Febuxostat Improves Postprandial Glucose Regulation and Insulin Sensitivity in Hyperuricemic Individuals with Prediabetes or Newly Diagnosed Type 2 Diabetes: A Prospective Cohort Study.

IF 4.7 2区 医学 Q1 CHEMISTRY, MEDICINAL
Drug Design, Development and Therapy Pub Date : 2025-06-05 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S522154
Shuang Liu, Qingsong Liu, Ronger Gu, Mian Wu, Shuo Meng, Le Yan, Qi Chen, Cuiling Zhu, Si Chen, Bei Xu, Fengjing Liu, Haibing Chen
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引用次数: 0

Abstract

Background: Hyperuricemia (HUA) has been linked to an elevated risk of impaired glucose metabolism. This study aimed to investigated the impact of the urate-lowering drug febuxostat on blood glucose levels, insulin sensitivity, and β-cell function in subjects with HUA who present with normoglycemia, prediabetes, or newly diagnosed type 2 diabetes (T2DM).

Methods: We assessed the glucose metabolism of participants with HUA using a 3-h oral glucose tolerance test (OGTT). Participants were categorized into two groups: those with HUA and normal glucose metabolism (NGM, n=28), and those with HUA and abnormal glucose metabolism (AbGM, n=32), including prediabetes (n=20) and newly diagnosed T2DM (n=12). Both groups received a daily dose of 40 mg febuxostat for 24 consecutive weeks and underwent 3-h OGTT at 12 and 24 weeks. Glucose, insulin, and C-peptide were measured to calculate insulin sensitivity (Stumvoll index, Gutt index) and β-cell function (Insulin Secretion-Sensitivity Index-2 and Disposition Index) indices. Differences in glucose levels and indices were analyzed by repeated measures ANOVA including interaction terms between groups and the time of visit.

Results: After 24 weeks of febuxostat treatment, subjects with HUA and AbGM showed significant reductions in postprandial 1-h (11.88±1.39mmol/L at baseline, 10.97±2.74mmol/L at 12 weeks, and 11.12±1.92mmol/L at 24 weeks, Ptime=0.031) and 2-h glucose (10.25±1.71mmol/L at baseline, 9.39±2.77mmol/L at 12 weeks, and 9.16±2.67mmol/L at 24 weeks, Ptime=0.014). Febuxostat significantly improved insulin sensitivity of subjects in the AbGM group, but did not affect β-cell function. Moreover, the improvement in insulin sensitivity in these subjects was not directly correlated with the improvement in uric acid. No significant changes were observed in subjects with NGM.

Conclusion: In subjects with HUA and prediabetes or newly diagnosed T2DM, febuxostat significantly enhanced postprandial glucose and insulin sensitivity, though it did not notably improve β-cell function. Further research is required to explore how febuxostat enhances insulin sensitivity.

非布司他改善糖尿病前期或新诊断的2型糖尿病高尿酸血症患者餐后血糖调节和胰岛素敏感性:一项前瞻性队列研究
背景:高尿酸血症(HUA)与糖代谢受损的风险升高有关。本研究旨在探讨降尿酸药物非布司他对血糖水平、胰岛素敏感性和β细胞功能的影响,这些患者包括血糖正常、前驱糖尿病或新诊断的2型糖尿病(T2DM)。方法:采用3小时口服葡萄糖耐量试验(OGTT)评估HUA患者的糖代谢。参与者被分为两组:HUA和正常糖代谢组(NGM, n=28)和HUA和异常糖代谢组(AbGM, n=32),包括糖尿病前期(n=20)和新诊断的T2DM (n=12)。两组均给予非布司他每日剂量40 mg,连续24周,并在12周和24周进行3小时OGTT。测定葡萄糖、胰岛素和c肽,计算胰岛素敏感性(Stumvoll指数、Gutt指数)和β细胞功能(胰岛素分泌敏感性指数-2和处置指数)指数。葡萄糖水平和指标的差异采用重复测量方差分析,包括组间相互作用项和就诊时间。结果:非布司他治疗24周后,HUA和AbGM组餐后1小时血糖(基线值11.88±1.39mmol/L, 12周值10.97±2.74mmol/L, 24周值11.12±1.92mmol/L, Ptime=0.031)和2小时血糖(基线值10.25±1.71mmol/L, 12周值9.39±2.77mmol/L, 24周值9.16±2.67mmol/L, Ptime=0.014)均显著降低。非布司他显著改善AbGM组受试者的胰岛素敏感性,但不影响β细胞功能。此外,这些受试者胰岛素敏感性的改善与尿酸的改善并不直接相关。在NGM患者中未观察到明显变化。结论:对于HUA合并糖尿病前期或新诊断的T2DM患者,非布司他可显著提高餐后血糖和胰岛素敏感性,但对β细胞功能无显著改善。非布司他如何增强胰岛素敏感性需要进一步的研究。
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来源期刊
Drug Design, Development and Therapy
Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY
CiteScore
9.00
自引率
0.00%
发文量
382
审稿时长
>12 weeks
期刊介绍: Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.
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