2017 Issues   /   November 2017

High Glycemic Levels Have ‘Legacy Effect’ Even After Diabetic Patients Start Dialysis

USM By Annette M. Boyle
November 9, 2017

Risks of Low HbA1c

While high glycemic levels appear to have long-term sequelae, very low levels also pose their own risks. Both the Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines advise against setting a target HbA1c below 7% in individuals at risk of hypoglycemia, including those with Stage 4 or 5 chronic kidney disease and patients on insulin, sulfonylureas and possibly metformin, Rhee noted.

“Note that we did not per se observe that our lowest averaged HbA1c and lowest averaged random glucose categories were associated with improved survival,” Rhee cautioned. The lowest measures and reference ranges had similar mortality rates in the study.

The lowest mean glycemic level seen in the study were in the moderately-low rather than in the hypoglycemic range, which may explain why the lowest levels were not associated with an increase in mortality as seen in previous reports, she said. The team is now researching the impact of very low glycemic levels on post-ESRD outcomes.

Pending the results of the follow-on studies, “we would still caution against aggressive glycemic targets in patients (including veterans) with diabetic kidney disease, including those already on dialysis. Among established dialysis patients, there are a number of studies that have shown a U-shaped association between BOTH lower (HbA1c below 6%) and higher (HbA1c above 8%) glycemic levels with higher mortality risk,” Rhee said.

The researchers studied the records of 52,172 patients in the VA’s national Transition of Care in CKD study who transitioned to dialysis between October 2007 and September 2011. Of those, the 15,549 veterans who had HbA1c or random blood glucose measurements recorded in the prelude year and a diagnosis of diabetes or cause-of-ESRD due to diabetes served as the primary cohort for the Long Beach study.

While guidelines recommend a target HbA1c above 7% in patients with comorbidities and limited life expectancy and those at risk of hypoglycemia, they do not specify the upper limit of the preferred glycemic range for these patients. The finding that mean HbA1c levels above 8% and random glucose measurements above 200 ml/dL in the year before dialysis initiation leads to worse outcomes in patients with diabetes and ESRD may help clinicians set appropriate targets for these patients.

“Based on the existing data and the findings from our study, we recommend that in patients with advanced diabetic kidney disease who may soon require dialysis therapy, a reasonable but not too aggressive glycemic status is associated with improved long-term outcomes that may last even after having transitioned to maintenance dialysis therapy,” Rhee and Kalantar-Zadeh said.

Clinicians may also want to consider the risks of various anti-diabetes medications on this population. The increase in mortality seen in the study was limited to insulin users with HbA1c levels above 8% or mean random glucose levels higher than 200mg/dL, the authors observed. In contrast, they noted that a recent Taiwanese study of diabetes patients on dialysis demonstrated an association between sulfonylurea, meglitinides and thiazolidinediones and elevated risk of myocardial infarction.2

  1. Rhee CM, Kovesdy CP, Ravel VA, Streja E, Brunelli SM, SoohooM, Sumida K, Molnar MZ, Brent GA, Nguyen DV, Kalantar-Zadeh K. Association of Glycemic Status During Progression of Chronic Kidney Disease with Early Dialysis Mortality in Patients with Diabetes. Diabetes Care 2017;40:1050-1057.
  2. Lin TT, Wu CC, Yang YH, et al. Anti-hyperglycemic agents and new-onset acute myocardial infarction in diabetic patients with end-stage renal disease undergoing dialysis. PLoS One 2016;11: e0160436.

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