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.