BMJ Open Diabetes Research & Care

Background: Digital diabetes programs have expanded quickly, but evidence of durable long-term benefit remains limited. In addition, as diabetes treatment guidelines changed to include cardiorenal-protective antihyperglycemics as first-line therapy, the effects of their adoption on glycemic control and program engagement within these programs remain poorly understood. Objective: To characterize longitudinal trends in glycemic control and estimate the extent to which these trends are associated with time-invariant and time-varying domains, among adults with T2D participating in Teladoc Health Remote Diabetes Monitoring Program (RDMP). Methods: This was a retrospective, longitudinal cohort study of adults with T2D participating in the Teladoc RDMP from 2021-2025. Domains were split into time-invariant (i.e. demographics and baseline clinical characteristic) and time-varying covariates (e.g. antihyperglycemic treatment complexity and adherence, program utilization and engagement, and adoption of cardiorenal protective antihyperglycemics). Primary outcome was estimated A1c (eA1c), calculated from FBG measurements captured through cellular-enable smart glucose meters. Longitudinal mixed-effects models were used to estimate adjusted annual trends in eA1c over 5 years, and Gelbach decomposition to quantify statistical contributions across domains. Secondary analyses examined attainment of eA1c <7% using GEE and complementary decomposition methods. Results: A total of 56,754 members with mean age 64.2 (SD 10.4), and 49% female were included in the analysis. Mean eA1c declined by 0.06 percentage points per year (95% CI, -0.06 to -0.06) and remained significantly lower after full adjustment for demographic, antihyperglycemic treatment and cardiorenal-protective therapy adherence, and program engagement factors ({beta}=-.04 percentage points/year; 95% CI, -.04 to -.03), demonstrating durable glycemic improvement over the five-year study period. Gelbach decomposition attributed most of the change between the base and fully adjusted trends to cardiorenal-protective therapies (170.8%), with an opposing contribution from program engagement (-71.9%) and minimal contribution from treatment history and complexity (1.1%). Adjusted odds of attaining eA1c <7% increased 8.0% annually (OR 1.08; 95% CI 1.07-1.09), corresponding to a 1.21-percentage-point annual increase in probability; adjusted predicted glycemic control increased from 75.2% in 2021 to 80.1% in 2025. Conclusion: In this five-year cohort, members who remained in the RDMP sustained improvements in eA1c and became more likely to reach an eA1c < 7%. Cardiorenal protective antihyperglycemics made the largest measured contribution to these trends, while program engagement contributed in the opposite direction. These findings show durable glycemic control but does not establish causal effects. Future evaluations of digital diabetes programs should account for pharmacotherapy, durability of improvements, and measure outcomes across cardiometabolic health.

IntroductionCurrent evidence suggests that patient health passports may improve care for patients with chronic illnesses. This systematic review aimed to evaluate the impact of patient health passports on health outcomes in adults with diabetes. MethodsA systematic review was conducted in February 2025 following PRISMA 2020 guidelines, using Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, Web of Science, and Scopus. The review included studies of adult diabetic patients using paper or digital patient health passport as part of their care in comparison with the standard of care. Data were analysed using meta-analysis and a thematic analysis where appropriate; otherwise, the data are presented narratively. Quality appraisal was undertaken using the Cochrane Collaboration tool for assessing risk of bias and Evidence-based librarianship checklist. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. ResultsEleven studies (n=14,350) were included. Seven studies were randomised controlled trials, two were retrospective in nature, one was a qualitative and one was a pre-post study. Overall, the studies are limited in design, resulting in high or unclear risk of bias across multiple domains. Results of the meta-analysis of five studies showed a statistically significant mean difference reduction in HbA1c and total cholesterol in favour of the intervention group; however, the certainty of the evidence is low or very low. The narrative analysis of the data revealed little to no improvement in body mass index, blood pressure, blood glucose, and cholesterol levels. Patients opinions and perceptions revealed some benefits in usability, perceived value, and in enhancing collaboration. ConclusionThis review provides evidence suggesting that patient health passports may improve patient care and can inform the design of future high-quality studies. However, the low certainty of the evidence highlights the need for high-quality studies with larger sample sizes. Key PointsO_LIPatient health passports show promise in enhancing diabetes management, however current evidence is limited by high risk of bias; future high-quality studies are required to confirm efficacy. C_LIO_LINurses are pivotal in this process as they play a central role in diabetes education, self-management support and continuity of care. C_LIO_LIPatient health passports could be considered as a structured tool to facilitate ongoing monitoring, reinforce adherence, enhance communication between patient and nurses/multidisciplinary team. C_LI

