AIMS:The aims of this review were to (1) estimate the ratio of male and female participants with type 1 diabetes (T1D) in clinical exercise studies, (2) ascertain the degree to which menstruation has been considered and (3) characterize the number of studies in which the elderly have been included. MATERIALS AND METHODS:Original clinical exercise research articles in individuals with T1D from 1985 to 2025 on PubMed were screened. The number and age of participants were analysed. A standardized menstrual-status tiering system was used to assess the quality of menstrual cycle (MC) information of females: Gold, Silver and Bronze were awarded based on the level of methodological control, including verification of MC characteristics and hormonal profiling. RESULTS:Of a total of 315 included studies, the majority (81%) contained a mixed-sex population with an overall male dominance in participant ratio (57% males vs 43% females). Since 1985, there have been six studies conducted exclusively in females compared to the 54 studies done in men, with six times fewer total participants (n = 99 vs n = 671, respectively). Across all studies, the mean age of participants was 29 ± 7 years, with only one study conducted solely in post-menopausal females. MC status was reported in 30 studies, 6 of which were graded Bronze and 3 Silver. None achieved Gold. CONCLUSIONS:Females and the elderly are under-represented in clinical exercise trials conducted in people with T1D. These data highlight the need for intensified efforts to bridge the current sex-and age-data gaps so as to improve practical implementation and clinical translation.
OBJECTIVE:This study aimed to explore whether GAS5 improves gestational diabetes mellitus (GDM)-associated insulin resistance (IR) via the miR-137/Nrf2 axis, thereby elucidating a potential novel mechanism underlying GDM pathogenesis. METHODS:GAS5 and Nrf2 expression was compared between GDM patients and normal glucose tolerance pregnant women, and their correlations with IR and lipid metabolism indexes were analysed. A dexamethasone-induced adipocyte IR model was constructed. Cellular functional changes in glucose uptake, fatty acid metabolism and lipid deposition were detected following GAS5 overexpression and miR-137/Nrf2 intervention to validate the regulatory mechanism. RESULTS:GAS5 and Nrf2 were markedly decreased in GDM peripheral blood and closely correlated with IR and lipid metabolic phenotypes. GAS5 overexpression increased adipocyte glucose uptake and alleviated IR and lipid disorders. Mechanistically, GAS5 directly binds and inhibits miR-137 to upregulate Nrf2. Rescue assays showed that miR-137 elevation or Nrf2 suppression partially reversed the protective effects of GAS5, reducing glucose uptake and fatty acid oxidation while increasing free fatty acid release and lipid accumulation. CONCLUSION:GAS5 and Nrf2 are lowly expressed in GDM patients. This study demonstrates that GAS5 ameliorates adipocyte IR and lipid metabolic dysfunction by sponging miR-137 to elevate Nrf2 expression, providing a novel mechanistic insight for GDM.
AIMS:Sodium-glucose co-transporter inhibitors (SGLT2i) have proven cardiorenal benefits in type 2 diabetes and are promising as adjunct-to-insulin therapy in participants with type 1 diabetes (T1D). However, clinical use in T1D has been limited owing to a lack of regulatory approval and the augmented risk of diabetic ketoacidosis (DKA). Participant and physician input is critical in understanding how and when the risk-benefit ratio with these therapies is perceived to be favourable for users. This study aimed to explore how risks and benefits of SGLT2i are considered by participants with T1D and physicians who treat the condition. METHODS:We used a qualitative descriptive study design, in which we conducted semi-structured interviews with people with T1D and physicians who treat this population. Participants were sampled from multiple Canadian sites via online recruitment. Transcripts were analysed inductively using conventional qualitative content analysis to identify themes. RESULTS:We interviewed 24 participants with long-standing T1D, whose duration of living with diabetes ranged from 8 to 62 years. We also interviewed 7 physicians, including endocrinologists and nephrologists with a range of 4 to 20+ years in practice. Our analysis revealed five major themes: (i) A prevailing inclination to 'stay in the safe zone', reflecting hesitancy to move beyond established therapeutic boundaries; (ii) A sense of 'feeling the disconnect', characterized by divergent lenses between patients and clinicians, and tension regarding who holds expertise in T1D care; (iii) Ongoing efforts to reconcile the trade-offs between risks and benefits when considering new therapeutic strategies; (iv) A cautiously optimistic search for a path forward, marked by both anticipation and restraint; and (v) The need for personalization of care-the overarching theme. CONCLUSIONS:While there is great interest and motivation toward the use of SGLT2i among people with T1D and the physicians who treat them, there is also a clear understanding of the need for personalization of therapy and support for robust evidence to inform care.
