Glucose Control in Severely Burned Patients

• Perform oral glucose tolerance test [ Time Frame: at 1-2 months post-admission, up to 6 months ] [ Designated as safety issue: No ]
  Standard fasting oral glucose tolerance test with an intake of 75 g of glucose. Subsequent measurements (in mg/dl) of glucose in blood, insulin and c-peptide will be conducted over 2 hours.
• Perform oral glucose tolerance test [ Time Frame: assessed at discharge (1-4 months post admission depending on the severity of injury) ] [ Designated as safety issue: No ]
  Standard fasting oral glucose tolerance test with an intake of 75 g of glucose. Subsequent measurements (in mg/dl) of glucose in blood, insulin and c-peptide will be conducted over 2 hours.

• Measure concentrations of serum cytokines [ Time Frame: weekly until discharge (1-4 months post admission depending on severity of injury) ] [ Designated as safety issue: No ]
  Inflammatory response will be assessed by measuring the concentrations (in pg/ml)of a panel of serum cytokines (IL-1, IFN, TNF etc.) using the Bio-Plex 17-Plex Suspension assay.
• Record the episodes of sepsis [ Time Frame: daily until discharge (1-4 months post admission depending on severity of injury) ] [ Designated as safety issue: No ]
  Patients will be assessed daily for episodes of sepsis. The total number of episodes over the course of hospital stay will be recorded.
• Record the episodes of Pneumonia [ Time Frame: daily until discharge (1-4 months post admission depending on severity of injury) ] [ Designated as safety issue: No ]
  Pneumonia is defined by new progressive and persistent infiltrate, consolidation or cavitations, inhalation injury based on chest X-ray. We will also follow the guidelines provided by the American Burn Association on the definition of Pneumonia in burn patients. Change in sputum (purulent or increased) will also be recorded.

The central aim of this application is to determine whether improved outcomes with tight euglycemic control are due to insulin-specific responses. The investigators hypothesize that improving insulin resistance will lead to decreased inflammatory and hypermetabolic responses, as well as restored glucose metabolism, and so result in improved clinical outcome of severely burned patients.

• Drug: Humulin R
  Humulin R (U-100) will be given i.v. The dose given will be adjusted in order to achieve a blood glucose level of 130-140 mg/dl.
• Drug: Metformin
  Metformin 850 mg q. 8 hours will be given to decrease blood glucose to 130-140 mg/dl.

• Experimental: Metformin
  Intervention: Drug: Metformin
• Experimental: Insulin
  Intervention: Drug: Humulin R
• No Intervention: Control

Inclusion Criteria:

• between 18 and 90 years of age
• >20% TBSA
• Admitted to the burn unit within 120 hours following burn
• At least 1 surgical intervention necessary

Exclusion Criteria:

• death upon admission
• decision not to treat due to burn injury severity
• presence of anoxic brain injury that is not expected to result in complete recovery
• known history of AIDS, ARC, HIV, Hepatitis B-E
• history of cancer within 5 years of malignancy currently under treatment
• inability to obtain informed consent
• previous or existing renal dysfunction, liver disease, or hepatic dysfunction
• pre-existing type I diabetes mellitus
• pregnancy
• allergy to metformin