Poor Glucose Control

Poor glycemic control , whether too high or too low, is associated with decreased survival in diabetic patients on hemodialysis, Kamyar Kalantar-Zadeh, MD, MPH, PhD, professor of medicine, pediatrics, and epidemiology at the University of California at Los Angeles David Geffen School of Medicine, reported here at Kidney Week 2011: American Society of Nephrology 44th Annual Meeting. Dr. Kalantar-Zadeh reported that in a 6-year study, moderate hyperglycemia raised the risk for all-cause or cardiovascular mortality of hemodialysis patients with diabetes, and levels of glycated hemoglobin (HbA1c) below 6% or blood glucose below 100 mg/dL were associated with an elevated risk for death. According to most studies, he said, if glucose is well controlled, there are improvements in mortality, microvascular complications, and cardiovascular disease. One study showed that for every 1% decrease in HbA1c, deaths related to diabetes decreased 21%, microvascular complications decreased 37%, and myocardial infarctions decreased 14%. "Diabetes mellitus is a potent cardiovascular risk factor in both the general population and dialysis patients, almost half of whom suffer from diabetes in the United States," Dr. Kalantar-Zadeh said during a news conference. "Some guidelines recommend that diabetic dialysis patients follow the same HbA1c target area as the American Diabetic Association." However, he said, although there are some data from studies with varying methodologies, there is no clear guidance on glucose targets for the dialysis patient population. He and his colleagues examined the predictive value of glycemic control on all-cause and cardiovascular mortality, using a large database (n = 54,757) of hemodialysis patients with HbA1c data from 2001 to 2006, and follow-up to 2007. Random (not necessarily fasting) serum glucose measurements correlated moderately well with HbA1c (correlation coefficient, r = 0.56). Examining a range of HbA1c values (from less than 5% to more than 10%), they found the lowest all-cause mortality between 6% and 8%. Above 8%, the higher the HbA1c, the greater the mortality; it is "up to 50% higher for HbA1c above 10%," Dr. Kalantar-Zadeh said. "At the same time,...a very low HbA1c level, below 5%...increased mortality." A similar relation was seen for cardiovascular mortality. A subgroup analysis showed that HbA1c above 7% had a detrimental effect on mortality for all parameters and groups of maintenance hemodialysis diabetic patients examined, including race, sex, age, and serum albumin, hemoglobin, and ferritin levels. The same sort of relation held when random glucose measurements were considered. All-cause mortality rose at glucose levels below 100 mg/dL, and rose dramatically above 200 mg/dL. The lowest death rates were seen at glucose levels between 100 mg/dL and 200 mg/dL. Cardiovascular mortality was lowest in this same range. Subgroup analyses in terms of glucose levels yielded results very similar to those of HbA1c. Potential limitations of the study are that it was observational, Dr. Kalantar-Zadeh noted. Patients were not randomized to receive treatments, treatments for diabetes were not considered, and medication data were lacking. In addition, HbA1c and glucose measurements were taken at random times. Dr. Kalantar-Zadeh concluded that poor glycemic control, with HbA1c above 8% or glucose above 200 mg/dL, "appears to be associated with decreased survival in prevalent diabetic dialysis patients, and moderate hyperglycemia increases the risk for all-cause or cardiovascular mortality of diabetic hemodialysis patients, especially in...Caucasians, men, and individuals with serum albumin less than 3.8 g/dL." Levels of HbA1c below 6% or glucose below 100 mg/dL "are bad, too," he said. He suggested performing controlled trials to target a certain range of HbA1c in diabetic dialysis patients to verify these observational findings. News conference moderator Katherine Tuttle, MD, executive director for research at Providence Sacred Heart Medical Center and professor of medicine at the University of Washington School of Medicine in Spokane, who was not involved in the study, said that clinical guidelines have been updated and will be issued soon. Although she could not elaborate before they are published, she said: "You will see a change in several things, including targets for glycemic control based on published data. I think the data presenting will only add to that." She said previous Kidney Disease Outcomes Quality Initiative guidelines were based on the primary prevention of kidney disease, and an HbA1c below 7% was shown to prevent new-onset kidney disease. But there were no data on the treatment of patients with kidney disease; those data are expected to figure in the new guidelines, with higher HbA1c targets for people with multiple comorbidities and limited life expectancies, which would include the dialysis population.