Patients on low-dose prednisolone may develop adrenal insufficiency causing reduced health-related quality of life (HRQoL) and increased risk of adrenal crisis. This study examines whether supplemental hydrocortisone during mild to moderate stress improves HRQoL in patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) with adrenal insufficiency on low-dose prednisolone.

A multicentre, randomised, double-blinded, placebo-controlled, clinical trial including patients with PMR/GCA receiving ongoing prednisolone ≤5 mg/day. Eligible patients undergo an adrenocorticotropic hormone (ACTH) test, and 250 patients with a stimulated cortisol

The study is approved by the Ethics Committee of the Capital Region of Denmark and the Danish Medicines Agency. Recruitment began June 2022. The last patient’s last visit is expected in 2026. Results will be disseminated via peer-reviewed publication and conference presentations.

EudraCT:2021-002528-18, CTIS:2024-518272-30-00, NCT05435781.

Adult-onset type 1 diabetes (T1D) is often misclassified as type 2 diabetes (T2D), resulting in delayed treatment, missed opportunities for referrals to specialists and increased risk of complications including diabetic ketoacidosis. An electronic medical record (EMR)-based algorithm—originally trained on a large national EMR dataset to identify likely misclassified adult-onset T1D cases—was tested and retrained on a health information exchange (HIE) dataset from HealthShare Exchange (HSX). Promising results were achieved on historical data, particularly when using the retrained algorithm. However, its prospective validation is essential to more reliably assess its clinical utility and real-world precision in flagging high-risk patients for clinician review.

This is a prospective, multicentre, non-interventional cohort study in two HSX-member healthcare organisations (HCOs) in southeastern Pennsylvania. At the onset of the study, all adult T2D patients are scored by the algorithm analysing HIE data on relevant predictors found in the 24-month lookback period. Patients meeting a prespecified score threshold estimated in retrospective testing to yield 10% recall will be presented to designated endocrinology or primary care providers for structured chart review, attribution confirmation and guideline-concordant follow-up (including autoantibody testing where appropriate). The primary endpoint is positive predictive value for confirmed adult-onset T1D among flagged patients. Secondary endpoints characterise operational cascade metrics (attribution, provider recommendation, test ordering/results and diagnosis updates) along with 95% CIs. Exploratory endpoints will assess provider adoption, interpretability and workflow integration via structured provider interviews.

This study was reviewed and approved by Advarra Institutional Review Board (protocol Pro00075945). The Institutional Review Board waived patient informed consent and granted a full waiver of HIPAA authorisation for patient records, while providers were required to provide written informed consent. HSX data were accessed and shared under its member-defined use cases. Findings will be disseminated via peer-reviewed publications and conference presentations. Reporting will follow Strengthening the Reporting of Observational Studies in Epidemiology guidance for cohort studies.

Pregnancy in women with pre-existing type 1 or type 2 diabetes (T1D, T2D) is associated with increased risk of complications, largely driven by maternal glucose control. Hormonal changes during pregnancy make glucose management more challenging. Physical activity (PA) may improve glucose control and reduce complications; however, little is known about PA patterns in this population and no pregnancy-specific PA guidance exists for women with pre-existing diabetes. Understanding the behaviours and experiences of both pregnant women and the healthcare professionals (HCPs) who support them is needed to inform evidence-based guidance.

This mixed-methods study comprises three sub-studies. The first will recruit 175 pregnant women (75 with T1D and 100 with T2D) who will complete three 7-day monitoring periods, one per trimester. PA will be assessed using wrist-worn accelerometers and exercise diaries, dietary intake via remote food photography, and corresponding continuous glucose monitor and diabetes-related well-being data will be collected.

The second involves a subsample of ~16 women participating in focus groups to explore experiences of being physically active during pregnancy.

The third invites ~100 HCPs involved in diabetes in pregnancy care to complete an online survey, ~10 HCPS will take part in an optional interview about their experiences of providing PA guidance.

The primary outcome is the change in PA across pregnancy. Secondary outcomes include associations between PA, glucose metrics, diet and diabetes-related well-being, and qualitative themes relating to experiences of women and HCP. Quantitative data will be analysed using multilevel modelling and regression analysis, and qualitative data using reflexive thematic analysis.