AIM:Deep intronic variants can disrupt splicing and cause monogenic disease but are missed by routine genetic testing. This study assessed the contribution of deep intronic variants to Wolcott-Rallison syndrome (WRS), a recessive disorder characterized by early-onset diabetes and progressive multisystem disease caused by loss-of-function EIF2AK3 variants. METHODS:We investigated a cohort of 116 individuals referred to the Exeter Genomics Laboratory for genetic testing who had diabetes diagnosed at ≤2 years and at least one additional feature consistent with WRS: hepatic dysfunction, skeletal abnormalities or developmental delay. No genetic cause had been identified after testing all known early-onset diabetes genes. We screened genome-sequencing data for rare homozygous intronic EIF2AK3 variants. Candidate variants predicted to affect splicing by SpliceAI were assessed using a minigene exon-trapping assay. RESULTS:We identified two rare homozygous intronic EIF2AK3 variants in two siblings. Only one variant, c.1651-180G>T, was predicted to disrupt splicing in silico. The two children, born to consanguineous parents, were diagnosed with early-onset diabetes (diagnosed at 1 year and 21 weeks), hepatic dysfunction, skeletal abnormalities, developmental delay, thyroid dysfunction, hip dysplasia and gait abnormalities. The minigene assay showed that c.1651-180G>T creates a cryptic donor splice site within intron 9, resulting in inclusion of a 79-nucleotide pseudoexon, causing a frameshift and premature stop codon. Using this evidence, the variant was reclassified as likely pathogenic according to ACMG/ACGS guidelines. CONCLUSIONS:We report the first deep intronic EIF2AK3 variant causing WRS, highlighting the need to consider systematic intronic analysis in unresolved cases.
AIMS:Determine associations between social determinants of health (SDOH) and use of diabetes-related mobile health (mHealth) applications in older individuals with type 2 diabetes. METHODS:We identified participants that self-reported having type 2 diabetes who completed the National Poll on Healthy Aging, a nationally representative survey of older adults in the United States. Co-primary outcomes were use of mHealth applications to (1) track diabetes medications and (2) track blood glucose levels. SDOH factors included household income, education, health insurance, lack of companionship or social isolation, homeownership and access to technology. Logistic regression models determine associations between SDOH factors and use of mHealth applications, adjusted for age. RESULTS:There were 348 participants with type 2 diabetes that completed the survey (mean [SD] age: 65.4 [7.9] years, 44.0% female, 69.5% White). We found 12.4% used mHealth applications to track blood glucose and 5.5% to track diabetes medications. Regression revealed higher income associated with a greater use of mHealth applications to track diabetes medications (OR: 4.3, 95% CI: 1.3-15.3) and blood glucose levels (OR: 52.0, 95% CI: 6.3-716.9). Additionally, older age (OR: 0.9, 95% CI: 0.8-0.99) was associated with decreased odds of using mHealth applications to track medications, whereas having graduate education (OR: 3.9, 95% CI: 1.2-12.8) was associated with increased odds of using mHealth applications to track blood glucose levels. CONCLUSIONS:We found that few older adults with type 2 diabetes use mHealth applications to assist in diabetes care, particularly among those with lower income. Future studies are needed to identify barriers and facilitators of mHealth use in these populations to develop and tailor future interventions.
