If a person is in diabetes remission, even if only for a short time, this reduces the risk of later diabetes complications and lowers healthcare costs. A recent study shows that long-term remission of type 2 diabetes can be achieved through calorie restriction using total diet replacement. However, this intervention involves support through face-to-face meetings every 2 to 4 weeks over a 2-year period, which is not feasible in routine care with limited resources. Therefore, we have developed an eHealth programme to help patients achieve diabetes remission through calorie restriction in a cost-effective manner. Our primary hypothesis is that an eHealth programme will be non-inferior to face-to-face meetings in helping patients with type 2 diabetes achieve remission through caloric restriction. Our second hypothesis is that eHealth support will be more cost-effective than face-to-face support.

The eHealth DIabetes remission Trial is a multicentre, two-arm, non-inferiority, open-label, randomised controlled parallel group trial with blinded endpoint assessment conducted at two centres in Sweden. The study duration is 2 years. People with type 2 diabetes (≤6 years duration) use total diet replacement (approximately 900 kcal/day) with the aim of losing 15 kg and achieving diabetes remission. Participants are randomly assigned to either the eHealth support group or the face-to-face support group. The treatment programme to achieve and maintain weight loss is the same in both groups, but the method of support differs between the groups. The primary outcome is haemoglobin A1c (HbA1c) after 1 year. The secondary outcome is HbA1c at 6 months and 2 years. Other important secondary outcomes are diabetes remission rate, body weight and cost-effectiveness. The latter is assessed using the incremental cost per quality-adjusted life-years gained.

The study was approved by the Swedish Ethical Review Authority (Dnr 2022-02242-01, 2023-03707-02). The results will be published in peer-reviewed scientific journals and discussed at national and international conferences and with patient organisations.

ClinicalTrials.gov (NCT05491005).

IntroductionPrediabetes (PD), defined by impaired glucose tolerance or impaired fasting glucose, represents a growing global health challenge, with a prevalence projected to increase substantially. PD is a critical intervention target because of its high annual progression rate (5-10%) to type 2 diabetes mellitus (T2DM) and elevated cardiovascular disease (CVD) risk. Non-surgical interventions (NSIs), particularly lifestyle modifications (LMs) and pharmacological therapies, are the cornerstone of PD management, demonstrating efficacy and cost efficiency over surgical options. However, despite LM's ability to reduce T2DM incidence by 40-70% in trials such as the Diabetes Prevention Program, real-world implementation faces barriers, including resource intensity and complex delivery requirements, which increase upfront costs. We aim to review scientific literature reporting on the effectiveness and cost-effectiveness of NSIs for preventing the progression of PD to T2DM among adults.

A comprehensive systematic search will be conducted across major biomedical databases (PubMed, Scopus, Cochrane Library, Web of Science) for records published up to July 2024. We will include studies involving adults diagnosed with PD according to the American Diabetes Association (ADA) or WHO criteria, focusing on LM and pharmacological treatments. Observational and interventional study designs, including economic evaluations, will be considered.

diabetes incidence (ADA or WHO glycaemic criteria).

(1) CVD risk factors, (2) health utilities and (3) healthcare cost analyses. The protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines and is registered with PROSPERO (CRD42024561294). Data extraction and quality assessment will be performed by two reviewers, with discrepancies resolved by the consensus of a third reviewer. Data will be narratively synthesised; if the data allow, a meta-analysis will be conducted.

This systematic review was exempt from ethical approval as it involved no collection of individual patient data and posed no confidentiality risks. The findings will be shared via publication in a peer-reviewed journal or presentation at relevant conferences.

CRD42024561294.

Using the community-based participatory research (CBPR) methodology, sustained peer group treatment has effectively improved medication adherence. Although many studies investigate the effectiveness of peer group therapy, there is a lack of evidence addressing the cost-effectiveness of CBPR models in low- and middle-income countries. This protocol outlines the methods for the economic evaluation of the PArticipatory Research model for medicaTIon adherenCe In People with diAbetes and hyperTEnsion (PARTICIPATE) trial to determine whether the CBPR approach to enhance medication adherence among patients with diabetes and/or hypertension is cost-effective in India.

