Markers of Beta Cell Dysfunction and Hypoglycemia in ACCORD

ACCORD 中 β 细胞功能障碍和低血糖的标志物

• 批准号: 8335452
• 负责人: ELIZABETH R. SEAQUIST
• 金额: $ 14.07万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8335452
• 关键词: Acute; African American; Age; Antibodies; Attenuated; Autoantibodies; Autoimmunity; Beta Cell; Biological Markers; C-Peptide; Cardiac; Caring; Cell physiology; Cessation of life; Clinical; Complication; Diabetes Mellitus; Diabetic Angiopathies; Educational Status; Epinephrine; Ethnic Origin; Fasting; Female; Fright; Functional disorder; Glucagon; Glycosylated hemoglobin A; Goals; Hormones; Hydrocortisone; Hypoglycemia; IA-2 protein; Insulin; Insulin-Dependent Diabetes Mellitus; Islet Cell; Knowledge; Measures; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Patients; Protein Tyrosine Phosphatase; Public Health; Risk; Risk Factors; Serum; Somatotropin; Study Subject; Testing; Time; Visit; arm; base; cohort; diabetes mellitus therapy; experience; glycemic control; improved; insulin secretion; islet; mortality; response; sex; trial comparing

DESCRIPTION (provided by applicant): Hypoglycemia is a feared complication of diabetes therapy, with consequences ranging from inconvenience to death. In the ACCORD cohort, severe symptomatic hypoglycemia was associated with an increased risk for mortality. The purpose of this project is to use the ACCORD cohort to identify biomarkers that would predict severe hypoglycemia, with the long-range goal of individualizing diabetes therapy based on selection of the safest approach for each patient. In this project we will test the overall hypothesis that two biomarkers of insulin deficiency - reduced fasting serum C-peptide concentrations and detectable levels of antibodies associated with islet autoimmunity - are strongly associated with severe hypoglycemia and death in the ACCORD cohort. Our specific aims are: Aim 1a: To measure baseline fasting serum C-peptide at baseline in subjects who died and experienced severe hypoglycemia during the ACCORD trial and compare to baseline values measured in matched ACCORD subjects who did not experience death and severe hypoglycemia during the trial. Aim 1b: To measure baseline autoantibodies to GAD 65 (GAD), intracytoplasmic domain of the tyrosine phosphatase-like protein IA-2 (IA-2A) and insulin (IAA) in subjects who died and experienced severe hypoglycemia during the ACCORD trial and compare to baseline values measured in matched ACCORD subjects who did not experience death and severe hypoglycemia during the trial. Aim 2a: To measure fasting serum C-peptide at baseline in subjects in the intensive arm who experienced severe hypoglycemia despite failing to achieve a hemoglobin A1c < 6.0% at any visit prior to study completion or death and compare to values measured in matched ACCORD subjects in the intensive arm who achieved target glycemia on at least one occasion and completed the trial without severe hypoglycemia. Aim 2b: To measure GAD, IA-2A, and IAA at baseline in subjects in the intensive arm who experienced severe hypoglycemia despite failing to achieve a hemoglobin A1c < 6.0% at any visit prior to study completion or death and compare to values measured in matched ACCORD subjects in the intensive arm who achieved target glycemia on at least one occasion and completed the trial without severe hypoglycemia.

描述（由申请人提供）：低血糖是糖尿病治疗中令人担忧的并发症，其后果包括不便甚至死亡。在 ACCORD 队列中，严重症状性低血糖与死亡风险增加相关。该项目的目的是利用 ACCORD 队列来识别可预测严重低血糖的生物标志物，长期目标是根据为每位患者选择最安全的方法来进行个体化糖尿病治疗。在这个项目中，我们将测试总体假设，即胰岛素缺乏的两个生物标志物——空腹血清 C 肽浓度降低和与胰岛自身免疫相关的抗体的可检测水平——与 ACCORD 队列中的严重低血糖和死亡密切相关。我们的具体目标是： 目标 1a：测量在 ACCORD 试验期间死亡并经历严重低血糖的受试者的基线空腹血清 C 肽，并与试验期间未经历死亡和严重低血糖的匹配 ACCORD 受试者测量的基线值进行比较。目标 1b：测量在 ACCORD 试验期间死亡并经历严重低血糖的受试者的 GAD 65 (GAD)、酪氨酸磷酸酶样蛋白 IA-2 胞浆内结构域 (IA-2A) 和胰岛素 (IAA) 的基线自身抗体，并与试验期间未经历死亡和严重低血糖的匹配 ACCORD 受试者测量的基线值进行比较。目标 2a：测量强化组受试者的基线空腹血清 C 肽，这些受试者尽管在研究完成或死亡之前的任何访视中均未能达到糖化血红蛋白 < 6.0%，但仍经历了严重低血糖，并与强化组中匹配的 ACCORD 受试者（至少一次达到目标血糖并在完成试验时未出现严重低血糖）的测量值进行比较。目标 2b：在研究完成或死亡之前的任何访视中，尽管未能达到 A1c 血红蛋白 < 6.0%，但仍经历严重低血糖的强化组受试者在基线时测量 GAD、IA-2A 和 IAA，并与至少一次达到目标血糖并在完成试验时未出现严重低血糖的强化组匹配的 ACCORD 受试者中测量的值进行比较。