The mystery remains, but the pieces are coming together: Why was there an increased risk of death among patients randomized to intensive glucose control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study?
The unexpected finding in 2008 shook the diabetes community and set researchers scrambling to find an answer. After all, high blood glucose levels have been definitively linked to microvascular (eye, kidney and nerve) complications in both type 1 and type 2 diabetes, and were presumed to play a role in macrovascular (i.e. cardiovascular) disease as well. But after the glycemic arm of the ACCORD study was halted two years early due to a 22% increase in mortality in those randomized to intensive versus standard therapy, people began to wonder whether low blood sugar might actually be the culprit.
New data say no. In fact, a study published this week in Diabetes Care showed that high, not low, blood sugar raised the risk of death regardless of which treatment group the patients were in. When the two groups were examined separately, there was a 66% increase in death among those in the intensive group for every one percentage point increase in hemoglobin A1c, compared with a mere 14% increase in the standard treatment group.
First, this clearly shows that even intensive management including two or more glucose-lowering medications plus counseling about blood sugar management doesn’t guarantee that diabetes patients will achieve the target, in this case an A1c of less than 6%. Furthermore, it was specifically those patients randomized to intensive treatment but who didn’t get to goal—in particular, those whose A1c levels remained above 7%—who were at greatest risk for death.
As ACCORD researcher Dr. Elizabeth R. Seaquist put it during a panel session at a meeting of the American Association of Clinical Endocrinologists last week, “Using an intensive strategy, some people with type 2 can safely achieve A1c levels below 7%, whereas others who do not readily reduce their A1c levels may be at increased risk if they persist with this strategy.”
It’s important to note that the 10,194 patients enrolled in ACCORD were older (average age 62 years) had had diabetes longer (average 10 years) than many patients, so the conclusions only apply to that population, which represents a bit less than half of all U.S. patients with type 2 diabetes, Dr. Faramarz Ismail-Beigi said during the AACE panel. “This cohort represents a large group of patients, but not everybody. We’re not talking about newly-diagnosed diabetes, middle aged, or younger people.” For those patients, he said, “I try to get them to normal if I can do it safely.”
More data from ACCORD are due out later this year.
Has your management strategy for type 2 diabetes changed since the 2008 ACCORD report? We’d be interested in your comments.
-Miriam E. Tucker (@MiriamETucker on Twitter)