BMJ Open Diabetes Research & Care

AimsTo identify barriers and facilitators to physical activity (PA) in adults with type 1 diabetes (T1D) living in the United States (U.S.) and identify sociodemographic factors related to meeting recommended PA. MethodsWe conducted a cross-sectional online survey study of adults with T1D aged [≥]18 years recruited through online-based platforms. Quantitative questions related to exercise quantity and intensity, demographic characteristics, and exercise barriers and facilitators. Wilcoxon rank sum tests or independent t-tests were used to compare quantitative responses in individuals meeting or below target PA. Barriers and facilitators were also assessed qualitatively with open-ended questions. Logistic regression was performed to determine if the following characteristics were independently associated with meeting PA recommendations: age, sex, income level, and automated insulin delivery system use. ResultsOf 281 respondents who completed questions about exercise quantity, 162 (57.7%) were women, mean age 52.6 {+/-} 16.6 years, and 151 (53.7%) met PA guideline recommendations. Common barrier themes related to T1D included hypoglycemia, time, lack of knowledge about glycemic management, cost, and failure of available treatments to accommodate exercise. Common facilitator themes were insurance reimbursement of exercise program/facility, peer exercise groups, health/fitness advising, and T1D tailored fitness. Middle (vs. upper) income level was independently associated with lower odds of meeting PA recommendations (adjusted odds ratio 0.46, 95% CI: 0.27, 0.78, p = 0.004). ConclusionsIn this predominately U.S. cohort with T1D, financial factors were common novel themes related to PA. Further validation in more socioeconomically diverse cohorts and research examining PA reimbursement cost-efficacy are needed. Novelty statementO_ST_ABSWhat is already known?C_ST_ABSO_LIIn prior qualitative studies in type 1 diabetes, hypoglycemia is a commonly reported barrier to physical activity (PA) engagement. Most studies were conducted outside the United States (U.S.). C_LI What this study foundO_LIIn a predominately U.S. cohort of adults with type 1 diabetes, cost is a newly identified barrier to PA. C_LIO_LIInsurance reimbursement of PA programs/facilities was a reported facilitator. C_LIO_LIIndividuals with highest income were 54% more likely to achieve recommended PA compared to other income categories. C_LI What are the implications of the study?O_LICost-efficacy research examining PA programs/facility reimbursement in type 1 diabetes is needed. C_LI

BackgroundType 2 diabetes (T2DM) and cognitive impairment are common long-term chronic conditions affecting older people in hospital. Cognitive impairment can complicate glucose monitoring and lead to diabetes-related emergencies in T2DM. Traditionally, point of care test (POCT) measurements of capillary blood glucose are conducted in-hospital for T2DM while continuous glucose monitoring (CGM) is not widely used. AimTo understand the feasibility, acceptability and tolerability of using CGM in older in-patients with T2DM and cognitive impairment. MethodsThirty-two older people (mean age = 78.7 {+/-}6.7 years) with comorbid T2DM and cognitive impairment (AMT [≤]8/10 and Mini-ACE [≤]22/30) were recruited within a tertiary care hospital in the UK. All participants were naive to CGM and were asked to wear blinded Dexcom G7 sensors for up to 10 days. Participants were asked about feasibility, acceptability and tolerability questions at the point of sensor removal. ResultsTwenty-nine participants (96%) reported no pain during CGM fitting. All participants (100%) agreed that they did not notice wearing the sensor, and it did not affect their day-to-day hospital activities. All participants (100%) found it very easy or easy to have the sensor fitted and wearing it for 10 days, with 27 participants (90%) finding CGM convenient. Seventeen participants (57%) reported favourable perceptions of the subcutaneous sensor sensation. ConclusionCGM use in older in-patients with T2DM and cognitive impairment is highly feasible and acceptable for patients. Future studies and trials are now needed to evaluate the clinical use of CGM for glucose monitoring in hospitalised or community-dwelling older individuals with T2DM and cognitive impairment.

