Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus (DM)

Exercise is a cornerstone of diabetes management. It helps reduce blood pressure, promote
weight loss, lower insulin resistance and improve glucose and lipid (triglyceride and
HDL-cholesterol) profiles. Unfortunately, the benefits of exercise are often not embraced by
diabetic individuals because of the fear of low blood sugar (hypoglycemia). My laboratory has
demonstrated that Autonomic nervous system (ANS) counterregulatory failure plays an important
role in exercise associated hypoglycemia in Type 1 DM. ANS responses are significantly
reduced in Type 1 DM and are further blunted by antecedent episodes of hypoglycemia.
Furthermore, there is a large sexual dimorphism of reduced ANS responses during submaximal
exercise in both Type 1 DM and healthy individuals that is unexplained. Accumulating data are
demonstrating that serotonergic pathways can regulate ANS discharge. Generally, serotonergic
pathways are inhibitory but both single and longer term administration of selective serotonin
reuptake inhibitors (SSRI's) such as Prozac has been demonstrated to increase basal
epinephrine levels and enhance baroreflex control of Sympathetic nervous system (SNS)
activity. What is unknown is whether fluoxetine can also enhance SNS responses and also
override the large ANS sexual dimorphism present during sub maximal exercise. Therefore, the
purpose of this study is to determine if the SSRI fluoxetine (Prozac) can improve SNS
responses during exercise.