BackgroundContinuous glucose monitoring-derived time in range (TIR; glucose 70-180 mg/dL) has emerged as a complementary glycemic metric, but its association with DKD (Diabetic Kidney Disease) has not been systematically quantified. We aimed to synthesize the evidence on the association between CGM-derived TIR and DKD in adults with type 1 or type 2 diabetes by conducting a systematic review and meta-analysis of the current evidence. MethodsThis systematic review and meta-analysis adhered to PRISMA guidelines. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched through March, 2026. Eligible studies were studies in adults with type 1 and type 2 diabetes that reported an association between CGM-derived TIR and any DKD outcome (albuminuria, eGFR decline, or composite nephropathy) with a quantifiable per-unit effect estimate. Random-effects meta-analysis (REML with Knapp-Hartung adjustment) pooled odds ratios per 10% TIR increment. Risk of bias was assessed using ROBINS-E and certainty of evidence using the GRADE framework. PROSPERO: CRD420261377763. ResultsEleven studies (n = 7,182; seven T2D, four T1D; ten cross-sectional, one retrospective cohort) were included. The pooled OR per 10% TIR was 0.89 (95% CI 0.84-0.95; P = 0.002; I{superscript 2} = 69.6%), and every leave-one-out iteration preserved significance (OR range 0.88-0.91; all P [&le;] 0.005). In the four studies adjusting for HbA1c, the association persisted (OR 0.91, 0.86-0.97; P = 0.015) with no detectable residual heterogeneity (I{superscript 2} = 0%), indicating the signal is not fully attributable to average glycemia. ConclusionsHigher CGM-derived TIR may be associated with lower odds of DKD (OR 0.89 per 10% increment). The HbA1c-adjusted subgroup (k = 4; I{superscript 2} = 0%) provided the most internally consistent signal, though its small size limits inference. Prospective studies with standardized CGM protocols and pre-specified hard kidney endpoints are needed to establish causality.

Background: Cardio-kidney-metabolic (CKM) diseases share risk factors, but their shared and distinct risk factors for disease progression remain unclear. We examined whether classical risk factors predict baseline CKM indicators and their longitudinal changes in a population-based German National Cohort (NAKO) sample. Methods: In 2,650 NAKO-IMMEDIATE participants selected for deep-phenotyping, baseline values and 5-year changes in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), pulse wave velocity (PWV), and estimated glomerular filtration rate (eGFR) were linearly regressed on age, sex, education, alcohol and tobacco consumption, body mass index (BMI), and residuals of BMI-adjusted waist circumference (WC) with mutual adjustment. Results: Baseline values for HbA1c were 34.6{+/-}5.8 mmol/mol, for PWV 8.3{+/-}1.5 m/s, for SBP 128.0{+/-}15.7 mmHg and for eGFR 96.0{+/-}14.6 ml/min/1.73 m2. Cross-sectionally, all risk factors were associated with one or more of the CKM indicators, with age and BMI being associated with all four indicators. Over 5 years, HbA1c (1.2{+/-}4.2 mmol/mol), PWV (0.5{+/-}1.2 m/s) and SBP (0.6{+/-}14.2 mmHg) increased, whereas eGFR (-2.3{+/-}9.5 ml/min/1.73 m2) decreased. Age (0.03 m/s per 5 year, 95% CI 0.01, 0.06 m/s) was associated with higher and BMI (-0.02 m/s per 1kg/m2, -0.03, -0.01) with lower PWV changes. No other risk factors were associated with CKM indicator changes. Conclusion: Classical risk factors were more frequently related to baseline CKM indicators than to their 5-year changes. Within longitudinal analyses, only age and BMI were related to PWV 5-year changes. Keywords: Cardio-kidney-metabolic function, risk factors, longitudinal studies

Aims: To understand how users believe continuous glucose monitoring (CGM) changes their behaviour, which app features they credit, and whether endorsing more mechanisms of action (MoAs) is linked to reported diet and physical activity change. Methods: We surveyed 112 U.S. adults with type 1 or type 2 diabetes who had used a Dexcom or Abbott Libre CGM within 12 months. Participants rated 26 MoA statements mapped to the Capability, Opportunity, Motivation-Behaviour (COM-B) model, identified contributing app features, and reported CGM-attributed diet and physical activity change. Logistic regression examined MoA count and COM-B domains as predictors of behaviour change. Results: Participants (mean age 54.5 years; 60.7% female) reported dietary (82.1%) and physical activity (46.4%) change and endorsed a median of 18 MoAs, most often relating to knowledge, skills and behavioural consequences. Real-time glucose and graphs were attributed to many MoAs. Each additional MoA was associated with higher odds of dietary (OR 1.27, 95% CI 1.15-1.44) and physical activity change (OR 1.27, 95% CI 1.16-1.43). Motivation made the strongest distinct contribution among COM-B domains. Conclusions: Users perceive CGM as engaging many behavioural mechanisms; endorsing more was linked to behaviour change. Motivation may be a key target for CGM-based behavioural support.

