Diabetic Children Grow Up: Cognitive Complications

描述（由申请人提供）：在1980年，我们开始了一系列的儿童神经心理学研究，10至19岁，有和没有1型糖尿病。我们发现，与诊断年龄较晚的患者或非糖尿病患者相比，那些在生命的前5或6年内患上糖尿病的患者更有可能表现出广泛的、临床上显著的认知障碍。尽管潜在的病理生理机制仍有争议，但我们现在认为，在大脑发育的关键时期发生糖尿病相关的慢性高血糖会对中枢神经系统产生不利影响，并增加其对随后脑损伤的脆弱性，特别是与中度严重低血糖发作相关的中枢神经系统。这些缺陷是否反映了可逆的发育迟缓，或者它们是否是永久性脑损伤（可能随着时间的推移而恶化）的证据，就像它们对成人功能的影响一样，仍然未知。我们提出的研究目标是重新联系那些在1980年至1983年（平均年龄为14.5岁，初始人数为226岁）期间首次就诊的患者，并邀请他们完成详细的神经心理学评估、精神病学诊断访谈、生活质量测量和职业调整。糖尿病患者还将进行体格检查，以确定生物医学并发症和回顾既往低血糖发作。我们的研究有两大目标：首先，为了检验早发性脆弱假说，预测6岁之前被诊断为糖尿病的成年人，随着时间的推移，与那些晚发性糖尿病的人相比，认知功能会出现更大的恶化，所有的认知领域都会受到影响，最终会导致更少的职业成就和更差的生活质量，这将通过间歇性低血糖发作的次数来预测，以及糖尿病并发症的发生率。其次，我们的目标是提供糖尿病患者在成年中期的神经精神状态的全面概况，并确定低血糖事件以及其他生物医学和社会心理因素预测这些结果的程度。这将是第一个描述从童年晚期到成年中期认知功能变化的糖尿病患者研究，也是第一个将功能变化与糖尿病相关的生物医学变量联系起来的研究。

DESCRIPTION (provided by applicant): In 1980, we initiated a series of neuropsychological studies of children, 10 to 19 years of age, with and without type 1 diabetes. We found that those who developed diabetes within the first 5 or 6 years of life were more likely to manifest widespread, clinically significant cognitive impairment, as compared to those with a later age at diagnosis, or to nondiabetic comparison subjects. Although the underlying pathophysiological mechanism remains controversial, we now believe that occurrence of diabetes-associated chronic hyperglycemia during a critical period of brain" development adversely affects the central nervous system, and increases its vulnerability to subsequent brain insults, particularly those associated with moderately severe hypoglycemic episodes. Whether these deficits reflect reversible developmental delays, or whether they are evidence of permanent brain damage (which may worsen over time) remains unknown, as does their effect on adult functioning. The goal of our proposed study is to re-contact those individuals first seen by us between 1980 and 1983 (Mean age = 14.5 yrs; initial number: 226) and invite them to complete a detailed neuropsychological assessment, a psychiatric diagnostic interview, and measures of quality of life and vocational adjustment. Diabetic subjects will also have a physical examination with tests to ascertain biomedical complications and review of prior hypoglycemic episodes. Our study has two broad aims: First, to test the early onset vulnerability hypothesis, predicting that adults diagnosed with diabetes before 6 years of age will show greater deterioration in cognitive functioning over time, compared to those with a later onset of diabetes, that all cognitive domains will be affected, that this will eventuate in less vocational attainment and poorer quality of life, and that this will be predicted by number of intercurrent episodes of hypoglycemia, as well as by the incidence of diabetic complications. Second, we aim to provide a comprehensive profile of diabetic patients' neuropsychiatric status in middle-adulthood, with determination of the extent to which hypoglycemic events as well as other biomedical and psychosocial factors predict those outcomes. This will be the first study of diabetic patients to delineate changes in cognitive functioning from late childhood into middle-adulthood, and the first to link functional changes to diabetes-related biomedical variables.