Leicester General Hospital

To determine whether early gestational diabetes (GDM) differs from later GDM in maternal characteristics and perinatal outcomes. This is a secondary analysis of an energy-restricted dietary intervention in GDM (DiGest) randomized controlled trial. We compared maternal weight, glycemia, and pregnancy/neonatal outcomes between the early GDM (< 20 weeks, n = 118) and standard GDM diagnosis (21–28 weeks, n = 299) groups. Early GDM was associated with higher antenatal (40 vs. 38 mmol/mol; p = 0.017) and postnatal HbA1c (38 vs. 36 mmol/mol; p = 0.002) and higher risk of diabetes/prediabetes postnatally (19 vs. 6%; p = 0.003). Despite higher medication requirements, perinatal outcomes did not differ. Lower gestational weight gain (2.5 vs. 5.3 kg, p = 0.003) and comparable glycemia at 36 weeks were found. Timing of diagnosis did not impact the effect of the DiGest intervention. Early GDM reflects more severe underlying hyperglycemia, but timely treatment and reduced gestational weight gain can offset adverse perinatal risks.

People exist at a combination of different individual and neighbourhood deprivations. Each of these combinations may have a unique impact on health. However, little is known about the intersectional inequality of these combinations on general and central obesity, including when considering their demographics. This study aims to answer these questions. The sample comprised 452,339 participants from the UK Biobank study. Individuals were grouped into 320 intersectional strata according to their household income, neighbourhood deprivation, sex, ethnicity and age. Linear and logistic multilevel analysis of individual heterogeneity and discriminatory accuracy was used to establish the total, additive and interactive inequality of body mass index (BMI), fat mass index (FMI), and waist to height ratio (WHtR), as well as the associated obesity classifications. 6.5%, 25.2% and 9.1% of the total variation in BMI, FMI and WHtR, respectively, was due to inequality between the strata. Of this, 26.5%, 3.5% and 22.0% is interactive. 79, 58 and 93 strata for BMI, FMI and WHtR demonstrate a significant interactive effect. We found some patterns; for example, affluent white women have an advantaged interactive effect, whilst deprived black women have a disadvantaged effect. Meanwhile men experience the inverse relationship. The relationship between individual and neighbourhood deprivation is not universally experienced by all strata. For example, black men living in areas of high deprivation have higher BMIs as their household income increases. A large proportion of variation in general and central obesity is due to intersectional inequality, with up to 26.5% being interactive. It is important that these intersectional effects are considered when designing policy interventions to avoid policy failure, such as by focussing on groups with high total and interactive risk.

In the Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT), surgical fixation was compared with cast immobilization, with the primary endpoint being the outcomes at one year. The aim of the current study was to assess the radiological outcomes (union and the development of osteoarthritis (OA)) of the two forms of treatment at five years. Patients who remained in the trial at five years after randomization were invited to have plain radiographs and a CT scan of the injured wrist, and a posterior-anterior radiograph of the contralateral wrist. This imaging was reviewed by three observers independently for union of the fracture and the distribution and severity of OA. This analysis followed a pre-specified statistical analysis plan. The relationship between OA and the Patient-Rated Wrist Evaluation (PRWE) scores at five years was assessed. Of the 439 patients who were randomized, 267 (60.8%) provided imaging at five years. Their characteristics were similar to those of the original cohort. A total of 182 patients (68.2%) (n = 92 fixation, n = 90 cast) had complete union and seven had a nonunion (2.6%; n = 3 fixation, n = 4 cast). Fractures with a minimum of 20% union at one year consolidated with the passage of time without intervention. Progression of OA in the joints around the scaphoid was seen in both groups from baseline to five years. By five years, 140 patients (52.4% of those with imaging at five years) had OA in at least one joint with similar prevalences in both groups. The prevalence of OA, the number of arthritic joints and the maximum severity of OA, was similar in the two groups. A total of 344 of the initial cohort of 439 patients (78.4%) provided a valid PRWE score at five years and the mean score was higher in those with more severe OA, indicating worse pain and function. Between one and five years after randomization, union consolidated in those with > 20% bridging without intervention. The proportion of patients with full, almost full, partial, slight, and nonunion for the two forms of treatment remained similar at five years. The prevalence and severity of OA increased during the five years but was similar in both groups.

