Diabetes, Obesity & Metabolism最新文献

Aims: To evaluate the effectiveness of combination therapy with sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) compared with continued SGLT-2 inhibitor therapy in routine practice among individuals with type 2 diabetes.

Materials and methods: We used nationwide BARMER health claims data and implemented a prevalent new-user design. Individuals initiating a GLP-1 RA, either simultaneously with SGLT-2 inhibitors or during ongoing SGLT-2 inhibitor exposure, were matched to SGLT-2 inhibitor continuers using hybrid exposure sets and time-conditional propensity scores. The study cohort included individuals enrolled between 2013 and 2023, with possible follow-up including 2024. The primary outcome was all-cause mortality. Secondary outcomes included a modified cardiovascular composite (all-cause mortality, myocardial infarction, stroke), heart failure, nephropathy, and renal failure. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Among 21 664 matched pairs with a median follow-up of 1.3 years, combination therapy was associated with a 29% lower hazard of all-cause mortality (HR 0.71, 95% CI 0.63-0.80), consistent across subgroups and sensitivity analyses. Hazard reductions were also observed for the modified cardiovascular composite (HR 0.81, 95% CI 0.74-0.88) and heart failure (HR 0.78, 95% CI 0.68-0.89).

Conclusions: In this large real-world cohort, combination therapy with SGLT-2 inhibitors and GLP-1 RAs was associated with a lower hazard of all-cause mortality, while most secondary cardiorenal outcomes showed generally favourable but imprecise estimates. These findings suggest that sustained concurrent use of both drug classes may offer meaningful clinical benefits in routine practice, although residual confounding cannot be fully excluded.

Aims: To assess whether preoperative sodium-glucose co-transporter 2 inhibitor (SGLT2i) use reduces the odds of postoperative acute kidney injury (AKI) in patients with type 2 diabetes undergoing surgery.

Methods: We conducted a target trial emulation using inverse probability of treatment weighting, utilising routinely collected data from a tertiary centre in Australia. Patients with type 2 diabetes were included. We compared patients undergoing surgery under general anaesthesia who were taking SGLT2i preoperatively with patients undergoing surgery who were not taking SGLT2i preoperatively. The primary outcome was postoperative AKI within 7 days of surgery. We estimated the average treatment effect on the treated and calculated adjusted odds ratios (ORs) and standardised risk differences.

Results: We included 2499 patients (738 taking SGLT2i preoperatively and 1761 not taking SGLT2i preoperatively). Over half of patients underwent emergency surgery. Postoperative AKI occurred in 18.6% taking SGLT2i preoperatively and 25.8% not taking SGLT2i preoperatively. Odds of postoperative AKI were significantly lower in those who used SGLT2i preoperatively (adjusted OR 0.71, 95% CI 0.56-0.91, p = 0.007). Effects were consistent across subgroup and sensitivity analyses.

Conclusions: In patients with type 2 diabetes who used SGLT2i preoperatively, its use reduced the odds of postoperative acute kidney injury.

Aims: The effective target for systolic blood pressure (SBP) control in patients with diabetes was inconsistent. We evaluated the emulated effect of maintaining SBP below clinical thresholds on the risk of cardiovascular disease (CVD) and all-cause mortality.

Materials and methods: This study included 4264 patients with type 2 diabetes from the Kailaun study. We implemented the parametric g-formula to simulate the hypothetical interventions on reducing SBP below 140, 130 and 120 mmHg over time, accounting for time-varying confounding, reporting risk ratio (RR) and number needed to treat (NNT) for 10-year risk of CVD and all-cause mortality.