AIMS:Islet autoantibodies characterise a period of immune-mediated destruction preceding clinical (symptomatic) type 1 diabetes. Screening and monitoring programmes for islet autoimmunity are being planned and implemented globally. The perspectives and experiences of healthcare professionals working in paediatric screening and monitoring of islet autoimmunity and clinical type 1 diabetes can inform these programmes. METHODS:We interviewed 32 healthcare professionals (81% women) caring for children with islet autoimmunity and/or clinical type 1 diabetes in Australia (median of 13 years of type 1 diabetes clinical experience). Data were analysed using reflexive thematic analysis. RESULTS:We developed seven themes: 1. implementing population screening and monitoring is contested, 2. considerations for the structure of screening and monitoring, 3. prioritising equitable access and convenience, 4. focus on managing children's testing experiences, 5. potential psychological impacts of islet autoimmunity on children, 6. caregivers' perceived coping ability and associated responses to screening and monitoring and 7. importance of relationships with and support from healthcare professionals. Participants expressed benefits, concerns and considerations necessary for the well-organised, equitable and acceptable implementation of screening and monitoring. They described varying effects of testing and islet autoimmunity on families, emphasising the importance of trusted relationships between families and healthcare professionals. CONCLUSIONS:Healthcare professionals' insights can guide how screening and monitoring programmes are designed and implemented, particularly in justifying their introduction, ensuring equitable care and reducing adverse impacts on families. Further research will focus on the experiences of children and caregivers to integrate wider input into the design of these programmes.
AIMS:To examine sex-based differences in estimated glomerular filtration rate (eGFR) trajectories for people with type 1 diabetes (T1D) over 10 years and to test the hypothesis that sex and ethnicity interaction predicts eGFR decline. METHODS:A cohort of 1495 individuals, 48% men (81% White, 12% African-Caribbean and 7% Other) and baseline eGFR ≥45 mL/min/1.73 m2 was analysed. Group-based trajectory modelling (GBTM) was used to identify eGFR sex-specific trajectories, and linear mixed models were used to evaluate the role of sex and ethnicity interaction in predicting eGFR heterogeneity. RESULTS:Five eGFR trajectories were identified in both women and men. Rapid decline (>3 mL/min/1.73 m2/year) occurred in 5.75% of women and 10% of men. Among women, the group included 12.3% of the African-Caribbean and 4.8% of the White; among men, it included 24.3% of the African-Caribbean, 22.2% of the Asian and 8.3% of the White. Mild/Stable decline was observed in 16% of women and 27% of men. Mean eGFR was lower by (-20 [95% CI -25, -15] mL/min/1.73 m2/year) in African-Caribbean women and (-15 [-21, -9]) in men, compared to White women and men respectively. The lowest eGFR sex gap observed in African-Caribbeans, and the highest in 'Other'. CONCLUSIONS:Interactions between sex and ethnicity may determine the heterogeneity in kidney function decline.
INTRODUCTION:Older adults with diabetes have an increased risk of falls due to neuropathy, impaired bone health and cardiovascular disease, resulting in significant morbidity and mortality. Conventional fall-prevention programmes primarily target strength and balance, while cognitive-motor integration, essential for safe mobility in complex environments, is often overlooked. Multicomponent exercise combining physical and cognitive training may therefore provide additional benefits in this population. METHODS:The DiaActive trial is a single-centre, stratified, parallel-group randomized controlled trial including adults aged ≥65 years with type 1 or type 2 diabetes. After comprehensive baseline assessments, 440 participants (220 with type 1 diabetes and 220 with type 2 diabetes) with low-to-moderate fall risk are randomized 1:1 within diabetes type to a 26-week cognitive-motor multicomponent exercise intervention (RYMA) or usual care. The intervention includes two weekly supervised sessions combining rhythm-based motor training with activities-of-daily-living-focused strength and balance exercises. RESULTS:The primary outcome is fall rate during the intervention, assessed using weekly fall calendars. Secondary outcomes include balance performance, fall-related outcomes, bone mineral density, fractures, neuropathy progression, cardiovascular risk markers, muscle strength and cognitive function. Follow-up continues to 104 weeks, with registry-based outcomes assessed at 5 years. CONCLUSION:The trial is approved by the North Denmark Region Ethics Committee (N-20240025). Written informed consent will be obtained. Results will be disseminated through peer-reviewed publications, conferences and stakeholder engagement.