Background and objectivesType 1 diabetes (T1D) is a largely self-managed condition that requires ongoing daily tasks and decisions. Many people living with T1D in Canada manage it alone, which can feel very isolating and negatively affect physical and mental health. Connecting with other people in similar situations may help to reduce the potential burden associated with managing this health condition. We aim to co-develop and evaluate a virtual peer support program called CommuniT1D, led by people with T1D, to improve the overall wellbeing of people across Canada whose lives are affected by T1D. Methods and analysisUsing a community-based participatory design and action research approach and a realist evaluation framework, we will first co-develop CommuniT1D by working together as a group of people with T1D, researchers, and clinicians. Over two thirds of steering committee members live with T1D (their own or their childs.) This collective lived expertise is complemented by experts in mental health, social support, health services research, and other relevant fields. Once the program is ready to welcome members, we will work with our partner organizations, networks, and use tailored ads to recruit CommuniT1D peer leaders and members. We will then form virtual peer support groups of people with shared lived experience. Within the program, we will hold monthly small group meetings led by peer leaders via an online platform. We will also hold monthly large webinars open to all CommuniT1D members and other interested people. To evaluate CommuniT1D, we will conduct surveys at baseline and every 6 months, collecting data about diabetes distress, life challenges, quality of life, wellbeing, management indicators, and access and use of management tools and services. We will analyze quantitative data using repeated measures analysis of variance. We will also conduct individual interviews with CommuniT1D members and peer leaders at two time points. We will analyze interview data thematically, and create a logic model by triangulating results from qualitative and quantitative analyses, applying a realist evaluation lens. DiscussionPeer support may help people with T1D feel less alone and better supported. This protocol outlines the design of a virtual peer support program called CommuniT1D to improve the wellbeing of people whose lives are affected by T1D in Canada. We hope that this program will help better equip people with T1D to cope with T1D-related stressors, thus improving the lives of people with T1D in Canada.

BackgroundEffective interventions are needed to support co-creation of diabetes care plans that fit patients lives. We evaluated the QBSafe agenda-setting kit (14 conversation cards) for its impact on care fit and glycemic control when added to usual primary care. MethodsThis single-center, clinician-level cluster-randomized, open-label trial was conducted at a federally qualified health center in New Haven, Connecticut (ClinicalTrials.gov NCT05553912). Clinicians and their patients with type 2 diabetes and HbA1c >8% were randomized 1:1 to usual care with or without QBSafe cards. In the intervention arm, patients selected up to 3 cards highlighting concerns about life with diabetes prior to their visit. Primary outcomes were change at 6 months in care fit (Illness Intrusiveness Ratings Scale, IIRS) and HbA1c, analyzed by intention to treat. Secondary outcomes were treatment burden (Treatment Burden Questionnaire, TBQ) and diabetes distress (Diabetes Distress Scale, DDS), and satisfaction with visits. ResultsBetween February 2023 and July 2024, 143 participants (mean age 56 years; 61% female; 73% Hispanic; mean HbA1c 10%) were enrolled: 74 received usual care with QBSafe, 69 usual care alone. At 6 months, there were no significant between-arm differences in changes in IIRS (-3.9 [95% CI -10.4, 2.6]), HbA1c (-0.2% [95% CI -0.9, 0.5]), TBQ (1.0 [95% CI -16.6, 18.6]), or DDS (-0.1 [95% CI -0.4, 0.2]). Clinicians reported greater satisfaction when using QBSafe. Patient satisfaction was high and did not differ across arms. ConclusionsQBSafe cards improved clinician satisfaction but did not improve care fit or glycemic control. Future tools should focus on helping clinicians respond effectively to patient-identified challenges.

BackgroundThe COVID-19 pandemic disrupted healthcare services, potentially affecting diabetes management and complications. ObjectiveTo investigate the impact of the pandemic on lower extremity amputation (LEA) rates among individuals with type 1 and type 2 diabetes mellitus, focusing on social determinants of health. MethodsA retrospective observational cohort study using de-identified claims data from a large U.S. health plan. LEA rates were compared before and after the onset of the COVID-19 pandemic using interrupted time series analysis. ResultsIndividuals with type 2 diabetes experienced an initial decline in LEA rates followed by a significant increase (p=0.022) as delayed care needs were addressed. Individuals with type 1 diabetes showed no significant fluctuations in amputation rates. Social determinants were significantly associated with changes in LEA rates among individuals with type 2 diabetes. Lower-income ([≤]$40,000/year) and less educated individuals experienced significant increases in amputation rates (p=0.027 and p=0.043, respectively). Individuals aged 45-64 years showed a significant increase in LEA rates (p=0.013), while those aged 18-44 experienced a decrease (p=0.017). Metropolitan residents saw significant increases in LEA rates (p=0.021). ConclusionsThe COVID-19 pandemic significantly disrupted healthcare access for individuals with type 2 diabetes, leading to increased LEA rates. Social determinants of health exacerbated existing disparities in diabetes outcomes. These findings underscore the need for targeted interventions to address healthcare disparities, especially during public health crises.

