Hemoglobin A1c Levels and Mortality in the Diabetic Hemodialysis Population

Abstract

OBJECTIVELowering hemoglobin A1c 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 A1c levels and mortality in an international prospective cohort study of hemodialysis patients.RESEARCH DESIGN AND METHODSIncluded 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 A1c measurement during the first 8 months after study entry. Associations between A1c and mortality were assessed with Cox regression, adjusting for potential confounders.RESULTSThe association between A1c and mortality was U-shaped. Compared with an A1c of 7–7.9%, the hazard ratios (95% CI) for A1c 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 A1c <6% and not prescribed for 29% of those with A1c ≥9%.CONCLUSIONSA1c levels strongly predicted mortality in hemodialysis patients with type 1 or type 2 diabetes. Mortality increased as A1c moved further from 7–7.9%; thus, target A1c in hemodialysis patients may encompass values higher than those recommended by current guidelines. Modifying glucose-lowering medicines for dialysis patients to target A1c levels within this range may be a modifiable practice to improve outcomes.

Associations of Glycemic Control With Cardiovascular Outcomes Among US Hemodialysis Patients With Diabetes Mellitus

“…Similarly, in an analysis of data from the Dialysis Outcomes and Practice Patterns Study of patients on hemodialysis with DM, mortality was lowest at HbA 1c levels of 7% to 7.9% and increased at both lower and higher levels as HbA 1c moved further from 7% to 7.9% 16. This may be due to a combined effect of net catabolic balance and poor nutritional status of patients on hemodialysis as well as other clinical characteristics that are present in hemodialysis, all of which can have varying effects on glycemic control 16. Indeed, in our sensitivity analysis, we found that variables such as albumin, normalized protein catabolic rate, and predialysis weight in addition to age, hemoglobin, and mean arterial pressure were some of the strongest negative confounders that drove the association between glycemic control and cardiovascular mortality.…”

“…When using time‐varying HbA 1c measures and adjusting for various confounders with follow‐up up to 3 years, Williams et al later found a U‐shaped association between HbA 1c and mortality risk, with the risks being higher at the extremes of HbA 1c (<48 mmol/mol [<6.5%] and >97 mmol/mol [>11%]) 32. Similarly, in an analysis of data from the Dialysis Outcomes and Practice Patterns Study of patients on hemodialysis with DM, mortality was lowest at HbA 1c levels of 7% to 7.9% and increased at both lower and higher levels as HbA 1c moved further from 7% to 7.9% 16. This may be due to a combined effect of net catabolic balance and poor nutritional status of patients on hemodialysis as well as other clinical characteristics that are present in hemodialysis, all of which can have varying effects on glycemic control 16.…”

“…Fifth, we used HbA 1c <48 mmol/mol (<6.5%) as the reference group, which also included patients with relatively low HbA 1c values. These patients have been shown to have particularly poor prognosis owing to cachexia and “burnt out” DM 3, 16. As a result, we cannot identify the best target HbA 1c for patients with DM and ESRD.…”

“…As a result, we cannot identify the best target HbA 1c for patients with DM and ESRD. Based on limited evidence, however, it is possible that higher HbA 1c goals rather than intensive glycemic control (HbA 1c <42 mmol/mol [<6.0%]) may be more appropriate in some patients with DM including those with chronic kidney disease 16, 32. Sixth, we excluded about one third of potentially eligible participants from the study because they were missing baseline HbA 1c data.…”

“…Although these trials excluded patients on hemodialysis, it has been argued that better glycemic control is key toward preventing DM‐related complications in this population 3, 7, 8, 9. In fact, surprisingly few studies have investigated the association between HbA 1c and clinical outcomes in the dialysis population 3, 10, 11, 12, 13, 14, 15, 16. Most of these studies focused only on all‐cause mortality as the outcome and were limited by small sample size and correspondingly low statistical power 11, 12, 13, 15…”