BackgroundStructured cognitive screening in diabetes is recommended only from age 65, leaving younger adults with prolonged type 2 diabetes mellitus (T2DM) exposure unmonitored. We quantified the association of HbA1c and diabetes duration with Montreal Cognitive Assessment (MoCA) screen-positive status in adults aged [&le;] 60 years with T2DM of [&ge;] 5 years, and examined against matched controls how the MoCA cutoff (< 26, < 24, < 23) affects the group contrast in a lower-education population. MethodsCross-sectional study at a tertiary-care centre in North India: 110 adults with T2DM and 50 controls frequency-matched for age, sex, and education. Within diabetics, HbA1c and duration were modelled continuously by modified Poisson regression at each pre-specified cutoff and by Spearman correlation with MoCA total score. Prevalence ratios (PR) for diabetics versus controls at each cutoff were adjusted for age, sex, education, BMI, and hypertension. ResultsWithin diabetics, MoCA total score correlated with HbA1c ({rho} = -0.456) and duration ({rho} = -0.318; both p < 0.001). Screen-positive prevalence rose 5% per 1% HbA1c at < 26 (PR 1.05, 95% CI 1.02-1.09), 12% at < 24 (PR 1.12, 1.06-1.18), and 17% at < 23 (PR 1.17, 1.09-1.26), and 11% per year of duration at < 23 (PR 1.11, 1.06-1.17). Median education was 10 and 9 years; 76.0% of controls screened positive at < 26, and the diabetes association was cutoff-dependent: adjusted PR 1.08 (0.89-1.29) at < 26, 1.70 (1.10-2.63) at < 24, and 6.72 (2.23-20.23) at < 23, where 44.5% of diabetics versus 6.0% of controls screened positive (absolute difference 38.5 percentage points, 95% CI 25.0 to 48.7). ConclusionsIn working-age adults with long-standing T2DM, screen-positive prevalence rose continuously with HbA1c at every cutoff, a glycaemic signal independent of threshold choice. The standard < 26 cutoff flagged over three-quarters of both groups and could not triage; < 23 separated diabetics from controls. Screen-positive status is not a diagnosis; MoCA triage at a population-appropriate cutoff in this group warrants prospective validation against a neuropsychological reference standard.

Objectives. To evaluate the impact of reimbursement restrictions for glucagon-like peptide-1 receptor agonists (GLP-1RAs) for type 2 diabetes, introduced in Denmark in November 2024, on injectable semaglutide (Ozempic) utilization patterns and subsequent HbA1c changes among discontinuers. Design. Nationwide registry-based cohort study. Setting. Denmark. Participants. Adults treated with injectable semaglutide for diabetes (January 2018 to December 2025). Main outcome measures. We described temporal patterns in injectable semaglutide use before and after the policy change. Among semaglutide continuers after the policy change, we assessed whether continuation met a key criterion in the new policy: non-feasibility of sodium-glucose cotransporter 2 inhibitor use and high cardiovascular risk. We characterized semaglutide discontinuers around the policy implementation (March 2024 to November 2024) and subsequent treatment switches. Among discontinuers, we evaluated HbA1c changes and performed interrupted time series (ITS) analyses. Results. Following the policy change, use of injectable semaglutide declined modestly before subsequently increasing. Among 61,120 individuals classified as semaglutide continuers, 27,143 (44%) were already using an SGLT2i. Of the remaining 33,977 (56%), only 1,862 (5.5%) met a key reimbursement criterion (i.e., non-feasibility of SGLT2i use and high cardiovascular risk). Among 79,305 individuals with a semaglutide fill between March 2024 and November 2024, 22,096 (28%) were classified as discontinuers. Within six months, ~40% of discontinuers switched to other glucose-lowering therapies, most commonly SGLT2is (24%). 37% of discontinuers later reinitiated semaglutide. Among individuals with an on-treatment HbA1c measurement (within 12 months before their last semaglutide fill) and an off-treatment HbA1c measurement (6-12 months after their last semaglutide fill) (n=13,017), mean HbA1c increased from 49 to 57 mmol/mol (mean change +7.4 mmol/mol, 95% CI 7.2-7.6). ITS analysis showed that HbA1c increased by 5.9 mmol/mol (95% CI 5.1-6.7) at six months post-discontinuation, which attenuated to 3.1 mmol/mol (95% CI 2.2-4.1) at 12 months; raw monthly means (not included in the ITS model) suggested this persisted through 18 months. Conclusions. Following the policy change, population-level use of injectable semaglutide declined modestly before increasing again. Most discontinuers did not initiate another glucose-lowering therapy and experienced an increase in HbA1c that did not fully return to pre-discontinuation levels during follow-up.