Results: Maintaining SBP below 140, 130 and 120 mmHg was associated with an 18%, 24%, and 31% relative risk reduction in the risk of CVD, with the RR (95% confidence interval [CI]) of 0.82 (0.75-0.88), 0.76 (0.69-0.86), and 0.69 (0.58-0.84), and the NNT of 32, 24, and 19, respectively, compared to no intervention. However, the benefits in reducing the risk of all-cause mortality did not reach a significant level with maintaining SBP below 140 and 130 mmHg, with the RR (95% CI) of 0.98 (0.93-1.06) and 1.04 (0.95-1.12), respectively. The risk of all-cause mortality significantly increased 15% with maintaining SBP ≤120 mmHg (RR, 1.15; 95% CI, 1.02-1.32). Subgroup analyses showed that maintaining SBP ≤120 mmHg tended to bring more harms than benefits in patients aged ≥60 years or without antihypertensive agents.

Conclusion: Among Chinese patients with type 2 diabetes, maintaining SBP ≤120 mmHg may not be an optimal target, in terms of the risk-benefit association of CVD and all-cause mortality.

Retraction: S. Wan , H. Yan , Q.-Y. Sun , J.-Q. Zhu , H.-H. Wang , K.-Y. Qu , and X. Yi , "Effects of GLP-1 Receptor Agonists on Cognitive Function in Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials," Diabetes, Obesity and Metabolism (Early View): https://doi.org/10.1111/dom.70201. The above article, published online on 17 October 2025 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Richard Donnelly; and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties and upon the authors' request. It was brought to the journal's attention that the original studies forming the basis of the meta-analysis presented in the article contain inconsistencies that are prone to misinterpretation. As a result, these studies were found not to be directly comparable. Consequently, the conclusions drawn in the article were determined to be affected by these issues, and their reliability was considered compromised. To their credit, the authors have agreed with this determination and requested the retraction of the article. The authors have acted responsibly after concerns were raised and following their own internal investigations of the research.

Background: The burden attributable to body mass index (BMI) remains a major public health concern in China and imposes substantial socio-economic costs.

Methods: Data from the Global Burden of Disease Study 2023 and economic projections were integrated to estimate and project the burden among Chinese adults aged 20-64 years. A multi-method approach was utilised, including burden estimation, joinpoint regression for trend analysis, demographic decomposition, age-period-cohort (APC) modelling, and Bayesian age-period-cohort (BAPC) modelling for future projections. This study introduced and applied the B-PALY framework, which integrates the BAPC model with productivity-adjusted life years (PALYs), to systematically predict the productivity impact and macroeconomic burden associated with high BMI-related diseases.

Results: In 2023, high BMI-related diseases caused 118 511 deaths and 9.7 million disability-adjusted life years (DALYs), accounting for approximately 20% of all deaths and 25% of all DALYs among China's working-age population. From 1990 to 2023, the burden showed significant upward trends. Demographic decomposition identified population aging and growth as primary drivers, partially offset by epidemiological changes. APC analysis revealed an increasing disease burden with age and elevated DALY risks in recent birth cohorts. Projections indicated a substantial rise in the burden of diseases attributable to high BMI, in terms of absolute deaths and DALYs, through 2050. The B-PALY framework estimated that, in 2023 alone, these diseases imposed a macroeconomic burden of approximately 129.77 billion Intl$ (about 0.03% of China's 2023 GDP). Projected cumulative losses from 2023 to 2029 amount to Intl $1.14 trillion.

Conclusion: High BMI-related diseases caused a substantial health and macroeconomic burden in China's working-age population, with rising trends projected to continue.

Background and aims: Methylglyoxal-derived hydroimidazolone (MG-H1), one of the advanced glycation end-products (AGEs), has been a potential biomarker of type 2 diabetes (T2DM), which is strongly related to insulin resistance. However, the relationship between the dynamics of MG-H1 and insulin resistance has not been characterized, and its mechanism on insulin resistance is unknown. In this study, we aimed to investigate the relationship between MG-H1 and insulin resistance in the clinical study of Japanese individuals and identify the molecular mechanisms underlying MG-H1 associated phenomena in vitro.