AIMS:Islet transplantation offers the potential of a cure for type 1 diabetes (T1D), but the limited availability of human donor islets means that this therapy is currently only available to a small group of people with T1D who have intractable hypoglycaemia. The shortage of donor human islets has driven extensive research efforts to generate human islets from pluripotent stem cells (SC-islets), and current protocols are producing SC-islets which are showing promising results in early clinical trials. As part of our T1D Grand Challenge research programme, we set up a Patient and Public Involvement (PPI) Steering Group with a diverse range of members with lived experience of T1D to interact with us and provide advice. The aim of this study was to explore how perceptions of human islet transplantation differ between people with lived experience of T1D and diabetes researchers. METHODS:To determine how perceptions of human islet transplantation may differ between people with lived experience of T1D and researchers, two islet transplant recipients recounted their experiences to members of the PPI group and the science researchers. RESULTS:We subsequently asked both groups for individual, anonymised responses to the presentations, and we here present an analysis of that survey. CONCLUSIONS:Overall, this exercise highlights different approaches to islet/SC-islet transplantation between people with lived experience of T1D and basic science diabetes researchers. This emphasises the continued need for open lines of communication between the two groups so each can benefit from the other's experience.
AIM:Physical activity (PA) is recommended during pregnancy for its health benefits. While general PA guidance exists for uncomplicated pregnancies, evidence specific to women with pre-existing type 1 diabetes or type 2 diabetes (T1D; T2D) is limited. This scoping review synthesised available evidence regarding PA during pregnancy among women with pre-existing diabetes to identify evidence gaps and inform future research. METHODS:Systematic searches of MEDLINE, Embase, Web of Science, Scopus, CINAHL, and SportDiscus were conducted. Studies were eligible if they reported PA participation, evaluated PA interventions, or explored PA-related experiences in pregnant women with T1D or T2D. Two reviewers independently screened titles, abstracts, and full texts. Data were extracted and synthesised narratively according to study design, PA measurement methods, and reported associations with diabetes or pregnancy outcomes. RESULTS:Twenty-three studies were included. Overall, the literature reports that PA levels among women with pre-existing diabetes are typically below recommended levels and decline across pregnancy. Qualitative studies identified barriers to PA, including physical discomfort, fear of glycaemic instability, and inadequate social support. Methodological limitations were common, including reliance on self-reported PA, frequent aggregation of different diabetes types, a lack of longitudinal study designs, and scarce integration of objective PA measurement with glucose monitoring. Additionally, qualitative studies rarely focused on PA behaviours and experiences, and no studies explored the experiences of healthcare professionals supporting these women. CONCLUSION:Evidence on PA during pregnancy in women with pre-existing diabetes remains sparse and methodologically limited. Future research should prioritise longitudinal designs, objective PA measures alongside contemporaneous glucose monitoring, and incorporate qualitative research focused on barriers and facilitators to PA.
AIMS:Telemonitoring in type 2 diabetes (T2D) care has demonstrated positive trends in terms of glycaemic control. However, evidence regarding its impact on patient-reported outcomes, such as general and diabetes-specific quality of life (QoL), remains inconclusive. In particular, the effect of telemonitoring in people with insulin-treated T2D is underexplored. This study aimed to evaluate the effect of telemonitoring on general and diabetes-specific QoL compared with usual care in people with insulin-treated T2D. METHODS:Participants were randomised (1:1) to telemonitoring or usual care for 3 months. The primary outcomes were changes in the Short Form-12 Health Survey (SF-12) and the DAWN2 Impact of Diabetes Profile (DIDP). Telemonitoring included a continuous glucose monitor (CGM), a connected insulin pen, and an activity tracker. Data were monitored by hospital staff, who also provided regular telephone support. Usual care comprised a blinded connected insulin pen and a blinded CGM during the first and final 20 days, but their data were not monitored. ANCOVA compared groups for normally distributed data, with baseline scores as covariates. The Mann-Whitney U test was applied for non-normally distributed outcomes. RESULTS:A total of 331 participants were included (telemonitoring: n = 166; usual care: n = 165). No significant between-group differences were found in SF-12 scores for neither the physical (p = 0.102) nor mental component summary score (p = 0.566). The telemonitoring group showed a statistically significant improvement in DIDP compared with usual care (p = 0.015). CONCLUSIONS:Telemonitoring had no effect on general QoL but led to a statistically significant improvement in diabetes-specific QoL.
