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Aim: Myo‐inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at‐risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo‐inositol‐containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. Methods: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo‐inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. Results: Higher 7‐week myo‐inositol, but not 28‐week myo‐inositol, associated with higher 1 h PG [βadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge μmol/L, p =.022] and 2 h PG [0.08 (0.03, 0.12), p =.001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7‐week myo‐inositol increase of 23.4 μmol/L with myo‐inositol supplementation. Higher 7‐week myo‐inositol associated with a lower 28‐week Stumvoll index (first phase), an approximation of insulin secretion [−0.08 (−0.15, −0.01), p =.020] but not with 28‐week Matsuda insulin sensitivity index. However, the clinical significance of a 7‐week myo‐inositol‐related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C‐peptide levels. In‐silico modelling found higher 28‐week myo‐inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7‐week myo‐inositol effects. Conclusion: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo‐inositol may slightly exacerbate later pregnancy post‐challenge glycaemia, indicating that the optimal timing for starting prenatal myo‐inositol supplementation needs further investigation. [ABSTRACT FROM AUTHOR]

Objective Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear. Methods We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model. Results We included data from 20 studies (22 reports; N  = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference −0.13, 95%CI: −0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: −0.69 to 0.95), cardiac death (RR 0.80, 95%CI: −0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59–0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis. Conclusions In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase. [ABSTRACT FROM AUTHOR]

Aim: Frequent hypoglycaemia results in disruption to usual hypoglycaemic autonomic responses leading to impaired awareness of hypoglycaemia, which is associated with an increased risk of severe hypoglycaemia requiring third‐party assistance (SH). The UK Driving and Vehicle Licensing Agency (DVLA) does not permit car driving if they have either a complete loss of hypoglycaemia awareness or more than one SH event a year. Methods: The FreeStyle Libre (FSL) Association of British Clinical Diabetologists (ABCD) Nationwide Audit consists of data collected by clinicians during routine clinical work, submitted into a secure web‐based tool held within the National Health Service (NHS) N3 network. Analysis of paired baseline and follow‐up data for people with type 1 diabetes who also held a driving licence was undertaken. Results: The study consisted of 6304 people who had data recorded about driving status from 102 UK specialist diabetes centres, of which 4218 held a driving licence: 4178 a group 1, standard licence, 33 a group 2, large lorries and buses, seven a taxi licence; 1819 did not drive. Paired baseline and follow‐up data were available for a sub‐cohort of 1606/4218. At a mean follow‐up of 6.9 months [95% CI (6.8, 7.1)], the Gold score had improved (2.3 ± 1.5 vs. 2.0 ± 1.3 p <.001), and the number of people who experienced an SH episode was also significantly lower (12.1% vs. 2.7%, p <.001). Conclusion: This study suggests that intermittently scanned continuous glucose monitoring may improve impaired awareness of hypoglycaemia and reduce the number of people with type 1 diabetes with a driving licence experiencing a severe hypoglycaemic episode. [ABSTRACT FROM AUTHOR]

Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicotinate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02–5.02], P < 0.0001, KORA: OR 1.3 [95% CI 1.16–1.52], P < 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97–8], P = 0.0002). Although these are host-produced metabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve >70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P < 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset. Article Highlights: Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We investigated whether there is a fecal metabolite signature of impaired fasting glucose (IFG) and the possible underlying mechanisms of action. We identified a fecal metabolite signature of IFG associated with prevalent IFG in two independent cohorts and incident type 2 diabetes in a subanalysis. Although the signature consists of metabolites of nonmicrobial origin, it is strongly correlated with gut microbiome composition. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes by affecting intestinal absorption or excretion of host compounds and xenobiotics. [ABSTRACT FROM AUTHOR]

Aims Treatment with sodium-glucose co-transporter 2 (SGLT2)-inhibitors reduces the risk of cardiovascular disease and mortality, but the mechanism is unclear. We hypothesized that a functional genetic variant in solute carrier family 5 member 2 (SLC5A2), known to be associated with familial renal glucosuria, would mimic pharmacological SGLT2-inhibition, and thus provide an opportunity to examine potential mediators of the effects on lower risk of cardiovascular disease and mortality. Methods and results We examined 112 712 individuals from the Copenhagen City Heart Study and Copenhagen General Population Study (CCHS + CGPS), 488 687 from the UK Biobank, and 342 499 from FinnGen, genotyped for SLC5A2 rs61742739, c.1961A > G; p.(Asn654Ser). The 2.0% heterozygotes and 0.01% homozygotes were pooled as carriers and compared with the 98% non-carriers. First, we examined the risk of cardiovascular disease and mortality; second, whether carrying the variant was associated with potential mediators of the effect; and third, whether identified potential mediators could explain the observed reduced risk of cardiovascular disease and mortality. In the CCHS + CGPS, carriers vs. non-carries had a 31% lower risk of heart failure, 21% lower risk of myocardial infarction, 16% lower risk of ischaemic heart disease, and 22% lower risk of all-cause mortality. Corresponding values in meta-analyses of the three studies combined were lower risk by 10%, 6%, 6%, and 10%, respectively. The SLC5A2 rs61742739 variant was not associated with a risk of ischaemic stroke or cardiovascular mortality. Of the lower risks observed in CCHS + CGPS, lower plasma glucose mediated 2.0%(P = 0.004) on heart failure, 3.1%(P = 0.09) on myocardial infarction, 4.1%(P = 0.02) on ischaemic heart disease, and 6.0%(P = 0.39) on all-cause mortality; corresponding values in the UK Biobank were 2.9%(P = 0.70), 1.5%(P = 0.77), 4.1%(P = 0.23), and 3.1%(P = 0.21), respectively. Conclusion A functional genetic variant in SLC5A2 , mimicking SGLT2-inhibition, was associated with a lower risk of heart failure, myocardial infarction, ischaemic heart disease, and all-cause mortality. These effects were at most minimally mediated through lower plasma glucose. [ABSTRACT FROM AUTHOR]

Continuous glucose monitoring (CGM) is used clinically and for research purposes to capture glycaemic profiles. The accuracy of CGM among healthy populations has not been widely assessed. This study assessed agreement between glucose concentrations obtained from venous plasma and from CGM (FreeStyle Libre2TM, Abbott Diabetes Care, Witney, UK) in healthy women. Glucose concentrations were assessed after fasting and every 15 min after a standardized breakfast over a 4-h lab period. Accuracy of CGM was determined by Bland–Altman plot, 15/15% sensor agreement analysis, Clarke error grid analysis (EGA) and mean absolute relative difference (MARD). In all, 429 valid CGM readings with paired venous plasma glucose (VPG) values were obtained from 29 healthy women. Mean CGM readings were 1.14 mmol/L (95% CI: 0.97 to 1.30 mmol/L, p < 0.001) higher than VPG concentrations. Ratio 95% limits of agreement were from 0.68 to 2.20, and a proportional bias (slope: 0.22) was reported. Additionally, 45% of the CGM readings were within ±0.83 mmol/L (±15 mg/dL) or ±15% of VPG, while 85.3% were within EGA Zones A + B (clinically acceptable). MARD was 27.5% (95% CI: 20.8, 34.2%), with higher MARD values in the hypoglycaemia range and when VPG concentrations were falling. The FreeStyle Libre2TM CGM system tends to overestimate glucose concentrations compared to venous plasma samples in healthy women, especially during hypoglycaemia and during glycaemic swings. [ABSTRACT FROM AUTHOR]

Congenital hyperinsulinism (CHI) is a condition characterised by severe and recurrent hypoglycaemia in infants and young children caused by inappropriate insulin over-secretion. CHI is of heterogeneous aetiology with a significant genetic component and is often unresponsive to standard medical therapy options. The treatment of CHI can be multifaceted and complex, requiring multidisciplinary input. It is important to manage hypoglycaemia in CHI promptly as the risk of long-term neurodisability arising from neuroglycopaenia is high. The UK CHI consensus on the practice and management of CHI was developed to optimise and harmonise clinical management of patients in centres specialising in CHI as well as in non-specialist centres engaged in collaborative, networked models of care. Using current best practice and a consensus approach, it provides guidance and practical advice in the domains of diagnosis, clinical assessment and treatment to mitigate hypoglycaemia risk and improve long term outcomes for health and well-being. [ABSTRACT FROM AUTHOR]

