糖尿病,高达746项的美国在研项目简述(2024)
Bringing medical advances from the lab to the clinic.
糖尿病(Diabetes)是一种慢性疾病,其特征是高血糖水平,这是由于患者机体无法有效地利用或产生胰岛素,该病也是美国人群中第七位的主要死因。
糖尿病的长期高血糖状态可能导致多种并发症,包括心血管疾病、视网膜病变、肾病变、神经病变等。因此,及时诊断和有效管理糖尿病至关重要,以防止或延缓这些并发症的发展。
尽管针对糖尿病现有许多治疗方法和管理策略,但仍存在一些重要而未解决的临床问题:
1)胰岛素抵抗性的机制和治疗:虽然胰岛素抵抗是2型糖尿病的核心问题,但目前对其确切机制的理解仍不完全,导致治疗策略未能完全解决这一问题。
2)并发症的早期诊断和预防:糖尿病的并发症,如视网膜病变、肾病变和神经病变,往往在显现症状之前已经发展多年。目前缺乏有效的早期诊断工具和更有力的预防措施。
3)心血管风险管理:糖尿病患者的心血管疾病风险显著增加,但如何有效管理这一风险仍是一个未解决的问题。
4)个性化治疗:由于糖尿病患者的个体差异极大,现有的一刀切治疗方案常常不能满足所有患者的需求。如何根据患者的具体情况制定个性化治疗方案是一个重大挑战。
5)精准医疗:虽然精准医疗已经在多个领域取得进展,但在糖尿病的应用还处于初步阶段,如何利用基因、环境和生活方式数据来精确预测和治疗糖尿病仍需进一步研究。
这些问题的解决需要跨学科的合作、科技的进步以及更多的临床研究和公共健康努力。
UNIVERSITY OF FLORIDA 的 ATKINSON, MARK A.
YALE UNIVERSITY 的 SHULMAN, GERALD I ARIZONA STATE UNIVERSITY-TEMPE CAMPUS 的 SHAIBI, GABRIEL QUANTUM DIABETES, DIGESTIVE, KIDNEY DISEASES 的 HANSON, ROBERT UNIVERSITY OF COLORADO DENVER 的 BENNINGER, RICHARD KP
科罗拉多大学丹佛分校 耶鲁大学 佛罗里达大学 密歇根大学安娜堡分校 斯坦福大学等
This U19 proposal focuses on one of the most important, complex questions in Alzheimer’s disease (AD) and Alzheimer’s disease-related dementias (ADRD) research: What are the determinants and the nature of cognitive impairment among persons with pre-diabetes (PreD) and type 2 diabetes (T2D), who are a high-risk group for cognitive impairment and represent a large fraction of the United States (US) population?
We propose 4 interrelated projects that will address these gaps, leveraging the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS) cohort and its detailed PreD/T2D phenotyping, adding state of the art AD/ADRD phenotyping.
We will address the complex overarching question of our project through the following aims:
(1) To establish 5 cores to support the 4 integrated scientific projects: An Administrative Core, a Clinical Operations and Procedures Core, a Cognitive Assessment and Adjudication Core, a Neuroimaging and Plasma Biomarkers Core, and A Biostatistics and Data Infrastructure Core:
(2) To conduct 4 integrated projects focused on key aspects of the central question of this proposal: Project 1 will examine the association of cognitive decline, MCI, and dementia in the DPPOS cohort with biomarkers of neuropathology and brain insulin signaling, and with sociodemographic and behavioral factors; Project 2 will examine the associations of cumulative glycemia, related metabolic factors, and microvascular and macrovascular complications, with cognitive syndromes and biomarkers of neuropathology;
Project 3 will examine the association of cumulative exposure to metformin and other T2D medications with cognitive syndromes and biomarkers of neuropathology;
Project 4 will evaluate the association of trajectories of physical activity, physical function and frailty with cognitive syndromes and biomarkers of neuropathology.