BackgroundThe self-management of type 2 diabetes (T2D) typically requires enacting various lifestyle changes, which can challenge people living with T2D. Clinical encounters between people with T2D and their clinicians, however, are often focused on metabolic management, leaving less time available for other self-management topics. The QBSAFE cards help patients articulate aspects of their experience with diabetes and prioritize issues for discussion. MethodsThis report details secondary outcomes of a randomized controlled trial; primary outcomes are reported elsewhere. All data was collected at Fair Haven Community Health Care, a federally qualified primary care clinic. 11 clinicians were randomly assigned to provide either usual care or usual care with QBSAFE cards to 155 of their patients with type 2 diabetes and hemoglobin A1c >8%. All patient encounters were video recorded for analysis. Patients and clinicians were not blinded to arm allocation but were kept unaware of the specific aims of the trial. Encounter video reviewers were blinded to arm allocation, but not to specific aims of the trial. The outcomes of interest for this report were the extent to which the QBSAFE cards were used as intended, their effect on the topics of discussion, and whether they enabled clinicians to notice and respond to each patients situation; comparisons between arms were conducted by a linear mixed model with fixed effect of arm and cluster effect of clinician, analyzed in both intent-to-treat and per-protocol populations. Findings12 patients were excluded post-randomization (A1c <8%). Of 143 eligible patients, 137 encounters (65 in the usual care arm, 72 in QBSAFE) yielded evaluable videos. QBSAFE was used as intended in 61 (85%) QBSAFE arm encounters. Conversations about burden of treatment related to non-pharmacological interventions (17 vs 33, p= 0{middle dot}04) and taking medications (11 vs 33, p= 0{middle dot}0008) and about the patients challenging environment (2 vs 10, p= 0{middle dot}04) were more prevalent in the QBSAFE group. There was no difference in the rate of conversations about metabolic management or of new care plans as a result of conversations between groups. InterpretationWhile there was a difference in the types of conversations observed between the two study arms, this difference was small and only apparent in a few domains. Future work could aim to modify the QBSAFE cards to more effectively stimulate patient-centered discussions and to further prepare clinicians to respond to a variety of issues raised during the clinical visit. FundingThis work was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK129616).

AimsTo evaluate the effectiveness of the Oishi-kenko mobile cooking application in improving glycemic control, body weight, and dietary behaviors among individuals with type 2 diabetes without professional intervention. MethodsThis 12-week observational study was conducted entirely online. Participants were recruited via the Oishi-kenko website, internet advertisements, and Tsukuba City public relations channels. Of 24,671 website visitors, 214 installed the app, and 65 were included in the final analysis; HbA1c data were available for 24 participants. The app provided personalized, culturally tailored recipe suggestions based on user profiles and dietary standards. Body weight and HbA1c were assessed at baseline and every 4 weeks, and dietary habits were evaluated using the Brief-type Self-administered Diet History Questionnaire (BDHQ). ResultsMean HbA1c decreased from 6.40% at baseline to 6.12% after 12 weeks (-0.28%, P<0.05). Among participants with baseline HbA1c >7%, the reduction was -0.63%. BMI declined from 23.47 to 23.28 overall, with greater reduction among those with baseline BMI [&ge;]25. More frequent app-based cooking and higher baseline HbA1c predicted greater improvement. BDHQ analyses showed reduced intake of salty condiments, noodle soup, and fatty meats, alongside healthier eating behaviors. Over 80% of participants reported improved dietary habits. ConclusionsUse of the Oishi-kenko app was associated with improved glycemic control, modest weight loss, and healthier eating patterns in individuals with type 2 diabetes. These findings support the potential of culturally tailored, stand-alone dietary support applications as scalable tools for diabetes self-management. (The trial registry number: UMIN-CTR, ID: R000053861) HighlightsO_LIOishi-kenko app use significantly reduced HbA1c and BMI in individuals with type 2 diabetes. C_LIO_LIThe study was conducted fully online, from recruitment to data collection, without human intervention. C_LIO_LIParticipants adopted healthier dietary behaviors, including reduced intake of salty condiments, noodle soup, and fatty meats, along with more mindful eating practices. C_LIO_LIThe app shows promise as a stand-alone, culturally tailored digital tool for diabetes self-management without professional intervention. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/25342210v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@771eeborg.highwire.dtl.DTLVardef@8ed68aorg.highwire.dtl.DTLVardef@1a70476org.highwire.dtl.DTLVardef@161b52_HPS_FORMAT_FIGEXP M_FIG C_FIG

Breastfeeding is associated with metabolic benefits for women with type 2 diabetes and their infants, yet breastfeeding rates in these women are poorly described. Obesity is associated with type 2 diabetes, and lower breastfeeding rates, making it difficult to disentangle type 2 diabetes vs. obesity effects on breastfeeding. AimsThe primary objective was to examine breastfeeding rates in women with type 2 diabetes, compared to normoglycaemic women with either (1) matched body mass index (BMI) or (2) normal BMI. The secondary objective was to examine variables associated with breastfeeding. MethodsPregnant women with type 2 diabetes (cases) or normoglycaemia (controls) were prospectively recruited. Each case was matched with two controls by age and parity and either (1) matched or (2) normal (18-25 kg/m{superscript 2}) BMI. Data were collected from in-person surveys antenatally, medical records, and a four-month postpartum telephone survey. Analysis included descriptive and inferential statistics. ResultsFour-month breastfeeding data were available for 29, 29 and 28 women in each group. Breastfeeding rates were similar in women with type 2 diabetes and BMI-matched controls, both significantly lower than normal-BMI controls. ConclusionsMaternal obesity, rather than type 2 diabetes, may be the major determinant of reduced breastfeeding rates four-months postpartum.