Glycemic control is key to prevention of complications of diabetes. Although eosinophils have been implicated in metabolic regulation, most human studies have been cross-sectional and have yielded inconsistent findings. We conducted a retrospective cohort study of adults with uncontrolled diabetes receiving primary care at Mass General Brigham. We evaluated the relationship between eosinophil count and HbA1c over one year, adjusting for demographic, socioeconomic, and clinical covariates. Among 21,447 patients included in the study, eosinophil count increased by a mean of 2.6 cells/L (SD 157.2 cells/L) and HbA1c decreased by a mean of 0.82% (SD 2.09%) during follow-up. Increases in eosinophil count were associated with reductions in HbA1c (parameter estimate -0.366 per 1,000 cells/L; 95% CI -0.526 to -0.206; P < 0.001), whereas baseline eosinophil count was not significantly associated with HbA1c changes. The association remained significant in a sensitivity analysis excluding systemic glucocorticoid users. Increases in eosinophil count were associated with improved glycemic control in adults with diabetes, whereas baseline eosinophil count was not. These findings extend prior cross-sectional observations and suggest that changes in eosinophils may represent a biomarker of glycemic improvement. Further prospective studies are needed to determine whether this relationship reflects underlying immune-metabolic mechanisms or treatment-related changes.

Objective: To estimate how often remission of type 2 diabetes is recorded in routine care, how long it lasts, and what ends it, separating a return of hyperglycemia from a restart of treatment. Research design and methods: We studied 136,781 adults aged 18 years or older with laboratory confirmed type 2 diabetes in the Protege linked electronic health record (EHR) and claims database. The 96,817 adults with glucose-lowering treatment recorded at or before cohort entry formed the primary (previously treated) cohort; 39,964 adults with no treatment recorded at entry were analyzed in parallel. Remission required two HbA1c values <6.5%, 90 to 365 days apart, the first at least 3 months after all glucose-lowering drugs were discontinued, with no therapy recorded between them. After remission we followed glycemic relapse (HbA1c over 6.5%) and treatment restart (a new outpatient prescription or dispensed fill) separately, with death as a competing event (Aalen Johansen). Results: Remission was documented in 4.33% of previously treated adults cohort and 15.57% in the cohort of untreated adults at entry. Five-year cumulative incidence (Aalen Johansen) was 3.82% (95% CI 3.69 ;3.93) and 13.27% (12.90;13.59) in each cohort, respectively. Remission was less common with greater baseline treatment burden: exploratory adjusted 5-year incidence was 4.65% in adults with 1 glucose-lowering class with a treatment episode recorded at or before entry, 3.62% with two, 2.69% with three, and 2.02% with four or more such drugs.. The Median Kaplan Meier duration of first remission was 226 days (IQR 93 to 855) in previously treated adults and 371 days (166 to 1,027) in adults untreated at entry; 37.9% (treated cohort) and 23.1% (untreated cohort) of episodes had ended by 152 days. Among remission episodes that had ended, median duration was 159 days (71 to 362) and 265 days (129 to 565) for the treated and untreated at entry cohort, respectively. Within 5 years of remission in previously treated adults, the first event ending remission was glycemic relapse in 31.94%, treatment restart in 47.83%, and death in 4.65%.Treatment restart was about 1.5 times as common as glycemic relapse as the first event ending remission. A second remission followed within 5 years in 19.53% of previously treated and 24.10% of untreated remitters. Conclusions: Recorded remission was uncommon and short-lived, and it ended more often with a treatment restart than with a rise in HbA1c. Studies of remission in real-world data should report relapse and restart separately and state how they confirm remission and establish that treatment stopped.

Background: Hypertension (HTN) and Type 2 diabetes mellitus (T2DM) are leading drivers of the global cardiometabolic disease burden and major contributors to preventable morbidity and mortality. In Hong Kong, where population ageing and lifestyle-related risk factors are increasingly prevalent, both conditions and their complications pose substantial challenges to the healthcare system. Although territory-wide prevalence figures are available, small area district-level evidence on the burden of these diseases and their associated complications remains limited. Disparities are likely due to heterogeneity in demographic composition, socioeconomic status, and primary care accessibility across Hong Kong's eighteen administrative districts. There is also a lack of accessible, age-adjusted, district-level disease visualization in Hong Kong. Objectives: This study estimates the age-standardized prevalence rates (ASPR) of HTN, T2DM, and their associated complications across the eighteen districts of Hong Kong, formally evaluate the statistical significance of inter-district disparities, and rank the districts according to disease burden to inform place-based health planning. Methods: This study analyzed the prevalence of chronic diseases from 2014 to 2023 in 18 districts among an adult cohort aged equal or above 35 years using data collected from the Hong Kong Hospital Authority (HA) electronic health records, using the International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes, the International Classification of Primary Care (ICPC) codes, and the disease flags to identify diseases. Sample weights are used to reflect the total population. HTN, T2DM, and their major complications were identified according to standardized diagnostic criteria. ASPR were calculated for each district with the WHO World Standard Population as the standard. Inter-district disparities in disease prevalence were assessed using Cochran's Q test, with statistical significance set at P <0.05. The slope index of inequality (SII) was also used to analyze the socioeconomic inequality between districts. Districts were subsequently ranked according to their ASPR for each condition to identify high-burden and low-burden areas. Results: 1,756,521 patients (52.71% females) contribute 9,906,729 patient-years from 2014 to 2023. Substantial inter-district variation and increasing trend were observed in the ASPR of HTN, T2DM, and their complications. The weighted ASPR of HTN varied by 27.3% from 46,701 (95% CI: 45,691-47,711) per 100,000 population in Tsuen Wan district to 59,445 (95% CI: 58,759-60,130) per 100,000 population in Yuen Long district, and the weighted ASPR of T2DM ranged from 20,464 (Tsuen Wan, 95% CI: 19,803-21,124) per 100,000 population to 28,275 (Yuen Long, 95% CI: 27,792-28,758) per 100,000 population across the districts in 2023. All diseases showed district disparities (all P <0.05). Cochran's Q test demonstrated statistically significant disparities across districts and showed no convergence through the period. The SII test also showed the most serious inequality exists in HTN, with the lower socioeconomic position districts have more burden. Conclusion: Significant geographic disparities exist in the prevalence of HTN, T2DM, and their complications across Hong Kong's eighteen districts. These findings highlight the need for district-specific public health strategies, equitable allocation of primary care resources, and targeted chronic disease prevention and management programs in high-burden areas.

