Extreme Glycemic Control Not Significantly Associated with Increased All-Cause Mortality

While the current ADA guidelines recommend targeting HbA1c levels to below 8% for high-risk patients with diabetes, reducing the level to 5.7% is safe, according to a linked database study presented at the American Diabetes Association 73^rd Scientific Sessions in Chicago, IL.

“Women and Mexican-Americans should have more intense blood glucose control, and may see benefits at levels of 6.5% or lower,” said Fangjian Guo, MD, a PhD student and graduate research assistant at the University of Alabama at Birmingham.

“At short-term follow-up, studies such as the ACCORD study, which was released in 2008, suggested that intensive glycemic control below 6.5% may predispose to cardiovascular events, and such populations may have more all-cause death,” said Guo, who presented oral session 278, “The Impact of HbA1c Level on All-Cause and CVD Mortality in Patients with Diabetes.”

“The problem is that after the data came out, now doctors don’t recommend intense glucose control, so now the mean glucose level is higher in recent patient populations, often as high as 8.5%,” he explained.“My study’s main finding is that tighter blood glucose control, to levels between 5.7% and 6.4%, did not pose any increase risk of mortality for these patients. Intensive control could actually have other benefits, like a lower rate of microvascular disease, such as damage to the kidney,” he added.

In the study, Guo and colleagues analyzed data from the NHANES 1999-2004 linked mortality files, resulting in a database of 2,706 subjects with diagnosed diabetes. To reach statistical power, an additional 848 subjects were added based on HbA1c levels of 6.5% or higher. Of the population, 836 were Mexican-American. The median patient age was 61.8, with more than 90% of the study population consisting of patients with type 2 diabetes, though it did include some type 1 diabetics, Guo said.

With a median follow-up of 7.5 years, there were 989 deaths, including 454 cardiovascular deaths, according to the abstract.

Hazard ratios were statistically similar in groups with HbA1c levels of less than 5.7%, between 5.7% and 6.4%, and between 6.5% and 7.4%.

The study used the group with HbA1c levels between 5.7% and 6.4% as a reference point, and found that the hazard ratio was slightly increased, to 1.17 for the reference group, those with HbA1c below 5.7%, and for those slightly above the reference point, between 6.5% and 7.5%.

For those with HbA1c greater than 7.5%, however, the risk for all-cause mortality was 1.63 times higher, and the risk of cardiovascular death was 1.54 times higher, the abstract said. The ‘p’ value was less than 0.05, Guo said.

However, for women and for Mexican-Americans, the danger threshold was lower, as having an HbA1c level between 6.5% and 7.5% was associated with higher all-cause mortality. Women with an HbA1c level below 5.7% had 1.36 times the risk of all-cause death, compared to the reference point. Those with an HbA1c between 6.5% and 7.5% had a 1.41 times greater risk of all-cause death, while for those with HbA1c above 7.5% the hazard ratio was 1.96, according to the abstract. Among women, the risks of cardiovascular death were about the same in the different groups.

For Mexican-Americans, the risk of all-cause mortality and cardiovascular death was not greatly elevated for subjects with HbA1c below 5.7%. But all-cause mortality was 1.75 times higher for those with HbA1c levels between 6.5% and 7.5%; if HbA1c was greater than 7.5%, the risk of all-cause mortality was magnified 2.05 times, according to the abstract.

The risk of cardiovascular death was only slightly increased in subjects with HbA1c levels between 6.5% and 7.5%, in whom it was 1.26 times higher; but in subjects with HbA1c above 7.5%, the risk of cardiovascular death was 1.68 times, the abstract said.

“My future research will explore the impact of HbA1c levels on non-fatal macro-cardiovascular and micro-cardiovascular and also non-fatal stroke, to see if diabetics with higher or lower HbA1c levels have more heart attacks, stroke, kidney damage or damage to the eye,” Guo explained.