulin secretion by meal tolerance test. Body composition, adipokine levels, and vascular compliance by pulse-wave analysis were also measured.Results: Significant weight loss occurred in both groups (P < 0.01), with no difference between groups (P = 0.40). Peripheral glucose uptake increased, but there was no difference between groups (P = 0.28), and suppression of endogenous glucose production was also similar between groups. Meal tolerance-related insulin secretion decreased with weight loss with no difference between groups (P = 0.71). The change in overall systemic arterial stiffness was, however, significantly different between diets (P = 0.04); this reflected a significant decrease in augmentation index following the low-fat diet, compared with a nonsignificant increase within the low-carbohydrate group.Conclusions: This study demonstrates comparable effects on insulin resistance of low-fat and low-carbohydrate diets independent of macronutrient content. The difference in augmentation index may imply a negative effect of low-carbohydrate diets on vascular risk. [ABSTRACT FROM AUTHOR]

The long-term impact of dietary carbohydrate type, in particular sucrose, on insulin resistance and the development of diabetes and atherosclerosis is not established. Current guidelines for the healthy population advise restriction of sucrose intake. We investigated the effect of high- versus low-sucrose diet (25 vs. 10%, respectively, of total energy intake) in 13 healthy subjects aged 33 +/- 3 years (mean +/- SE), BMI 26.6 +/- 0.9 kg/m(2), in a randomized crossover design with sequential 6-week dietary interventions separated by a 4-week washout. Weight maintenance, eucaloric diets with identical macronutrient profiles and fiber content were designed. All food was weighed and distributed. Insulin action was assessed using a two-step euglycemic clamp; glycemic profiles were assessed by the continuous glucose monitoring system and vascular compliance by pulse-wave analysis. There was no change in weight across the study. Peripheral glucose uptake and suppression of endogenous glucose production were similar after each diet. Glycemic profiles and measures of vascular compliance did not change. A rise in total and LDL cholesterol was observed. In this study, a high-sucrose intake as part of an eucaloric, weight-maintaining diet had no detrimental effect on insulin sensitivity, glycemic profiles, or measures of vascular compliance in healthy nondiabetic subjects. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is a disorder characterised by pregnancy-induced hypertension and new-onset proteinuria occurring in the second half of pregnancy. Worldwide, approximately 2-3% of all pregnant women develop pre-eclampsia. The condition is a major cause of maternal and fetal morbidity and mortality. Abnormal placentation is an important predisposing factor for pre-eclampsia, while endothelial activation appears to be central to the pathophysiological changes, possibly indicative of a two-stage disorder characterised by reduced placental perfusion and a maternal syndrome. There is increasing evidence that pre-eclampsia is associated with both increased oxidative stress and reduced antioxidant defences, which has led to the hypothesis that oxidative stress may play an important role in the pathogenesis of pre-eclampsia, perhaps acting as the link in a two-stage model of pre-eclampsia. In support of this hypothesis a small, but important, preliminary study has shown a highly significant (P=0.02) reduction in the incidence of pre-eclampsia in women at risk who were taking a supplement of vitamins C and E from mid-pregnancy. Furthermore, these findings support the hypothesis that oxidative stress is at least partly responsible for the endothelial dysfunction of pre-eclampsia. Several larger multicentre trials are currently underway to evaluate the efficacy, safety and cost benefits of antioxidant supplementation during pregnancy for the prevention of pre-eclampsia in both low- and high-risk women, including women with diabetes. The results of these trials are awaited with interest. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines in the UK and elsewhere do not specifically address hybrid closed loop (HCL) use in the postpartum period when the demands of caring for a newborn are paramount. Our aim was to evaluate the safety and efficacy of HCL use during the first 6 months postpartum compared with standard care., Methods: In this prespecified extension to a multicentre, randomised controlled trial, pregnant women with type 1 diabetes at nine UK sites were followed up for 6 months postpartum. Eligible participants (AiDAPT participants recruited after the implementation of the postpartum protocol amendment approval, those still pregnant or within six months of delivery at the time of amendment implementation and still using HCL or continuous glucose monitoring [CGM] therapy) continued their randomly assigned treatment, either standard insulin therapy with CGM or HCL therapy (CamAPS FX system version 0.3.1, CamDiab, Cambridge, UK). Participants were randomised in a 1:1 ratio with stratification by clinical site using randomly permuted block sizes of 2 or 4. The primary outcome was the between-group difference in percentage time in range ([TIR] 3·9-10·0 mmol/L [70-180mg/dL]), measured during the periods of month 0 up to 3, months 3 to 6, and over 6 months postpartum. The study is registered at ClinicalTrials.gov (ISRCTN56898625) and is complete., Findings: Of the 124 AiDAPT trial participants, 66 (53%) were ineligible for inclusion in the postpartum extension, and 57 participants consented to continue their treatment per original random allocation. The mean age was 31 years (SD 4), and all participants had early pregnancy HbA 1c 59·4 mmol/mol (SD 10·5 [7·6% SD 1·0%]). In the 6 months postpartum, mean time with glucose levels within the target range was higher in the HCL group compared with the standard care group (72% [SD 12%] vs 54% [17%]), with an adjusted treatment difference of 15% (95% CI 7 to 22). Results for hyperglycaemia (>10·0 mmol/L) and mean CGM glucose also favoured HCL (-14% [95% CI -23% to -6%] and -1·3 mmol/L [-2·3 to -0·3], respectively). Hypoglycaemia rates were low, with no between-group differences (2·4% vs 2·6%). There were no treatment effect changes depending on postpartum period (0 up to 3 months vs 3 to 6 months) and no unanticipated safety problems., Interpretation: Participants in the HCL group maintained 70% TIR during the first 6 months postpartum, supporting continued use of HCL rather than standard insulin therapy for people with diabetes once they have given birth., Funding: National Institute for Health Research, Juvenile Diabetes Research Foundation, and Diabetes Research & Wellness Foundation. CGM devices were provided by Dexcom at a discounted price., Competing Interests: Declaration of interests HRM sits on the Medtronic European Scientific Advisory Board and reports speaker honoraria from Dexcom, Abbott, Medtronic, Novo Nordisk, and Ypsomed. EMS reports receiving speaker honoraria from Abbott Diabetes Care and Eli Lilly. RH reports receiving speaker honoraria from Eli Lilly, Dexcom, and Novo Nordisk, receiving license or consultancy fees from B Braun and Abbott Diabetes Care; patents related to closed‑loop systems, and being a director at CamDiab. MEW reports patents related to closed‑loop systems, and being a consultant at CamDiab. SH is a UK member of the Medtronic Advisory Board, reports being a consultant at CamDiab, and providing training for Dexcom. Dexcom was supplied continuous glucose monitoring (CGM) systems at reduced cost., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real-world setting., Methods: This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA 1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre-eclampsia, pre-term delivery, large for gestational age at birth, stillbirth and fetal malformations., Results: There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score-adjusted analyses. However, maternal HbA 1c was lower in the IAsp group at the end of the third trimester (adjusted difference, -0.16% point [95% CI -0.28;-0.05]; -1.8 mmol/mol [95% CI -3.1;-0.6]; p = 0.0046)., Conclusions: No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA 1c with IAsp in late pregnancy should be confirmed in other studies., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Objective: This study examined the influence of a pregnancy and postnatal multicomponent lifestyle intervention for women with gestational diabetes mellitus (GDM) and overweight/obesity from 6 weeks to 12 months postnatal. The primary outcome was weight at 12 months. Secondary outcomes included change in body mass index (BMI), waist circumference (WC) and fasting plasma glucose (FPG)., Methods: The study involved 235 pregnant women with GDM and BMI ≥ 25 kg/m 2 during pregnancy. Intervention components included an educational session, activity tracker (Fitbit), monthly phone calls, weekly motivational text messages, 12-week voucher for a commercial weight management organization and anthropometric, biochemical, and clinical measurements taken at 6 weeks, 6 months, and 12 months postnatal. The control group received routine local maternity care., Results: A mean weight change of -2.0 (SD 7.1) kg was observed in the intervention group compared with -0.6 (SD 8.0) kg in the control group, difference -1.4 (95% CI -4.4, 1.5) kg from 6 weeks to 12 months postnatal, but this was not statistically significant ( P = .34). Neither were significant differences obtained for any secondary outcomes: BMI -0.6 (-1.6, 0.5) kg/m 2 , WC -1.0 (-5.1, 3.2) cm and FPG 0.07 (-0.15, 0.29) mmol/L., Conclusion: This lifestyle intervention among women with overweight/obesity and GDM resulted in a statistically nonsignificant 1.4 kg greater weight loss compared with routine care at 12 months postnatal. Further research is needed to understand how the different components of this lifestyle intervention might be better applied to elicit more successful results., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