Abstract Continuous glucose monitoring (CGM) is recommended for type 1 diabetes, but the supporting evidence derives almost entirely from high-income settings, and the technology is not routinely available in Kenya's public sector. This prospective study assessed the feasibility and sustainability of CGM implementation and changes in glycemic control after three months of use in a public-sector pediatric diabetes clinic in Nairobi. Forty patients aged 4 to 25 years, recruited by proportional quota sampling across age bands at Kenyatta National Hospital, used an intermittently scanned sensor system across five visits combining sensor data review, standardized diabetes education and insulin titration. Glycated hemoglobin (HbA1c) was measured at baseline and three months, alongside sensor-derived glucose metrics, wear time and diabetes-related admissions. Thirty-eight patients (95%) completed the study; median sensor wear time was 89.0%. Adjusted mean HbA1c fell from 10.82% to 9.42%, a difference of minus 1.40 percentage points (95% confidence interval minus 2.07 to minus 0.68). Time in target range (3.9 to 10.0 mmol/L) rose from 32.4% to 38.0%, and time above 10.0 mmol/L fell from 63.1% to 56.9%. Time below 3.9 mmol/L rose minimally, from 3.7% to 4.2%, while time below 3.0 mmol/L did not increase significantly, by 0.2%. Diabetes-related admissions fell from 7 of 40 in the three months before the study to 1 of 38 by its end. The uncontrolled design and small sample preclude an unbiased effect estimate. Since CGM efficacy is established internationally, these data add local evidence of transferability, which national guidelines and benefit-package decisions require.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have rapidly expanded from primarily glucose-lowering agents for type 2 diabetes (T2D) to therapies used across diabetes, obesity, and cardiometabolic disease. Prescribing has risen sharply since 2018, especially with the broader uptake of semaglutide-based products. Still, real-world initiation patterns remain incompletely characterized in older adults with varying levels of cognitive vulnerability and frailty. Methods: We analyzed treatment patterns of GLP-1RA use in a retrospective cohort of adults aged >=65 years with T2D in a regional healthcare system from 2018 to 2026. We describe the demographic and clinical characteristics of new initiators of GLP-1RAs compared with initiators of alternative therapies, including sodium-glucose cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i). We analyzed a sub-cohort of patients to identify the prevalence of baseline cognitive concerns using a large language model (LLM). We used a LASSO logistic regression to identify important predictors of GLP-1RA initiation compared to other therapies. Results: Of 58,754 adults aged 65 years or older with T2D, 5,095 initiated GLP-1RA, 5,483 initiated a SGLT2 inhibitor, and 1,516 initiated a DPP-4 inhibitor. GLP-1RA initiators were younger (mean 75.2 [SD 4.9] vs 77.7 [6.0] and 79.5 [7.1] years) and less often aged 80 years or older (17.7% vs 35.0% and 47.6%). The largest difference across groups was adiposity: mean BMI was 33.8 (6.2) vs 29.7 (5.7) and 28.6 (5.6) kg/m2 (SMD 0.592), with a BMI of 30 kg/m2 or higher in 72.1% vs 41.9% and 34.0%. Glycemic control was similar (mean HbA1c 7.46% vs 7.38% and 7.70%; SMD 0.165). GLP-1RA initiators were younger; more likely to be overweight; had lower average comorbidity index; and less dementia, heart failure, and renal disease than those initiating alternative therapies. GLP-1RA initiators had fewer hospitalizations 1-year prior to drug initiation. In a LASSO model, BMI greater than 27 kg/m2 was the strongest predictor of GLP-1RA initiation (positive), followed by baseline congestive heart failure (negative) and baseline hospitalization (negative). Conclusion: In this cohort of older adults, those with T2D who initiated GLP-1RAs were younger and had less comorbidities at baseline compared to initiators of other T2D therapies. Overweight BMI was the strongest predictor of GLP-1RAs initiation, whereas baseline HbA1c was similar across groups, suggesting that the decision to start GLP1-RA is more influenced by adiposity than glycemic control. Our analysis of real-world prescribing patterns appear to be in alignment with guidelines for Type II diabetes treatment1, which recommend GLP-1RA treatment for glucose lowering and weight management and SGLT2 treatment in those with risk of cardiovascular disease or heart failure.