AIMS:To evaluate the performance of conventional adherence assessment methods against objective chemical adherence testing (CAT) in people with type 2 diabetes. METHODS:In this prospective cohort study, 90 participants with type 2 diabetes attending primary care were assessed using CAT (n = 49), medication possession ratio (MPR; n = 60) and Hill-Bone Medication Adherence Scale (HBMAS; n = 58). Associations with HbA1c and blood pressure (BP) were assessed, and within-person diagnostic performance was evaluated in 21 participants with all three measures. RESULTS:Only CAT-defined non-adherence was associated with significantly higher HbA1c, while CAT and MPR showed a significant association with diastolic BP. Within-person analysis suggested poor sensitivity for both MPR (16.7%; 95% CI 4.7-44.8) and HBMAS (66.7%; 95% CI 39.1-86.2), although HBMAS demonstrated very low specificity (11.1%; 95% CI 2.0-43.5) compared with CAT. CONCLUSIONS:Conventional adherence methods are low-sensitivity diagnostic tests, and CAT offers improved diagnosis of non-adherence in people with type 2 diabetes.
BACKGROUND:Type 1 diabetes (T1D) is a common disease. Although genome-wide association studies (GWASs) have identified hundreds of associated single nucleotide polymorphisms (SNPs), very few T1D GWAS have simultaneously addressed both Asian and European populations. METHODS:Here, we conducted a large-scale trans-ancestry meta-analysis including 680,539 European individuals (12,525 T1D cases and 668,014 controls) and 133,251 Asian individuals (1,219 T1D cases and 132,032 controls) to identify genetic associations with T1D. Subsequently, fine-mapping and Summary-data-based Mendelian randomization (SMR) analyses were performed to further refine T1D-related genetic signals. RESULTS:We identified 27 T1D-associated loci, including 8 potentially novel loci (near CDKAL1, NRSN1, FAM65B, LRRC16A, TULP1, SLC17A3, LRIG2, C6orf1). Fine-mapping was performed and helped pinpoint 7 putative causal variants (posterior probability, PP > 0.95) with T1D. Among them, rs9366622 (PP = 0.976) and rs1165190 (PP = 0.996) are located near LRRC16A and SLC17A3, respectively. These two variants are the lead SNPs of identified novel loci. SMR analysis identified a putative risk gene (U91328.19) at the novel locus SLC17A3-rs1165190, whose expression level is causally associated with T1D. CONCLUSIONS:These findings suggest that, for T1D, increasing ancestral diversity in genetic studies helps identify core genes and provides new insights into pathogenesis.
AIMS:To conduct a scoping review of the application of ecological momentary assessment (EMA) in adolescents with type 1 diabetes (T1DM), providing references for future research and practice in this field. METHODS:This review followed the JBI scoping review methodology framework and systematically searched 10 databases, including CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, Cochrane Library, EMbase, PsycINFO and CINAHL, from the establishment of the databases to 29 September 2025. The included literature was summarised and analysed. RESULTS:Sixteen studies were included. EMA was used to investigate self-management, glycaemic control, psychosocial factors and cognitive function in adolescents with T1DM. Key findings revealed dynamic, real-time associations: self-management behaviours showed time- and context-dependent effects on glycaemic control (e.g. higher risk of omissions in mornings or social situations); affect and glucose levels exhibited bidirectional interactions, with negative affect impairing and positive affect improving glycaemic stability; social environment (peer and family support) and cognitive function (e.g. executive function) significantly moderated management outcomes. Most identified associations were within-person and contemporaneous; few studies examined between-person differences or time-lagged predictive effects. EMA demonstrated acceptable feasibility across diverse protocols. However, considerable methodological heterogeneity existed across studies, and most evidence was limited to Western populations. CONCLUSION:EMA is a feasible method for managing type 1 diabetes in adolescents and is capable of capturing real-time, dynamic associations among behaviour, affect, social context and glycaemic control. Future research should prioritise methodological standardisation, develop culturally adapted assessment tools and explore real-time intervention strategies to enable precise and personalised diabetes management. From a clinical perspective, EMA can guide individualised care by identifying high-risk time windows (e.g. mornings), social contexts (e.g. peer dining) and emotional triggers (e.g. negative affect), supporting targeted patient education, just-in-time behavioural reminders and collaborative mental health interventions.
