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一型糖尿病近三年研究进展
在过去三年中，一型糖尿病（T1D）领域的研究取得了一些重要进展，涉及疾病的筛查、预防、治疗方法以及其与其他健康问题的关联。以下是根据当前研究证据总结的主要进展：
1. 疾病筛查与预测
近年来，针对一型糖尿病的筛查方法出现了重要的变化。传统上，筛查主要针对有家族病史的人群，而研究显示，大约90%的一型糖尿病患者并没有家族历史，这推动了对普通人群进行筛查的探索。通过基因或自身抗体筛查的现有项目已经取得了显著的信息，不仅有助于疾病的早期识别，还为临床实践中的筛查时机提供了指导。
特别是在2021年，针对普通人群的筛查努力得到关注，这些努力的初步结果表明，早期检测具有潜在的医疗益处，如改善健康结果和长期预后。通过监测与糖尿病相关的胰岛自身抗体，能够在症状出现前识别出糖尿病患者，从而有助于更好地理解预症状阶段的糖尿病进展和相应的预防策略。
2. 预防策略
一型糖尿病的预防方法正在逐步发展。通过早期识别和教育，改善的干预措施使得可以更有效地延缓或预防疾病的发生。例如，最近批准的teplizumab作为一种免疫治疗手段，可以在高风险群体中延缓临床糖尿病的出现。这种治疗方法的一个重要里程碑是，它不仅能够减少异常的葡萄糖耐量，还能显示出良好的耐受性，副作用轻微。
此外，主要预防策略旨在阻止在无症状的高风险人群中出现胰腺β细胞自身免疫，而次要预防策略则致力于在自身免疫已存在时保护尚未被破坏的β细胞，显示出一种从临床前期到临床阶段的全面预防体系的构建。
3. 新的治疗方法与技术
在治疗方面，糖尿病管理技术，尤其是数字健康工具的应用日益增多，显著提高了年轻患者的血糖控制。此外，行为干预的研究在年轻儿童中也显示出了积极的结果，提高了其父母的心理状态及整体管理能力。2023年发布的研究也强调了teplizumab在延缓糖尿病进展中的有效性，使其成为临床实践的重要组成部分。
与此同时，新的治疗方法也在不断开发。例如，由于肥胖在糖尿病患者中的趋增，新的应对策略也被提出。这些策略包括运动疗法、营养疗法以及药物治疗等，为一型糖尿病患者提供了更全面的管理方案。
4. 合并症和并发症
一型糖尿病患者往往面临多种合并症的风险，其中心血管疾病尤为突出。最近的研究指出，糖尿病与非缺血性心肌病（NICM）之间存在因果关系，并探讨了这种关系的潜在机制。这一发现凸显了糖尿病患者需要更加综合的管理，以预防心血管相关的健康问题。
5. 遗传学与个体化医疗
在遗传学研究方面，识别影响一型糖尿病风险的 genética 位点有了新的进展，遗传风险评分（GRS）开始在不同种族中得到应用，促进了个体化医疗的可能性。这些研究强调了根据个体遗传背景制定精准医疗方案的重要性，使得高风险人群的早期诊断与干预成为可能。
总结
综上所述，近三年来，一型糖尿病的研究进展涵盖了疾病的筛查、预防、治疗以及与其他健康问题的相互影响。这些进展为患者提供了更多的管理选择及机会，最终能够改善患者的生活质量和健康结果。随着研究持续深入，尤其是在精准医学和个体化治疗方面，未来在一型糖尿病领域可能会迎来更多革命性的变化。
References
1Heterogeneity and endotypes in type 1 diabetes mellitus.PubMed
Maria J Redondo, Noel G Morgan
Despite major advances over the past decade, prevention and treatment of type 1 diabetes mellitus (T1DM) remain suboptimal, with large and unexplained variations in individual responses to interventions. The current classification schema for diabetes mellitus does not capture the complexity of this disease or guide clinical management effectively. One of the approaches to achieve the goal of applying precision medicine in diabetes mellitus is to identify endotypes (that is, well-defined subtypes) of the disease each of which has a distinct aetiopathogenesis that might be amenable to specific interventions. Here, we describe epidemiological, clinical, genetic, immunological, histological and metabolic differences within T1DM that, together, suggest heterogeneity in its aetiology and pathogenesis. We then present the emerging endotypes and their impact on T1DM prediction, prevention and treatment.
2Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective.PubMed
Emily K Sims, Rachel E J Besser, Colin Dayan, et al.
Most screening programs to identify individuals at risk for type 1 diabetes have targeted relatives of people living with the disease to improve yield and feasibility. However, ∼90% of those who develop type 1 diabetes do not have a family history. Recent successes in disease-modifying therapies to impact the course of early-stage disease have ignited the consideration of the need for and feasibility of population screening to identify those at increased risk. Existing population screening programs rely on genetic or autoantibody screening, and these have yielded significant information about disease progression and approaches for timing for screening in clinical practice. At the March 2021 Type 1 Diabetes TrialNet Steering Committee meeting, a session was held in which ongoing efforts for screening in the general population were discussed. This report reviews the background of these efforts and the details of those programs. Additionally, we present hurdles that need to be addressed for successful implementation of population screening and provide initial recommendations for individuals with positive screens so that standardized guidelines for monitoring and follow-up can be established.
3Young Children with Type 1 Diabetes: Recent Advances in Behavioral Research.PubMed
Maureen Monaghan, Breana L Bryant, Hailey Inverso, et al.
PURPOSE OF REVIEW: This review provides a recent update of behavioral research pertinent to young children with T1D and addresses current priorities and future directions. RECENT FINDINGS: Rates of type 1 diabetes (T1D) in young children (ages 1-7) are continuing to rise. Since 2014, changes to diabetes care and management have impacted young children and reinforced the need for increased attention and interventions to support diabetes management, especially in caregivers who are primarily responsible for their young child's diabetes management. T1D is associated with unique physiologic challenges in young children, with constant management demands elevating parental diabetes-related stress and fear of hypoglycemia. Diabetes technology use has significantly increased in young children, contributing to improvements in glycemic levels and parent and child psychosocial functioning. Yet despite the positive outcomes demonstrated in select clinical behavioral interventions, research with this young child age group remains limited in scope and quantity.
4Teplizumab: type 1 diabetes mellitus preventable?PubMed
Saurav Misra, Ajay Kumar Shukla
Type 1 diabetes mellitus (T1DM) is an autoimmune condition driven by T lymphocytes that specifically declines the function of beta cells of pancreas. Immunological treatments aim to stop this decline in β-cell function thus preventing TIDM. Although TIDM occur at any age, it is one of the most common chronic disorders in children. T1DM accounts for 5 to 10% of all cases of diabetes amounting 21-42 million affected persons. Teplizumab is a novel drug recently approved by the US FDA for the treatment of T1DM. This drug reduces abnormal glucose tolerance who are at high risk for developing T1DM and have antibodies suggesting an immunological attack on their pancreas. A 14-day infusion of the drug prevents T cells' attack of the insulin-producing cells of the pancreas. Adverse events due to teplizumab reported so far mild and of limited duration. This review gives an overview of the preclinical and clinical research on teplizumab for their role in new-onset T1DM.
5Screening and Prevention of Type 1 Diabetes: Where Are We?PubMed
Kimber M Simmons, Emily K Sims
A diagnosis of type 1 diabetes (T1D) and the subsequent requirement for exogenous insulin treatment is associated with considerable acute and chronic morbidity and a substantial effect on patient quality of life. Importantly, a large body of work suggests that early identification of presymptomatic T1D can accurately predict clinical disease, and when paired with education and monitoring, can yield improved health outcomes. Furthermore, a growing cadre of effective disease-modifying therapies provides the potential to alter the natural history of early stages of T1D. In this mini review, we highlight prior work that has led to the current landscape of T1D screening and prevention, as well as challenges and next steps moving into the future of these rapidly evolving areas of patient care.
6Type 1 diabetes in diverse ancestries and the use of genetic risk scores.PubMed
Maria J Redondo, Christopher R Gignoux, Dana Dabelea, et al.
Over 75 genetic loci within and outside of the HLA region influence type 1 diabetes risk. Genetic risk scores (GRS), which facilitate the integration of complex genetic information, have been developed in type 1 diabetes and incorporated into models and algorithms for classification, prognosis, and prediction of disease and response to preventive and therapeutic interventions. However, the development and validation of GRS across different ancestries is still emerging, as is knowledge on type 1 diabetes genetics in populations of diverse genetic ancestries. In this Review, we provide a summary of the current evidence on the evolutionary genetic variation in type 1 diabetes and the racial and ethnic differences in type 1 diabetes epidemiology, clinical characteristics, and preclinical course. We also discuss the influence of genetics on type 1 diabetes with differences across ancestries and the development and validation of GRS in various populations.