BackgroundThe diagnostic accuracy of HbA1C for prediabetes has been questioned due to its discordance with fasting plasma glucose (FPG) and 2 h oral glucose tolerance test (OGTT) glucose in non-white populations. This study aims to estimate concordance in the diagnosis of prediabetes using HbA1C FPG, and OGTT in a Filipino-American cohort. MethodsCross-sectional data from 149 Filipino-Americans without known diabetes living in the San Francisco Bay Area were used to compare prevalence of prediabetes as diagnosed by HbA1C, versus diagnosis by FPG and OGTT. ResultsThirty nine percent of subjects met the diagnosis of prediabetes using any one of the measures. Overall agreement between HbA1C, FPG and OGTT was low. Prevalence was 8.1% by FPG, 8.7% by OGTT and 35% by HbA1C. BMI, waist-hip ratio, insulin, HOMA-IR, blood pressure, and triglycerides were significantly higher in those with prediabetes by HbA1C versus normal HbA1C. ConclusionsThere is significant discordance between HbA1C, FPG, and OGTT in diagnosing prediabetes in a Filipino-American cohort. HbA1C detected four times as many individuals with prediabetes than FPG or OGTT. Individuals classified with prediabetes by HbA1C had indicators of more insulin resistance compared to individuals with normal HbA1C suggesting that HbA1C appears to detect true metabolic abnormalities on the path to diabetes as opposed to detecting false positives. These results have important implications for diabetes and prediabetes screening in Filipinos.

Background/ObjectivesOur objective was to understand the role of clinical and continuous glucose monitoring (CGM) parameters in predicting the risk of hypoglycemia in type 1 diabetes pediatric patients. MethodsPediatric patients with type 1 diabetes (n=71) at the Oradea County Clinical Emergency Hospital, Romania, underwentCGM during their initial visit and were followed for at least 6 months, with in-clinic visits every 3 months. Age, body mass index, time in range, mean daily glucose(MDG) concentration, coefficient of variation(%CV)were considered as potential predictors of the risk of hypoglycemia (presented as the percentage of time spent below two glycemic thresholds: 3.9 and 3.0 mmol/L, corresponding to mild, respectively clinically significant hypoglycemia). ResultsLooking at a total of 142 glycemic profiles, MDG was significantly lower in those with hypoglycemia compared to those without, while %CV was significantly higher(p<0.0001). Regression tree models identified %CV as the dominant variable for both thresholds, while classification tree models identified %CV for clinically significant hypoglycemia and MDG for mild hypoglycemia. It was observed that in profiles with a %CV below 36.15% and MDG above 7.16 mmol/L, the mean percentage of time spent below the 3.9 mmol/L threshold was 4.8%--a value close to that recommended in American Diabetes Association guidelines. Patients younger than 7 years presented the highest frequency of both mild and clinically significant hypoglycemic episodes. ConclusionsOur study supports %CV and MDG concentration as key factors in predicting hypoglycemia risk. Minimizing the risk of hypoglycemia in pediatric patients requires a %CV below 36%.

BackgroundGLP-1 receptor agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2Is) have established cardiovascular benefits for patients with type 2 diabetes mellitus (T2DM), with similar class-level effectiveness found in previous studies. However, real-world comparative effectiveness assessments of individual agents remain limited. ObjectivesTo compare the cardiovascular effectiveness of individual GLP-1RAs and SGLT2Is. MethodsWe conducted a multi-national, retrospective, new-user active-comparator cohort study using 10 US and non-US administrative claims and electronic health record databases. The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy with one of six GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or one of four SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin). Empagliflozin (393,499; 31.6%), semaglutide (235,585; 18.9%), dapagliflozin (208,666; 16.8%), and dulaglutide (207,348; 16.8%) were most commonly used. A secondary subgroup analysis included 316,242 patients with established cardiovascular diseases (CVD). Primary outcomes were 3-point major adverse cardiovascular events (MACE: acute myocardial infarction, stroke, sudden cardiac death) and 4-point MACE (adding hospitalization/ER visit with heart failure). Secondary outcomes included the individual components. Hazard ratios (HRs) were estimated for pairwise agent comparisons while on-treatment (per-protocol) and over total follow-up using Cox proportional hazards models, with propensity score adjustments, negative control calibration, and pre-specified study diagnostics to guard against potential confounding. Random-effects meta-analysis produced summary HR estimates across data sources that passed diagnostics. ResultsAcross the study cohort, individual GLP-1RAs and SGLT2Is demonstrated broadly similar cardiovascular effectiveness, both within and across drug classes. For example, semaglutide and empagliflozin showed comparable risks for 3-point MACE (meta-analytic HR 1.05; 95% CI 0.79-1.39) and 4-point MACE (meta-analytic HR 0.95; 95% CI 0.81-1.12), with consistent findings in the CVD subgroup. Study diagnostics confirmed adequate equipoise, covariate balance and statistical power to detect similarity in HRs between 0.8 and 1.2 for commonly used agents. ConclusionsIn this large-scale real-world study, individual GLP-1RAs and SGLT2Is exhibited largely comparable cardiovascular benefits, including in patients with established CVD. These findings align with network meta-analytic estimates from major cardiovascular outcome trials and broadly support current treatment guidelines. Clinical choices should be guided by relevant factors such as safety, adherence, tolerability, cost, and patient preference, where further work is needed.

