This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.ABSTRACT Previously type 2 diabetes mellitus (T2DM) was considered a disease of the adult; however, the incidence of T2DM in children is on the rise. Consequently, complications may occur at an earlier age, underscoring the importance of improving glycemic control in the pediatric population. Postprandial hyperglycemia contributes significantly to poor glycemic control in T2DM. We now understand that in addition to insulin other hormones (glucagon, amylin and GLP-1) may play a role in the postprandial glucose metabolism. The role of gastric emptying has been increasingly recognized as an important factor in regulating glucose appearance into the circulation. Abnormalities in the pancreatic hormone amylin and the incretin GLP-1 have emerged as contributors to the alterations in gastric emptying and postprandial hyperglycemia in T2DM. Although much is know about the abnormalities related to postprandial hyperglycemia in adults with T2DM, little information is available in the pediatric population. This protocol will examine gastric emptying, glucagon, GLP-1 and amylin secretions in healthy lean, obese children with and without diabetes post-ingestion of a mixed meal. The subject will be age and Tanner stage matched. The goal of this project is to better understand the metabolic adaptations of postprandial glucose homeostasis in T2DM by comparing our study group to obese (normal glucose tolerance) and healthy (lean) controls. The long-term goal for the PI is to use the data gathered with this protocol to develop a K-23 proposal incorporating new therapeutic options through the use of amylin and GLP-1 analogs in children with T2DM to improve postprandial hyperglycemia.I. HYPOTHESISAdolescents with T2DM will have decreased postprandial amylin and GLP-1 secretion and accelerated gastric emptying when compared with healthy (lean) and obese controlsII.
SPECIFIC AIMS To study postprandial metabolism in obese and T2DM adolescents using a mixed meal challenge. Specifically we will be measuring the following parameters of postprandial metabolism:1. Postprandial glucose excursions 2. Gastric emptying 3. Insulin, amylin, glucagon and GLP-1 secretion4. Ghrelin secretion5. Glucose Turnover rate
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