Sulfonylurea Effects on Glucagon Regulation During Hypoglycemia in Type 1 DM

• rate of glucose recovery following insulin induced hypoglycemia with and without glibenclamide pretreatment [ Time Frame: cross-sectional ]
• cognitive function during insulin induced hypoglycemia with and without glibenclamide pretreatment [ Time Frame: cross-sectional ]

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).

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.

• Drug: glibenclamide
  glibenclamide 15 mg single dose
  Other Name: Daonil 5 mg pills
• Drug: placebo
  placebo capsules, single dose

• Experimental: A
  Glibenclamide 5 mg tablets
  Intervention: Drug: glibenclamide
• Placebo Comparator: B
  placebo capsules
  Intervention: Drug: placebo

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