Introduction: Real-time continuous glucose monitoring (rt-CGM) involves the measurement and display of glucose concentrations, potentially improving glucose control among insulin-treated patients with type 2 diabetes (T2D). The present analysis aimed to conduct a cost-effectiveness analysis of rt-CGM versus self-monitoring of blood glucose (SMBG) based on a USA retrospective cohort study in insulin-treated people with T2D adapted to the UK. Methods: Long-term costs and clinical outcomes were estimated using the CORE Diabetes Model, with clinical input data sourced from a retrospective cohort study. Patients were assumed to have a baseline glycated hemoglobin (HbA1c) of 8.3%. Patients using rt-CGM were assumed to have a 0.56% reduction in HbA1c based on the mean difference between groups after 12 months of follow-up. Reduced fingerstick testing when using rt-CGM was associated with a quality of life (QoL) benefit. The analysis was performed over a lifetime time horizon from a National Health Service (NHS) perspective, including only direct costs from published data. Future costs and clinical outcomes were discounted at 3.5% per annum. Extensive sensitivity analyses were performed. Results: Projections showed that rt-CGM was associated with increased quality-adjusted life expectancy of 0.731 quality-adjusted life years (QALYs) and increased mean total lifetime costs of Great British pounds (GBP) 2694, and an incremental cost-effectiveness ratio of GBP 3684 per QALY compared with SMBG. Key drivers of outcomes included HbA1c reduction and reduced fingerstick testing QoL benefit. Conclusions: Over patient lifetimes, rt-CGM was associated with improved clinical outcomes and is highly likely to be cost effective versus SMBG in people with T2D on insulin therapy in the UK. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is diagnosed by the presence of high scores on three or more metabolic traits, including systolic and diastolic blood pressure (SBP, DBP), glucose and insulin levels, cholesterol and triglyceride (TG) levels, and central obesity. A diagnosis of MetS is associated with increased risk of cardiovascular disease and type 2 diabetes. The components of MetS have long been demonstrated to have substantial genetic components, but their genetic overlap is less well understood. The present paper takes a multi‐prong approach to examining the extent of this genetic overlap. This includes the quantitative genetic and additive Bayesian network modeling of the large TwinsUK project and examination of the results of genome‐wide association study (GWAS) of UK Biobank data through use of LD score regression and examination of the number of genes and pathways identified in the GWASes which overlap across MetS traits. Results demonstrate a modest genetic overlap, and the genetic correlations obtained from TwinsUK and UK Biobank are nearly identical. However, these correlations imply more genetic dissimilarity than similarity. Furthermore, examination of the extent of overlap in significant GWAS hits, both at the gene and pathway level, again demonstrates only modest but significant genetic overlap. This lends support to the idea that in clinical treatment of MetS, treating each of the components individually may be an important way to address MetS. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID-19., Design: Retrospective multicentre cohort., Setting: Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland., Population: 4915 women with GDM pre-pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021)., Methods: We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia., Main Outcome Measures: Intervention at birth, perinatal mortality, large-for-gestational-age infants and neonatal unit admission., Results: The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre-existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre- and during the pandemic., Conclusions: Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre-existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Aims: Enteral feeding is commonly used to manage a variety of medical conditions in hospitals. For people with diabetes this can present a specific challenge for glucose management. To address gaps in our understanding of modern enteral feeding outcomes and to help with the development of more specific guidance on maintaining glycaemic control, we conducted a national survey on the management of enteral feeding against the standards in the nationally adopted Joint British Diabetes Societies for Inpatient Care (JBDS) guidelines., Methods: A questionnaire was developed using the 2018 JBDS guideline as a template this questionnaire was sent out by email to all 220 UK specialist diabetes teams. Databases of Diabetes UK, the Association of British Diabetologists (ABCD) and the Diabetes Inpatient Specialist Nurse UK Group were used., Results: Twenty-six hospitals responded, 11 had guidelines for the management of insulin with enteral feeding. There were three main feed regimens used: continuous 24-h feeding, a single feed with one break in 24 h, or multiple feeds in 24 h. There were five regimens in common use: premixed insulin, isophane insulin, analogue basal insulin, variable rate intravenous insulin or basal bolus insulin. Overall glucose control was poor for all regimens and combinations. Continuous feed showed better glucose control than a single feed with a break, mean (±SD) glucose 12.4 mmol/L (5.6) versus 15.1 mmol/L (6.9) p < 0.005, but no group showed optimal control., Conclusions: Managing diabetes control during enteral feeding remains a challenge. Our survey showed that glucose control during this treatment is suboptimal., (© 2023 Diabetes UK.)

Background: Gestational diabetes mellitus (GDM) can adversely affect the health of the developing fetus. Women of South Asian origin are particularly at risk of developing GDM. Insulin resistance (IR) contributes to the etiology of GDM, and although studies have shown associations of vitamin B12 (B12) and folate status with GDM and IR, only a limited number of B12 and folate markers have been used.Objective: We used a comprehensive panel of B12 and folate markers to examine their association with IR in pregnant women with diet-controlled GDM and normal glucose tolerance (NGT).Methods: In this cross-sectional study, 59 British-Bangladeshi women (24 GDM and 35 NGT) with a mean age of 29 y, BMI (in kg/m2) 26.7 and gestational age 33 wk were recruited. Serum total B12, holotranscobalamin, folate, methylmalonic acid, plasma homocysteine, 5-methyltetrahydrofolate, and red cell folate (RCF) were measured along with other parameters. The independent sample t-test and chi-squared test were used to assess differences in markers between GDM and NGT women. Spearman's test was used to look for correlations. A simple multiple regression analysis was used to investigate if markers of B12 and folate status predicted IR, using the HOMA-IR and adjusting for age, GDM status, and BMI.Results: There were no differences in concentrations of B12 and folate markers between GDM and NGT women. In Spearman's analysis HOMA-IR correlated negatively with total serum B12 (P < 0.001) and holotranscobalamin (P < 0.05), and positively with BMI (P < 0.001), blood pressure (P < 0.05) and triglycerides (P < 0.05) in all women. MMA did not correlate with any of the B12 markers. In regression analysis, total B12 (β = -0.622, P = 0.004), RCF (β = 0.387, P = 0.018), and BMI (β = 0.024, P < 0.001) were the significant predictors of HOMA-IR variance.Conclusions: Significant associations between markers of B12 and folate status with HOMA-IR were found during the third trimester in British-Bangladeshi women. B12 markers correlated poorly with each other. [ABSTRACT FROM AUTHOR]