Ethical approval was granted by the East Midlands Nottingham 1 Research Ethics Committee (25/EM/0190) and University of Exeter Public Health and Sport Sciences ethics committee. Findings will be disseminated through peer-reviewed publications and conference presentations.

Diabetes mellitus is a highly prevalent metabolic disorder associated with chronic, low-grade inflammation. Of recent interest is the association between diabetes and circadian rhythm disruption. The aim of this review is to evaluate and synthesise clinical evidence for whether diabetes affects homeostatic diurnal patterns to proinflammatory markers in the human body. This could inform the optimal timing of immune-targeted therapies over the course of the day.

This systematic review will include primary clinical research studies reporting on diurnal variations, defined as an afternoon/evening (PM) minus a morning (AM) value, within a timeframe of 12±4 hours, for predefined proinflammatory markers, in individuals with diabetes (type 1 or type 2) compared with healthy controls. A search of online databases (Cochrane CENTRAL, Ovid MEDLINE and Ovid Embase) will be performed. Grey literature searches will be performed in clinical trial registries. Two review authors will independently screen retrieved citation records at the title/abstract and full-text levels. Study quality will be assessed using an appropriate National Institute of Health quality assessment tool. A meta-analysis will be performed if more than one study reports equivalent data for any outcome. Statistical heterogeneity will be assessed using the ² test. Where a meta-analysis is not possible or unlikely to be meaningful, a narrative synthesis of the findings will be provided.

Ethics approval is not required for this systematic review as no original data will be collected. The results will be disseminated through peer-reviewed publication and conference presentations.

CRD420251115780.

Despite adherence to guideline-based pharmacotherapy, many people with diabetic kidney disease (DKD) were unable to meet glycaemic and blood pressure targets. The purpose of this paper was to report the unmet needs of people with early-stage DKD.

A sequential mixed-methods approach was used, comprising a quantitative survey followed by an exploratory qualitative phase using nominal group technique (NGT) discussions with people with DKD.

Patients were recruited from 45 primary care clinics in Peninsular Malaysia from March to May 2024.

Survey data were collected from 131 adults with an estimated glomerular filtration rate between 30 and 89 mL/min/1.73 m² and with suboptimal glycaemia and blood pressure outcomes. Exploratory NGT discussions were conducted with seven participants.

The online survey used the WHO definition of unmet healthcare need as the ‘failure to seek healthcare when needed during the past twelve months’ to assess the prevalence and associated factors. Qualitative data and ranking of other perceived unmet needs of these people with DKD and suboptimal clinical outcomes were collected through NGT discussions.

The prevalence of reported unmet healthcare needs per the WHO definition was 13%, with history of diabetic foot ulcer (adjusted OR (AOR) 6.67, 95% CI 1.22 to 37.25) and urban residence (AOR 3.70, 95% CI 1.26 to 12.89) reported as associated factors. NGT identified three patient-prioritised unmet needs: ‘dietary support’, ‘better medication’ and ‘mental health support’. Female participants prioritised obtaining medication and kidney health information, whereas male participants emphasised self-monitoring support.

The low prevalence of WHO-defined unmet need, alongside patient-prioritised concerns extending beyond standard measures, suggests that current operational definitions may not fully capture patient-perceived unmet healthcare needs in DKD.

Diabetic foot ulceration represents a prevalent, persistent and resource-intensive complication of diabetes. These ulcers are slow to heal, prone to recurrence and impose a substantial burden on both patients and healthcare providers. The reducing the impact of diabetic foot ulcers (REDUCE) intervention has been designed as a multifaceted approach targeting psychological and behavioural determinants linked to diabetic foot ulcer (DFU) outcomes. Following a successful pilot trial, the REDUCE trial has been designed as a pragmatic, multicentre randomised trial to compare the effectiveness and cost-effectiveness of the REDUCE intervention plus usual care versus usual care alone in reducing recurrence in people with healed DFUs. Additionally, there is an embedded process evaluation and two sub-studies which will be carried out alongside the main trial.

