Glucagon-like Peptide-1 in Type 1 Diabetes

Study Overview
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Brief Summary
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The hypotheses to be tested in this application is: GLP-1 will acutely protect arterial endothelial function and reduce pro-atherothrombotic and pro-coagulant effects of repeated hypoglycemia in T1DM.

Detailed Description
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The naturally occurring hormone GLP-1 when co-administered during hypoglycemia (low blood sugar) in non-diabetic individuals can reduce the deleterious effects of hypoglycemia on the vasculature. We have shown that IV infusion of GLP-1 during a single moderate episode of hypoglycemia can preserve endothelial function and protect the vasculature from pro-coagulant and pro-inflammatory effects in healthy individuals. It is unknown whether GLP-1 could protect the vasculature during episodes of repeated hypoglycemia and whether GLP-1 would have protective effects in T1DM individuals.

Official Title
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Reducing Hypoglycemic, Pro-coagulant and Pro-atherothrombotic Responses and Preventing Hypoglycemia Associated Autonomic Failure in Type 1 DM. The Effects of Glucagon-like Peptide-1

Conditions
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Type1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Glucagon-like peptide-1
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40 (20 males, 20 females) individuals with type 1 diabetes aged 18-50 yr. HbA1c < 11.0% Body mass index < 40kg • m-2 No clinically diagnosed diabetic tissue complications (i.e. history of retinopathy, neuropathy, stasis ulcers, etc) Exclusion Criteria: Subjects unable to give voluntary informed consent Pregnancy 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 unwillingness or inability to comply with approved contraception measures Subjects with a history of severe uncontrolled hypertension (i.e., blood pressure greater than 160/100), heart disease, cerebrovascular incidents Clinically significant cardiac abnormalities (e.g. heart failure, arrhythmias, ischemic tachycardia, S-T segment deviations, etc.) from history or from cardiac stress testing in subjects ≥ 40 years old. Pneumonia Hepatic failure /jaundice Abnormal results following screening tests and physical examination that are clinically significant Acute cerebrovascular/ neurological deficit Fever greater than 38.0 C Screening Laboratory Tests Exclusion Criteria Hematocrit lower than 32 WBC lower than 3 thou/ul or greater than 14 thou/ul Liver function tests: SGOT and SGPT greater than twice upper limit of normal range (i.e. > 80 U/L) TBil > 2 mg/dl Creatinine > 1.6 mg/dl Alkaline phosphatase > 150U/L Hepatic transaminase > 2x normal

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo 1<br>The participants will be randomized to placebo infusion. | Drug: Placebos<br>* Infusion of normal saline solution that will mimic Glucagon-like peptide-1<br>|
| Placebo Comparator: Placebo 2<br>The participants will be randomized to placebo infusion. | Drug: Placebos<br>* Infusion of normal saline solution that will mimic Glucagon-like peptide-1<br>|
| Experimental: GLP-1<br>The participants will be randomized to Glucagon-like peptide-1 infusion. | Drug: Glucagon-like peptide-1<br>* Infusion of Glucagon-like peptide-1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the level of catecholamines in plasma |  | 3 years |