Introduction: 4.2 million individuals in the UK have type 2 diabetes, a known risk factor for dementia and mild cognitive impairment (MCI). Diabetes treatment may modify this association, but existing evidence is conflicting. We therefore aimed to assess the association between metformin therapy and risk of incident all-cause dementia or MCI compared with other oral glucose-lowering therapies (GLTs)., Research Design and Methods: We conducted an observational cohort study using the Clinical Practice Research Datalink among UK adults diagnosed with diabetes at ≥40 years between 1990 and 2019. We used an active comparator new user design to compare risks of dementia and MCI among individuals initially prescribed metformin versus an alternative oral GLT using Cox proportional hazards regression controlling for sociodemographic, lifestyle and clinical confounders. We assessed for interaction by age and sex. Sensitivity analyses included an as-treated analysis to mitigate potential exposure misclassification., Results: We included 211 396 individuals (median age 63 years; 42.8% female), of whom 179 333 (84.8%) initiated on metformin therapy. Over median follow-up of 5.4 years, metformin use was associated with a lower risk of dementia (adjusted HR (aHR) 0.86 (95% CI 0.79 to 0.94)) and MCI (aHR 0.92 (95% CI 0.86 to 0.99)). Metformin users aged under 80 years had a lower dementia risk (aHR 0.77 (95% CI 0.68 to 0.85)), which was not observed for those aged ≥80 years (aHR 0.95 (95% CI 0.87 to 1.05)). There was no interaction with sex. The as-treated analysis showed a reduced effect size compared with the main analysis (aHR 0.90 (95% CI 0.83 to 0.98))., Conclusions: Metformin use was associated with lower risks of incident dementia and MCI compared with alternative GLT among UK adults with diabetes. While our findings are consistent with a neuroprotective effect of metformin against dementia, further research is needed to reduce risks of confounding by indication and assess causality., Competing Interests: Competing interests: NC receives funds from AstraZeneca to serve on data safety and monitoring committees for clinical trials. R. Mathur is part of the Genes & Health Program, which is part-funded (including salary contributions) by a Life Sciences Consortium comprising AstraZeneca, Bristol-Myers Squibb Company, GlaxoSmithKline Research and Development Limited, Maze Therapeutics, Merck Sharp & Dohme, Novo Nordisk, Pfizer, and Takeda Development Center Americas. All other authors report no conflicts., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To quantify maternal hypertensive disorder of pregnancy (HDP) prevalence in late preterm and term infants admitted to neonatal units (NNU) and assess opportunities to avoid admissions., Design: A retrospective population-based study using the National Neonatal Research Database., Setting: England and Wales., Population: Infants born ≥34 weeks' gestation admitted to NNU between 2012 and 2020., Methods: Outcomes in HDP infants are compared with non-HDP infants using regression models., Main Outcome Measures: Hypertensive disorder of pregnancy, primary reason for admission, clinical diagnoses and resource use., Results: 16 059/136 220 (11.8%) of late preterm (34 +0 to 36 +6 weeks' gestation) and 14 885/284 646 (5.2%) of term (≥37 weeks' gestation) admitted infants were exposed to maternal HDP. The most common primary reasons for HDP infant admission were respiratory disease (28.3%), prematurity (22.7%) and hypoglycaemia (16.4%). HDP infants were more likely to be admitted with primary hypoglycaemia than were non-HDP infants (odds ratio [OR] 2.1, 95% confidence interval [CI] 2.0-2.2, P < 0.0001). 64.5% of HDP infants received i.v. dextrose. 35.7% received mechanical or non-invasive ventilation. 8260/30 944 (26.7%) of HDP infants received intervention for hypoglycaemia alone (i.v. dextrose) with no other major intervention (respiratory support, parenteral nutrition, central line, arterial line or blood transfusion)., Conclusions: The burden of maternal HDP on late preterm and term admissions to NNU is high, with hypoglycaemia and respiratory disease being the main drivers for admission. Over one in four were admitted solely for management of hypoglycaemia. Further research should determine whether maternal antihypertensive agent choice or postnatal pathways may reduce NNU admission., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Aims/hypothesis: Out‐of‐hospital hypoglycaemia is a common complication for individuals with diabetes mellitus and represents a significant burden to emergency medical services (EMS). We aim to identify the factors associated with receiving parenteral treatment and hospital conveyance. Methods: We retrospectively analysed a 6‐month data set of all London EMS hypoglycaemia. Individuals with a known diabetes diagnosis were included in our analysis and stratified as either having type 1 diabetes or type 2 diabetes. Results: A total of 2862 incidents occurred within the area served by London Ambulance Service between January and June 2018. Fifty percent of incidents required parenteral treatment (intravenous glucose or intramuscular glucagon) and were conveyed to hospital. A higher arrival of blood glucose, intact consciousness and receiving oral glucose treatment were all negative predictors for requiring parenteral therapy. Forty‐three percent of incidents were labelled as 'hypoglycaemia' by the EMS call handler, and greater odds of hospitalisation were observed among incidents that received parenteral treatment (OR 2.52 [95% CI 1.46, 4.33] p < 0.01) and individuals with type 2 diabetes (OR 2.67 [95% CI 1.52, 4.71] p < 0.01). Repeated callouts from 2% (n = 50) of individuals accounted for 10% (286) of all incidents attended, and 56.4% of individuals attended by EMS on more than one occasion had type 1 diabetes. Conclusions/interpretation: Severe hypoglycaemia requiring emergency service attendance remains common, as does the requirement for parenteral therapy and conveyance to hospital. Early intervention, education and improved accessibility to risk prevention strategies may reduce the necessity for emergency parenteral treatment and hospitalisation, especially among individuals suffering from recurrent hypoglycaemia and high‐risk individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Prospective studies have shown differences in some disease risks between vegetarians and nonvegetarians, but the potential biological pathways are not well understood.Objectives: We aimed to assess differences in concentrations of biomarkers related to disease pathways in people with varying degrees of animal foods exclusion.Methods: The UK Biobank recruited 500,000 participants aged 40-69 y (54.4% women) throughout the United Kingdom in 2006-2010. Blood and urine were collected at recruitment and assayed for more than 30 biomarkers related to cardiovascular diseases, bone and joint health, cancer, diabetes, renal disease, and liver health. In cross-sectional analyses, we estimated adjusted geometric means of these biomarkers by 6 diet groups (regular meat eaters, low meat eaters, poultry eaters, fish eaters, vegetarians, vegans) in 466,058 white British participants and 2 diet groups (meat eaters, vegetarians) in 5535 British Indian participants.Results: We observed differences in the concentrations of most biomarkers, with many biomarkers showing a gradient effect from meat eaters to vegetarians/vegans. Of the largest differences, compared with white British regular meat eaters, white British vegans had lower C-reactive protein [adjusted geometric mean (95% CI): 1.13 (1.03, 1.25) compared with 1.43 (1.42, 1.43) mg/L], lower low-density lipoprotein cholesterol [3.13 (3.07, 3.20) compared with 3.65 (3.65, 3.65) mmol/L], lower vitamin D [34.4 (33.1, 35.9) compared with 44.5 (44.4, 44.5) nmol/L], lower serum urea [4.21 (4.11, 4.30) compared with 5.36 (5.36, 5.37) mmol/L], lower urinary creatinine [5440 (5120, 5770) compared with 7280 (7260, 7300) μmol/L], and lower γ-glutamyltransferase [23.5 (22.2, 24.8) compared with 29.6 (29.6, 29.7) U/L]. Patterns were mostly similar in British Indians, and results were consistent between women and men.Conclusions: The observed differences in biomarker concentrations, including lower C-reactive protein, lower LDL cholesterol, lower vitamin D, lower creatinine, and lower γ-glutamyltransferase, in vegetarians and vegans may relate to differences in future disease risk. [ABSTRACT FROM AUTHOR]

Background: Continuous glucose monitoring systems are increasingly being adopted as an alternative to self-monitoring of blood glucose (SMBG) by persons with diabetes mellitus receiving insulin therapy. Main body: The FreeStyle Libre flash glucose monitoring system (Abbott Diabetes Care, Witney, United Kingdom) consists of a factory-calibrated sensor worn on the back of the arm which measures glucose levels in the interstitial fluid every minute and stores the reading automatically every 15 min. Swiping the reader device over the sensor retrieves stored data and displays current interstitial glucose levels, a glucose trend arrow, and a graph of glucose readings over the preceding 8 h. In patients with type 2 diabetes (T2D) receiving insulin therapy, pivotal efficacy data were provided by the 6-month REPLACE randomized controlled trial (RCT) and 6-month extension study. Compared to SMBG, the flash system significantly reduced the time spent in hypoglycemia and frequency of hypoglycemic events, although no significant change was observed in glycosylated hemoglobin (HbA1c) levels. Subsequent RCTs and real-world chart review studies have since shown that flash glucose monitoring significantly reduces HbA1c from baseline. Real-world studies in both type 1 diabetes or T2D populations also showed that flash glucose monitoring improved glycemic control. Higher (versus lower) scanning frequency was associated with significantly greater reductions in HbA1c and significant improvements in other measures such as time spent in hypoglycemia, time spent in hyperglycemia, and time in range. Additional benefits associated with flash glucose monitoring versus SMBG include reductions in acute diabetes events, all-cause hospitalizations and hospitalized ketoacidosis episodes; improved well-being and decreased disease burden; and greater treatment satisfaction. Conclusion: T2D patients who use flash glucose monitoring might expect to achieve significant improvement in HbA1c and glycemic parameters and several associated benefits. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether intermittently scanned continuous glucose monitoring (isCGM) significantly improves glycemic control compared with capillary self-monitored blood glucose (SMBG) in youth with type 1 diabetes and high-risk glycemic control.Research Design and Methods: This multicenter 6-month randomized, controlled, parallel-arm trial included 64 participants aged 13-20 years with established type 1 diabetes and glycated hemoglobin (HbA1c) ≥9% (≥75 mmol/mol). Participants were allocated to 6-month intervention (isCGM; FreeStyle Libre; Abbott Diabetes Care, Witney, U.K.) (n = 33) or control (SMBG; n = 31) using minimization. The primary outcome was the difference in change in HbA1c from baseline to 6 months.Results: There was no evidence of a difference between groups for changes in HbA1c at 6 months (adjusted mean 0.2% greater improvement for isCGM [95% CI -0.9 to 0.5] [-2.1 mmol/mol (95% CI -9.6 to 5.4)]; P = 0.576). However, glucose-monitoring frequency was 2.83 (95% CI 1.72-4.65; P < 0.001) times higher in the isCGM group compared with that in the SMBG group at 6 months. The change in the Diabetes Treatment Satisfaction Questionnaire mean item score also favored isCGM at 6 months (P = 0.048), with no significant differences between groups for fear of hypoglycemia and quality of life (both general and diabetes specific) (all P > 0.1).Conclusions: For youth with high-risk glycemic control, isCGM led to improvements in glucose testing frequency and diabetes treatment satisfaction. However, these did not translate to greater improvement in glycemic control over usual care with SMBG at 6 months. [ABSTRACT FROM AUTHOR]

Background: Mechanisms linking habitual consumption of coffee and tea to the development of type 2 diabetes and cardiovascular diseases remain unclear.Objectives: We leveraged dietary, genetic, and biomarker data collected from the UK Biobank to investigate the role of different varieties of coffee and tea in cardiometabolic health.Methods: We included data from ≤447,794 participants aged 37-73 y in 2006-2010 who provided a blood sample and completed questionnaires regarding sociodemographic factors, medical history, diet, and lifestyle. Multivariable linear regression was used to examine the association between coffee or tea consumption and blood concentrations of glycated hemoglobin, fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, fasting triglycerides (TGs), apoA-1, apoB, lipoprotein-a, and C-reactive protein (CRP). Lifestyle and genetic factors affecting caffeine metabolism, responses, or intake were tested for interactions with beverage intake in relation to biomarker concentrations.Results: Compared with coffee nonconsumers, each additional cup of coffee was significantly associated with higher total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations and lower TG and CRP concentrations in both men and women (P-trend < 0.002). Higher consumption of espresso coffee (≥2 compared with 0 cups/d) was associated with higher LDL cholesterol in men (β: 0.110 mmol/L; 95% CI: 0.058, 0.163 mmol/L) and women (β: 0.161 mmol/L; 95% CI: 0.088, 0.234 mmol/L), whereas no substantial association was observed for instant coffee. Compared with tea nonconsumers, higher tea consumption was associated with lower total and LDL cholesterol and apoB and higher HDL cholesterol (P-trend < 0.002); these associations were similar for black and green tea. Associations were not modified by genetics.Conclusions: In the UK Biobank, consumption of certain coffee brews such as espresso had unfavorable associations with blood lipids, whereas consumption of tea had favorable associations. Findings were not modified by genetic variants affecting caffeine metabolism, suggesting a role of noncaffeine constituents of these beverages in cardiometabolic health. [ABSTRACT FROM AUTHOR]