Adults over 18 years of age, with a recently healed DFU and two lower limbs, will be identified from around 30 specialist multidisciplinary diabetic foot clinics at participating National Health Service Trusts in the UK. Patients with active Charcot neuro-osteoarthropathy, active DFU or ulcers healed for more than 12 weeks will be excluded. We will aim to recruit 544 participants (1:1 randomisation). The primary outcome for this trial will be total ulcer-free days with limbs intact (ie, without amputation) between randomisation and the end of follow-up (18 months post-randomisation). Secondary outcomes include time to re-ulceration, total number of ulcers, amputation, quality of life (EQ-5D-5L), Patient Health Questionnaire-9, Nottingham Assessment of Functional Footcare, ICEpop capability measure for adults and resource use. As part of the process evaluation, up to 20 REDUCE intervention patient-participants will be interviewed, and the healthcare professionals delivering the intervention will also be interviewed. An assessment of intervention fidelity will also be carried out.

Ethics approval was granted by Wales 3 Research Ethics Committee (REC reference 22/WA/0053) on 16 March 2022. The findings will be presented at relevant conferences and disseminated via peer-reviewed research publications and to relevant stakeholders.

ISRCTN15570706.

To assess the burden of diabetes and prediabetes in the educational sector in Bahawalpur City, Pakistan.

Cross-sectional study.

Teaching institutes of Bahawalpur, Pakistan, during January 2024 to December 2024.

A total of 955 participants from 15 universities, colleges and schools were included. Eligible participants were aged 18–75 years and employed as teachers or academic staff and enrolled using a non-probability consecutive sampling technique. Primary anthropometric measurements, blood pressure, smoking status and HbA1c levels were recorded. Prediabetes was defined as HbA1c 5.7–6.4% and type 2 diabetes mellitus (T2DM) as HbA1c ≥6.5%.

Among 955 participants, 622 (65.1%) were male and 713 (74.7%) were teaching staff. The median age was 42 years, and median BMI was 27.3 kg/m². The prevalence of prediabetes and T2DM was 31.7% and 15.4%, respectively, with 8.5% newly diagnosed cases of T2DM. Multivariate binary logistic regression analysis found that age (p=0.006), BMI (p=0.008) and family history of diabetes (p

This study highlights a significant prevalence of T2DM and prediabetes in the educational sector of Bahawalpur, Pakistan. Increasing age, BMI and positive family history of diabetes were independent predictors of prediabetes/T2DM.

To elicit stated preferences and willingness-to-pay (WTP) for artificial intelligence (AI)-enabled blended care in type 2 diabetes mellitus (T2DM), and to examine preference heterogeneity by digital experience and socioeconomic status (SES).

Cross-sectional discrete choice experiment (DCE).

12 community health centres in Jiaozuo and Puyang, Henan Province, China. Data were collected between June and August 2025.

423 adults diagnosed with T2DM for at least 6 months, recruited using consecutive convenience sampling from routine follow-up appointments. Of 769 participants who completed the survey, 346 were excluded following prespecified data quality criteria (retention rate: 55.0%).

Outcome measures included preference weights and WTP (in Chinese Yuan, ¥) for five DCE attributes: monthly subscription fee, recommendation source, feedback modality, in-person follow-up frequency and expert oversight, estimated using mixed logit models. Simulated uptake probabilities for tailored service packages across four user profiles were computed.

Among 423 participants, 80.6% had never used AI tools. Price was the dominant driver of choice (62.7% relative attribute importance). Profound preference heterogeneity emerged across subgroups: rural residents (n=78) were highly price-sensitive but preferred physician endorsement (WTP ¥17.58 (US$2.55), 95% CI ¥5.98 to ¥29.17); female participants (n=224) valued guideline recommendations (WTP ¥18.45 (US$2.67), 95% CI ¥7.81 to ¥29.40); and diabetes app users (n=34) were the least price-sensitive but showed a negative preference for AI instant feedback, instead preferring human dietitian feedback. Expert oversight carried a consistent negative WTP across all profiles. Targeting tailored service bundles to intended subgroups increased uptake by 8–16 percentage points compared with non-targeted bundles.

