Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus

The purpose of this study is to determine what corticosteroid receptor (and the dose of) is responsible for cortisol inducing hypoglycemia associated autonomic dysfunction in Type 1 DM. Specifically, we aim to determine whether stimulating the type 1 corticosteroid receptor (via fludrocortisone), the type 2 corticosteroid receptor (via dexamethasone), or both causes hypoglycemia associated autonomic dysfunction in Type 1 DM.

• Drug: Fludrocortisone
  Oral Fludrocortisone 0.2 mg x 2 prior to each experimental period on Day 1
• Drug: Dexamethasone
  Oral Dexamethasone 0.75 mg x 2 administered prior to each experimental period on Day 1

• Experimental: 1
  Day 1 hyperinsulinemic euglycemic clamps with either 0.2 mg fludrocortisone, 0.75 mg Dexamethasone, or both given orally before each morning and afternoon clamp. Day 2 hyperinsulinemic hypoglycemic glucose clamp.
  Intervention: Drug: Fludrocortisone
• Experimental: 2
  Fludrocortisone will be administered in doses of 0.05mg, 0.1mg and 0.2 mg form at the start of each clamp period on day 1. Dexamethasone will be administered orally in the doses of 0.18 mg, 0.375mg and 0.75mg doses. The combination of the 0.05mg fludrocortisone and 0.18mg dexamethasone and 0.1mg of fludrocortisone and 0.375 mg doses will be administered at the start of each day 1 clamp period. Day 2 90 minutes of moderate exercise.
  Intervention: Drug: Dexamethasone

Inclusion Criteria:

• 16 (8 males, 8 females) Type 1 diabetic patients aged 18-45 yr.
• HbA1c > 7.0%
• Had diabetes for 2-15 years
• No clinical evidence of diabetic tissue complications
• 16 (8 males, 8 females) Healthy volunteers aged 18-45 yrs.
• Body mass index < 27kg · m-2

Exclusion Criteria:

• Prior or current history of poor health
• Abnormal results following blood and physical examination
• Pregnancy