University of Minnesota Clinical Center for the Restoration of Impaired Awareness of Hypoglycemia in Type 1 Diabetes

点击翻译按钮获取中文摘要

Hypoglycemia (HG) is common in the lives of people with type 1 diabetes (T1D) and may prevent them from achieving the benefits associated with optimal glycemic control. Recurrent HG over a few days to weeks may lead to the condition of impaired awareness of HG (IAH) where the first sign of a low blood sugar is confusion or unconsciousness. Avoiding HG is associated with a reduced risk of IAH and when strictly done, may restore HG in some but not all patients with IAH. The reason for this heterogeneity in response remains uncertain.The purpose of this application is to apply to become part of a consortium that will implement a protocol designed to restore awareness of HG in persons with T1D and IAH. As instructed by the FOA, we address the following objectives in our application: 1. Determine if diabetes care with use of the most up-to-date management strategies with T1D and IAH. 2. Determine the physiological factors that are associated with restoration of HG awareness, including but not limited to age, duration of diabetes and metrics of glycemia. 3. Determine the association of the current self-report questionnaires (or develop new questionnaires or metrics) for identification of IAH with measurement of CRR using "state of the art" metabolic assessments. To meet objective 1, we propose the consortium enroll 650 subjects with T1D and IAH into a randomized clinical trial where a 12-month intervention of HG avoidance education and use of a hybrid closed loop system for insulin infusion is compared to standard care (which includes HG avoidance education, insulin administration via regular pump or injections, and CGM usage). With epinephrine response during the hypoglycemic clamp at 12 months as our primary outcome variable, we will test the hypothesis that subjects in the closed loop intervention arm will have a greater epinephrine response during the hypoglycemic clamp at 12 months of follow- up than will subjects in the control arm. To meet objective 2, we will collect information about glycemic variability, food quality and quantity, physical activity, sleep, stress, mood, and feelings about HG as well as patient characteristics such as HG induced glucagon secretion, residual C-peptide secretion, and diabetes duration. This information will then be explored using machine learning techniques to see what exposures and experiences correlate with IAH restoration. To meet objective three, we will compare the concordance of the Clarke, Gold, and Hypo-AQ questionnaires at categorizing subjects into IAH and NAH groups. The scores on each of the questionnaires will also be correlated with objective measures of the counterregulatory response.