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

Study Overview
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Brief Summary
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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.

Official Title
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Hypoglycemia Associated Autonomic Failure in Type 1 DM, SSRI and Exercise

Conditions
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Type 1 Diabetes, Hypoglycemia Associated Autonomic Failure

Intervention / Treatment
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* Drug: Fluoxetine
* Drug: Placebo control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 32 (16 males, 16 females) Healthy controls aged 18-45 yr. 32 (16 males, 16 females) Type 1 diabetic patients aged 18-45 yr. HbA1c 6-10.0% Has been diagnosed Type 1 DM No clinically diagnosed diabetic tissue complications (i.e. history of retinopathy, neuropathy, stasis ulcers, etc) Body mass index < 40kg • m-2 Exclusion Criteria: Pregnant women Subjects unable to give voluntary informed consent Subjects on anticoagulant drugs, anemic or with known bleeding diatheses Subjects taking any of the following medications will be excluded: Non-selective Beta Blockers, Sedative-Hypnotics, Anticonvulsants, Antiparkinsonian drugs, Antipsychotics, Antidepressants, Mood stabilizers, CNS Stimulants, Opioids, Hallucinogens Subjects with a recent medical illness Subjects with a history of hypertension, heart disease, cerebrovascular incidents Current tobacco use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Trial 1-SSRI<br>90 minute exercise baseline with 6 weeks treatment with SSRI (Prozac). Repeat 90 minute exercise after 6 week treatment. | Drug: Fluoxetine<br>* 20 mg week 1, 40 mg week 2, 60 mg week 3, 80 mg week 4-6<br>* Other names: Prozac;|
| Placebo Comparator: Trial 2-Placebo<br>90 minute exercise at baseline with 6 weeks treatment with placebo. Repeat 90 minute exercise after 6 weeks treatment of placebo. | Drug: Placebo control<br>* 20 mg Week 1, 40 mg Week 2, 60 mg Week 3, 80 mg Week 4-6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Catecholamines | This change in catecholamines will be compared to another 90 minute experimental period after 8 weeks administration of SSRI or placebo. | During 90 minute experimental period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, diabetes, SSRIs