Hemoglobin A(1c) levels and mortality in the diabetic hemodialysis population: findings from the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Abstract

Objective: Lowering hemoglobin A(1c) to <7% reduces the risk of microvascular complications of diabetes, but the importance of maintaining this target in diabetes patients with kidney failure is unclear. We evaluated the relationship between A(1c) levels and mortality in an international prospective cohort study of hemodialysis patients.

Research design and methods: Included were 9,201 hemodialysis patients from 12 countries (Dialysis Outcomes and Practice Patterns Study 3 and 4, 2006-2010) with type 1 or type 2 diabetes and at least one A(1c) measurement during the first 8 months after study entry. Associations between A(1c) and mortality were assessed with Cox regression, adjusting for potential confounders.

Results: The association between A(1c) and mortality was U-shaped. Compared with an A(1c) of 7-7.9%, the hazard ratios (95% CI) for A(1c) levels were 1.35 (1.09-1.67) for <5%, 1.18 (1.01-1.37) for 5-5.9%, 1.21 (1.05-1.41) for 6-6.9%, 1.16 (0.94-1.43) for 8-8.9%, and 1.38 (1.11-1.71) for ≥9.0%, after adjustment for age, sex, race, BMI, serum albumin, years of dialysis, serum creatinine, 12 comorbid conditions, insulin use, hemoglobin, LDL cholesterol, country, and study phase. Diabetes medications were prescribed for 35% of patients with A(1c) <6% and not prescribed for 29% of those with A(1c) ≥9%.

Conclusions: A(1c) levels strongly predicted mortality in hemodialysis patients with type 1 or type 2 diabetes. Mortality increased as A(1c) moved further from 7-7.9%; thus, target A(1c) in hemodialysis patients may encompass values higher than those recommended by current guidelines. Modifying glucose-lowering medicines for dialysis patients to target A(1c) levels within this range may be a modifiable practice to improve outcomes.

Figure 1

A: Risk of mortality by initial A_1c, adjusted for age, sex, race, BMI, years of dialysis, albumin, creatinine, 10 comorbid conditions, insulin use, hemoglobin, HDL cholesterol, country, and study phase. B: Risk of mortality by mean A_1c, adjusted for age, sex, race, BMI, years of dialysis, albumin, creatinine, 10 comorbid conditions, insulin use, hemoglobin, HDL cholesterol, country, and study phase. (A high-quality color representation of this figure is available in the online issue.)

Figure 2

Risk of mortality by initial A_1c among patients with and without indicators of poor nutrition, adjusted for age, sex, race, BMI, years of dialysis, albumin, creatinine, 10 comorbid conditions, insulin use, hemoglobin, HDL cholesterol, country, and study phase. (A high-quality color representation of this figure is available in the online issue.)