7Lessons and gaps in the prediction and prevention of type 1 diabetes.PubMed
Chiara Mameli, Taylor M Triolo, Francesco Chiarelli, et al.
Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the root cause of T1D development has yet to be determined, enough is known about the natural history of T1D pathogenesis to allow study of interventions that may delay or even prevent the onset of hyperglycemia and clinical T1D. Primary prevention aims to prevent the onset of beta cell autoimmunity in asymptomatic people at high genetic risk for T1D. Secondary prevention strategies aim to preserve functional beta cells once autoimmunity is present, and tertiary prevention aims to initiate and extend partial remission of beta cell destruction after the clinical onset of T1D. The approval of teplizumab in the United States to delay the onset of clinical T1D marks an impressive milestone in diabetes care. This treatment opens the door to a paradigm shift in T1D care. People with T1D risk need to be identified early by measuring T1D related islet autoantibodies. Identifying people with T1D before they have symptoms will facilitate better understanding of pre-symptomatic T1D progression and T1D prevention strategies that may be effective.
8The emergence of obesity in type 1 diabetes.PubMed
Martin T W Kueh, Nicholas W S Chew, Ebaa Al-Ozairi, et al.
Obesity, a chronic low-grade inflammatory disease represented by multifactorial metabolic dysfunctions, is a significant global health threat for adults and children. The once-held belief that type 1 diabetes is a disease of people who are lean no longer holds. The mounting epidemiological data now establishes the connection between type 1 diabetes and the subsequent development of obesity, or vice versa. Beyond the consequences of the influx of an obesogenic environment, type 1 diabetes-specific biopsychosocial burden further exacerbates obesity. In the course of obesity management discussions, recurring challenges surfaced. The interplay between weight gain and escalating insulin dependence creates a vicious cycle from which patients struggle to break free. In the absence of weight management guidelines and regulatory approval for this population, healthcare professionals must navigate the delicate balance between benefits and risks. The gravity of this circumstance highlights the importance of bringing these topics to the forefront. In this Review, we discuss the changing trends and the biopsychosocial aspects of the intersection between type 1 diabetes and obesity. We highlight the evidence supporting the therapeutic means (i.e., exercise therapy, nutritional therapy, adjunct pharmacotherapy, and bariatric surgery) and directions for establishing a more robust and safer evidence-based approach.
9Type 1 diabetes, its complications, and non-ischemic cardiomyopathy: a mendelian randomization study of European ancestry.PubMed
Yunyue Zhao, Enxi Quan, Tao Zeng, et al.
BACKGROUND: Type 1 diabetes (T1D) is a significant risk factor for a range of cardiovascular diseases. Nonetheless, the causal relationship between T1D and non-ischemic cardiomyopathy (NICM) remains to be elucidated. Furthermore, the mechanisms responsible for the progression from T1D to NICM have not been definitively characterized. OBJECTIVE: The aim of this study was to conduct a Mendelian randomization (MR) study to investigate the causal effects of T1D and its complications on the development of NICM. Additionally, this study aimed to conduct a mediation analysis to identify potential mediators within this correlation. METHODS: Genetic variants were used as instrumental variables for T1D. The summary data for T1D were obtained from two genome-wide association study datasets. The summary data for T1D with complications and NICM were obtained from the Finnish database. Two-sample MR, multivariable MR and mediation MR were conducted in this study. RESULTS: The study revealed a causal association between T1D, T1D with complications, and NICM (with odds ratios of 1.02, 95% CI 1.01-1.04, p = 1.17e-04 and 1.03, 95% CI 1.01-1.05, p = 3.15e-3). Even after adjusting for confounding factors such as body mass index and hypertension, T1D remained statistically significant (with odds ratio of 1.02, 95% CI 1.01-1.04, p = 1.35e-4). Mediation analysis indicated that monokine induced by gamma interferon may play a mediating role in the pathogenesis of T1D-NICM (mediation effect indicated by odds ratio of 1.005, 95% CI 1.001-1.01, p = 4.9e-2). CONCLUSION: The study demonstrates a causal relationship between T1D, its complications, and NICM. Additionally, monokine induced by gamma interferon may act as a potential mediator in the pathogenesis of T1D-NICM.