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., (© 2024 John Wiley & Sons Ltd.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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/m 2 , 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., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.)., (Copyright © 2023 Massachusetts Medical Society.)

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/cm 2 in boys and 0.010 g/cm 2 in girls) and BMAD (0.005 g/cm 3 in boys and 0.003 g/cm 3 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., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

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.

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/m 2 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., Competing Interests: The authors declare that the research will be conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 McAuley, Fleck, Cassidy, Kemp, Cupples, Kelly, Creighton, Graham, Wallace, Patterson and McCance.)

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., (© 2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

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., (© The Author(s) 2023.)

Aims: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs)., Methods: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16., Results: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA 1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage., Conclusions: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Background: The present study aimed to explore the relationships between carbohydrate intake, body mass index (BMI) and glycaemic control (HbA1c) in pregnant women with type 1 diabetes mellitus (T1DM) METHODS: Secondary analysis of data was undertaken to assess dietary intake in a cohort of women who participated in a randomised controlled trial (RCT) of antioxidant supplementation to prevent preeclampsia (DAPIT 10 ). Study-specific peripheral venous blood samples were obtained for HbA1c at 26 and 34 weeks. Diet was collected using a validated semiquantitative food frequency questionnaire at 26-28 weeks of gestation which assessed dietary intake over 2 weeks. Mean daily average nutrient intakes were analysed using Q Builder nutritional software and SPSS, version 25., Results: Dietary data were available for 547 pregnant women (72% of cohort) aged 29 years (95% confidence interval [CI] = 28.9-29.9) with average diabetes duration 11.8 years (95% confidence interval = 11.1-12.6). Average body mass index (BMI) (<16 weeks of gestation) was 26.7 kg/m 2 (95% CI = 26.3 -27, range 18.8-45.6 kg/m 2 ); 43% (n = 234) were overweight (BMI = 25.0-29.9 kg/m 2 ) and 20% (n = 112) were obese (BMI ≥ 30 kg/m 2 ). Differences in HbA1c and carbohydrate quantity and quality were found when adjusted for age and insulin dose. No differences between BMI group were observed for total carbohydrate and glycaemic control; however, differences were noted in fibre and glycaemic index., Conclusions: Average quantity of dietary carbohydrate influenced HbA1c when adjusted for insulin dose however, BMI had less impact. More research is required on the relationship between carbohydrate consumption and glycaemic control in pregnancy., (© 2022 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)