Purpose: Intermittent energy restriction (IER) is a popular weight loss (WL) strategy; however, its efficacy in clinical practice remains unknown. The present study compared the effects of IER compared to continuous energy restriction (CER) on WL and cardiometabolic risk factors in primary care. Methods: A (self-selected) cohort study was conducted at the Rotherham Institute for Obesity (RIO), a primary care-based weight management service. 197(24% male) obese patients volunteered to participate and selected their diet group. IER participants (n = 99) consumed ~ 2600 kJ for two days/week. CER participants (n = 98) restricted their diet by ~ 2100 kJ/day below estimated requirements. Both interventions were delivered alongside RIO standard care. Changes in anthropometry and cardiometabolic disease risk markers (fasting biochemistry and blood pressure) were assessed after a 6-month intervention period and then participants were followed up again 6 months later (month 12). Results: 27 IER patients (27%) and 39 CER patients (40%) completed the 6-month weight loss phase. Among completers, mean (SEM) WL was greater in the IER group at 6 months (5.4 ± 1.1% versus 2.8 ± 0.6%; p = 0.01), as were reductions in fat mass (p < 0.001) and improvements in systolic blood pressure (p < 0.001). Fasting insulin (p = 0.873) and diastolic blood pressure (p = 0.701) were reduced similarly in both groups. However, in the IER group, changes in anthropometry and blood pressure in the IER group had reverted to baseline by 12-month follow-up, whilst the CER group maintained weight loss but showed an increase in blood pressure. Conclusions: Among completers, IER resulted in superior short-term changes in anthropometry and some cardiometabolic risk factors. However, rates of attrition and weight regain were higher compared with standard care, providing important insights in the implementations of IER within a "real-life" NHS setting. Trial registration number: ISRCTN31465600. [ABSTRACT FROM AUTHOR]

Background: This study assessed whether i.v. sildenafil citrate prevented acute kidney injury in at-risk patients undergoing cardiac surgery with cardiopulmonary bypass.Methods: In a double-blind RCT, adults at increased risk of acute kidney injury undergoing cardiac surgery in a single UK tertiary centre were randomised to receive sildenafil citrate 12.5 mg kg-1 i.v. over 150 min or dextrose 5% at the commencement of surgery. The primary outcome was serum creatinine measured at six post-randomisation time points. The primary analysis used a linear mixed-effects model adjusted for the stratification variables, baseline estimated glomerular filtration rate, and surgical procedure. Secondary outcomes considered clinical events and potential disease mechanisms. Effect estimates were expressed as mean differences (MDs) or odds ratios with 95% confidence intervals.Results: The analysis population comprised eligible randomised patients that underwent valve surgery or combined coronary artery bypass graft and valve surgery, with cardiopulmonary bypass, between May 2015 and June 2018. There were 60 subjects in the sildenafil group and 69 in the placebo control group. The difference between groups in creatinine concentration was not statistically significant (MD: 0.88 μmol L-1 [-5.82, 7.59]). There was a statistically significant increase in multiple organ dysfunction scores in the sildenafil group (MD: 0.54 [0.02, 1.07]; P=0.044). Secondary outcomes, and biomarkers of kidney injury, endothelial function, and inflammatory cell activation, were not significantly different between the groups.Conclusions: These results do not support the use of i.v. sildenafil citrate for kidney protection in adult cardiac surgery.Clinical Trial Registration: ISRCTN18386427. [ABSTRACT FROM AUTHOR]

We investigated the impact of recent caffeine drinking on glucose and other biomarkers of cardiometabolic function under free-living conditions while also accounting for lifestyle and genetic factors that alter caffeine metabolism and drinking behaviour. Up to 447 794 UK Biobank participants aged 37–73 years in 2006–2010 provided a non-fasting blood sample, for genetic and biomarker measures, and completed questionnaires regarding sociodemographics, medical history and lifestyle. Caffeine drinking (yes/no) about 1 h before blood collection was also recorded. Multivariable regressions were used to examine the association between recent caffeine drinking and serum levels of glycated Hb, glucose, lipids, apo, lipoprotein(a) and C-reactive protein. Men and women reporting recent caffeine drinking had clinically and significantly higher glucose levels than those not recently drinking caffeine (P < 0·0001). Larger effect sizes were observed among those 55+ years of age and with higher adiposity and longer fasting times (P ≤ 0·02 for interactions). Significant CYP1A2 rs2472297×caffeine and MLXIPL rs7800944 × caffeine interactions on glucose levels were observed among women (P = 0·004), with similar but non-significant interactions in men. Larger effect sizes were observed among women with rs2472297 CC or rs7800944 CC genotypes than among rs2472297 T or rs7800944 T carriers, respectively. In summary, men and women drinking caffeine within about 1 h of blood draw had higher glucose levels than those not drinking caffeine. Findings were modified by age, adiposity, fasting time and genetic factors related to caffeine metabolism and drinking behaviour. Implications for clinical and population studies of caffeine-containing beverages and cardiometabolic health are discussed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether high glucose levels in the normoglycemic range and higher have a causal genetic effect on risk of retinopathy, neuropathy, nephropathy, chronic kidney disease (CKD), peripheral arterial disease (PAD), and myocardial infarction (MI; positive control) in the general population.Research Design and Methods: This study applied observational and one-sample Mendelian randomization (MR) analyses to individual-level data from 117,193 Danish individuals, and validation by two-sample MR analyses on summary-level data from 133,010 individuals from the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC), 117,165 from the CKDGen Consortium, and 452,264 from the UK Biobank.Results: Observationally, glucose levels in the normoglycemic range and higher were associated with high risks of retinopathy, neuropathy, diabetic nephropathy, PAD, and MI (all P for trend <0.001). In genetic causal analyses, the risk ratio for a 1 mmol/L higher glucose level was 2.01 (95% CI 1.18-3.41) for retinopathy, 2.15 (1.38-3.35) for neuropathy, 1.58 (1.04-2.40) for diabetic nephropathy, 0.97 (0.84-1.12) for estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, 1.19 (0.90-1.58) for PAD, and 1.49 (1.02-2.17) for MI. Summary-level data from the MAGIC, the CKDGen Consortium, and the UK Biobank gave a genetic risk ratio of 4.55 (95% CI 2.26-9.15) for retinopathy, 1.48 (0.83-2.66) for peripheral neuropathy, 0.98 (0.94-1.01) for eGFR <60 mL/min/1.73 m2, and 1.23 (0.57-2.67) for PAD per 1 mmol/L higher glucose level.Conclusions: Glucose levels in the normoglycemic range and higher were prospectively associated with a high risk of retinopathy, neuropathy, diabetic nephropathy, eGFR <60 mL/min/1.73 m2, PAD, and MI. These associations were confirmed in genetic causal analyses for retinopathy, neuropathy, diabetic nephropathy, and MI, but they could not be confirmed for PAD and seemed to be refuted for eGFR <60 mL/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Current intermittently scanned continuous glucose monitoring (isCGM) devices do not allow calibration and require confirmatory self-monitored blood glucose (SMBG) under specific defined conditions. The overall time spent in an SMBG-indicated state while using isCGM has not been reported in the existing literature. We present the time spent in an SMBG-indicated state and the daily number of transitions to an SMBG-indicated state during isCGM use in a high-risk cohort of adults with type 1 diabetes. This is a post hoc analysis of participants randomized to isCGM as part of a clinical study. The percentage of values meeting one or more of the criteria for SMBG testing (hours per day) and the number of transitions to an SMBG-indicated state per day were calculated according to the manufacturer's label in the United Kingdom. Complete data sets for 20 participants on isCGM for 8 weeks were included in the analysis. Participants spent a mean (SD) of 5.61 (1.81) h/day in an SMBG-indicated state and there were 5.43 (1.42) transitions to an SMBG-indicated state per day while using isCGM. These findings have important implications for cost-effectiveness and for decision-making around insulin dose calculations and driving. Our findings emphasize the need for continued SMBG testing among people at high risk of hypoglycemia who use isCGM. Cost-effectiveness analyses for isCGM may require revision. [ABSTRACT FROM AUTHOR]

• Excessive negative energy balance in dairy cows was associated with a number of risk factors. • Significant individual cow risk factors included body condition score, parity and milk yield. • Significantly more cows had excessive negative energy balance in the summer (April to October). • Significant dietary risk factors included not feeding conserved forages to dry cows, and access to grazed grass. This study assessed risk factors associated with excessive negative energy balance (eNEB) in UK dairy cows between April 2006 and March 2015. Blood samples were analysed for β-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and glucose. Following removal of all potential duplicate cows, a final dataset of 69,161 unique individual cows was obtained including biochemical results, individual cow and feed data. Generalised linear mixed-effect models and multivariable classification tree-based models showed that individual cow risk factors for eNEB included: (1) days relative to predicted calving date (dry cows); (2) days in milk (lactating cows); (3) body condition score (BCS; lactating cows ≥ BCS 4; OR 2.1); (4) milk yield (around 40 L per day); (5) parity (first lactation heifers; odds ratio [OR] 0.46 compared to older cows during lactation); and (6) chronic inflammatory conditions as assessed by globulin concentrations ≥ 50 g/L (OR 0.79 for cows with evidence of chronic inflammation). There was a higher prevalence during April to October (OR 1.19), and the lowest prevalence was in November. Feeding grass silage and wholecrop (silage made from cereal crops) to dry cows was associated with a reduced prevalence of eNEB, whereas access to grazed grass was associated with a higher prevalence in both the dry period (OR 1.32) and lactation (OR 1.33). Knowledge of the risk factors associated with eNEB in commercial dairy herds assists in both the implementation of herd monitoring programs and reduction of eNEB in dairy herds, with associated reductions in the risk of periparturient diseases and improved dairy cow performance. [ABSTRACT FROM AUTHOR]