Prediabetes is a high-risk dysglycemic state. We used a real-world endocrine/diabetes clinic registry from Najaf, Iraq to characterize patients labeled as having pre-diabetes and to explore factors associated with follow-up engagement. We identified prediabetes visits using keyword-based case finding (English and Arabic terms including prediabetes/pre-diabetes, IFG, IGT, and impaired fasting glucose/tolerance) across semi-structured registry fields. Visit-level data were collapsed to patient-level records. Binary indicators of hypertension, dyslipidemia/statin use, obesity/weight management, smoking, and common glucose-lowering therapies were derived from registry text using keyword/brand-name matching. The primary outcome was follow-up engagement defined as [&ge;]2 recorded visits. The prediabetes subset comprised 242 unique patients and 302 visits. Median age was 45 years (IQR 35-55); 47 patients (19.4%) had [&ge;]2 visits. Median follow-up duration was 0 days (maximum 321). Obesity/weight-management indicators were frequent (71.1%), as were hypertension (43.4%) and dyslipidemia/statin indicators (46.3%). In multivariable logistic regression, no evaluated predictor reached conventional statistical significance for follow-up engagement. Registry enhancements to capture laboratory confirmation and standardized follow-up fields may improve the ability to evaluate diabetes prevention pathways.

1PurposeThe KIND (KINder mit Diabetes) cohort investigates diabetic peripheral neuropathy (DPN) in paediatric type 1 diabetes (T1D). Current guidelines recommend DPN screening at puberty or from 11 years and 2-5 years after T1D diagnosis, yet subclinical neurophysiological changes occur within the first 2 years. The cohort examines: (1) longitudinal associations between glycaemic metrics (HbA1c and continuous glucose monitoring-derived variability metrics) and peripheral nerve function and structure; (2) comparative predictive value of different variability metrics; (3) developmental trajectories of nerve maturation in T1D versus controls; (4) effects of residual beta-cell function on neuropathy progression; and (5) how early signs of DPN differ between patients with multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII) therapy. ParticipantsThis prospective cohort, initiated in June 2019, continuously enrols children and young adults with T1D ([&le;]21 years) at two Swiss centres. The care-embedded design integrates research into quarterly diabetes care and annual comprehensive assessments. So far, 141 T1D cohort participants (median age: 12.2; IQR: [8.4; 14.3] years; 47.5 % female) and 103 healthy controls (10.9 [7.5; 14.2] years; 53.4 % female) were recruited. Controls for neurophysiological examinations comprise measurements from the healthy, contralateral side of children with limb injuries in the surgical outpatient clinic of the Childrens hospital of Eastern Switzerland (OKS). Multimodal assessments comprise nerve conduction studies (peroneal, tibial, median motor and sensory) and high-resolution ultrasound, with development-adjusted analyses distinguishing diabetes effects from normal growth. Findings to dateCross-sectional analysis showed reduced nerve conduction velocities across all nerves, particularly peroneal in T1D patients (n=53) compared to healthy controls (n=50). Height-adjusted peroneal velocity (dNCV) correlated negatively with glucose variability (SD: r=-0.45, p=0.009), HbA1c (r=-0.27, p=0.049). During the first five years, dNCV correlated negatively with diabetes duration (r=-0.41, p=0.004), independent of glycaemic control. The cross-sectional area of the median nerve increased on average by 0.217 mm{superscript 2} per 1% HbA1c (p=0.004) and was already detectable with diabetes duration <2 years. Longitudinal analysis (n=45, 21.4{+/-}8.6 months) demonstrated that HbA1c changes predicted dNCV changes ({beta}=-0.59, p=0.014), and in some patients, early impairment was reversible with improved glycaemic control. Future plansA planned 2026 extension of this continuously recruited and prospectively followed cohort will integrate physical activity measures (Swiss National Science Foundation Grant 10006264). Future analyses will compare glycaemic variability metrics as predictors of functional and structural nerve changes, investigate their temporal relationships as well as influencing factors, and examine residual beta-cell function effects across developmental stages. All data produced in the present study may be made available upon reasonable request and in accordance with legal and ethical requirements.

