Patients in the intensive-control group recorded three times as many low blood glucose levels as did patients in the standard-control group. That might lead one to think that excess hypoglycemia was the cause of excess mortality in the intensive group, but that wasn’t the case. In the intensive control group, patients who died had more high blood glucose readings than did patients who survived, but not more low blood glucose readings.
The point is that patients who died diverged from their targets, Dr. Bergenstal said. Investigators expected to see low glucose levels in the intensive control group. Patients who died had a lot of blood glucose readings of 200 mg/dL or 300 mg/dL.
Patients in the standard-control group recorded twice as many high blood sugar readings as did patients in the intensive-control group. Patients in the standard group who died were more likely to have high or low blood glucose values compared with patients who survived.
"Again, they diverged" from the goal. "We were trying to keep these people about in the middle," he said.
The findings imply that clinicians should relax the intensity of therapy, he added. The HbA1c and self-monitored blood glucose values diverged significantly from targets, despite reasonably intensive efforts at control.
High HbA1c levels were associated with both dangerously high glucose values and dangerously low glucose values. High levels were dangerous because of hyperglycemia but also because people who had some of the worst hypoglycemia had high HbA1c levels, he said.
Severe hypoglycemia increased risk for death in both patient groups.
And mild to moderate hypoglycemia? "We want to minimize it, particularly in those patients for whom we relax our A1c and self-monitored blood glucose targets, such as the frail elderly," Dr. Bergenstal advised. "Be very careful about even mild to moderate hypoglycemia in those individuals."
Characteristics of patients with self-monitored blood glucose data were similar to those without the data, so this sample was fairly representative of all patients in ACCORD, he said.
The investigators are working to distill the findings into a practical message about how to quantify stability or variability in self-monitored blood glucose levels.
Dr. Bergenstal holds stock in Merck. He has received research support from, or been an adviser or consultant to, many companies including Abbot Diabetes Care, Amylin Pharmaceuticals, Bayer Health Care, Biodel, Calibra Medical, Eli Lilly, Hygieia, Intuity Medical, Lifescan, MannKind Corp., Medtronic, Novo Nordisk, Pfizer, ResMed, Roche Diagnostics, Roche Pharmaceuticals, Sanofi-Aventis, Takeda Pharmaceutical Company, Valeritas, United Health Group/i3 Statprobe, Dexcom, and Intarcia Therapeutics.
The ACCORD trial was sponsored by Abbot Laboratories, Amylin Pharmaceuticals, AstraZeneca Pharmaceuticals, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, Sanofi U.S., Takeda Pharmaceuticals, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Eye Institute, the National Institute on Aging, and the Centers for Disease Control and Prevention.