Iatrogenic hypoglycemia is the most serious acute complication in intensively insulin-treated diabetes and it remains the limiting factor in maintaining proper glycemic control. The brain, and especially the ventromedial hypothalamus (VMH), plays a crucial role in sensing hypoglycemia and in initiating the physiological "counterregulatory" responses that correct it. However, both reoccurring exposure to hypoglycemia and longstanding diabetes can impair the mechanisms that normally correct hypoglycemia. This research proposal addresses whether diabetes and antecedent hypoglycemia alter brain fuel metabolism in a manner that prevents it from properly sensing falling blood glucose levels. The long-term objectives of this research are to understand how the brain senses changes in blood glucose levels, how it communicates these signals to peripheral organs to initiate counterregulatory responses and why these mechanisms are impaired with antecedent hypoglycemia and in diabetes. It is essential that we achieve a better understanding of how the body detects and activates defense mechanisms against hypoglycemia so that appropriate therapies can be developed to more effectively prevent hypoglycemia outcomes in diabetic patients. If proven successful, these studies could potentially reveal new therapeutic targets for the development of insulin co-therapies.

Public Health Relevance

Achieving a better understanding of how the body detects and activates defense mechanisms against low blood sugars or hypoglycemia is essential for developing appropriate therapies to more effectively prevent hypoglycemia outcomes in diabetic patients. If hypoglycemia can be prevented, it will enable physicians to treat diabetes more aggressively and allow patients to achieve more optimal glucose targets, decrease the risk of diabetic complications and improve lifelong outcomes. This will undoubtedly have a significant impact on the ~24 million Americans who currently suffer from diabetes and alleviate some of the $174B in healthcare dollars that go into treating diabetes and its associated complications such as neuropathy, cardiovascular and renal complications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK099315-01
Application #
8559134
Study Section
Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
Program Officer
Teff, Karen L
Project Start
2013-08-15
Project End
2018-05-31
Budget Start
2013-08-15
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$362,138
Indirect Cost
$144,638
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520