Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review.
Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review.
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DOI：
10.1038/s43856-023-00357-y
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发表时间：
2023-10-05
期刊：
影响因子：
--
通讯作者：
Sims, Emily K
中科院分区：
文献类型：
--
作者：
Felton, Jamie L;Griffin, Kurt J;Oram, Richard A;Speake, Cate;Long, S Alice;Onengut-Gumuscu, Suna;Rich, Stephen S;Monaco, Gabriela S F;Evans-Molina, Carmella;DiMeglio, Linda A;Ismail, Heba M;Steck, Andrea K;Dabelea, Dana;Johnson, Randi K;Urazbayeva, Marzhan;Gitelman, Stephen;Wentworth, John M;Redondo, Maria J;Sims, Emily K
1型糖尿病（T1D）是由免疫介导的胰岛素生成β细胞破坏所致。预防工作集中在诊断前或诊断前后的免疫调节以及维持β细胞健康；然而，疾病进展和治疗反应的异质性限制了其在临床实践中的应用，这凸显了对1型糖尿病疾病修正采用精准医学方法的必要性。
为了解该领域的知识现状，我们对过去25年在PubMed或Embase中收录的、有50名参与者的随机对照试验进行了系统综述，这些试验测试了1型糖尿病疾病修正疗法和/或确定了与治疗反应相关的特征，并使用Cochrane偏倚风险工具分析了偏倚。
我们确定并总结了75篇文献，其中15篇描述了针对1型糖尿病风险增加个体的11项预防试验，60篇描述了旨在预防疾病发作时β细胞丢失的治疗方法。17种干预措施（主要是免疫疗法）与安慰剂相比显示出益处（在1型糖尿病发病前仅有两种）。57项研究采用精准分析来评估与治疗反应相关的特征。年龄、β细胞功能指标和免疫表型是最常被检测的。然而，分析通常不是预先设定的，报告方法不一致，且往往报告阳性结果。
虽然预防和干预试验的质量总体较高，但精准分析的质量较低，使得难以得出有意义的结论以指导临床实践。为了促进1型糖尿病预防的精准医学方法，未来精准研究的考虑因素包括在未来试验设计中纳入统一的结果指标、可重复的生物标志物以及预先设定的、有足够效力的精准分析。
1型糖尿病是一种因胰腺中产生胰岛素的一种细胞遭到破坏而导致的疾病，患者终生依赖胰岛素注射。1型糖尿病的预防仍然是一个具有挑战性的目标，这主要是由于疾病过程和进展存在巨大差异。迄今为止在医学研究环境（临床试验）中测试的疗法仅对一部分人有效，这凸显了需要更具针对性的预防方法。我们综述了针对1型糖尿病疾病过程的疗法的临床试验。虽然试验的总体质量较高，但测试影响治疗反应的个体特征的研究质量较低。这项综述揭示了一个重要需求，即仔细规划对影响1型糖尿病治疗反应的特征进行高质量分析，以确保有朝一日针对性的方法能够应用于临床实践。
费尔顿等人进行了一项系统综述，以评估测试用于预防1型糖尿病的疾病修正疗法以及与治疗反应相关特征的研究。虽然发现预防和干预试验的质量较高，但对与治疗反应相关因素的精准分析质量较差。
Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification. To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with 50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument. We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. Seventeen interventions, mostly immunotherapies, show benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employ precision analyses to assess features linked to treatment response. Age, beta cell function measures, and immune phenotypes are most frequently tested. However, analyses are typically not prespecified, with inconsistent methods of reporting, and tend to report positive findings. While the quality of prevention and intervention trials is overall high, the low quality of precision analyses makes it difficult to draw meaningful conclusions that inform clinical practice. To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design. Type 1 diabetes (T1D) is a condition that results from the destruction of a type of cell in the pancreas that produces the hormone insulin, leading to lifelong dependence on insulin injections. T1D prevention remains a challenging goal, largely due to the immense variability in disease processes and progression. Therapies tested to date in medical research settings (clinical trials) work only in a subset of individuals, highlighting the need for more tailored prevention approaches. We reviewed clinical trials of therapies targeting the disease process in T1D. While the overall quality of trials was high, studies testing individual features affecting responses to treatments were low. This review reveals an important need to carefully plan high-quality analyses of features that affect treatment response in T1D, to ensure that tailored approaches may one day be applied to clinical practice. Felton et al. conducted a systematic review to evaluate studies testing disease-modifying therapies and features linked to treatment response for type 1 diabetes prevention. While the quality of prevention and intervention trials is found to be high, precision analyses on factors associated with treatment response are of poorer quality.
影响因子：
3.7
作者：
Martin S;Herder C;Schloot NC;Koenig W;Heise T;Heinemann L;Kolb H;DIATOR Study Group
通讯作者：
DIATOR Study Group