For Diabetic Dialysis Patients, Low A1C is Good, but Even Lower Isn’t

Two new studies show that when it comes to hemoglobin A1c in dialysis patients, Goldilocks had it right—the best level is not too high, but not too low either. Both studies show that the lowest mortality occurred in patients with intermediate levels, ranging between 6.5 percent and 9 percent, and that dropping below that was associated with worse patient outcomes.

The guidelines for control of blood sugar in the Kidney Disease Outcomes Quality Initiative (KDOQI), dating to 2007, state that the target A1c level for people with diabetes “should be less than 7 percent, irrespective of the presence or absence of chronic kidney disease.” However, according to Kamyar Kalantar-Zadeh, MD, professor of medicine and pediatrics and epidemiology at the UCLA David Geffen School of Medicine in Los Angeles, “There is no consistent evidence to support these targets for dialysis patients.” Kalantar-Zadeh was lead investigator on one of the new studies.

Previous large observational studies have come to different conclusions about the effect of A1c on mortality in dialysis patients. But these studies have generally been relatively short-term, he said. To determine the long-term effect of A1c, he and his colleagues examined outcomes in over 54,000 dialysis patients with diabetes over a seven-year period.

They found that mortality from all causes followed a U-shaped curve in relation to time-averaged A1c. The lowest rate of mortality occurred when A1c was between 7 percent and 8 percent. In line with previous studies, it rose sharply above that, with the hazard ratio rising to approximately 1.4 when A1c was in the 9 percent to 10 percent range. Surprisingly, though, the hazard ratio also rose when A1c was below 7 percent, increasing gradually when the level was between 6 percent and 7 percent, and then steeply as the level dropped below 6 percent. The risk of death at an A1c level of 5 percent was higher than at levels between 9 percent and 10 percent.

The same U-shaped curve was found for mortality from cardiovascular events, again with a nadir at A1c levels between 7 percent and 8 percent, with approximately similar magnitudes of risk on either side. Kalantar-Zadeh also analyzed mortality as a function of glucose levels directly, using random glucose samples in over 50,000 patients. The lowest mortality was seen in patients with time-averaged glucose in the 150–200 mg/dL range, with the risk increasing from either more, or less, glucose.

A second study, part of the Dialysis Outcomes and Practice Pattern Study (DOPPS), reached similar conclusions, according to investigator Fritz Port, MD, of Arbor Research in Ann Arbor, Michigan. In this prospective study of over 6000 dialysis patients with diabetes from 12 countries, after fully adjusting for a range of variables affecting mortality, the lowest mortality occurred in patients with A1c levels between 7 percent and 7.9 percent.

“The desirable range for diabetic dialysis patients is 7 percent to 9 percent,” Port said, “which is higher than the guidelines for the general diabetes population.” To improve patient survival, he said, diabetes medications could be reduced in patients with low blood sugar, a step that may be particularly important for patients with poor nutritional status.

“I think the take-home message is that the target may need to be reconsidered in diabetic dialysis patients,” Kalantar-Zadeh said, suggesting 6.5 percent to 8 percent as the appropriate range. Importantly, “the target has a lower threshold, not just an upper threshold.”

“It also has practical implications,” he said. “Patients do not need to be pressured all the time to achieve the same very low levels as in the general diabetes population. We may be satisfied with patients reaching the middle range.”

The reason that dialysis patients differ from other diabetic patients is not clear. One reason may be that dialysis patients have adapted to moderately high glucose, reaching a new normal, and so for them, lowering glucose below 6.5 percent or 7 percent is not beneficial.

While the findings of the two studies coincide, neither was a randomized trial comparing different target glucose levels. Thus, Kalantar-Zadeh said, there is a need for controlled trials to further confirm these findings.

The findings were presented at Kidney Week 2011.

December 2011 (Vol. 3, Number 12)