BACKGROUNDCardiovascular disease (CVD) is a leading cause of diabetes-related mortality in Mexico. Although diabetes subgroups capture underlying disease heterogeneity, their association and utility for risk prediction for fatal CVD in Mexican adults remain unclear. METHODSWe analyzed 24,943 adults with diabetes from the Mexico City Prospective Study. Participants were classified into mild obesity-related (MOD), severe insulin-deficient (SIDD), severe insulin-resistant (SIRD), and mild age-related (MARD) diabetes using a self-normalizing neural network algorithm. Fatal CVD was defined as death from ischemic heart disease or stroke (ICD-10 I20-I25, I60-I69). SCORE2-Diabetes was recalibrated and validated overall and by diabetes subgroup. Cox proportional hazards models were used to estimate subgroup-specific risk, and sequential models evaluated the incremental predictive value of diabetes subgroups combined with SCORE2-Diabetes and traditional risk factors. RESULTSOver a median follow-up of 19.3 years (IQR 12.7-20.6), 2,223 fatal CVD events (8.9%) were recorded. SIDD was the most prevalent subgroup (50.6%), followed by SIRD (17.3%), MARD (16.8%), and MOD (15.4%). SIDD and MARD showed the highest adjusted risk of fatal CVD (RR 1.58 [95%CI 1.38-1.81] and 1.35 [1.13-1.60]), whereas MOD and SIRD had lower risk. Recalibrated SCORE2-Diabetes demonstrated adequate discrimination overall (c-statistic 0.759, 95%CI 0.745-0.773) and for most subgroups but underperformed in MARD, with recalibration improving risk assessment. The combination of diabetes subgroups and SCORE2-Diabetes improved prediction for fatal CVD outcomes. CONCLUSIONSDiabetes subgroups show heterogeneity in fatal CVD risk in Mexican adults. SIDD and MARD identify high-risk individuals and integration subgroup classification with SCORE2-Diabetes enhances risk prediction.

ObjectivesTo estimate potential launch prices of generic semaglutide following patent expiry from 2026 and to quantify the global obesity and type 2 diabetes (T2DM) burden in countries where generic access may become possible. MethodsWe used World Bank population data and World Obesity and Diabetes Atlas prevalence estimates to calculate obesity and T2DM burden in countries where semaglutide patents expire in 2026 or were not filed. Patent status was identified using MedsPaL and cross-checked with regional databases. We updated established cost-plus pricing methodologies using 2024-2025 Indian API shipment data to estimate production costs for oral and injectable semaglutide, incorporating formulation, packaging, taxation, and profit assumptions. ResultsTen countries with 2026 patent expiry represent 44% of the global population and 48% of the global obesity burden. No patent filings were identified in 150 additional countries. By the end of 2026, generic injectable semaglutide could be distributed in 160 countries where 69% of global T2DM and 84% of clinical obesity occurs. Estimated generic injectable costs ranged from $28-140 per person-year, while oral formulations ranged from $186-380 per person-year. Injection devices contributed disproportionately to total cost. ConclusionPatent expiry could substantially expand access to semaglutide at dramatically lower prices, particularly in high-burden settings. However, device costs, secondary patents, and health system constraints may limit equitable uptake without coordinated policy action. Study ImportanceO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LISemaglutide is highly effective for obesity and cardiometabolic disease but remains unaffordable in many low- and middle-income countries due to high branded prices and patent protections. C_LIO_LIPrevious cost-plus analyses show that generic competition can substantially reduce prices of essential medicines after patent expiry. C_LI What are the new findings in your manuscript?O_LIUsing 2024-2025 API shipment data, we estimate generic injectable semaglutide could be produced for $28-140 per person-year following 2026 patent expiry. C_LIO_LIBy 2026, generic semaglutide could be available in 160 countries comprising 69% of global T2DM and 84% of clinical obesity burden. C_LI How might your results change the direction of research or the focus of clinical practice?O_LIProvides an evidence base for procurement planning and price negotiations ahead of patent expiry. C_LIO_LIHighlights the importance of addressing device costs and secondary patents to ensure equitable global access. C_LI

