Diabetes, Obesity & Metabolism最新文献

Aims: Targeting the glucose dependent insulinotropic polypeptide receptor (GIPR) is of growing interest for treating type 2 diabetes and obesity, though the optimal approach remains unclear. Both GIPR agonism and antagonism, respectively, incorporated into drugs like tirzepatide and maridebart cafraglutide, have paradoxically both shown significant weight loss effects in humans.

Materials and methods: In this study, the metabolic impacts of a GIPR agonist (GIP108) and antagonist (NN-GIPR-Ant) were evaluated in lean and high-fat diet (HFD)-induced obese male mice. We assessed the impacts on food intake, body weight, glucose and insulin tolerance, liver triglyceride levels, bone markers and adipose tissue lipolytic gene expression.

Results: In lean mice, neither peptide affected food intake or body weight, but GIP108 improved glucose tolerance. In obese mice, both agents reduced food intake and body weight, with NN-GIPR-Ant producing more sustained appetite suppression. Energy expenditure remained unchanged, as weight loss matched that of pair-fed controls. GIP108 improved glucose tolerance independently of weight loss, whereas NN-GIPR-Ant reduced insulin sensitivity compared to pair-fed controls. Both treatments slightly increased liver triglyceride content compared to their pair-fed controls, and no treatment significantly affected plasma bone marker levels. Finally, NN-GIPR-Ant reduced the expression of adipose tissue lipolytic genes.

Conclusions: Our data highlights the distinct metabolic effects of GIPR agonism and antagonism, offering insights for their future application in personalised metabolic disease treatments. Further human studies are needed to understand the long-term metabolic impacts of these therapies.

Aims: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women, associated with insulin resistance, hyperandrogenism, and menstrual irregularities. Nutraceutical interventions-bioactive compounds derived from foods or supplements that provide health benefits beyond basic nutrition-may support conventional therapy. This study aimed to systematically evaluate the effects of nutraceutical interventions on reproductive and metabolic outcomes in PCOS.

Materials and methods: This systematic review and meta-analysis was registered in PROSPERO (CRD42024521879) and followed PRISMA 2020. Searches were performed in PubMed, Embase, Cochrane Library, Web of Science, and regional databases (January 2013-December 2024) and included 78 eligible studies. Eligible randomized and quasi-experimental studies assessed nutraceuticals such as vitamin D, inositol, and quercetin. Risk of bias was evaluated with standardized tools; certainty of evidence was graded by GRADE.

Results: Seventy-eight studies met inclusion criteria. Nutraceutical interventions significantly reduced fasting insulin (MD = -2.14 μIU/mL; 95% CI -3.12 to -1.16) and luteinizing hormone (MD = -1.34 mIU/mL; 95% CI -2.10 to -0.58) and increased sex-hormone-binding globulin (MD = +3.72 nmol/L; 95% CI 1.35 to 6.09). Vitamin D supplementation showed the strongest metabolic and hormonal improvements. Results for ovarian follicle count and menstrual bleeding were inconsistent.

Conclusions: Nutraceutical interventions targeting metabolic and hormonal regulation may complement lifestyle therapy in women with PCOS. Interpretation is limited by study heterogeneity and variable methodological quality. No external funding was received.

Aim: This study aimed to investigate the efficacy and safety of bi-weekly cofrogliptin treatment as a replacement for daily dipeptidyl peptidase-4 inhibitors (DPP-4is) in Chinese patients with type 2 diabetes mellitus (T2DM).

Methods: This multicenter, open-label, randomized controlled study assigned participants in a 1:1 ratio to either the daily DPP-4i group or the 10 mg cofrogliptin group. The DPP-4i group continued their original daily DPP-4i regimen for 24 weeks, whereas the cofrogliptin group discontinued the daily DPP-4i and received the investigational drug orally once every 2 weeks. All participants underwent 14-day continuous glucose monitoring at weeks 10-12 and 22-24 during the treatment period. The main endpoint was the change in glucose time in range (TIR; 3.9-10.0 mmol/L) from baseline to week 24. Additionally, the Diabetes Treatment Satisfaction Questionnaire scores, adverse events, and hypoglycaemic events were compared between groups.

Results: The enrolment period was from 31 January 2024 to 20 November 2024. A total of 64 participants were randomized to receive either cofrogliptin (n = 31) or a daily DPP-4i (n = 33). The least squares (LS) mean (standard error) change in TIR from baseline after 24 weeks was 0.037% ± 2.506% in the cofrogliptin group compared to -9.891% ± 2.435% in the daily DPP-4i group. The LS mean difference was 9.929% (95% confidence interval: 3.064%-16.793%), which was statistically significant (p = 0.0046). The incidence, classification, and severity of adverse events were similar between the two groups.

Conclusion: Bi-weekly cofrogliptin treatment, instead of daily DPP-4i, could effectively control blood glucose levels in a 24-week treatment period and their fluctuations and was well tolerated in Chinese patients with T2DM.

Aim: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been established as effective treatments for type 2 diabetes, offering benefits beyond glycaemic control; however, their associations across multiple health outcomes remain insufficiently assessed. Thus, we conducted an umbrella review of meta-analyses of randomised controlled trials (RCTs) to comprehensively evaluate the broad spectrum of their effects.