Background/objectives: Short sleep duration has been linked to maternal hyperglycaemia following a 1-h 50 g oral glucose tolerance test (OGTT) in observational studies conducted primarily in the USA. Our objective was to examine the relationship between objectively measured sleep duration and plasma glucose values following the 2-h 75 g OGTT routinely used in the UK amongst women with obesity.Methods: Sleep and OGTT data were available for 49 pregnant women who wore wrist actigraphs for at least two nights, and took a 2-h 75 g OGTT at the end of their second trimester. Multivariable regression was used to evaluate associations between sleep duration and OGTT results.Results: Higher 2-h plasma glucose values were significantly associated with shorter sleep duration and higher maternal age and BMI, with no association observed between wake after sleep onset (WASO) and 2-h plasma glucose values. No associations were observed between fasting plasma glucose values and any sleep parameters.Conclusions: We found that shorter sleep duration, as measured using actigraphy, is associated with higher 2-h plasma glucose values following a 2-h 75 g OGTT in the UK. These findings are in keeping with those observed elsewhere in the world, employing alternative OGTT protocols. Future studies should investigate sleep extension as a potential candidate for inclusion in future RCTs aiming to improve glucose tolerance and prevent GDM amongst those at risk. [ABSTRACT FROM AUTHOR]

• Excessive negative energy balance affected 52% of UK dairy cows in late pregnancy. • In the first 20 days after calving, 75.2% of UK dairy cows were affected. • The herd prevalence of excessive negative energy balance was 37.5% in late pregnancy and 59.8% in early lactation. • Such excessive negative energy balance has been associated with harmful effects on cow health, milk production and fertility. The objectives of this study were to determine the individual animal and herd level prevalence of excessive negative energy balance (eNEB) in commercial UK dairy herds. Between April 2006 and March 2015, blood samples from 84,369 individual cows from 1748 different UK farms were received by a commercial laboratory service specializing in dairy cow nutritional monitoring. Following removal of all potential duplicate cows, the final dataset comprised 69,161 unique individual cows. The prevalence of eNEB was determined using plasma thresholds of β-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and glucose. Overall prevalence of subclinical ketosis (SCK) in the first 20 days of lactation was 28.5%, 17.3% and 11.7% using BHB thresholds of 1.0, 1.2 and 1.4 mmol/L respectively. Prevalence of NEFA values ≥0.5 mmol/L in the last 10 days prior to calving was 26.0%, and 40.3% of cows had NEFA values ≥0.7 mmol/L in the first 20 days in milk (DIM). Combining BHB, NEFA and glucose showed that 52.0% of cows had one or more of the three biochemical measures of energy balance outside the respective threshold value in the last 10 days pre-calving, and 75.2% of cows showed a similar biochemical pattern in the first 20 DIM. The median herd prevalence of elevated BHB and/or NEFA was 37.5% in late pregnancy and 59.8% in the first 20 DIM, with substantial herd variation. Using multiple measures for the assessment of energy balance, this study has shown that eNEB affects substantial numbers of UK dairy cows. [ABSTRACT FROM AUTHOR]

Objective: To investigate associations between different glycemic status and biological age indexed by retinal age gap., Methods: A total of 28,919 participants from the UK Biobank study with available glycemic status and qualified retinal imaging data were included in the present analysis. Glycemic status included type 2 diabetes mellitus (T2D) disease status and glycemic indicators of plasma glycated hemoglobin (HbA1c) and glucose. Retinal age gap was defined as the difference between the retina-predicted age and chronological age. Linear regression models estimated the association of different glycemic status with retinal age gap., Results: Prediabetes and T2D was significantly associated with higher retinal age gaps compared to normoglycemia (regression coefficient [β] = 0.25, 95% confidence interval [CI]: 0.11-0.40, P = 0.001; β = 1.06, 95% CI: 0.83-1.29, P < 0.001; respectively). Multi-variable linear regressions further found an increase of HbA1c was independently associated with higher retinal age gaps among all subjects or subjects without T2D. Significant positive associations were noted across the increasing HbA1c and glucose groups with retinal age gaps compared to the normal level group. These findings remained significant after excluding diabetic retinopathy., Conclusions: Dysglycemia was significantly associated with accelerated ageing indexed by retinal age gaps, highlighting the importance of maintaining glycemic status., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lactic acid bacteria are being consumed more frequently as awareness of their health benefits has increased. The industrial production of lactic acid bacteria requires a comprehensive understanding of their survival stress, especially regarding changes in metabolic substances in a glucose-limited environment. In the present study, a metabolomic approach was applied to investigate Lactobacillus casei Zhang using cultures from a common ancestor that were permitted to evolve under conditions with normal or glucose-restricted media for up to 4,000 generations. Metabolomic analyses of intracellular and extracellular differential metabolites under De Man, Rogosa and Sharpe broth (2% vol/vol glucose; Oxoid Ltd., Basingstoke, UK) and glucose-restricted (0.02% vol/vol glucose in De Man, Rogosa and Sharpe broth) conditions were performed at generations 0, 2,000, and 4,000 and revealed 23 different metabolites. Myristic acid, ergothioneine, Lys-Thr, and palmitamide contents exhibited significant reductions between 0 and 4,000 generations, whereas nicotinate, histidine, palmitic acid, l -lysine, urocanate, thymine, and other substances increased. The dynamics of the pathways involved in AA metabolism, including glycine, serine, and threonine metabolism, histidine metabolism, lysine degradation, and arginine and proline metabolism, were also a focus of the present study. There were also changes in several other metabolic pathways, including vitamin B 6 , thiamine, nicotinate, and nicotinamide, according to generation time. Additionally, in the present study we screened for key metabolites involved in the glucose-restricted response and provided a theoretical basis for comprehensively revealing the regulatory mechanisms associated with L. casei Zhang glucose restriction at the metabolic level. These findings also provide novel ideas and methods for analyzing the glucose-restricted stress response at the metabolic level. [ABSTRACT FROM AUTHOR]

Introduction: Gestational diabetes mellitus (GDM) is the most common pregnancy complication worldwide and is associated with short- and long-term health implications for both mother and child. Prevalence of GDM varies between ethnicities, with South Asians (SAs) experiencing up to three times the risk compared to white Europeans (WEs). Recent evidence suggests that underlying metabolic difference contribute to this disparity, but an investigation of causality is required., Methods: To address this, we paired metabolite and genomic data to evaluate the causal effect of 146 distinct metabolic characteristics on gestational dysglycemia in SAs and WEs. First, we performed 292 GWASs to identify ethnic-specific genetic variants associated with each metabolite (P ≤ 1 x 10-5) in the Born and Bradford cohort (3688 SA and 3354 WE women). Following this, a one-sample Mendelian Randomisation (MR) approach was applied for each metabolite against fasting glucose and 2-hr post glucose at 26-28 weeks gestation. Additional GWAS and MR on 22 composite measures of metabolite classes were also conducted., Results: This study identified 15 novel genome-wide significant (GWS) SNPs associated with tyrosine in the FOXN and SLC13A2 genes and 1 novel GWS SNP (currently in no known gene) associated with acetate in SAs. Using MR approach, 14 metabolites were found to be associated with postprandial glucose in WEs, while in SAs a distinct panel of 11 metabolites were identified. Interestingly, in WEs, cholesterols were the dominant metabolite class driving with dysglycemia, while in SAs saturated fatty acids and total fatty acids were most commonly associated with dysglycemia., Discussion: In summary, we confirm and demonstrate the presence of ethnic-specific causal relationships between metabolites and dysglycemia in mid-pregnancy in a UK population of SA and WE pregnant women. Future work will aim to investigate their biological mechanisms on dysglycemia and translating this work towards ethnically tailored GDM prevention strategies., Competing Interests: 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 Fuller, Iles, Moore and Zulyniak.)