Background & Aims: Dysglycemia is associated with increased risk for hepatic features, including steatosis and fibrosis. Yet, the associations of dynamic measures of glycemia with hepatic features among individuals without diabetes remain understudied. Methods: We included participants from the Framingham Heart Study (FHS) Third Generation cohorts without diabetes who underwent assessment for hepatic steatosis (controlled attenuation parameter [CAP]) and fibrosis (liver stiffness measurement ([LSM]), using vibration-controlled transient elastography, had [&ge;]3 days of continuous glucose monitor data (blinded Dexcom G6 Pro CGM) and completed a mixed meal tolerance test, containing a total of 600 kcal, 75 g carbohydrate, 21 g fat, and 29 g protein (MMTT, 2022-2025). We performed multivariable linear and logistic regression to investigate the associations of standardized 2-h postprandial glucose (2-h PPG) following MMTT, as well as CGM-derived measures, with CAP and log-transformed LSM, as well as hepatic steatosis (CAP[&ge;]274ndB/m) and fibrosis (LSM[&ge;]8.2 kPa), adjusting for confounders. Results: In 1071 FHS participants (58.3% female, 56.4% normoglycemia), mean age was 60.2 years and BMI 28.2 kg/m2. Higher 2-h MMTT-PPG and CGM summary measures of glycemic burden (e.g., % time >140 mg/dL) were associated with 23-36% higher odds of steatosis and higher CAP. Similarly, CGM summary measures of glycemic burden (e.g., % time >140 mg/dL) and glycemic variability (e.g., coefficient of variation) were associated with 28-59% higher odds of hepatic fibrosis but not log-LSM. Conclusion: Measures of postprandial and continuous glucose dynamics are associated with hepatic features among individuals without diabetes.

Type 1 diabetes mellitus (T1DM) remains a growing global health priority, with disproportionate underdiagnosis, delayed diagnosis, and mortality in sub-Saharan Africa. Despite the introduction of the Life for a Child (LFaC) programme in Kenya, which provides free insulin, glucose-monitoring supplies, and specialist education, no published studies have examined the determinants of glycaemic control among Kenyan children and adolescents with T1DM. This study aimed to determine the proportion of children and adolescents achieving good glycaemic control and to identify the socio-demographic and clinical determinants of glycaemic control at a tertiary hospital in Kenya. This cross-sectional study enrolled 160 children and adolescents with T1DM attending the paediatric diabetes clinic at Kenyatta National Hospital, Nairobi, between September 2025 and May 2026. Sociodemographic and clinical data were collected through structured interviews and physical examination. Poor glycaemic control was defined as HbA1c >7.5%. Associations between candidate determinants and glycaemic control were assessed using chi-square or Fisher's exact tests. Variables with p<0.2 on bivariate analysis were entered into a multivariable logistic regression model; Firth's penalized-likelihood method was used given the small number of participants achieving good control. Only 9 participants (5.6%) achieved the target HbA1c of [&le;]7.5% (mean HbA1c 11.02%, SD {+/-}2.29), and only 5 of 133 patients (3.8%) had [&ge;]70% of glucometer readings within the target blood glucose range (3.9-10.0 mmol/L).On bivariate analysis, household income (p=0.026) and self-monitored blood glucose (SMBG) frequency (p=0.018) were significantly associated with glycaemic control. In an exploratory multivariable regression analysis (Firth penalized logistic regression, given the small number of participants with good control), only SMBG frequency [&ge;]4 tests/day remained independently associated with lower odds of poor control (adjusted OR 0.19, 95% CI 0.04-0.84, p=0.028); the effect of household income was attenuated after adjustment. Glycaemic control remains markedly poor among children and adolescents with T1DM in this Kenyan tertiary hospital setting despite structured programmatic support. Frequency of self-monitoring, rather than household income alone, was the factor most strongly associated with glycaemic control, suggesting that strengthening access to glucose-testing supplies and supporting their consistent use should be prioritised in care, alongside attention to socioeconomic barriers. Longitudinal studies are needed to confirm these associations.