PURPOSE:The COVID-19 pandemic disrupted primary care delivery and may have exacerbated disparities in chronic disease management, particularly for diabetes mellitus. This study sought to investigate how living in areas with low access to primary care providers (PCP) affected the delivery of diabetes care during the pandemic. METHODS:This is a retrospective longitudinal study using the Panel 24 of the Medical Expenditure Panel Survey data merged with the 2019 County Health Rankings data to classify areas by PCP availability (low vs. high). Dependent variables included measures of care processes (e.g., number of HbA1c tests), quality (e.g., diet modification) and outcomes (e.g., eye complications). Multivariable models were adjusted for demographics, insurance status and COVID-19 diagnosis. FINDINGS:HbA1c testing, foot examinations and retinal examinations decreased during the pandemic for both groups, with much more pronounced declines in low PCP density areas. The largest change occurred in the frequency of attending group classes, dropping nearly 80% in low PCP areas. Individuals in low PCP areas were more likely to initiate oral diabetes medications (as opposed to insulin) compared with those in high PCP areas (0.84% vs. 0.28%, p = 0.015). Older age was associated with new diabetes (HR = 1.05) and new kidney disease (HR = 1.04), but less likely to start diet modification (HR = 0.99). Being female (HR = 0.69) and non-Hispanic whites (HR = 0.60) were associated with a lower likelihood of diabetes incidents. CONCLUSIONS:These findings highlight the importance of preparing public health responses for future events that limit access to routine care, particularly for individuals with or at risk of diabetes. Strengthening both in-person and virtual primary care services is critical to reducing gaps in chronic disease management and to supporting ongoing PCP follow-up.
AIMS:Type 2 diabetes (T2D) disproportionately affects African American adults in the United States, who experience higher complication rates and poorer outcomes. Social support is a key determinant of diabetes self-care, yet evidence in this population remains fragmented. This review aimed to synthesize evidence on the types, soucres and impact of social support on diabetes self-care behaviours among African American adults with T2D. METHODS:A systematic review was conducted following PRISMA guidelines and registered with PROSPERO (CRD420261284391). Four databases (PubMed, CINAHL, APA PsycINFO and Web of Science) were searched for studies published between January 2015 and December 2025. Eligible studies included African American adults (≥18 years) with T2D and examined at least one component of social support. Data extraction and quality appraisal using the Mixed Methods Appraisal Tool were performed by multiple reviewers. A convergent narrative synthesis approach was used to integrate qualitative, quantitative and mixed-methods findings due to substantial methodological heterogeneity. RESULTS:Eleven studies (four quantitative, six qualitative and one mixed methods) were included. Social support types included emotional, informational, instrumental, appraisal, spiritual and companionship support, delivered through family, peers, healthcare providers, community health workers and faith-based organizations. Overall, social support was associated with improved adherence to diet, physical activity, medication use and glucose monitoring. Peer-led and culturally tailored interventions were associated with enhanced engagement through shared identity, trust and accountability. Conversely, negative or controlling support was associated with poorer adherence and greater diabetes-related distress. CONCLUSIONS:Social support is a multifaceted and culturally embedded determinant of diabetes self-care among African American adults with T2D. Findings suggest that culturally relevant, autonomy-supportive and community-based interventions may strengthen self-management behaviours and help address persistent diabetes disparities.