Background: Objectively measured physical activity (PA) intensity has traditionally been categorized as light, moderate, and vigorous using laboratory calibrated cut points. The relative contribution of time spent across a spectrum of accelerometer-determined intensities on health outcomes is less clear. Purpose: This study aimed to assess the relationship between objectively measured PA intensity on a continuous scale and markers of insulin sensitivity (IS). Methods: Participants at high risk of type 2 diabetes mellitus were recruited from primary care (Leicestershire, UK). PA was measured using an ActiGraph accelerometer. Fasting and postchallenge glucose and insulin levels were assessed using an oral glucose tolerance test. IS was calculated using the Matsuda-IS and the HOMA-IS indices. Log-linear regression modeling was used to assess the relationship between PA intensity, in increments of 500 counts per minute, with markers of IS. Models were controlled for known confounders. Results: Complete data were available for 569 participants. PA intensity was favorably associated with fasting and 2 h of insulin and IS, with the association increasing in magnitude with each increment of 500 counts per minute. Differences in HOMA-IS per 10 min of PA ranged from 12.4% (95% confidence interval = 3.7%-21.8%) to 26.8% (11.0%-44.7%) within the moderate-intensity PA category (from 2000-2499 to 3500-3999 counts per minute). For Matsuda-IS, these differences were 22.0% (10.3%-34.9%) and 34.7% (13.9%-59.3%), respectively. Significant associations for fasting insulin were no longer observed after controlling for body mass index, whereas differences associated with 2-h insulin and IS were attenuated but still significant. Conclusion: PA of any intensity may positively influence glucose regulation and insulin sensitivity in individuals at high risk of type 2 diabetes mellitus in a dose-response manner. Further research is required to identify the intensity thresholds at which clinically relevant benefits occur in this population. [ABSTRACT FROM AUTHOR]

Background: The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, two simple surrogate indicators of insulin resistance, have been demonstrated to predict cardiovascular disease (CVD). However, very few studies have investigated their associations with CVD in European populations., Methods: A total of 403,335 participants from the UK Biobank with data for TyG index and TG/HDL-C ratio and free from CVD at baseline were included. Cox models were applied to evaluate the association between TyG index and TG/HDL-C ratio and incident CVD. Mediation analyses were performed to evaluate the contribution of prevalent diabetes, hypertension, and dyslipidemia to observed associations., Results: During a median follow-up of 8.1 years, 19,754 (4.9%) individuals developed CVD, including 16,404 (4.1%) cases of CHD and 3976 (1.0%) cases of stroke. The multivariable-adjusted hazard ratios of total CVD in higher quartiles versus the lowest quartiles were 1.05, 1.05, and 1.19, respectively, for TyG index, and 1.07, 1.13, and 1.29, respectively, for TG/HDL-C ratio. There were significant trends toward an increasing risk of CVD across the quartiles of TyG index and TG/HDL-C ratio. In mediation analyses, dyslipidemia, type 2 diabetes, and hypertension explained 45.8%, 27.0%, and 15.0% of TyG index's association with CVD, respectively, and 40.0%, 11.8%, and 13.3% of TG/HDL-C ratio's association with CVD, respectively., Conclusions: Elevated baseline TyG index and TG/HDL-C ratio were associated with a higher risk of CVD after adjustment for the well-established CVD risk factors. These associations were largely mediated by greater prevalence of dyslipidemia, type 2 diabetes, and hypertension., (© 2023. The Author(s).)

Aim: To conduct a pharmacoepidemiological study to explore the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and gout in patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: A retrospective open cohort study using the IQVIA Medical Research Data UK database was performed between November 1, 2012 and December 31, 2018, estimating the risk of gout in patients with T2DM who were new users of SGLT2 inhibitors, compared to propensity-score-matched new users of dipeptidyl peptidase-4 (DPP-4) inhibitors., Results: A total of 85 incident cases of gout were recorded over 30 389 person-years of observation in 13 617 new users of SGLT2 inhibitors and 29 426 new users of DPP-4 inhibitors. Crude incidence rates (IRs) per 1000 person-years were 2.90 and 2.47 for new users of SGLT2 inhibitors and DPP-4 inhibitors, respectively. The unadjusted hazard ratio (HR) was 1.18 (95% confidence interval [CI] 0.76-1.83). The adjusted HR was 1.20 (95% CI 0.77-1.86). In the at-treatment analysis, crude IRs per 1000 person-years were found to be 2.68 and 2.53 for SGLT2 inhibitor and DPP-4 inhibitor users, respectively. In the adjusted model, the adjusted HR was 1.3 (95% CI 0.90-2.29). Sensitivity analyses did not change the findings., Conclusions: In this nationwide study, no difference in the incidence of gout was documented in patients treated with SGLT2 inhibitors compared to DPP-4 inhibitor users. This neutral finding remained consistent in sensitivity analyses., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To assess the association between the use of sodium-glucose cotransporter-2 (SGLT2i) and cardiovascular outcomes and death as a function of obesity among patients with type 2 diabetes.Methods: This new-user, active-comparator cohort study used U.K.'s Clinical Practice Research Datalink linked to Hospital Episodes Statistics repository and Office for National Statistics. The cohort included 34,128 new-users of SGLT2i matched 1:1 to 34,128 new-users of dipeptidyl peptidase-4 inhibitors (DPP-4i) on body mass index and propensity score. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of major adverse cardiovascular events (MACE), overall and in body mass index (BMI) categories (≤24.9 kg/m2, 25.0-29.9 kg/m2, 30.0-39.9 kg/m2, ≥40 kg/m2). Secondary outcomes included all-cause mortality and hospitalization for heart failure.Results: SGLT2i were associated with a decreased risk of MACE (HR: 0.78, 95 %CI: 0.69-0.88) compared to DPP-4i. This decreased risk was most pronounced among obese and severely obese patients (HR: 0.77, 95 %CI: 0.66-0.91; HR: 0.67, 95% CI: 0.49-0.91, respectively) but not among overweight patients (HR: 0.94, 95 %CI: 0.73-1.22). Similar patterns were observed for cardiovascular mortality, all-cause mortality, and heart failure.Conclusion: Compared with DPP-4i, the cardioprotective effect associated with SGLT2i is stronger among patients with higher BMI. [ABSTRACT FROM AUTHOR]

Background: Diabetes, obesity and metabolic syndrome are highly prevalent in patients with severe mental illness and can impose a major physical health burden. Objective: To determine how anthropometric and metabolic features changed over time in a retrospective cohort of people with Severe Mental Illness living in Cheshire, UK. Methods: In all, 1307 individuals on the severe mental illness Register were followed up between 2002 and 2012 in UK general practice. Subjects were identified through a pseudanonymised search of general practice registers. Results: Baseline body mass index was 28.6 kg/m2 increasing to 31.0 at 10-year follow-up (r² = 0.84; p = 0.0002). There was a significant increase in fasting blood glucose from 5.72 to 6.79 mmol/L (r² = 0.48; p = 0.026). Correspondingly, there was a strong positive univariate relation between increase in body mass index and fasting blood glucose (r² = 0.54; p < 0.0001) taking into account all measurements. Fasting blood glucose also increased slightly with age (p = 0.028). With increasing use of statins, total cholesterol fell from 4.5 to 3.9 mmol/L (r² = 0.88; p = 0.0001), as did low-density lipoprotein cholesterol from 3.43 to 2.35 mmol/L (r² = 0.94; p = 0.0001). In multivariate models, adjusting for age, gender, smoking and blood pressure, each unit increase in body mass index (odds ratio = 1.07 [1.01, 1.13]; p = 0.031) and triglycerides (odds ratio = 1.28 (1.06, 1.55); p = 0.009) was independently associated with an increased risk of having type 2 diabetes. Conclusion: Increasing body mass index relates to increasing rates of dysglycaemia over time. Measures to encourage weight reduction should be key strategies to reduce dysglycaemia rates in severe mental illness. Prescribing statins may have been effective in improving the lipid profile in this group. [ABSTRACT FROM AUTHOR]

Background: The human SLC30A8 gene encodes the secretory granule-localised zinc transporter ZnT8 whose expression is chiefly restricted to the endocrine pancreas. Single nucleotide polymorphisms (SNPs) in the human SLC30A8 gene have been associated, through genome-wide studies, with altered type 2 diabetes risk. In addition to a role in the control of insulin release, recent studies involving targeted gene ablation from the pancreatic α cell (Solomou et al., J Biol Chem 290(35):21432-42) have also implicated ZnT8 in the control of glucagon release. Up to now, however, the possibility that increased levels of the transporter in these cells may impact glucagon secretion has not been explored. Methods: Here, we use a recently-developed reverse tetracyline transactivator promoter-regulated ZnT8 transgene to drive the over-expression of human ZnT8 selectively in the α cell in adult mice. Glucose homeostasis and glucagon secretion were subsequently assessed both in vivo during hypoglycemic clamps and from isolated islets in vitro. Results: Doxyclin-dependent human ZnT8 mRNA expression was apparent in both isolated islets and in fluorescence-activated cell sorting- (FACS) purified α cells. Examined at 12 weeks of age, intraperitoneal glucose (1 g/kg) tolerance was unchanged in transgenic mice versus wild-type littermates (n = 8-10 mice/genotype, p > 0.05) and sensitivity to intraperitoneal insulin (0.75U/kg) was similarly unaltered in transgenic animals. In contrast, under hyperinsulinemic-hypoglycemic clamp, a ~45 % (p < 0.001) reduction in glucose infusion rate was apparent, and glucagon release was significantly (~40 %, p < 0.01) impaired, in transgenic mice. Correspondingly, examined in vitro, glucagon secretion was significantly reduced (~30 %, p < 0.05) from transgenic versus control islets at low, stimulatory glucose concentrations (1 mM, p < 0.05) but not at high glucose (17 mM) glucose (p > 0.05). Over-expression of ZnT8 in glucagonoma-derived αTC1-9 cells increased granule free Zn2+ concentrations consistent with a role for Zn2+ in this compartment in the action of ZnT8 on glucagon secretion. Conclusions: Increased ZnT8 expression, and a likely increase in intragranular free Zn2+ concentration, is deleterious in pancreatic α cells for stimulated glucagon release. These data provide further evidence that type 2 diabetes-associated polymorphisms in the SLC30A8/ZnT8 gene may act in part via alterations in glucagon release and suggest that ZnT8 activation may restrict glucagon release in some settings. [ABSTRACT FROM AUTHOR]