Materials and methods: We conducted a systematic search of PubMed/MEDLINE, Embase, CINAHL, and Google Scholar through June 13, 2025, to identify meta-analyses of RCTs assessing the effects of GLP-1RAs on various health outcomes, including cardiovascular, renal, metabolic, oncologic, gastrointestinal and other domains. Effect sizes were recalculated using random-effects models and converted to equivalent odds ratios (eORs) with 95% confidence intervals (CIs) for consistency. The methodological quality of each review was assessed using the AMSTAR 2, and the certainty of evidence for each association was evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation framework (high, moderate, low or very low certainty). We preregistered our study protocol with PROSPERO (CRD420251112823).

Results: After applying predefined inclusion and exclusion criteria, 17 studies comprising 432 RCTs were included, covering 65 unique outcomes across 6 clinical domains. GLP-1RAs use was associated with reduced risks of heart failure (eOR, 0.71 [95% CI, 0.64-0.79]; low certainty) and peripheral artery disease (0.75 [0.67-0.84]; low certainty). Drug-specific analyses exhibited protective effects of liraglutide (eOR, 0.86 [95% CI, 0.80-0.91]), albiglutide (0.65 [0.47-0.89]), and dulaglutide (0.78 [0.68-0.90]) for major cardiovascular events, myocardial infarction and stroke, respectively. Renal outcomes indicated that GLP-1RAs use was associated with reducing the risk of kidney-specific composite outcomes (eOR, 0.76 [95% CI, 0.66-0.87]; low certainty), including nephropathy (0.74 [0.61-0.92]; low certainty) and albuminuria (0.73 [0.55-0.97]; very low certainty). GLP-1RAs were also associated with reductions in body weight (eOR, 0.46 [95% CI, 0.36-0.60]; moderate certainty) and glycated haemoglobin A1c (0.83 [0.71-0.97]; high certainty), but no substantial association with cancer risk was found. Gastrointestinal adverse events, including nausea (9.62 [4.60-20.10]; high certainty), dyspepsia (4.85 [1.52-15.45]; moderate certainty), and constipation (3.39 [1.54-7.47]; high certainty), were consistently reported. GLP-1RAs use was associated with higher lumbar spine (eOR, 1.99 [95% CI, 1.38-2.85]; low certainty) and hip-neck bone mineral density (1.79 [1.08-2.98]; low certainty).

Conclusions: In this study, GLP-1RAs were associated with cardiovascular, renal, and metabolic benefits in type 2 diabetes without increasing cancer risk, though gast

Aims: Calcific aortic valve disease (CAVD) is the most common valve disease. The impact of long-term glycemic exposure and glycemic control on the risk of CAVD remains poorly understood, particularly in Asian populations. We examined the association of serum levels of glucose and its long-term changes with the risk of CAVD.

Materials and methods: This study recruited 10 309 participants without cardiovascular disease and free of CAVD at initial echocardiographic examination from the Kailuan Study. CAVD cases were ascertained through linkage with hospitals' electronic medical record system. Data from three consecutive surveys prior to the recruitment were used to calculate the changes in glucose. Data were analysed using Cox proportional hazards regression. All participants were monitored biennially until 31 December 2023.

Results: A total of 2062 patients developed CAVD during a median follow-up of 4.62 years. In multivariable Cox proportional hazards regression models, the hazard ratios for CAVD were as follows: 1.42 (95% CI, 1.29-1.57) for type 2 diabetes, 1.20 (95% CI, 1.01-1.44) for time weighted average (TWA) FBG level, 1.37 (95% CI, 1.14-1.65) for cumulative fasting blood glucose (FBG) level and 0.72 (95% CI, 0.60-0.86) for FBG time in target range (TTR).

Conclusion: Type 2 diabetes, long-term elevated FBG and FBG change are associated with CAVD risk. Efforts to attain healthy glucose status may be an effective strategy to prevent CAVD.

Objective: We aim to compare second-generation automated insulin delivery systems (AIDs) with other treatment modalities regarding both glucose management outcomes and person-reported outcomes/experiences (PROs/PREs, measured by the Hypoglycemia Fear Survey, Hypoglycemic Confidence Scale, Hyperglycemia Avoidance Scale, Diabetes Distress Scale, Pittsburgh Sleep Quality Index, Well-being Scale, and treatment satisfaction) among adults with type 1 diabetes.

Research design and methods: Cross-sectional analysis of the Canadian BETTER type 1 diabetes registry. Adult participants were divided into five groups: second-generation AIDs, first-generation AIDs, continuous glucose monitoring (CGM) + pump, CGM + multiple daily injections (MDI), and non-CGM using MDI or pump. Generalized linear models were used to assess differences between the second-generation AID group and each of the other groups, with p < 0.05 considered significant.

Results: Among 1731 participants (69.2% females), mean age was 45.3 ± 15.3 years with 24.7 ± 16.0 years of diabetes. The second-generation AID group had the highest proportion of achieving target haemoglobin A1c ≤ 7% (58.1%) compared to 40.6% in the first-generation AID group, 40.5% in the Pump + CGM group, 37.3% in the MDI + CGM group, and 32.3% in the non-CGM group, even after adjustment for multiple imbalanced characteristics (p < 0.001). While second-generation AID users reported higher treatment satisfaction, no other differences in measures of PROs/PREs were found between second-generation AID and other groups. Elevated diabetes distress (55%) and poor sleep quality (63%) remained common across all treatment groups, and even among those who had reached the optimal HbA1c target (48% and 60%, respectively).

Conclusions: In real-world settings, second-generation AIDs were associated with lower haemoglobin A1c and higher treatment satisfaction but not better PROs/PREs. Mental burden remained high despite the use of advanced diabetes technologies and optimal glucose management.