Accelerometer data are commonly reduced into epoch summary measures (ESMs) for analysis, e.g. ENMO (Euclidean Norm Minus One), MAD (Mean Amplitude Deviation), MIMS (Monitor Independent Movement Summary) or Counts. We compared associations with all-cause mortality of the volume and intensity of physical activity when derived from those four measures in the Whitehall II and UK Biobank cohorts. Volume (Average Acceleration, AvAcc) and intensity (Intensity Gradient, IG) were derived from each ESM. Associations with mortality were estimated using Cox models. 3733 (25.1% female, median age 68.3 years) and 89,848 (56.4% female, 63.5 years) participants were included from Whitehall II and UK Biobank, respectively. Median (IQR) follow-up was 11.0 (10.7, 11.3) and 8.0 (7.5, 8.5) years, with 563 (15.1%) and 3656 (4.1%) deaths. Associations with mortality were largely consistent between ESMs with the lowest mortality risk for those high (above the median) in both AvAcc and IG (Whitehall: HR = 0.59–0.68; Biobank: 0.55–0.61, reference: low/low), and IG associated with lower mortality risk, irrespective of AvAcc. AvAcc was associated with lower mortality irrespective of IG in Biobank only. In conclusion, associations of AvAcc and IG with mortality are broadly consistent across common ESMs, supporting comparability of activity-health findings across studies using different ESMs.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-30237-5.

Despite advancements in diabetes management, adherence to HbA1c, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) targets remains suboptimal. This review presents an updated meta-analysis of the achievement of these guideline targets globally in individuals with type 2 diabetes. This study included studies from 2017 to 2025, supplementing our prior meta-analysis covering 2006-2017. Observational studies assessing adherence to HbA1c, BP, and LDL-C targets and a combined target attainment were included. Random-effects meta-analysis was used to estimate pooled proportions, and meta-regression assessed the impact of study characteristics on target achievement. A total of 63 studies from 2006 to 2025, encompassing 1,618,972 patients, were included. Overall, 44% (95% CI: 41-48%) of individuals achieved HbA1c targets, 41% (95% CI: 34-47%) achieved BP targets, and 47% (95% CI: 42-51%) achieved LDL-C targets. Only 12% (95% CI: 7-16%) of individuals met all three targets simultaneously. Meta-regression analysis revealed no significant improvement in HbA1c target attainment from 1997 to 2023 in Europe and North America. Despite advances in pharmacotherapy, the achievement of targets for risk factor control in type 2 diabetes remains alarmingly low, with little progress over time. This review highlights the urgent need to address barriers in achieving guideline targets.

Plain Language SummaryAs people age, they are more likely to develop multiple long-term health problems such as heart disease, stroke, high blood pressure, and diabetes. When someone has two or more of these conditions at the same time, it is called cardiometabolic multimorbidity (CMM). Identifying people who are at higher risk of developing CMM early on can help prevent these diseases and improve quality of life. This study looked at a simple measure called the lipid accumulation product (LAP), which combines a person’s waist size and blood fat levels (specifically, triglycerides). LAP is thought to be a good indicator of harmful belly fat, which is closely linked to heart and metabolic diseases. We used data from a long-term study of over 3,000 adults in England aged 50 years and older. At the beginning of the study, none of the participants had CMM. We followed them for up to 15 years to see who developed two or more conditions like heart disease, stroke, high blood pressure, or diabetes. We found that people with higher LAP scores were more likely to develop CMM. This link remained even after accounting for other known risk factors like age, smoking, blood pressure, cholesterol levels, physical activity, and muscle strength. We also found that adding LAP to existing risk assessment tools slightly improved our ability to predict who would go on to develop CMM. Our findings suggest that LAP may be a helpful, low-cost tool for identifying older adults at risk for multiple long-term health conditions.

Distinguishing between anaphylaxis and bradykinin-mediated angioedema can be difficult in the acute setting, particularly when airway compromise dominates the presentation. Recognition is crucial, as management strategies differ substantially. An 84-year-old woman presented to the Emergency Department in Preston with rapidly progressive swelling of the lips, tongue, and neck, accompanied by dysphagia and a hoarse voice. She had self-administered multiple doses of an adrenaline autoinjector before arrival. On examination, she was hemodynamically stable and afebrile, with marked tongue and floor-of-mouth edema but no urticaria or pruritus. Considering refractory anaphylaxis, she received intravenous dexamethasone, an adrenaline nebulizer, and an adrenaline infusion. ENT and ICU teams were involved; flexible nasendoscopy confirmed edema of the floor of the mouth and arytenoids, with mild epiglottic involvement but an adequate glottic opening. This episode followed several similar admissions since 2022, each previously treated as anaphylaxis with limited response to adrenaline. Further investigation revealed normal mast-cell tryptase (6.1 µg/L) and persistently low C4 (<0.03 g/L) with normal C3 (1.29 g/L), findings consistent with C1-esterase inhibitor (C1-INH) deficiency. Given her history of CD5-negative low-grade B-cell lymphoproliferative disorder, a diagnosis of acquired angioedema was made following multidisciplinary review, and treatment with icatibant was initiated. This case highlights the importance of considering bradykinin-mediated angioedema in patients with recurrent “refractory anaphylaxis.” The absence of urticaria, normal tryptase, and low complement levels should prompt evaluation for C1-INH deficiency, allowing timely, targeted management and improved outcomes.