Background: Carbohydrate (CHO) supplementation during prolonged exercise is widely acknowledged to blunt in vitro immunoendocrine responses, but no study has investigated in vivo immunity. Purpose: To determine the effect of CHO supplementation during prolonged exercise on in vivo immune induction using experimental contact hypersensitivity with the novel antigen diphenylcyclopropenone (DPCP). Methods: In a double-blind design, 32 subjects were randomly assigned to 120 min of treadmill exercise at 60 % $$\dot{V}{\text{O}}_{2} { \hbox{max} }$$ with CHO (Ex-CHO) or placebo (Ex-PLA) supplementation. Responses were also compared to 16 resting control (CON) subjects from a previous study (for additional comparison with a resting non-exercise condition). Standardised diets (24 h pre-trial) and breakfasts (3.5 h pre-trial) were provided. Subjects received a primary DPCP exposure (sensitisation) 20 min after trial completion, and exactly 28 days later the strength of immune reactivity was quantified by magnitude of the cutaneous response (skin-fold thickness and erythema) to a low dose-series DPCP challenge. Stress hormones and leucocyte trafficking were also monitored. Results: CHO supplementation blunted the cortisol and leucocyte trafficking responses, but there was no difference ( P > 0.05) between Ex-CHO and Ex-PLA in the in vivo immune responses (e.g. both ~46 % lower than CON for skin-fold response). Conclusions: CHO supplementation does not influence the decrease in in vivo immunity seen after prolonged exercise. The effects with more stressful (or fasted) exercise remain to be determined. However, there appears to be no benefit under the conditions of the present study, which have practical relevance to what many athletes do in training or competition. [ABSTRACT FROM AUTHOR]

Objective: Continuous Glucose Monitoring (CGM) is gaining in popularity for patients with paediatric hypoglycaemia disorders such as Congenital Hyperinsulinism (CHI), but no standard measures of accuracy or associated clinical risk are available. The small number of prior assessments of CGM accuracy in CHI have thus been incomplete. We aimed to develop a novel Hypoglycaemia Error Grid (HEG) for CGM assessment for those with CHI based on expert consensus opinion applied to a large paired (CGM/blood glucose) dataset., Design and Methods: Paediatric endocrinology consultants regularly managing CHI in the two UK centres of excellence were asked to complete a questionnaire regarding glucose cutoffs and associated anticipated risks of CGM errors in a hypothetical model. Collated information was utilised to mathematically generate the HEG which was then approved by expert, consensus opinion. Ten patients with CHI underwent 12 weeks of monitoring with a Dexcom G6 CGM and self-monitored blood glucose (SMBG) with a Contour Next One glucometer to test application of the HEG and provide an assessment of accuracy for those with CHI., Results: CGM performance was suboptimal, based on 1441 paired values of CGM and SMBG showing Mean Absolute Relative Difference (MARD) of 19.3% and hypoglycaemia (glucose <3.5mmol/L (63mg/dL)) sensitivity of only 45%. The HEG provided clinical context to CGM errors with 15% classified as moderate risk by expert consensus when data was restricted to that of practical use. This provides a contrasting risk profile from existing diabetes error grids, reinforcing its utility in the clinical assessment of CGM accuracy in hypoglycaemia., Conclusions: The Hypoglycaemia Error Grid, based on UK expert consensus opinion has demonstrated inadequate accuracy of CGM to recommend as a standalone tool for routine clinical use. However, suboptimal accuracy of CGM relative to SMBG does not detract from alternative uses of CGM in this patient group, such as use as a digital phenotyping tool. The HEG is freely available on GitHub for use by other researchers to assess accuracy in their patient populations and validate these findings., Competing Interests: 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 © 2022 Worth, Dunne, Salomon-Estebanez, Harper, Nutter, Dastamani, Senniappan and Banerjee.)

Aims: To confirm the reno-protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with dipeptidyl peptidase-4 (DPP-4) inhibitors on the onset and progression of chronic kidney disease (CKD) in routine clinical practice., Materials and Methods: We conducted a retrospective cohort study using the Clinical Practice Research Datalink Aurum database linked to Hospital Episode Statistics. The primary outcome was risk of the composite CKD endpoint based on the recent consensus guidelines for kidney disease: >40% decline in estimated glomerular filtration rate (eGFR), kidney death or end-stage kidney disease (ESKD; a composite of kidney transplantation, maintenance of dialysis, sustained low eGFR <15 ml/min/1.73m² or diagnosis of ESKD). Secondary outcomes were components of the composite CKD endpoint, analysed separately. Patients were propensity-score-matched 1:1 for SGLT2 inhibitor versus DPP-4 inhibitor use., Results: A total of 131 824 people with type 2 diabetes (T2D) were identified; 79.0% had no known history of CKD. During a median follow-up of 2.1 years, SGLT2 inhibitor initiation was associated with lower risk of progression to composite kidney endpoints than DPP-4 inhibitor initiation (7.48 vs. 11.77 events per 1000 patient-years, respectively). Compared with DPP-4 inhibitor initiation, SGLT2 inhibitor initiation was associated with reductions in the primary composite CKD endpoint (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.56-0.74), all-cause mortality (HR 0.74, 95% CI 0.64-0.86) and ESKD (HR 0.37, 95% CI 0.25-0.55), reduced the rate of sustained low eGFR (HR 0.33, 95% CI 0.19-0.57), and reduced diagnoses of ESKD in primary care (HR 0.04, 95% CI 0.01-0.18). Results were consistent across subgroup and sensitivity analyses., Conclusions: In adults with T2D, initiation of an SGLT2 inhibitor was associated with a significantly reduced risk of CKD progression and death compared with initiation of a DPP-4 inhibitor., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Diet is a modifiable risk factor for common chronic diseases and mental health disorders, and its effects are under partial genetic control. To estimate the impact of diet on individual health, most epidemiological and genetic studies have focused on individual aspects of dietary intake. However, analysing individual food groups in isolation does not capture the complexity of the whole diet pattern. Dietary indices enable a holistic estimation of diet and account for the intercorrelations between food and nutrients. In this study we performed the first ever genome-wide association study (GWA) including 173,701 individuals from the UK Biobank to identify genetic variants associated with the Dietary Approaches to Stop Hypertension (DASH) diet. DASH was calculated using the 24 h-recall questionnaire collected by UK Biobank. The GWA was performed using a linear mixed model implemented in BOLT-LMM. We identified seven independent single-nucleotide polymorphisms (SNPs) associated with DASH. Significant genetic correlations were observed between DASH and several educational traits with a significant enrichment for genes involved in the AMP-dependent protein kinase (AMPK) activation that controls the appetite by regulating the signalling in the hypothalamus. The colocalization analysis implicates genes involved in body mass index (BMI)/obesity and neuroticism ( ARPP21, RP11-62H7.2, MFHAS1, RHEBL1 ). The Mendelian randomisation analysis suggested that increased DASH score, which reflect a healthy diet style, is causal of lower glucose, and insulin levels. These findings further our knowledge of the pathways underlying the relationship between diet and health outcomes. They may have significant implications for global public health and provide future dietary recommendations for the prevention of common chronic diseases.

Background: Characteristics of patients using newer 2 nd and 3 rd line antidiabetic drugs in a real-world setting are poorly understood. We described the characteristics of new users of sodium-glucose co-transporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in Canada and the United Kingdom (UK) between 2016 and 2018., Methods: We conducted a multi-database cohort study using administrative health databases from 7 Canadian provinces and the UK Clinical Practice Research Datalink. We assembled a base cohort of antidiabetic drug users between 2006 and 2018, from which we constructed 3 cohorts of new users of SGLT-2i, DPP-4i, and GLP-1 RA between 2016 and 2018., Results: Our cohorts included 194,070 new users of DPP-4i, 166,722 new users of SGLT-2i, and 27,719 new users of GLP-1 RA. New users of GLP-1 RA were more likely to be younger (mean ± SD: 56.7 ± 12.2 years) than new users of DPP-4i (67.8 ± 12.3 years) or SGLT-2i (64.4 ± 11.1 years). In Canada, new users of DPP-4i were more likely to have a history of coronary artery disease (22%) than new users of SGLT-2i (20%) or GLP-1 RA (15%)., Conclusion: Although SGLT-2i, DPP-4i, and GLP-1 RAs are recommended as 2 nd or 3 rd line therapy for type 2 diabetes, important differences exist in the characteristics of users of these drugs. Contrary to existing guidelines, new users of DPP-4i had a higher prevalence of cardiovascular disease at baseline than new users of SGLT2i or GLP-1RA., (© 2022. The Author(s).)

