Metabolic Adaptation to Diabetes

There is very little data available on the neuroendocrine response to hypoglycemia in intensively treated (sulfonylurea or insulin) NIDDM patients. The data that are available on the neuroendocrine response to hypoglycemia in NIDDM patients were obtained under conditions following a single IV bolus of insulin or single SQ regular insulin injection. The neuroendocrine response following a large IV bolus of insulin differs greatly from the clinical paradigm of a slow progression into hypoglycemia. Therefore, clinically relevant data cannot be obtained from short experiments involving rapid changes in plasma glucose levels and insulinemia. Furthermore, a comparison between neuroendocrine responses to hypoglycemia in NIDDM and normal man is not available due to the fact that glycemia has never been equally controlled. In short, virtually nothing is known about the neuroendocrine response to hypoglycemia in these subjects. This is of great concern as following the positive outcome of the Kumamato study, large numbers of NIDDM subjects are going to receive intensive therapy with all its altendent risks of severe hypoglycemia. The Kumamato study was a trial in NIDDM patients to determine if intensive therapy reduces tissue complications of diabetes. Similar to the results of the Diabetes control and complications trial in IDDM patients the Kumamato study proved that intensive therapy in NIDDM patients also prevents diabetic tissue complications. Therefore, the goals of this study are 1) to define in greater detail how the body defends itself against hypoglycemia in NIDDM patients and 2) to determine if differing levels of insulin affect hypoglycemic counterregulation in NIDDM patients.