IntroductionDementia presents with significant heterogeneity across age groups, particularly in early-onset cognitive decline (EOCD), which poses diagnostic and management challenges. The Cognitive and Neuroimaging for Neurodegenerative Disorders (CogNID) study aims to characterise clinical, cognitive, neuroimaging, and biomarker features across a diverse cohort of individuals with cognitive impairment, with a focus on diagnostic complexity, biomarker utility, and mortality.MethodsOut of 680 study participants within this prospective cohort enrolled from the real-world clinics within the National Health Service, who consented to take part in the study, we analysed data from 429. Individuals were recruited between December 2018 and November 2024 from the Memory Clinics, including the early-onset dementia service and associated services. Participants underwent structured cognitive assessments, neuroimaging (MRI/CT), and Cerebrospinal fluid (CSF) biomarker evaluation, where available. Diagnoses were made by multidisciplinary consensus. Group comparisons were conducted between early-onset (EOCD, <65 years) and late-onset cognitive decline (LOCD, ≥65 years).ResultsOf the 429 participants, 349 (81.4%) had EOCD and 80 (18.6%) had LOCD. The mean age was 60.05 years, with no significant difference in sex or ethnicity across groups. Depression and anxiety were common (29.6%), as were cardiovascular risk factors. Lumbar punctures were more frequently performed in EOCD (p = 0.03), with 36.4% of tested participants demonstrating biomarker profiles consistent with Alzheimer’s disease (A+T+). Functional cognitive disorder (FCD) was more common in EOCD (22.3% vs. 5.0%, p < 0.001). Subgroup analysis revealed significantly lower ACE-III scores and higher pathological CSF findings in Alzheimer’s disease versus FCD. Mortality was higher in the LOCD group (11.3% vs. 4.6%, p = 0.03).ConclusionThe CogNID study highlights the clinical and diagnostic heterogeneity of individuals with cognitive impairment, particularly in younger adults. Incorporating neuroimaging and CSF biomarkers into routine clinical pathways enhances diagnostic precision and reveals distinct phenotypic profiles between EOCD and LOCD. These findings underscore the need for harmonised diagnostic protocols, broader biomarker accessibility, and inclusive recruitment strategies in dementia research and clinical services.

ABSTRACTBackground and AimsSarcopenia is the accelerated loss of skeletal muscle mass and function associated with aging, and can significantly impact a person's quality of life. Sarcopenia can also occur with other health conditions, such as excess adipose tissue and bone weakness. The presence of multiple long‐term conditions can exacerbate sarcopenia, and it has been observed in tandem with a variety of chronic illnesses. Biological markers can act as an early identifier or predictor of disease, enabling simple surveillance and prompt treatment. The need for effective screening and intervention has become more important as our population ages. This protocol outlines our approach to summarize the evidence on the diagnostic accuracy of various blood‐based biomarkers for diagnosing sarcopenia, including sarcopenic obesity and osteosarcopenia, through a systematic review and meta‐analysis.MethodsThe protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis for Diagnostic Test Accuracy Studies (PRISMA‐DTA) 2018 statement and prospectively registered (PROSPERO: CRD42024609060). A comprehensive literature search using electronic databases including MEDLINE, Embase (via SCOPUS), CINAHL, Cochrane, and Web of Science, will be conducted. The review will include studies that meet the specific inclusion criteria, and the risk of bias in the included studies will be assessed using the Quality Assessment of Diagnostic Accuracy 2 quality assessment tool (QUADAS‐2). A meta‐analysis will be conducted using random‐effects approaches, based on the level of heterogeneity. Subgroup and sensitivity analysis will be performed if necessary.ResultsThe results of this review will be reported in accordance with PRISMA‐DTA standards, and published in a peer‐reviewed journal.ConclusionThe proposed systematic review and meta‐analysis will assess the diagnostic accuracies of potential blood‐based biomarkers for screening sarcopenia, sarcopenic obesity, and osteosarcopenia. The results will provide important evidence on the use of biomarkers to diagnose sarcopenia and its associated syndromes, which can inform the development of targeted screening and intervention in research and practice.