Effect of Ethanol Intoxication on the Anti-Hypoglycemic Action of Glucagon

This study will test the hypothesis that a BAC (blood alcohol content) of 0.1% will not significantly alter the anti-hypoglycemic effect of mico-dose glucagon in individuals with type 1 diabetes. The study will aim to quantify the effect of a blood alcohol content on the anti-hypoglycemic efficacy of glucagon using a hyperinsulinemic -normoglycemic clamp technique in volunteers with type 1 diabetes in a randomized crossover trial.

• Inclusion Criteria:

• Age 21 to 80 years old with type 1 diabetes for at least one year.
• Diabetes managed using an insulin infusion pump using rapid-acting insulin such as insulin aspart (NovoLog), insulin lispro (Humalog), or insulin glulisine (Apidra) for at least one week prior to enrollment.
• Alcohol exposure on at least one occasion in the last year consisting of at least 4 drinks in one sitting.
• Exclusion Criteria:

• Unable to provide informed consent.
• Unable to comply with study procedures.
• Unable to refrain from the consumption of alcohol at least 24 hours prior to study start.
• Current participation in another diabetes-related clinical trial that, in the judgment of the principle investigator, will compromise the results of the clamp study or the safety of the subject.
• Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception.
• Aldehyde dehydrogenase deficiency as determined by a screening questionnaire
• End stage renal disease on dialysis (hemodialysis or peritoneal dialysis).
• History of pheochromocytoma (because glucagon has been reported to precipitate hypertensive crisis in the setting of pheochromocytoma). Fractionated metanephrines will be tested in patients with a history increasing the risk for a catecholamine secreting tumor:
• Paroxysms of tachycardia, pallor, or headache. Personal or family history of MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease, Episodic or treatment of refractory (requiring 4 or more medications to achieve normotension) hypertension.
• History of adverse reaction to glucagon (including allergy) besides nausea, vomiting, or headache.
• Inadequate venous access as determined by study nurse or physician at time of screening.
• Liver failure or cirrhosis
• Hemoglobin < 12 gm/dl.
• History of problem drinking or alcoholism, regardless of whether active or in remission.
• Use of benzodiazepines or barbiturates or opiates or other central nervous system depressant drugs that could act synergistically with ethanol to lower the level of consciousness
• Any other factors that, in the judgment of the principal investigator, would interfere with the safe completion of the study procedures.