Sulfonylurea Effects on Glucagon Regulation During Hypoglycemia in Type 1 DM

Study Overview
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Brief Summary
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We aim to demonstrate that oral administration of glibenclamide stimulates pancreatic glucagon secretion during hypoglycemia in insulin-deficient (C-peptide negative) patients with type 1 diabetes when compared to type 1 diabetic patients with residual insulin secretion (C-peptide positive).

Detailed Description
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The glucagon response during insulin induced hypoglycemia and rate of glucose recovery will be monitored in 10 C-peptide positive and 10 C-Peptide negative patients with type 1 DM following the application of glibenclamide and placebo in a randomized, single-blind, cross-over study. Cognitive function during hypoglycemia with and without glibenclamide pretreatment will be a secondary outcome.

Official Title
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Effect of a Sulfonylurea Compound on the Glucagon Response to Insulin-induced Hypoglycemia in Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: glibenclamide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 to 50 years Patients diagnosed with C-peptide negative diabetes type 1 (C-peptide <200 pmol/L 6 min after 1 mg glucagon i.v. at plasma glucose concentrations between 5 and 11 mmol/l) Patients diagnosed with C-peptide positive diabetes type 1 (C-peptide > 500 pmol/l 6 min after 1 mg glucagon i.v. at plasma glucose concentrations between 5 and 11 mmol/l) Stable metabolic control; HbA1c levels <8.0 % and without episodes of antecedent severe hypoglycemias in the past four weeks Exclusion Criteria: Patients treated with medications potentially interfering with glucose metabolism, such as systemic steroids, immunosuppressive drugs (cyclosporine, tacrolimus, sirolimus), highly active antiretroviral therapy History coronary artery disease History of epilepsy or seizures Current smokers Any significant or unstable hepatic, cardiac, pulmonary, renal, neurological, musculoskeletal, hematological or endocrine disease. Pregnant or breast feeding women Woman of childbearing potential not using a reliable method of birth control such as oral contraceptives or IUD. Subjects refusing or unable to give written informed consent

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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Glibenclamide 5 mg tablets | Drug: glibenclamide<br>* glibenclamide 15 mg single dose<br>* Other names: Daonil 5 mg pills;|
| Placebo Comparator: B<br>placebo capsules | Drug: placebo<br>* placebo capsules, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma glucagon concentrations during insulin induced hypoglycemia with and without glibenclamide pretreatment |  | cross-sectional | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of glucose recovery following insulin induced hypoglycemia with and without glibenclamide pretreatment |  | cross-sectional | 
| cognitive function during insulin induced hypoglycemia with and without glibenclamide pretreatment |  | cross-sectional | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes mellitus type 1, hypoglycemia, sulfonylurea, glucagon