A ‘digital experience paradox’ exists whereby digitally experienced users view human interaction as a premium service, while underserved groups rely on specific trust markers such as physician endorsement. To avoid widening the digital divide, AI-enabled blended diabetes care must move beyond standardised models towards configurable, equity-driven service pathways.

Effective treatment for clinical obesity is available but is rarely offered by healthcare systems, which often treat complications without treating the underlying cause. The LightWAY trial will investigate the clinical benefits and harms as well as cost-effectiveness of an intensive weight loss intervention compared with existing weight management programmes for people with clinical obesity.

LightWAY is an investigator-initiated, international, randomised, parallel-group clinical superiority trial with blinded outcome assessment. Six hundred people seeking treatment for clinical obesity (body mass index ≥35 kg/m² with comorbidities) will be recruited in centres in the UK and Denmark and randomised 1:1 to one of two groups. The experimental group will be offered a 2-year intensive weight loss programme providing support and advice to follow a total diet replacement programme, followed by gradual transition to an energy-reduced diet in combination with increased physical activity and if needed, prescription of weight loss medication. The control group will receive usual care, typically comprising brief behavioural support for weight loss and treatment of the complications of obesity or occasionally referral to specialist weight management services. The two co-primary outcomes are cardiometabolic risk, assessed with metabolic syndrome severity Z-score, and body weight assessed at 2 years. The secondary outcomes include the Short Form-36 mental component scale, 4-metre gait speed and proportion of participants achieving ≥20% weight loss. The key adverse effects will be the proportion of participants with at least one serious adverse event, incidence of eating disorders and disproportional loss of bone mass. Incremental cost-effectiveness will be assessed over the trial period and over the lifetime through modelling.

Ethical approval was granted in the UK (August 2024, 24/SC/0211) and Denmark (December 2023, H-23065222). Findings will be disseminated through peer-reviewed journals and scientific conferences and to participants in the trial and clinicians.

NCT06321458.

Aboriginal women in the remote Northern Territory (NT) experience high rates of adverse pregnancy outcomes related to hyperglycaemia in pregnancy. Oral glucose tolerance test (OGTT) screening was recommended in early pregnancy but barriers to uptake exist.

To examine uptake of screening for hyperglycaemia in pregnancy among Aboriginal women in remote NT communities and explore adverse pregnancy outcome rates among women who did not have early OGTT screening compared with women who did undergo screening in early pregnancy and those with pre-existing diabetes.

Retrospective observational cohort study of pregnancies among Aboriginal women in remote NT clinics from January 2017 to December 2019. Screening for hyperglycaemia in pregnancy included having an early OGTT (

Among 1191 pregnancies in 52 remote communities, pre-existing type 2 diabetes (T2D) was diagnosed in 6.4% (n=76) and gestational diabetes mellitus (GDM) was diagnosed in 13% (154/1191). Excluding women with pre-existing diabetes, 226 (20%) had an early OGTT. Guideline-directed screening (with either (a) an early OGTT diagnosing GDM or (b) a negative early OGTT followed by a routine OGTT) occurred in 14% of pregnancies (n=158). Compared with women who had an early pregnancy OGTT, the combined adverse pregnancy outcome was more common among women with pre-existing T2D (89% vs 54%, adjusted OR 6.06 (95% CI 2.75 to 13.35)) and similar among women who did not undergo early OGTT (50%, adjusted OR 0.97 (95% CI 0.71 to 1.32)).

Uptake of guideline-directed screening in Aboriginal women in remote NT was low, although there was no difference in pregnancy outcomes for women who were and were not screened with an early OGTT. Rates of adverse pregnancy outcomes were concerningly high in women with pre-existing T2D, highlighting a need to strengthen diabetes care for these women.