Objective: To determine the extent to which the presence of acanthosis nigricans confers additional risk for insulin resistance, in addition to obesity alone (body mass index, BMI) within a young, overweight, UK population., Research Design and Methods: Retrospective data were collected to compare the degree of insulin resistance within a sample of 94 young people with acanthosis nigricans, and a matched cohort of 94 participants with obesity alone. Insulin resistance was assessed by fasting glucose, fasting insulin and Homeostatic Model Assessment of insulin resistance (HOMA-IR) score (a mathematical model derived to measure insulin resistance)., Results: The acanthotic and control group were well matched for age, BMI, BMI SDS and sex, although the groups were not matched for ethnicity. The acanthotic group showed a significantly greater median fasting insulin (215 pmol/L), mean fasting glucose (4.7 mmol/L) and median HOMA-IR score (6.4), compared with the control group (126 pmol/L, 4.5 mmol/L and 3.7, respectively). The presence of acanthosis nigricans as an indicator of insulin resistance was found to have a positive predictive value of 81% (within this study population)., Conclusion: Individuals with both acanthosis nigricans and obesity had significantly greater degrees of insulin resistance than individuals with obesity alone. The findings support the potential for acanthosis nigricans as a visible marker of type 2 diabetes in young people., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We are a nation addicted to sugar – so how can dental teams help break those habits of a lifetime? Timothy Ives shares his insight on the power of the 'tribe'. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Due to the risk of hypoglycennia-related incapacitation, diabetic pilots requiring insulin are assessed as unfit according to the International Civil Aviation Organization and most national authorities. Some authorities, such as those from Canada, the United Kingdom, and the United States, permit selected insulin-treated pilots (ITDM-pilots) to fly subject to a protocol requiring pre-and in-flight capillary glucose measurements to show/safe levels (>100-<300 mg⋅dl-1). Critics of such permission question the practicability of these in-flight measurements and whether clinically desired glycemic targets can be achieved while keeping glucose levels in the safe range. Subcutaneous continuous glucose monitoring (CGM) has recently been approved by the FDA as a stand-alone method to provide accurate glucose levels and treatment decision guidance in patients. This commentary considers that use of CGM by ITDM pilots facilitates practicability and recording of in-flight glucose measurements and facilitates achievement of clinically desired glycemic targets without increasing hypoglycemia risks. [ABSTRACT FROM AUTHOR]

[Display omitted] • Evaluation of bread waste (BW) as feedstock for 2,3-butanediol (BDO) production. • Glucose yield of 330–530 g/kg BW was obtained by acid and enzymatic hydrolysis. • BDO titer of 144.5 g/L and yield of 0.47 g/g was achieved on pure glucose. • BDO titer of 135.4 g/L with a yield of 0.42 g/g was amassed from acid hydrolysed BW. • Enzyme hydrolysed BW generated 138.8 g/L BDO with a yield of 0.48 g/g. Bread is Europe's most wasted food, and the second most wasted food after potatoes in UK. Bread waste (BW) is a clean source of high-quality fermentable sugars. In this study, the potential of Enterobacter ludwigii to accumulate 2,3-butanediol (BDO) from BW was evaluated. Initially, the optimal inoculum size and yeast extract concentration were determined, followed by extraction of sugars from BW using acid and enzymatic hydrolysis. A glucose yield of 330–530 g/kg BW was obtained, and the sugars released were utilised for BDO production by E. ludwigii. The fed-batch cultivation using pure glucose and glucose rich hydrolysates from acid and enzymatic hydrolysis resulted in BDO titres of 144.5, 135.4, and 138.8 g/L, after 96 h, with yield of 0.47, 0.42 and 0.48 g/g yield, respectively. The innovation of the work is valorisation of BW to BDO with a circular biorefining approach and thus, reducing BW disposal and associated environmental burden. [ABSTRACT FROM AUTHOR]

There is lack of evidence on the differential impact of maternal macronutrient consumption: carbohydrates (CHO), fats and protein on birth weight. We investigated the association between maternal dietary macronutrient intakes and their sub-components such as saccharides and fatty acids and birth weight. This analyses included 1,196 women with singleton pregnancies who were part of the CAffeine and REproductive health study in Leeds, UK between 2003 and 2006. Women were interviewed in each trimester. Dietary information was collected twice using a 24-h dietary recall about 8-12 weeks and 13-27 weeks of gestation. Multiple linear regression models adjusted for alcohol and smoking in trimester 1, showed that each additional 10 g/d CHO consumption was associated with an increase of 4 g (95% CI 1, 7; P= 0·003) in birth weight. Conversely, an additional 10 g/d fat intake was associated with a lower birth weight of 8 g (95% CI 0, 16; P =0·04) when we accounted for energy contributing macronutrients in each model, and maternal height, weight, parity, ethnicity, gestational age at delivery and sex of the baby. There was no evidence of an association between protein intake and birth weight. Maternal diet in trimester 2 suggested that higher intakes of glucose (10 g/d) and lactose (1 g/d) were both associated with higher birth weight of 52 g (95% CI 4, 100; P =0·03) and 5 g (95% CI 2, 7; P <0·001) respectively. These results show that dietary macronutrient composition during pregnancy is associated with birth weight outcomes. An appropriately balanced intake of dietary CHO and fat during pregnancy could support optimum birth weight. [ABSTRACT FROM AUTHOR]

Summary Objective To examine the utility of Body Mass Index (BMI), Waist-to-Height-Ratio (WHtR) and cardiorespiratory fitness thresholds to identify cardiometabolic risk in youth. Methods Cross-sectional cardiometabolic risk factor variables on 534 children aged 10.4–17.6 years of age (52% boys) from the United Kingdom were used. Binary logistic regression and receiver operating characteristic curves were used to examine the utility of established age and gender specific thresholds for BMI, WHtR and cardiorespiratory fitness to identify individuals with increased cardiometabolic risk (increased clustered triglycerides, HDL-cholesterol, systolic blood pressure and glucose). Results A WHtR ≥ 0.5 increased the odds by 11.4 (95% confidence interval 4.7, 27.4, P < 0.001) of having increased cardiometabolic risk in boys and by 2.5 (1.2, 5.3, P = 0.020) for girls. Similar associations were observed for BMI and cardiorespiratory fitness in both boys and girls with increased cardiometabolic risk. BMI-z, WHtR and cardiorespiratory fitness all showed a significant ability in identifying individuals for increased cardiometabolic risk in boys and girls ( P < 0.05) despite poor area under the curve (AUC) values (<0.70). Combining anthropometrical variables did improve the diagnostic accuracy for identifying cardiometabolic risk in boys, evidenced by an increased AUC of 0.74 (0.64, 0.85, P < 0.001), but not in girls. Conclusion The magnitude of associations was broadly similar for BMI, WHtR and cardiorespiratory fitness in identifying individuals at increased cardiometabolic risk. Yet, combining BMI with WHtR in boys may provide a more accurate method for identifying those at increased cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Background Government and health organisations worldwide have recently reviewed the evidence on the role of dietary sugars in relation to health outcomes. Hence, it is timely to review current intakes of dietary sugars with respect to this guidance and as a benchmark for future surveillance. Methods This review collates data from nationally representative dietary surveys across the world and reports estimates of intakes of total and added sugars, and sucrose in different population subgroups. Total sugars includes all mono- and disaccharides; namely, glucose, fructose, lactose, sucrose and maltose. Added and free sugars differ in the quantity of natural sugars included in their definitions. Free sugars include sugars naturally present in honey, syrups, fruit juices and fruit juice concentrates, whereas added sugars typically only refer to those added during processing. Results Most countries reported intakes of total sugars, with fewer reporting intakes of added sugars and sucrose. No country reported intakes of free sugars. The available data suggest that total sugars as a percentage of energy were highest in the infant (<4 years), with mean values ranging from 20.0% to 38.4%, and decreased over the lifespan to 13.5-24.6% in adults. Intakes of added sugars were higher in school-aged children and adolescents (up to 19% of total energy) compared to younger children or adults. Conclusions Further research into the dietary patterns contributing to added sugars intake in children and adolescents is warranted. It would also be beneficial to policy guidance if future dietary surveys employed a uniform way of expressing sugars that is feasible to measure and has public health significance. [ABSTRACT FROM AUTHOR]

Purpose: Although previous research has associated the glycaemic load (GL) of a meal with cognitive functioning, typically the macro-nutrient composition of the meals has differed, raising a question as to whether the response was to GL or to the energy, nutrients or particular foods consumed. Therefore, the present study contrasted two breakfasts that offered identical levels of energy and macro-nutrients, although they differed in GL. Methods: Using a repeated-measures, double-blind design, 75 children aged 5-11 years, from socially deprived backgrounds, attended a school breakfast club and on two occasions, at least a week apart, they consumed a meal sweetened with either isomaltulose (Palatinose™) (GL 31.6) or glucose (GL 59.8). Immediate and delayed verbal memory, spatial memory, sustained attention, reaction times, speed of information processing and mood were assessed 1 and 3 h after eating. Results: The nature of the meals did not influence any measure of cognition or mood after an hour; however, after 3 h, children's memory and mood improved after the lower-GL breakfast. If children had eaten the lower-GL meal on the second day of testing, they were able to process information faster and had better spatial memory later in the morning. Conclusions: Towards the end of a morning in school, having consumed a lower-GL breakfast resulted in better mood and aspects of cognitive functioning. [ABSTRACT FROM AUTHOR]

The cost of intravenous insulin infusion to the NHS is unknown. The aim of this study was to estimate the direct cost of insulin infusions to the NHS in England and Wales in the first 24-hour period of infusion. Data from the National Inpatient Diabetes Audit 2013 in the UK were used to estimate the number of insulin infusions in use across England and Wales. Costs were calculated for six models for setting up and maintenance of insulin infusions, depending on the extent of involvement of different healthcare professionals in the UK. In this study, the direct costs of intravenous insulin infusions to the NHS in England and Wales have been estimated to vary from £6.4-8.5 million in the first 24-hour period on infusion. More appropriate use of these infusions could result in substantial cost savings. [ABSTRACT FROM AUTHOR]