Pilot 10: Mechanisms of Late Hypoglycemia in Cystic Fibrosis
P.I.: Steven Kahn, MB, ChB
Professor of Medicine
Metabolism, Endocrinology and Nutrition
Kristina Utzschneider, MD
Associate Professor of Medicine
Metabolism, Endocrinology and Nutrition
With the increased life expectancy of patients with cystic fibrosis (CF), other co-morbidities have become apparent in these patients. One of these is abnormal glucose metabolism, where CF-related diabetes (CFRD) is common. More recently, another abnormality of glucose metabolism has been recognized; namely late hypoglycemia following oral glucose loading. In this study, we propose to test the hypothesis that the post-glucose load hypoglycemia observed in patients with CF results from a deficient counterregulatory hormone response and/or an insulin response that is exaggerated and delayed. This increased insulin response could be the result of an exaggerated incretin hormone response or altered gastric emptying. To address this hypothesis, we will perform a 3-hour oral glucose tolerance test during which we will measure counterregulatory, islet and incretin hormone responses and determine the rate of gastric emptying using acetaminophen. To determine whether patients with CF and late hypoglycemia also have episodes of hypoglycemia during daily living that includes mixed meals, we will use a continuous glucose monitoring system (CGMS) to examine 24-hour glucose profiles for 3 days. All these measures will be compared between patients with CF who develop late hypoglycemia, CF patients who do not develop hypoglycemia, and age and body mass index-matched healthy controls. The findings from this study will provide important new information regarding the mechanism(s) responsible for the late hypoglycemia observed in patients with CF and the data could be used as the basis for future grant applications. The ultimate goal is to gain insight into the condition of late hypoglycemia in order to better manage patients with CF.