Objective: To measure adherence to a national inpatient hyperglycemia guideline at the level of its individual recommendations across a hospital network, to determine whether it changed after the guideline was issued, and to identify which recommendations track subsequent outcomes. Materials and Methods: Retrospective multicenter study of 48,354 admissions among 29,577 adults with diabetes or inpatient hyperglycemia at six Israeli general hospitals, August 2022 to December 2025. Each of 14 recommendations was formalized as a quality-assessment temporal pattern over knowledge-based temporal abstractions of the record, scored wherever it applied. Pre-post adherence was compared by Welch t-test with false discovery rate correction. Associations with 10 complications were estimated by bias-reduced logistic regression over 24-, 48-, and 72-hour windows, and by inverse probability of treatment weighting contrasting above- with at-or-below-median adherence. Results: Adherence ranged from near-universal admission and medication-management actions to substantial gaps in insulin management (means, 0.15-0.28). Overall adherence rose modestly after issue (0.682 to 0.703, P < .001), with marked inter-hospital heterogeneity. After weighting, above-median adherence carried 44% lower odds of 30-day mortality (odds ratio [OR], 0.557; 95% CI, 0.514-0.603), 82% lower odds of hyperglycemia (OR, 0.175) and 52% lower odds of severe hyperglycemia (OR, 0.485), against 20% higher odds of hypoglycemia (OR, 1.204). Discussion: The least-implemented recommendations were largely those whose adherence tracked outcomes: repeated insulin decisions spread across a stay, rather than discrete actions on admission. Conclusion: Guideline adherence can be assessed automatically and per-recommendation at national scale, identifying where fuller implementation would most plausibly matter. Keywords: inpatient diabetes; clinical guideline adherence; quality assessment; temporal abstraction; electronic health records; propensity score; causal inference

Objective: To estimate the impact of removing race-adjusted antihypertensive treatment recommendations for Black adults on health outcomes, healthcare utilization, and racial/ethnic disparities. Materials and methods: A discrete-time state-transition microsimulation model of hypertension natural history and health system utilization was developed to simulate lifetime trajectories among 100,000 non-Hispanic Black and non-Hispanic white 40-year-old adults. We evaluated the effect of removing race-adjusted antihypertensive treatment recommendations under two scenarios: one assuming racial heterogeneity in treatment effectiveness, reflecting evidence behind prior race-specific guidelines, and the other assuming no racial heterogeneity. Our main outcomes included life expectancy, cumulative incidence and duration of hypertension, and blood pressure control with antihypertensive treatment. Results: Under assumptions of heterogeneous treatment effectiveness by race, guidelines without race adjustment decreased life expectancy among non-Hispanic Black adults by 0.4 years, increasing the life expectancy gap with non-Hispanic white adults from 4.1 to 4.5 years. Hypertension control among non-Hispanic Black adults also worsened. Years with uncontrolled hypertension increased by 0.8 years, widening the disparity with non-Hispanic white adults from 1.7 to 2.5 years. Assuming no racial heterogeneity, these effects were diminished: life expectancy decreased by 0.1 years and years with uncontrolled hypertension increased by 0.2 years, less than one-half and one-quarter of the effects observed under assumptions of heterogeneous treatment effectiveness by race. Discussion: The potential effects of removing race-adjusted antihypertensive treatment guidelines depended on assumptions of racial heterogeneity in treatment effectiveness. Conclusion: Our findings highlight the importance of understanding drivers of previously observed racial differences when considering modifying antihypertensive treatment guidelines.

Aims: The risks of dementia, stroke, and mortality increase from normoglycemia to prediabetes and type 2 diabetes (T2D). Blood pressure variability (BPV) is associated with adverse vascular and neurological outcomes, but its role in glycemia-associated risks remains unclear. We examined the interplay between glycemia, BPV, and these outcomes. Methods and Results: In a large prospective cohort, visit-to-visit BPV was quantified using absolute and directional measures of systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse pressure (PP). Glycemic status was defined as normoglycemia, prediabetes, and T2D. Time-updated Cox models estimated outcome associations, adjusting for confounders and mean blood pressure. We evaluated the joint and independent associations of BPV and glycemic status with outcomes, effect modification, and attenuation of glycemia-associated risks after BPV adjustment. Among 57,611 participants (median follow-up, 5.1 years; IQR, 3.3-9.5 years), compared with normoglycemia and low BPV, T2D with high SBP variability was associated with higher risks of all-cause mortality (HR 2.80, 95% CI 2.12-3.69) and nominally higher risk of all-cause dementia (HR 2.46, 95% CI 1.37-4.42). All absolute BPV measures were independently associated with mortality, while DBP and MAP variability were associated with overall stroke after FDR correction. Additional adjustment for BPV minimally attenuated glycemia-associated risk, and no multiplicative interaction remained significant after multiple-testing correction. Conclusions: Absolute BPV was associated with mortality, and DBP and MAP variability with overall stroke, after accounting for glycemic status and mean blood pressure. Additional BPV adjustment changed the glycemic association only minimally.