Methods: We performed the meal tolerance test (MTT) and hyper-insulinemic-euglycemic clamp analysis in 19 patients with T2DM and 19 participants without diabetes (non-DM). We measured their fasting and postprandial MG-H1 using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the effects of MG-H1 on glucose uptake and insulin signalling in C2C12 skeletal myocytes.

Results: The postprandial MG-H1 and the area under the curve (AUC) of MG-H1 in MTTs were significantly negatively correlated with the glucose disposal rate (GDR) in clamp studies both in the T2DM (r = -0.72 [p < 0.001]) and non-DM (r = -0.54 [p < 0.05]) groups. In cultured C2C12 skeletal myocytes, pre-treatment with MG-H1 inhibited insulin-stimulated phosphorylation of Akt and glucose uptake, via the activation of mechanistic target of rapamycin complex 2 (mTORC2).

Conclusions: In clinical study findings revealed that postprandial MG-H1 was a novel marker of insulin resistance in Japanese individuals, and in vitro findings using cultured C2C12 skeletal myocytes suggested that MG-H1 disturbs insulin signalling via the mechanisms of mTORC2 activation.

Aim: To evaluate the effects of tirzepatide on physical function in adults with overweight or obesity.

Methods: We searched PubMed, Embase, and the Cochrane Library up to July 20, 2025 for randomized controlled trials (RCTs) comparing once-weekly tirzepatide 10 or 15 mg with placebo and reporting validated physical function outcomes. Primary endpoints were changes from baseline in the 36-Item Short Form Health Survey (SF-36) physical function domain and in the Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) physical function subscale. Random-effects models were used to calculate pooled mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed with I² statistics.

Results: Six RCTs comprising 4531 participants, of whom 2802 underwent tirzepatide treatment were included. Tirzepatide significantly improved physical function compared with placebo, both in SF-36 physical function (MD 2.26 points; 95% CI, 1.76-2.76; I² = 99.8%; p < 0.001) and IWQOL-Lite-CT physical function (MD 10.10 points; 95% CI, 8.61-11.60; I² = 99.8%; p < 0.001). Subgroup analyses by dose demonstrated consistent benefits for both 10 and 15 mg groups. The overall certainty of evidence, rated by GRADE, was moderate due to risk of bias and inconsistency across studies.

Conclusions: Tirzepatide 10 and 15 mg once weekly significantly improve patient-reported physical function in adults with overweight or obesity. These findings suggest tirzepatide enhances perceived physical capacity and quality of life, although the extremely high between-study heterogeneity limits the interpretability of pooled estimates and warrants cautious interpretation.

Aims: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by progressive destruction of pancreatic β cells. Increasing evidence suggests that neutrophils and neutrophil extracellular traps (NETs) may contribute to early islet inflammation; however, their precise role in T1DM pathogenesis remains incompletely understood. This study aimed to investigate the involvement of neutrophils and NET formation in the development and progression of T1DM and to explore their potential immunopathological significance.

Materials and methods: Relevant clinical samples from patients with newly diagnosed T1DM and appropriate controls were analyzed, together with experimental data derived from established animal models of T1DM. Neutrophil activation and NET formation were assessed using established biomarkers, including citrullinated histone H3 and myeloperoxidase-DNA complexes. Inflammatory responses and pancreatic islet injury were evaluated using immunological, histological, and molecular approaches.

Results: Elevated levels of circulating NET-associated markers were observed in patients with newly diagnosed T1DM and in early-stage diabetic animal models. Neutrophil infiltration into pancreatic islets was evident at early disease stages and was associated with increased inflammatory activity and β-cell dysfunction. Excessive NET formation correlated with enhanced immune activation, suggesting a contributory role of neutrophils and NETs in amplifying islet inflammation and autoimmune responses.

Conclusions: These findings indicate that neutrophils and NETs participate in the early immunopathogenesis of T1DM and may promote β-cell injury through inflammatory and immune-mediated mechanisms. Targeting dysregulated neutrophil activation and NET formation may represent a potential therapeutic strategy for preserving β-cell function and modifying disease progression in T1DM.