ObjectiveTo examine dose-response associations of vigorous intermittent lifestyle physical activity micropatterns (VILPA; bouts [&le;]1 minute) and its moderate-to-vigorous equivalent (MV-ILPA; bouts [&le;]3 minutes) with incident type 2 diabetes. Research Design and MethodsProspective data from UK Biobank accelerometry sub-study participants who reported no leisure-time exercise and had no type 2 diabetes at baseline were analysed. Daily duration and frequency of VILPA and MV-ILPA were derived from wrist-worn accelerometry. Incident type 2 diabetes was ascertained through linked primary care, hospital and death records. Dose-response associations were examined using multivariable-adjusted Fine-Gray subdistribution hazard models accounting for competing risks. ResultsAmong 22,706 participants (mean age 62.3 years; 56.4% female), 665 developed type 2 diabetes over an average follow-up of 7.9 years. Daily durations of VILPA and MV-ILPA showed inverse, non-linear L-shaped associations with incident type 2 diabetes. Median durations of 3.9 minutes/day of VILPA and 25.3 minutes/day of MV-ILPA were associated with 36% and 46% lower risk of type 2 diabetes, respectively, compared with those completing no VILPA or 3.9 minutes/day of MV-ILPA. Daily VILPA frequency showed a near-linear inverse association, with 10.4 bouts/day (median) corresponding to a hazard ratio (HR) of 0.64 (95% CI 0.51-0.81) compared with 0 bouts/day. Daily MV-ILPA frequency showed a U-shaped pattern, with risk reductions plateauing at approximately 56 bouts/day (HR 0.54, 95% CI 0.39-0.76). ConclusionsAmong adults who do not do leisure-time exercise, accruing brief, intermittent bouts of moderate-to-vigorous intensity physical activity during day-to-day routines may be a promising strategy for prevention of type 2 diabetes.

Aims/hypothesisTo investigate the feasibility and preliminary efficacy of a 12-week remotely-delivered exercise snacks (ES) intervention in adults with type 2 diabetes. MethodsInsufficiently active adults with type 2 diabetes (N=69; 46 females; mean age {+/-} SD: 58{+/-}11 years) were randomized to an ES or mobility/stretching comparator group (CON), which involved 4 x 1-min bouts of either vigorous or low intensity exercise, respectively, on [&ge;]5 days/week. The primary outcome was feasibility based on adherence. Secondary outcomes included exercise enjoyment (1-7 scale), rating of perceived exertion (RPE; 0-10 scale), heart rate (HR), hemoglobin A1c (HbA1c), blood biomarkers of cardiometabolic health, 30-second sit-to-stand capacity, grip strength, estimated maximal oxygen uptake, and anthropometrics. ResultsWeekly adherence (estimated marginal mean [95% confidence interval]: 18 bouts [16 to 21] for both groups; P=0.99) and total enjoyment (ES: 4.5 [4.1 to 4.8] vs CON: 4.3 [4.0 to 4.7]; P=0.64) were high and not different between groups. Despite higher RPE (5.7 [5.4 to 6.1]) and peak HR (73 [70 to 77] % of age-predicted HR maximum) in ES vs CON (2.0 [1.7 to 2.4] and 61 [58 to 64] % of age-predicted HR maximum, respectively) (all P<0.001), there were no between-group differences in the change in any secondary outcome (all P>0.05) except for greater sit-to-stand capacity in ES after training (between-group effect estimate [95% confidence interval]: 1.9 repetitions [0.3 to 3.4]; P=0.02). Conclusions/interpretationExercise snacks were feasible to perform in the real-world and improved physical capacity to a greater extent than CON in adults living with type 2 diabetes. Trial registrationClinicalTrials.gov ID: NCT06407245 Research in ContextO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIExercise snacks ([&le;]1-min bouts of vigorous exercise spaced out across the day) are a time-efficient and practical approach to promote vigorous exercise and break up sedentary time. C_LIO_LIReal-world exercise snack interventions appear feasible for middle-aged and older adults. C_LI What is the key question?O_LIAre 12 weeks of exercise snacks performed in the real-world feasible for insufficiently active adults living with non-insulin treated type 2 diabetes? C_LI What are the new findings?O_LIExercise snacks are feasible for those living with type 2 diabetes to perform unsupervised in the real-world based on high adherence, enjoyment, and participant retention rates. C_LIO_LIExercise snacks improved 30-second sit-to-stand capacity and reduced waist circumference suggesting enhancements in physical capacity and body composition. C_LI How might this impact on clinical practice in the foreseeable future?O_LIExercise snacks could be utilized to help individuals living with type 2 diabetes build a routine or habit of incorporating small amounts of physical activity into their daily lives. C_LIO_LIThe improved physical capacity observed in the current study could contribute to lower fall risk and greater lower body strength in those with type 2 diabetes as they age. C_LI

