Christopher J Hill1, Alexander P Maxwell2, Christopher R Cardwell3, Barry I Freedman4, Marcello Tonelli5, Masanori Emoto6, Masaaki Inaba6, Yasuaki Hayashino7, Shunichi Fukuhara8, Tomonari Okada9, Christiane Drechsler10, Christoph Wanner10, Anna Casula11, Amanda I Adler12, Claudia Lamina13, Florian Kronenberg13, Elani Streja14, Kamyar Kalantar-Zadeh14, Damian G Fogarty15. 1. Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland; Regional Nephrology Unit, Belfast City Hospital, Belfast, Northern Ireland. Electronic address: chill05@qub.ac.uk. 2. Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland; Regional Nephrology Unit, Belfast City Hospital, Belfast, Northern Ireland. 3. Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland. 4. Wake Forest School of Medicine, Winston-Salem, NC. 5. University of Alberta, Edmonton, Alberta, Canada. 6. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan. 7. Department of Endocrinology, Tenri Hospital, Nara, Japan. 8. Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan; Fukushima Medical University Center for Innovation in Clinical Research, Fukushima, Japan. 9. Department of Nephrology, Tokyo Medical University, Tokyo, Japan. 10. Department of Medicine, Division of Nephrology, University Hospital, Würzburg, Germany. 11. United Kingdom Renal Registry, Southmead Hospital, Bristol, United Kingdom. 12. Addenbrooke's Hospital, Cambridge, United Kingdom. 13. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria. 14. Division of Nephrology and Hypertension, University of California, Irvine, CA. 15. Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland; Regional Nephrology Unit, Belfast City Hospital, Belfast, Northern Ireland; Department of Medicine, Division of Nephrology, University Hospital, Würzburg, Germany.
Abstract
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.
BACKGROUND: Studies investigating the association between glycated hemoglobin (HbA1c) level and mortality risk in diabeticpatients 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: Diabeticpatients 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.
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