WASHINGTON — Diabetes doesn't kill inpatients; high blood sugar does. That was the underlying theme of a consensus conference sponsored by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the American Diabetes Association.
In separate talks at the meeting, Dr. Anthony P. Furnary and Dr. Irl B. Hirsch presented some of the accumulating evidence supporting the notion that the “diabetic disadvantage” in morbidity and mortality—particularly with regard to cardiovascular outcomes—can be largely mitigated by normalization of glucose levels while patients are in the hospital.
“Diabetes per se is not a risk factor for increased mortality, length of stay, deep sternal wound infection, or postoperative complication rates in cardiac surgery patients. [Hyperglycemia] is the true risk factor,” said Dr. Furnary, a cardiothoracic surgeon at Providence Heart and Vascular Institute and Providence St. Vincent Medical Center, Portland, Ore.
He presented the latest data from the ongoing Portland Diabetic Project, a prospective, nonrandomized interventional study of the relation between inpatient glucose levels and hospital outcomes in patients with diabetes undergoing cardiac surgery. The study began in 1987. In 1992, the group instituted the Portland Protocol, a finely tuned set of orders for insulin infusions for use in the operating room, in the intensive care unit, and on the wards.
Of the 5,619 diabetic patients who underwent open heart surgery from 1987 through the end of 2005, 91% underwent coronary artery bypass grafting (CABG). Glucose levels were measured every 30–120 minutes throughout the patients' stay, and the average glucose from the first 3 perioperative days was calculated. This average, termed “3-BG,” was used to assess overall glycemia for each patient.
Glucose targets for the insulin infusion protocol have been ratcheted down over the years, from 150–200 mg/dL in 1992 to 70–120 mg/dL in 2005. At first, the infusion was used only in the ICU, but in 1995 its use was expanded into the operating room and onto the non-ICU floors as well. For the 210 diabetic patients who underwent open heart surgery at the Portland hospital in 2005, the daily average 3-BG across all three hospital settings was 121 mg/dL.
During 1987–2005, inpatient CABG mortality was 1.6% for the 2,886 CABG patients with a 3-BG less than 200 mg/dL, compared with 4.4% for the 1,552 with 3-BG greater than 200 mg/dL. When broken down by glucose sextile, mortality ranged from 0.7% for those with 3-BG less than 150 mg/dL to 2.5% with 3-BG 175–200 mg/dL, up to 14% for those whose blood sugars averaged more than 250 mg/dL during their first 3 perioperative days.
In a multivariate analysis, the highly significant impact of 3-BG on CABG mortality was independent of epinephrine use. After adjustment for other preoperative risk factors such as age, ejection fraction, and renal failure, the insulin infusions independently reduced mortality by 60%, said Dr. Furnary. Mortality in CABG patients in the Portland Diabetic Project has dropped steadily over time, whereas mortality in nondiabetic patients hasn't changed. Now the mortality for both groups averages 0.9%, compared with 3.4% in diabetic CABG patients nationwide, he said.
Rates of other outcomes are also being found to be strongly related to 3-BG levels. Deep sternal wound infections have occurred in just 0.6% of patients with 3-BG less than 150 mg/dL, compared with 1.1% with 3-BG 175–200 mg/dL and 3.7% with 3-BG greater than 250 mg/dL. Compared with 3-BG below 175 mg/dL, deep sternal wound infections are more than three times more likely among patients with levels above that value.
Dr. Hirsch, medical director of the University of Washington Diabetes Care Center, Seattle, said two major trials published in 2005 supporting the same conclusion have been misinterpreted as negative.
One was a multinational study of 1,253 patients with type 2 diabetes and suspected MI randomized to either a glucose/insulin/potassium (GIK) infusion for 24 hours followed by a home insulin prescription, GIK infusion followed by standard glucose control, or routine metabolic management. Although there were no differences in survival at 2 years by treatment group, an epidemiologic analysis confirmed that fasting blood glucose at baseline and during the study strongly predicted mortality, with an odds ratio of 1.20 (Euro. Heart J. 2005;26:650–61).
In another large international, randomized trial that received a lot of attention last year, GIK infusions also had no effect on mortality, cardiac arrest, or cardiogenic shock among more than 10,000 patients with acute ST-segment elevation MI (JAMA 2005;293:437–46). But in this study, the GIK group actually had higher blood glucose values at 24 hours than did the controls (155 mg/dL vs. 135 mg/dL).