Type 2 diabetes (T2D) presents a global healthcare burden. Despite widespread use of non-insulin glucose lowering therapies, many individuals still require insulin to achieve recommended target glycated haemoglobin (HbA1c). Insulin injections improve HbA1c but can lead to problematic hypoglycaemia. The objective of this study is to determine whether fully closed-loop insulin delivery improves HbA1c at 26 weeks compared with standard insulin therapy with continuous glucose monitoring (CGM) in adults with T2D.

This study adopts an open-label, multinational, randomised, single-period parallel design and aims to randomise 224 adults with T2D to either standard insulin therapy with CGM (control group) or fully closed-loop insulin delivery (intervention group) for a period of 26 weeks. Participants will complete a run-in period of 2–3 weeks wearing a masked CGM followed by randomisation to either the control or intervention group. The primary endpoint is the between-group difference in HbA1c at 26 weeks. Key endpoints include time in target glucose range (3.9–10.0 mmol/L), mean sensor glucose, time above range (>10.0 mmol/L) and non-inferiority for time below target (

The study has received ethical approval from the East of England Cambridgeshire and Hertfordshire Research Ethics Committee (24/EE/0149) in the UK. Ethical approval for non-UK site has been obtained by local Research Ethics Committees.

Results will be disseminated by peer-reviewed publications and conference presentations, and findings will be shared with people living with diabetes, healthcare providers and relevant stakeholders.

NCT06579404.

Neonatal hypoglycaemia is a common metabolic disorder in newborns and may be more frequent in infants delivered by caesarean section because of altered metabolic adaptation after birth. Evidence specific to Chinese caesarean-delivered newborns remains limited.

To determine the incidence of neonatal hypoglycaemia and identify factors associated with its occurrence in Chinese newborns delivered via caesarean section.

Cross-sectional study.

Three regional obstetric care centres in East China.

A total of 1232 mother-newborn pairs, including both term and preterm singleton infants delivered via caesarean section.

Data were extracted from hospital electronic medical records. Neonatal hypoglycaemia was defined as a blood glucose level below 2.6 mmol/L within 24 hours after birth. Maternal, obstetric and neonatal characteristics were analysed. Bivariable analyses were performed to assess associations between neonatal hypoglycaemia and candidate variables, followed by multivariable logistic regression to identify independent factors. Predictive performance of the final model was evaluated using receiver operating characteristic analysis.

Neonatal hypoglycaemia occurred in 800 of 1232 newborns, giving an incidence of 64.9% (95% CI 62.3% to 67.6%). In multivariable logistic regression, higher gestational age was independently associated with lower odds of neonatal hypoglycaemia (OR 0.781, 95% CI 0.684 to 0.891; p

Neonatal hypoglycaemia was common among Chinese newborns delivered via caesarean section, but most episodes were asymptomatic and resolved with routine feeding within 24 hours. Gestational age, fetal growth classification, elective caesarean delivery, parity and amniotic fluid characteristics were associated with hypoglycaemia in the current model. Early glucose monitoring and targeted nutritional support may be particularly important for newborns at increased risk.

This qualitative study aims to explore the experiences and preferences of Hispanic men participating in the National Diabetes Prevention Program (NDPP), an intensive lifestyle change intervention that effectively reduces diabetes risk, considering Hispanic men experience diabetes disproportionately yet remain underrepresented in the NDPP.

Individual semi-structured interviews were conducted over the phone in English or Spanish between June 2023 and February 2024. Transcripts were analysed using a framework analysis.

17 Hispanic men engaged in the NDPP for ≥4 sessions. The majority were foreign-born (n=11) and self-identified as English proficient (n=11).

Through three major themes, Hispanic men reflected on their experiences: (1) Going into the NDPP: despite not knowing what to expect from the NDPP, their fear of diabetes motivated them to enrol in the programme; (2) During the NDPP: they felt relief from gaining critical knowledge about diet, exercise and diabetes prevention; and finally (3) Impressions of the NDPP: they appreciated the NDPP’s informational resources, personalised coaching, group format and acknowledgement of traditional cultural diets and found men-only groups often offered additional emotional safety but had mixed feelings about the programme’s virtual format.