A within-trial cost-effectiveness analysis (CEA) from a societal perspective will be conducted alongside a multicentre cluster randomised controlled trial to identify, measure and evaluate the key resource and outcome impacts of a CBPR model compared with usual care aimed at improving medication adherence in adult rural Indian patients with diabetes and/or hypertension. The CEA will provide results in terms of the cost per improvement in medication adherence score, and a cost-utility analysis (CUA) will express the findings as the cost per disability-adjusted life year (DALY) or quality-adjusted life year (QALY) gained. Intervention costs and effects will be projected for the population of Indian adults with diabetes and/or hypertension who are on medication, analysed over the cohort's lifetime. Results from the modelled CUA will detail incremental costs, costs per death averted and costs per DALY averted/QALY gained for the interventions relative to the comparator. Incremental cost-effectiveness ratios will be computed by dividing the cost difference between the intervention and comparator by the difference in benefits. Health economic evaluation methods, including a lifetime horizon, a 3% discount rate for costs and benefits and a societal perspective, will be followed. The effects of sampling uncertainty on estimated incremental costs and effectiveness parameters, as well as the influence of methodological assumptions (such as the discount rate and study perspective), will be examined through both deterministic and probabilistic sensitivity analyses. Relevant differences in costs, outcomes or cost-effectiveness disparities among subgroups of patients with varying baseline characteristics will also be reported. Results will be illustrated using cost-effectiveness acceptability curves across a range of willingness-to-pay thresholds. Modelled CUA will broaden the target population and time frame to offer decision-makers insights into the cost-effectiveness of the CBPR approach for enhancing medication adherence. Furthermore, a return on investment analysis will be performed to express benefits in monetary terms relative to investments made, allowing for a comprehensive expression of both costs and the full spectrum of intervention benefits in monetary units.

The Institutional Ethics Committee of Sri Aurobindo Medical College and PGI, Indore, provided ethics approval. The results of the main trial and economic evaluation will be submitted for publication in a peer-reviewed journal and disseminated through reports to Indian Council of Medical Research and conference presentations.

Clinical Trial Registry of India (CTRI) CTRI/2024/01/061939.

Melioidosis, caused by Burkholderia pseudomallei, is an underdiagnosed cause of community-acquired pneumonia (CAP) in India. Due to overlapping features with other bacterial pneumonias and limited access to culture facilities, early diagnosis and treatment remain challenging. This study aimed to develop a clinical scoring system to distinguish melioidosis from other bacterial causes of CAP in an endemic setting.

We conducted a retrospective cohort study of 337 patients with radiologically confirmed blood or respiratory culture-positive CAP cases at a tertiary care hospital in South India from 2017 to 2023. This included 55 melioidosis cases and 282 controls with other documented bacterial etiologies. Demographic, clinical, laboratory, and radiological variables were compared. Multivariable logistic regression identified independent predictors of melioidosis. A scoring system was developed using the natural logarithms of adjusted odds ratios (aORs).

Four independent predictors were retained in the final model: monsoon season exposure (aOR = 9.0, 95% CI: 3.6-22.6), diabetes mellitus (aOR = 10.1, 95% CI: 3.6-28.5), shock at presentation (aOR = 17.2, 95% CI: 5.9-49.9), and extrapulmonary focal involvement (aOR = 36.5, 95% CI: 11.0-121.4). The model showed excellent discrimination. A score of ≥ 4 out of 11 yielded a sensitivity of 87.3% and specificity of 83.6%, while a score of ≥ 5 yielded a sensitivity and specificity of 67.3% and 95.4%, respectively.

We propose a simple four-point clinical scoring tool to identify melioidosis in patients with CAP. This score can guide early suspicion and appropriate therapy in endemic resource-limited settings. Prospective validation in other endemic regions is warranted.

To compare the short-term (3-month) outcomes of intravitreal aflibercept injections versus intravitreal aflibercept combined with dexamethasone sodium phosphate in treating diabetic macular edema.

In this Phase-2 clinical trial, 16 eyes of 16 participants with diabetic macular edema were randomly assigned to one of 2 groups. Participants in the aflibercept monotherapy group received 2 mg of intravitreal aflibercept (0.05 mL), while those in the combination therapy group received 2 mg of intravitreal aflibercept (0.05 mL) plus 0.04 mg dexamethasone sodium phosphate (0.01 mL). Identical injections were repeated after 30 and 60 days. The primary outcome was the change in central macular thickness, as measured by optical coherence tomography, from baseline to 1 month after the last injection. Secondary outcomes included changes in best-corrected visual acuity and intraocular pressure over the same period.

