Higher levels of HbA1c do not increase the composite risk for end-stage kidney disease and death in adults with diabetes, according to findings published in the Journal of Diabetes and its Complications.
“Intensive glucose-lowering therapy is proven to reduce the risk of developing [diabetic kidney disease]. However, the effects of intensive glucose-lowering therapy on progression of existing [diabetic kidney disease] are unclear,” Cassianne Robinson-Cohen, PhD, assistant professor of medicine in the division of nephrology at Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues wrote.
In addition, these agents pose their own risks to patients with diabetes, the researchers wrote in the study background.
“In order to help define the risk-benefit balance of tight glycemic control among persons with diabetes and established [chronic kidney disease], we examined the associations of HbA1c with risks of progression to [end-stage kidney disease] and death in a well-characterized nephrology clinic-based cohort,” they wrote.
Robinson-Cohen and colleagues examined data from the ongoing Seattle Kidney Study, a prospective study of adults from nephrology clinics associated with the University of Washington recruited between 2004 and 2017. A total of 618 participants (mean age, 60 years; 33% women; 308 with diabetes) from the study were included for analysis.
The primary outcome was the composite of end-stage kidney disease and death, which were both determined based on data from the National Death Index and the United States Renal Data System. End-stage kidney disease was confirmed when a participant began maintenance dialysis or had a kidney transplant.
In the study population, there were 343 instances of composite end-stage kidney disease and death, but higher HbA1c levels were not linked to these events in participants with diabetes. Researchers observed a nonstatistically significant 1% lower risk of composite outcome per 1% higher level of HbA1c (95% CI, 12% lower to 10% higher).
When dividing the composite outcome into its individual components, the researchers found 185 instances of end-stage kidney disease, with 112 events reported in participants with diabetes. At all HbA1c levels, adults with vs. without diabetes had increased risk for end-stage kidney disease; however, the risk for end-stage kidney disease was not associated with HbA1c level among those with diabetes (HR = 1.06; 95% CI, 0.9-1.25).
There were 232 reported deaths, with unadjusted mortality rates for participants with diabetes (8.78 per 100 person-years) higher than those without diabetes (4.43 per 100 person-years). However, as with end-stage disease, mortality was not associated with HbA1c levels in participants with diabetes (HR = 1.06; 95% CI, 0.93-1.2).
HbA1c levels were also not associated with end-stage kidney disease, death or a composite of the two in participants with diabetes who were prescribed insulin therapy (HR = 0.94; 95% CI, 0.82-1.08) or those who were not (HR = 1.08; 95% CI, 0.9-1.29).
“A more customized approach to target HbA1c levels might be necessary to prevent the adverse effects of overtreatment in these patients. Long-term diabetes may cause autonomic dysfunction and ‘hypoglycemic unawareness,’ and ‘self -monitoring glucose’ should be emphasized and routinely done in diabetic CKD to prevent subclinical hypoglycemic episodes,” the researchers wrote. “Finally, these data suggest that glycemic control alone may be insufficient to account for the progression of diabetic complications, especially in diabetic CKD patients.” – by Phil Neuffer
Disclosures: This study was supported by an unrestricted gift from the Northwest Kidney Centers to the Kidney Research Institute in Seattle and received support from the U.S. Department of Veterans Affairs, the National Center for Advancing Translational Sciences, Vanderbilt O’Brien Kidney Center and the National Institute of Diabetes and Digestive and Kidney Diseases. Robinson-Cohen reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.