Findings suggest that Hispanic men appreciate the knowledge and skills attained from the NDPP and value its resources, group format, culturally-tailored content and gender-tailored structure. Recruitment efforts may benefit from emphasising how the programme reduces uncertainty about prediabetes and from more clearly conveying the structure of the programme. Strategies to improve sustained engagement should consider how to feasibly offer delivery formats that accommodate diverse preferences.

This study aimed to explore the lived experiences of fear of complications (FoC) among hospitalised people with type 2 diabetes (T2D) in China and to provide insights for targeted nursing interventions.

A phenomenological research approach was employed to conduct semistructured interviews and the Colaizzi’s seven-step analysis method was used for data analysis. This study followed the Consolidated Criteria for Reporting Qualitative Research checklist.

15 people with T2D were purposively recruited between March and July 2025 from the endocrinology departments of two tertiary hospitals in Daqing City, Heilongjiang Province.

Three themes and 11 subthemes were identified: (1) experiencing multiple negative psychological responses (distress from negative emotions, contradictory and painful psychological states, social alienation); (2) the triggers of fear are complex (adverse outcomes of similar patients, illness uncertainty, symptom burden, self-perceived burden, economic burden) and (3) employing diverse coping strategies (negative avoidance, positive self-adjustment, seeking social support).

Healthcare professionals should pay greater attention to FoC among people with T2D. Early psychological assessment, identification of fear triggers, strengthening social support and promoting adaptive coping strategies may help reduce fear and improve quality of life.

Type 1 diabetes is a chronic autoimmune disease, preceded by the presence of islet autoantibodies, a preclinical state defined as islet autoimmunity. Several environmental exposures have been associated with the initiation of islet autoimmunity but the triggers remain largely unknown. Rapid growth and weight gain during childhood are some of the exposures that have been proposed to promote islet autoimmunity. A high intake of protein and animal milks in early childhood is consistently associated with increased later obesity. Growth during early childhood is directly related to dietary intake and especially protein intake and this association has been linked to increased risk of islet autoimmunity and type 1 diabetes. The Intensive Dietary and Activity Counselling (IDAC) study aims to determine whether a healthy lifestyle counselling from age 3 months to age 2 years improves β-cell health in children with increased risk for islet autoimmunity.

The IDAC study is a randomised trial (1:1 allocation) with two parallel groups, aiming to enrol 1244 children at increased genetic risk of type 1 diabetes before the age of 4 months. Participants will be randomised to either the control or intervention group based on the child’s current breastfeeding status (currently breastfeeding or no longer breastfeeding). The intervention group will receive regular dietary and physical activity counselling. The primary outcome is β-cell health at 36 months, assessed by fasting and stimulated proinsulin-to-C-peptide ratio. Secondary outcomes include accelerated growth during infancy, overweight at 36 months, and time to development of persistent confirmed islet autoantibodies or type 1 diabetes. Growth measures, blood samples for serological markers, stool samples, dietary intake (nutrients and food group data) and questionnaire data will be collected regularly throughout the study period. Regression models will be used to estimate the effects of the intervention on the primary outcome.

The research protocol was approved by the Swedish Ethical Review Authority (dnr 2024-05217-01, 2024-08622-02, 2025-01759-02). Study findings will be presented at national and international conferences, submitted for publication in peer-reviewed journals, shared on social media and disseminated through patient-education materials.

NCT06670625.

Effective management of type 2 diabetes mellitus (T2DM) in older adults requires interventions that address both metabolic control and functional capacity. Exercise improves insulin sensitivity, glucose uptake and cardiometabolic health, while high-protein diets support muscle mass preservation, satiety and glycaemic regulation. Evidence suggests that integrating structured exercise with a high-protein diet may provide additive benefits; however, research evaluating this combined approach in older adults with T2DM, particularly in low-resource settings, is limited. This study aims to determine whether a 12-week multimodal exercise programme combined with a high-protein diet improves glycaemic control and broader health outcomes compared with exercise alone.

