Overview
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.
Description
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.
Eligibility
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