AimsThe gut microbiome has been implicated in type 2 diabetes progression, but reproducible biomarkers across studies remain limited due to technical and population heterogeneity. This study investigated whether specific gut microbiome shifts occur progressively across stages of type 2 diabetes. MethodsWe systematically reanalysed 16S rRNA datasets from 12 published studies (n=1,247 samples) after quality control, examining five groups (healthy controls, prediabetes (PD), new-onset type 2 diabetes, established type 2 diabetes, and type 2 diabetes with complications. Sequencing reads were quality-filtered, denoised, and resolved into amplicon sequence variants with genus-level taxonomic assignments using the SILVA database. Centered log-ratio (CLR)-transformed abundance data were analysed using PERMANOVA, meta-analysis with leave-one-study-out validation, differential abundance testing (Wilcoxon and ANCOM), and Random Forest classification. Eligible studies were identified through comprehensive searches of PubMed, Ovid Medline and Web of Science from June 2010 - June 2025 using predefined inclusion and exclusion criteria following PRISMA 2020 guidelines. Studies were investigated by two independent reviewers and included if they provided 16S rRNA data on adults across diabetes stages. Study quality was assessed based on metadata completeness and raw data availability. This systematic review and meta-analysis was registered in the Open Science Framework (OSF; registration https://osf.io/eth7a; embargoed until October 2026) and conducted according to PRISMA guidelines. ResultsEarly disease transitions showed minimal microbiome alterations, with only 4 genera, (notably enrichment of Allisonella and Escherichia-Shigella) were significantly different between healthy and PD (q < 0.05), and no significant genera between PD and new-onset type 2 diabetes. Advanced disease exhibited robust dysbiosis, with 9 genera differentially abundant in type 2 diabetes vs complicated type 2 diabetes and 5 genera in healthy vs complicated type 2 diabetes comparisons. Complicated type 2 diabetes was characterised by enrichment of Hungatella and [Clostridium] innocuum group and depletion of Faecalibacterium and compared to both uncomplicated type 2 diabetes and healthy controls. Random Forest classification achieved poor performance for early contrasts (AUC [&le;] 0.79) but strong discrimination for advanced disease (type 2 diabetes vs complicated type 2 diabetes: AUC = 0.89; Healthy vs complicated type 2 diabetes: AUC = 0.96). ConclusionGut microbiome alterations are subtle and inconsistent in early dysglycemia but become pronounced and reproducible with diabetic complications, suggesting microbiome-based biomarkers may be most clinically useful for identifying disease progression rather than early detection. Limitations include heterogeneity of sequencing methods and reliance on 16S rRNA data, which may restrict taxonomic and functional resolution. To our knowledge, this is the first meta-analysis to systematically evaluate gut microbiome alterations across multiple clinical stages of type 2 diabetes progression.

Stratifying progression from early-stage type 1 diabetes to clinical disease is essential for optimally timing disease-modifying therapies. We previously developed a progression likelihood score (PLS) that includes quantitative IA-2 autoantibody (IA-2A) measurements. This study aligned IA-2A thresholds used for PLS calculation between the radiobinding assay (RBA) and a commercially available RSR IA-2A ELISA to support broader clinical application. Serum samples from 349 children with stage 1 type 1 diabetes were analyzed using both assays. IA-2A positivity was similar by RBA (61.6%) and ELISA (59.0%). Centile-based alignment of ELISA-positive samples defined thresholds corresponding to RBA IA-2A categories. ELISA-derived PLS low (PLS < 0.5), moderate (PLS 0.5-4.0) and high (PLS > 4.0) risk groups stratified progression to stage 3 disease comparably to RBA-derived groups. The 3-year progression rate for children with an ELISA IA-2A PLS >4.0 was 52.4% (95% CI, 30.5- 66.1), similar to the RBA-derived PLS >4.0 group (58.7%; 95% CI, 37.1-72.8). These results demonstrate that the commercial ELISA can be used for PLS-based risk stratification.

BackgroundTimely access to screening, diagnosis, and treatment services is essential to prevent complications among people with diabetes. We evaluated trends and factors associated with self-reported diabetes screening, diagnosis, and treatment among Peruvian adults aged 18 years and older from 2014 to 2024. MethodsWe analyzed data from the Health Questionnaire of the Demographic and Family Health Survey (ENDES). We used information on diabetes screening, diagnosis, and treatment, along with socio-demographic and clinical covariates. We fitted generalized linear models of the Poisson family with log link and robust variance, and performed Joinpoint regression to assess temporal trends. ResultsThe prevalence of screening increased from 24% to 31% (APC: 1%; p=0.483). Higher screening was associated with being female, having higher educational attainment, not being single, belonging to higher wealth quintiles, being insured, and having hypertension. In contrast, smoking and living in rural areas or the Highlands were associated with lower screening. The prevalence of diagnosis increased from 3% to 5% (APC: 7%; p<0.001). Higher diagnosis was associated with being female, not being single, higher wealth, being insured, and living in the Rainforest, while lower diagnosis was associated with higher education and living in rural areas or the Highlands. Among individuals with diabetes, treatment prevalence increased from 65% to 74% between 2014 and 2019 (APC: 2%; p=0.014), but decreased to 63% in 2024 (APC: -2%; p<0.001). Higher treatment was associated with being married/widowed/divorced, being insured, higher wealth, and having hypertension. Lower treatment was associated with higher education and living in the Highlands. ConclusionsAlthough the prevalences of diabetes screening and diagnosis have increased over the past 11 years, treatment has declined in the last five. Socio-demographic and clinical inequalities persist across all three indicators and should be considered in the planning of diabetes health services in Peru.