Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery

Several prospective cohort studies as well as randomized clinical trials (RCT) in cardiac
surgery patients have shown that intensified insulin therapy (target BG: 110-140 mg/dl)
results in a reduction in short- and long-term mortality compared with conventionally
treated patients. The results of recent international trials in critically ill patients;
however, have failed to show a significant improvement in mortality or have even shown
increased mortality risk as well as increased number of hypoglycemic events with intensive
compared to less intensive glycemic control. Based on the results of these ICU trials, new
ADA and AACE guidelines recommended a glycemic target between 140 and 180 mg/dl in the ICU
including cardiac surgery patients. There is concern that such high BG targets might
increase the risk of hospital complications in cardiac surgical patients in whom intensive
glucose control has consistently reduced infections, length of hospital stay, resource
utilization, and cardiac-related mortality. The overall objective of this proposal is to
conduct the first prospective RCT to determine the optimal BG target during the
perioperative period in hyperglycemic subjects who undergo CABG in the United States.
Subjects will be randomized to undergo intensive insulin therapy adjusted to maintain a BG
between 100 mg/dl and 140 mg/dl or to a conventional glucose control with a target BG
between 141 mg/dl and 200 mg/dl in the ICU. The central hypothesis of this proposal is that
intensive insulin management will reduce perioperative complications compared to a
conventional BG control in cardiac surgery patients.

Inclusion Criteria:

1. Males or females between the ages of 18 and 80 years undergoing primary, elective and
isolated CABG.

2. Post surgical hyperglycemia (BG > 140 mg/dl).

3. Patients with and without a history of type 2 diabetes

Exclusion Criteria:

1. Patients requiring combination CABG with additional procedures such as valve surgery
or aorta replacement.

2. Patients with severely impaired renal function (serum creatinine ≥3.0 mg/dl or GFR <
30 ml/min) or clinically significant hepatic failure.

3. Subjects with acute hyperglycemic crises such as diabetic ketoacidosis (DKA) and
hyperosmolar hyperglycemic state.

4. Moribund patients and those at imminent risk of death (brain death or cardiac
standstill).

5. Patients or next-to-kin with mental condition rendering the subject or family member
unable to understand the nature, scope, and possible consequences of the study.

6. Female subjects who are pregnant or breast-feeding at time of enrollment into the
study.