Glycated hemoglobin and risk of death in diabetic patients treated with hemodialysis: a meta-analysis

Background: Studies investigating the association between glycated hemoglobin (HbA1c) level and mortality risk in diabetic patients receiving hemodialysis have shown conflicting results.

Study design: We conducted a systematic review and meta-analysis using MEDLINE, EMBASE, Web of Science, and the Cochrane Library.

Setting & population: Diabetic patients on maintenance hemodialysis therapy.

Selection criteria for studies: Observational studies or randomized controlled trials investigating the association between HbA1c values and mortality risk. Study authors were asked to provide anonymized individual patient data or reanalyze results according to a standard template.

Predictor: Single measurement or mean HbA1c values. Mean HbA1c values were calculated using all individual-patient HbA1c values during the follow-up period of contributing studies.

Outcome: HR for mortality risk.

Results: 10 studies (83,684 participants) were included: 9 observational studies and one secondary analysis of a randomized trial. After adjustment for confounders, patients with baseline HbA1c levels ≥ 8.5% (≥ 69 mmol/mol) had increased mortality (7 studies; HR, 1.14; 95% CI, 1.09-1.19) compared with patients with HbA1c levels of 6.5%-7.4% (48-57mmol/mol). Likewise, patients with a mean HbA1c value ≥ 8.5% also had a higher adjusted risk of mortality (6 studies; HR,1.29; 95% CI, 1.23-1.35). There was a small but nonsignificant increase in mortality associated with mean HbA1c levels ≤ 5.4% (≤ 36 mmol/mol; 6 studies; HR, 1.09; 95% CI, 0.89-1.34). Sensitivity analyses in incident (≤ 90 days of hemodialysis) and prevalent patients (>90 days of hemodialysis) showed a similar pattern. In incident patients, mean HbA1c levels ≤ 5.4% also were associated with increased mortality risk (4 studies; HR, 1.29; 95% CI, 1.23-1.35).

Limitations: Observational study data and inability to adjust for diabetes type in all studies.

Conclusions: Despite concerns about the utility of HbA1c measurement in hemodialysis patients, high levels (≥ 8.5%) are associated with increased mortality risk. Very low HbA1c levels (≤ 5.4%) also may be associated with increased mortality risk.