Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q2

Due to the fundamental importance of glucose as a cerebral fuel, a complex and redundant counterregulatory response to hypoglycemia exists in man. Some studies have shown that prior activation of GABA(A) receptors may result in blunting of counterregulatory responses during next day hypoglycemia.

The Specific Aim is to determine if repeated activation of GABA(A) receptors using Alprazolam will result in blunting of neuroendocrine, ANS and metabolic counterregulatory mechanisms during next day hypoglycemia in T1DM and healthy man.

Inclusion criteria

• 16 (8 males, 8 females) Type 1 diabetes patients aged 18-45 yr.
• 16 (8 males, 8 females) healthy controls aged 18-45 yr.
• HbA1c > 7.0% (Type 1 diabetes patients)
• Had diabetes for 2-15 years (Type 1 diabetes patients)
• No clinical evidence of diabetic tissue complications (Type 1 diabetes patients)
• Body mass index 21-30 kg · m-2
• Normal bedside autonomic function
• Normal results of routine blood test to screen for hepatic, renal, and hematological abnormalities
• Female volunteers of childbearing potential: negative HCG pregnancy test

Exclusion criteria

• Prior history of poor health: any current or prior disease condition that alters carbohydrate metabolism and prior cardiac events and/or evidence for cardiac disease
• Hemoglobin of less than 12 g/dl
• Abnormal results following screening tests
• Pregnancy
• Subjects unable to give voluntary informed consent
• Subjects with known liver or kidney disease
• Subjects taking steroids
• Subjects taking beta blockers
• Subjects on anticoagulant drugs, anemic, or with known bleeding diseases