The mean baseline central macular thickness was 444 ± 86 μm in the combination therapy group and 394 ± 96 μm in the aflibercept monotherapy group (p=0.293). By day 90, the mean reduction in central macular thickness was significantly greater in the combination therapy group (176 ± 129 μm) compared to the aflibercept monotherapy group (54 ± 49 μm; p=0.034). Best-corrected visual acuity also improved significantly more in the combination therapy group, with a median gain of 0.31 ± 0.16 LogMAR, whereas the aflibercept monotherapy group experienced a minimal change (-0.06 ± 0.13 LogMAR; p=0.020). Intraocular pressure remained stable in both groups, with no significant difference (p=0.855). None of the participants developed elevated intraocular pressure (>21 mmHg) or required ocular hypotensive medications. No significant ocular or systemic adverse events were reported.

The addition of dexamethasone sodium phosphate to the standard intravitreal aflibercept regimen for diabetic macular edema can improve short-term structural and functional outcomes.

Brazilian Clinical Trials Registry (RBR-7468j4q).

Aim: To evaluate the associations of lower extremity arterial calcification (LEAC) with clinical profile of peripheral artery disease (PAD) patients with concomitant stable coronary artery disease (SCAD).

Materials and Methods: The cross-sectional study enrolled and analyzed clinical and instrumental data from 110 lower extremity PAD (chronic limb-threatening ischemia) patients (mean age [mean ± standard deviation] 71±8 years; 77 [70 %] males and 33 [30 %] females) with concomitant SCAD, underwent endovascular treatment during the period 2021-2025. LEAC was evaluated by CT-angiography with the assessment of Agatson calcium score (CS). The enrolled sample was subdivided into group 1 (CS <1000 units [n=60]) and group 2 (CS ≥1000 units [very extensive LEAC; n=50]).

Results: Group 2 (vs. group 1) was characterized by higher prevalence of atherosclerotic risk factors, namely smoking, overweight/obesity, and the cases of family history of cardiovascular diseases. Hypertension and diabetes mellitus tended to be more prevalent in group 2, as opposed to group 1. In addition, patients with CS ≥1000 units (vs. <1000) presented more frequently with atrial fibrillation/flutter, heart failure stage C, previous acute cerebrovascular event and the most advanced Rutherford stage 6.

Conclusions: The PAD patients with concomitant SCAD and very extensive LEAC demonstrated more severe PAD and higher comorbidity burden, as compared to their counterparts with less calcified lower extremity arteries. The obtained data substantiate the integrated approach to be implemented in the management of such polyvascular patients, particularly by the use of LEAC as a potential predictor of adverse cardiovascular events.

Aim: To improve the results of surgical treatment of patients with ischemic form of diabetic foot syndrome (IF DFS) with stenotic-occlusive lesion (SOL) of the tibial segment arteries by creating an algorithm of diagnostic and treatment tactics.

Materials and Methods: An analysis of the surgical treatment outcomes of 137 patients with type 2 diabetes mellitus (DM2) and IF DFS with SOL of the tibial segment arteries, critical limb ischemia, and ischemic foot necrosis was conducted.

Results: According to the obtained indicators of the popliteal artery debit after performing balloon angioplasty (BAP) of the tibial segment arteries, the patients were divided into three groups. All patients, depending on the degree of increase in the popliteal artery debit after BAP (group A - <1,5 times; 1,5-2 times; >2 times), transcutaneous oxygen pressure (TcPO2) and the option of revascularization according to the angiosomal concept, were assigned a certain number of points and compared with the quality and timing of wound healing in the groups. It is considered that the calculation of quantitative changes in the popliteal artery debit after performing BAP accurately determines the prospects for healing of foot wounds after necrotectomy in patients with IF DFS and can be a criterion for formulating further treatment tactics.

Conclusions: Measuring TcPO2 and determining the revascularization option based on the results of BAP allow the DM2 patients in groups A, B, and C to be assigned the appropriate number of points, the sum of which shows the prognosis for healing of foot wounds and the timing of using other methods of revascularization or performing amputation.

Randomized placebo-controlled clinical trials showed that glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce kidney risk in patients with type 2 diabetes (T2D), prominently in those with chronic kidney disease. It is unclear whether these findings may apply to broader populations of patients with T2D treated in real-world settings and compared to active controls. We summarised real-world data of adverse kidney outcomes among patients with T2D initiating GLP-1 RA versus other glucose-lowering agents.

We searched PubMed and Embase for observational cohort studies (April 2005-January 2025; PROSPERO CRD42023405356). Initiators of GLP-1 RA were compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl-peptidase 4 inhibitors (DPP4i), sulfonylureas, or basal insulin. Outcomes included risks of albuminuria progression, ≥ 40 or ≥ 50% eGFR reduction from baseline, acute kidney injury (AKI), kidney-related hospitalizations, and end-stage kidney disease (ESKD), per data availability. We synthesised the data using inverse variance-weighted averages of logarithmic hazard ratios (HR)s in random-effect models.