Aims/Hypothesis: Atypical forms of diabetes often provide diagnostic challenges and are suboptimally treated. We sought to determine whether type 1 and 2 diabetes polygenic scores (PS) would help improve classification of islet autoantibody-negative (IAb-) atypical diabetes cases. Methods: We implemented type 1 diabetes PS (T1D PS) and type 2 diabetes PS (T2D PS) in 309 IAb- individuals' genome sequencing from the Rare and Atypical Diabetes Network (RADIANT), the largest and most comprehensively phenotyped collection of unsolved and atypical diabetes cases. We performed regression analyses to assess associations between PS, clinical characteristics, and glycemic measures. Results: Both T1D and T2D PS were significantly higher in RADIANT than in ancestry-matched controls from UK Biobank. Both PS were associated with C-peptide measures throughout participant oral glucose tolerance tests (OGTT), although in opposite directions; T1D PS was associated with lower C-peptide measures, while T2D PS was associated with higher measures. Participants with T1D PS above a previously established optimal PS value for differentiating cases and controls (T1D PS GRS2>12.88) had 13-fold higher odds of both insulin deficiency on OGTT and use of both basal and bolus insulin therapy. Conclusions/Interpretation: Individuals in RADIANT with ambiguous diabetes subtypes displayed genetic enrichment for both type 1 and type 2 diabetes, despite ascertainment to remove standard type 1 and type 2 diabetes. T1D PS identified individuals with an unrecognized "type 1 diabetes-like" phenotype with insulin deficiency and need for intensive insulin in the absence of islet autoantibodies. PS may help identify individuals with atypical diabetes who will ultimately benefit from insulin therapy.

Background: Nutrition education and physical activity support are important components of type 1 diabetes mellitus (T1DM) care, but their association with body composition outcomes in routine Ugandan diabetes services remains uncertain. We evaluated a culturally tailored health promotion programme among adolescents and young adults living with T1DM. Methods: We conducted a trial study in Wakiso Health Centre IV, Uganda. Sixty participants aged 13 to 26 years were allocated through an alternating clinic-week schedule to an intervention group or usual-care control group, with 30 participants per group. The eight-week Active Hearts, Healthy Lives programme combined nutrition education, personalised dietetic counselling, physical activity support, and practical self-management activities. Anthropometric and bioelectrical impedance measurements were obtained at baseline and six months after baseline. Separate linear regression models compared follow-up outcomes, adjusting for the corresponding baseline measurement, age, and sex. Results: Participants had a mean age of 19.45 years (SD 3.02), and 33 (55.0%) were female. Compared with controls, the intervention group had lower adjusted fat mass and BMI and higher fat-free mass and muscle mass. These differences reflected modest changes among intervention participants alongside increased fat mass and decreased fat-free mass and muscle mass among controls. Conclusion: Participation in the programme was associated with differences in estimated body composition at six months. Larger randomised evaluations incorporating clinical and functional outcomes are needed to establish whether the programme provides meaningful health benefits.

BCG is a well recognized old generic drug that can mold the human immune system through Immune Training. Broad basic science studies support Immune Training, but formal randomized placebo control trials are frequently lacking for confirmation of human benefits. Here we report on a randomized, double-blind, placebo-controlled phase 2 trial with up to 8 years of follow-up. The primary outcome was mean percent change from baseline in HbA1c. At year 5, HbA1c in the BCG group was reduced from baseline by 7.04% (P=0.0006) and at year 8 by 12.84% (P=0.0001), whereas HbA1c did not change from baseline in the placebo group at either time point. Longitudinal percentage changes in HbA1c from baseline using mixed model repeated measures analysis with a comparison of BCG versus Placebo arms was significant (p=0.0017). This shows durable long term improvements lowering of HbA1c only with BCG immunotherapy. Secondary outcomes were also significant. There was a statistically significant reduction in average insulin dose only in the BCG-treated group (P=0.024). Glycemic improvements occurred without recovery of C-peptide from negligible baseline levels, suggesting no pancreas contribution. Blood sugar values obtained from continuous glucose monitoring (CGM) similarly showed BCG immunotherapy lowers blood sugars compared to the Placebo arm (P=0.0189). CGM data also showed BCG immunotherapy resulted in an up to 183.7% improvement over baseline in time spent in normoglycemia (blood sugar in the normal range of 70-99 mg/dL) (P=0.0391). A sensitivity analysis confirmed BCG specific reductions in HbA1c were robust and durable at least to Year 08 (P<0.0001). BCG was safe. These finding support improved blood sugar control through immune training of metabolism without a contribution of the pancreas even after long standing T1D. Trial registration: NCT02081326.