In this randomised controlled trial (RCT), 140 adults aged ≥60 years with T2DM will be allocated 1:1 to an experimental group (multimodal exercise with high-protein diet, n=70) or a control group (multimodal exercise alone, n=70). All participants will engage in three supervised exercise sessions per week for 12 weeks. Additionally, the experimental group will follow a high-protein diet that provides approximately 30% of total energy from protein, with a 500-kcal daily energy deficit. The primary outcome is glycaemic control, measured by Glycated haemoglobin (HbA1c). Secondary outcomes include anthropometric measures, fasting blood glucose, lipid profile, functional capacity (6-minute walk test) and health-related quality of life Short Form-36 Health Survey (SF-36). All outcomes will be assessed at baseline, postintervention (week 12) and follow-up (week 24). Participants, outcome assessors and statisticians will remain blinded. Intervention fidelity, adherence and safety will be systematically monitored, and final results will be analysed using SPSS (v.26.0). The study will follow ethical standards and comply with Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) guidelines.

The protocol has been approved by the Institutional Review Board of the Department of Physiotherapy and Rehabilitation, Jashore University of Science and Technology (Approval No.: PTR-JUST/IRB/2025/09/192404) and registered with the Clinical Trials Registry of India. Findings will be disseminated via peer-reviewed journals, conference presentations and structured knowledge-sharing sessions to inform clinical practice in diabetes management.

Trial registration number: CTRI/2025/08/092509

To assess the beneficial and harmful effects of regular human insulins versus rapid-acting insulin analogues in children and adolescents with type 1 diabetes.

Systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to 30 January 2026.

Randomised clinical trials comparing regular human insulins versus rapid-acting insulin analogues (insulin aspart, lispro, glulisine) in children and adolescents with type 1 diabetes.

Data were analysed using meta-analysis and trial sequential analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool, V.2, and the certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Severe hypoglycaemia, ketoacidosis and serious adverse events.

10 trials randomising 1107 participants were included. The certainty of evidence was very low mainly due to high risk of bias and small sample sizes. Meta-analysis showed no evidence of a difference between regular human insulins and rapid-acting insulin analogues on severe hypoglycaemia (risk ratio (RR) 1.28, 95% CI 0.81 to 2.03; I²=0.0%; p=0.2851; nine trials), ketoacidosis (RR 0.88, 95% CI 0.26 to 2.93; I²=0.0%; p=0.8593; two trials) and serious adverse events (RR 1.00, 95% CI 0.44 to 2.25; I²=0.0%; p=0.9958; two trials). Trial sequential analysis showed that all meta-analyses of primary outcomes were underpowered.

Current research shows no differential effects between regular human insulins and rapid-acting insulin analogues for children and adolescents with type 1 diabetes, but the evidence is very uncertain.

CRD42024508625.

Glycated haemoglobin A1c (HbA1c) measurement is essential for managing diabetes, yet limited data exist on the performance of point-of-care (POC) HbA1c devices in low- and middle-income countries (LMICs). This study evaluated the analytical performance and usability of HbA1c devices in different LMIC settings.

This prospective, cross-sectional multicentre study evaluated the accuracy and usability of four POC devices (i-SENS A1Care, HemoCue HbA1c 501 System, Abbott Afinion 2 and Siemens DCA Vantage) against a laboratory-based HbA1c method at two hospitals in Nigeria and Cambodia.

Adults with or without diabetes and haemoglobin ≥8 g/dL were enrolled.

The primary objective was to evaluate HbA1c POC device accuracy versus laboratory reference testing; secondary objectives evaluated device usability and technical characteristics when used by trained professionals.

Capillary and venous blood samples were tested on all devices using two cartridge lots followed by reference testing. Usability was assessed via operator questionnaires. Accuracy was evaluated using regression slopes, intercept, absolute bias at 30, 48 and 75 mmol/mol, and Bland-Altman analysis, including capillary-venous concordance.

A total of 248 participants completed all study procedures (n=125 in Cambodia, n=123 in Nigeria). Siemens DCA Vantage and Abbott Afinion 2 showed strong agreement with the reference method, with no clinically significant differences and narrow limits of agreement. In contrast, i-SENS A1Care and HemoCue HbA1c 501 System displayed greater bias, especially at elevated HbA1c levels. Most results fell within limits of agreement, though high-HbA1c outliers were more common with the A1Care and HbA1c 501 System devices. Usability feedback was positive overall, when devices were rated across various dimensions, such as clarity of instructions, safety and labelling, although limited user sample size constrains the generalisability of these findings.