Thirty-one studies were eligible, encompassing 1,601,389 patients (mean age 49-78 years, 5%-64% women), with 21, 6, 5, and 1 of them using SGLT2i, DPP4i, basal insulin, and sulfonylureas as a comparator, respectively. Compared with SGLT2i, GLP-1 RA initiators had higher risks for AKI (HR [95% CI] 1.12 [1.05-1.20]), kidney-related hospitalizations (1.66 [1.01-2.73]), and ≥ 40% reduction in eGFR (1.40 [1.27-1.53]), without evidence for differences in risks of ≥ 50% eGFR reduction or ESKD. Compared to DPP4i, GLP-1 RA initiators had lower risks for experiencing ≥ 50% eGFR reduction (0.84 [0.76-0.92]), kidney-related hospitalizations (0.73 [0.65-0.83]), and ESKD (0.70 [0.63-0.78]). Similar benefits were observed when comparing GLP-1 RA to sulfonylureas. Compared to basal insulin, GLP-1 RA initiation was associated with a lower risk of albuminuria progression (0.89 [0.80-0.99]), with inconsistent data regarding possible benefits in reducing ESKD risk.

In patients with T2D, initiation of GLP-1 RA in real-world settings may be associated with improved kidney outcomes compared to DPP4i, sulfonylureas, and basal insulin, and worse kidney outcomes compared to SGLT2i.

Initiating oral antidiabetic therapy, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, is generally not recommended during hospitalization. However, guidelines since 2021 have supported their use in heart failure with reduced ejection fraction (HFrEF), and since 2023 in preserved ejection fraction (HFpEF).

To assess the safety and outcomes of initiating SGLT2 inhibitors during hospitalization for acute heart failure (HF).

We conducted a historical cohort study of 307 patients admitted with acute HF between October 2018 and April 2022. Patients were grouped as chronic SGLT2i users, new initiators during hospitalization, or controls who did not receive SGLT2i.

Among the 307 patients, 50.4% had HFrEF, 30.8% HFpEF, and 18.8% HF with mildly reduced ejection fraction. In-hospital mortality was 3.6% (11 patients); 2-year mortality was 37.7% (116 patients). New SGLT2i initiators had the lowest 2-year mortality (22.2%) compared to controls (43.9%) and chronic users (41.8%) (P = 0.008). They also had the lowest 1-year rehospitalization rates (18.3% vs. 35.5% vs. 32.8%; P = 0.025). Multivariable analysis identified older age and co-morbidities as independent predictors of mortality. SGLT2i initiation was associated with reduced rehospitalization. Adverse effects occurred in 15.6% of SGLT2i users, mainly acute kidney injury.

In-hospital SGLT2 inhibitor initiation in patients with HF appears safe and is associated with reduced post-discharge mortality and readmission rates.

The Iron Swords war created stressful circumstances that could negatively impact glycemic control in individuals with type 1 diabetes (T1D).

To evaluate changes in continuous glucose monitoring (CGM) metrics in pediatric T1D patients during the war.

This retrospective study included T1D patients monitored by CGM. Metrics from three selected 2-week periods were compared (before the war, after the war outbreak, and 4 months later). Study variables included time-in-range (70-180 mg/dl; 3.9-10 mmol/L), time-in-tight-range (70-140 mg/dl; 3.9-7.8 mmol/L), time-in-marked-hypoglycemia (< 54 mg/dl; < 3 mmol/liter), and time-in-severe-hyperglycemia (> 250 mg/dl; >13.3 mmol/liter). Patients were treated with either a multiple daily insulin (MDI) regimen or insulin pump, with or without an open-source automated insulin delivery (OS-AID) system.

Data of 99 patients were analyzed (mean age 12.2 ± 4.0 years, mean diabetes duration 4.6 ± 3.9 years, 52.5% males). No significant changes in CGM metrics were observed across the entire cohort at any time point. Patients with higher socioeconomic position (SEP; cluster > 7) had better CGM metrics, with an increase in time-in-tight-range in the lower SEP group and in time-in-severe-hyperglycemia in the higher SEP group (P = 0.003). OS-AID users (n=20) had superior pre-war CGM metrics and maintained stable glycemia during the war, MDI users showed increased time-in-severe-hyperglycemia post-outbreak (P = 0.05).

Throughout the war, children and adolescents with T1D treated with insulin pumps maintained relatively stable glycemic control. Susceptibility to change following the onset of war was influenced by SEP and mode of insulin therapy.