Effect of Ethanol Intoxication on the Anti-Hypoglycemic Action of Glucagon
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1
Intervention: Ethanol; Glucagon
Intervention description: IV infusion of ethanol to stabilize BAC (blood alcohol content) at 0.1%; injection of 50 micrograms of glucagon
Intervention MeSH terms: Ethanol; Glucagon
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Type 1 Diabetes; Bionic Pancreas; Artificial Pancreas; Insulin; Glucagon; Alcohol; Alcohol Clamp

Summary:

      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.
    

Eligibility criteria:

        -  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.