Siemens DCA Vantage and Abbott Afinion 2 demonstrated reliable accuracy and usability. In contrast, i-SENS A1Care and HemoCue HbA1c 501 System require cautious interpretation at high HbA1c levels. Ongoing evaluation is critical to ensure the appropriate use of POC devices in diverse clinical settings.

NCT06170515.

Primary hyperparathyroidism (PHPT) increases the risk of renal stones and progressive renal dysfunction. Parathyroidectomy is recommended for patients with renal involvement, yet whether surgery improves renal outcomes compared with non-surgical management remains unclear. Prior reviews have focused mainly on biochemical or skeletal outcomes, included few renal events and largely predate recent large cohort studies using contemporary methods to evaluate renal stones, chronic kidney disease (CKD) progression and long-term estimated glomerular filtration rate (eGFR) decline. A contemporary renal-focused synthesis is needed to clarify the true renal benefits of parathyroidectomy. We aim to evaluate the effect of parathyroidectomy versus non-surgical management on renal stones and broader renal outcomes in adults with PHPT.

This Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P)-aligned protocol describes a systematic review and meta-analysis comparing parathyroidectomy with non-surgical management in adults (≥18 years) with PHPT. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be searched from inception to 5 November 2025. Eligible studies include randomised trials, non-randomised interventional studies and observational comparative designs. Studies without a comparator, those focused exclusively on secondary or normocalcaemic hyperparathyroidism and case reports or series will be excluded. Primary outcomes are renal stones and renal functional outcomes (eg, CKD progression, ≥30% decline in eGFR, dialysis initiation). Secondary outcomes include health-related quality of life and adverse events. Two reviewers will independently screen records, extract data and assess risk of bias (Cochrane Risk-of-Bias 2 and Risk Of Bias In Non-randomised Studies of Interventions). Random-effects models will be used where appropriate, and heterogeneity assessed using I². Publication bias will be assessed using appropriate quantitative or qualitative methods based on the available evidence.

Ethics approval is not required as only published data will be used. Findings will be disseminated through peer-reviewed publication and conference presentations.

CRD420251240480.

To investigate the associations among serum sodium, Geriatric Nutrition Risk Index (GNRI) and the risks of fragility fractures in patients with type 2 diabetes (T2D).

A retrospective cohort study.

The restricted cubic spline model was used to analyse the relationships between exposures (serum sodium and GNRI) and the risks of fragility fractures. The independent and combined effects between exposures and fragility fractures were examined using the Cox proportional hazards model. Subgroup analysis and sensitivity analysis were used to further examine the relationships between exposures and fragility fractures.

6221 participants diagnosed with T2D between January 2009 and March 2020 who were older than 45 years were included.

Assessing the risks of fragility fractures in patients with T2D based on discharge diagnoses in the hospital discharge records.

Serum sodium and fragility fractures had a U-shaped relationship, while GNRI and fragility fractures had a reverse S-shaped relationship. In the fully adjusted model 3, low sodium was significantly linked to around double the elevated risks of fragility fractures (HR, 1.87; 95% CI 1.23 to 2.83). Moderate (HR, 1.60; 95% CI 1.20 to 2.12) and low (HR, 2.28; 95% CI 1.40 to 3.71) GNRI levels were associated with increased risks of fragility fractures in the model 1. In the joint model 4, low sodium in conjunction with moderate (HR, 2.35; 95% CI 1.29 to 4.28) and low (HR, 3.62; 95% CI 1.50 to 8.71) GNRI levels significantly elevated the risks of fragility fractures. The associations between exposures and fragility fractures were more likely in individuals older than 60 years.

Low sodium and low GNRI levels were associated with increased risks of fragility fractures in patients with T2D. Clinicians should carefully monitor serum sodium levels and nutritional status, and consider early intervention to lower the incidence of fragility fractures in older patients with T2D.