Does Treatment Affect Cognition in Type 1 Diabetes?

描述（由申请人提供）： 1型糖尿病的神经心理学影响，其治疗及其代谢后果仍然存在争议。由于强化糖尿病治疗（IDT）大大增加了严重低血糖的风险，因此人们普遍认为（尽管未经证实）接受IDT治疗的患者的认知能力可能会受到影响。其他研究表明，持续的高血糖可能会影响中枢神经系统的完整性，从而损害认知能力。为了解决这些问题，我们建议研究一组特征明确、仔细随访的1型糖尿病患者，这些患者接受传统治疗或IDT治疗，作为糖尿病控制和并发症试验（DCCT）的参与者，并在医学和神经心理学结局方面进行评估。这些个体（n = 1409）目前正在接受额外12年的随访，作为糖尿病干预和并发症流行病学（EDIC）研究的一部分。到该研究结束时，该队列将平均随访18年，年龄约为46岁，平均糖尿病持续时间为24年。并发症的生物医学测量和评估，包括视网膜病变、神经病变和心血管风险因素和结果，在队列中定期和常规评估，并将可用于我们的分析，被认为与认知功能相关的遗传标记物也是如此，血管紧张素转换酶（ACE）和载脂蛋白E（APOE）基因型。我们将在EDIC结束时重新评估认知能力，使用原始DCCT神经心理学测试组合，并通过使我们能够在先前发现受糖尿病代谢异常影响的认知功能的几个方面表征患者的措施进行增强。我们的研究旨在解决三个主要假设：1）与常规治疗组相比，DCCT期间接受强化糖尿病治疗（IDT）的患者在DCCT进入期间的六个认知功能领域的下降较少。2)具有更好的先前血糖控制的个体，如通过在DCCT和EDIC的持续时间内较低的平均HbAlc所指示的，将表现出相对于DCCT进入的较少的认知下降，特别是在精神效率（处理速度）和简单运动速度的领域。3)在DCCT和EDIC持续时间内严重低血糖发作较少的个体相对于DCCT条目显示出较少的认知下降，特别是在抽象推理，积木设计，物体组装和符号数字学习的测量上。此外，我们将研究关键的人口统计学和生物医学变量，如糖尿病发病年龄，性别和当前年龄，高血压史，血脂水平和心血管状态（通过颈动脉内膜中层增厚和冠状动脉钙化评估）对认知功能的影响。这项研究具有独特的地位，可以为糖尿病及其治疗对中枢神经系统功能的影响提供重要证据，并将扩大我们对生物医学因素和认知相互作用的理解。

DESCRIPTION (provided by applicant): The neuropsychological effects of type 1 diabetes, its treatment and its metabolic consequences remain controversial. Because intensive diabetes therapy (IDT) greatly increases the risk of severe hypoglycemia, it is widely believed -- though unproven -- that cognitive skills may be compromised in patients treated with IDT. Other research suggests that persistent hyperglycemia may affect the integrity of the central nervous system and thereby compromise cognitive ability. To resolve these issues, we are proposing to study a well-characterized, carefully followed group of patients with type 1 diabetes who were treated with either conventional therapy, or with IDT as participants in the Diabetes Control and Complications Trial (DCCT), and were evaluated in terms of medical and neuropsychological outcomes. These individuals (n = 1409) are currently being followed for an additional 12 years, as part of the Epidemiology of Diabetes Intervention and Complications (EDIC) study. By the end of that study, the cohort will have been followed for 18 years on average and will be approximately 46 years old with an average duration of diabetes of 24 years. Biomedical measures and assessments of complications, including retinopathy, neuropathy, and cardiovascular risk factors and outcomes are regularly and routinely assessed in the cohort and will be available for our analyses, as will genetic markers thought to be associated with cognitive functioning e.g., angiotensin converting enzyme (ACE) and apolipoprotein E (APOE) genotypes. We will reassess cognitive ability at the end of the EDIC, using the original DCCT neuropsychoiogical test battery, augmented by measures that will allow us to characterize patients on several aspects of cognitive functioning previously found to be affected by metabolic abnormalities of diabetes. Our research aims to address three primary hypotheses: 1) The group treated with intensive diabetes therapy (IDT) during the DCCT will show less of a decline on six domains of cognitive function relative to DCCT entry compared to those in the conventional therapy group. 2) Individuals with better prior glycemic control, as indexed by a lower mean HbAlc over the duration of the DCCT and the EDIC, will manifest less cognitive decline relative to DCCT entry, particularly on domains of psychomotor efficiency (processing speed) and simple motor speed. 3) Individuals with fewer episodes of severe hypoglycemia over the duration of the DCCT and EDIC will show less of a cognitive decline relative to DCCT entry, particularly on measures of abstract reasoning, block design, object assembly and symbol digit learning. In addition, we will examine the effects of key demographic and biomedical variables such as age of diabetes onset, gender and current age, history of hypertension, lipid levels and cardiovascular status (assessed by carotid intimal-medial thickening and calcification of coronary arteries) on cognitive functioning. The proposed study is in unique position to provide important evidence about the effects of diabetes and its treatment on central nervous system functioning and will extend our understanding of the interplay of biomedical factors and cognition.