HbA 1c measured in stored erythrocytes is positively linearly associated with mortality in individuals with diabetes mellitus

Diewertje Sluik, Heiner Boeing, Jukka Montonen, Rudolf Kaaks, Annekatrin Lukanova, Annelli Sandbaek, Kim Overvad, Larraitz Arriola, Eva Ardanaz, Calogero Saieva, Sara Grioni, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, Annemieke M W Spijkerman, Daphne L. van der A, Joline W J Beulens, Susan van Dieren, Peter M. Nilsson, Leif C. Groop & 4 others Paul W. Franks, Olov Rolandsson, Bas Bueno-de-Mesquita, Ute Nöthlings

Research output: Contribution to journalArticle

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Abstract

Introduction: Observational studies have shown that glycated haemoglobin (HbA 1c) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA 1c measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. Methods: Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA 1c was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA 1c in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. Results: After a median follow-up of 9.3 years, 460 participants died. Higher HbA 1c was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity =0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA 1c and medication. Conclusion: This prospective study showed that persons with lower HbA 1c had better survival than those with higher HbA 1c. The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA 1c appears to be associated with reduced mortality risk.

Original languageEnglish
Article numbere38877
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 13 2012

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Medical problems
diabetes mellitus
Diabetes Mellitus
drug therapy
erythrocytes
Erythrocytes
Mortality
duration
Hazards
observational studies
Observational Studies
diabetes
Metformin
Glycosylated Hemoglobin A
hypoglycemic agents
Nutrition
metformin
Morbidity
Hypoglycemic Agents
glycohemoglobin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sluik, D., Boeing, H., Montonen, J., Kaaks, R., Lukanova, A., Sandbaek, A., ... Nöthlings, U. (2012). HbA 1c measured in stored erythrocytes is positively linearly associated with mortality in individuals with diabetes mellitus. PLoS One, 7(6), [e38877]. https://doi.org/10.1371/journal.pone.0038877

HbA 1c measured in stored erythrocytes is positively linearly associated with mortality in individuals with diabetes mellitus. / Sluik, Diewertje; Boeing, Heiner; Montonen, Jukka; Kaaks, Rudolf; Lukanova, Annekatrin; Sandbaek, Annelli; Overvad, Kim; Arriola, Larraitz; Ardanaz, Eva; Saieva, Calogero; Grioni, Sara; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Spijkerman, Annemieke M W; van der A, Daphne L.; Beulens, Joline W J; van Dieren, Susan; Nilsson, Peter M.; Groop, Leif C.; Franks, Paul W.; Rolandsson, Olov; Bueno-de-Mesquita, Bas; Nöthlings, Ute.

In: PLoS One, Vol. 7, No. 6, e38877, 13.06.2012.

Research output: Contribution to journalArticle

Sluik, D, Boeing, H, Montonen, J, Kaaks, R, Lukanova, A, Sandbaek, A, Overvad, K, Arriola, L, Ardanaz, E, Saieva, C, Grioni, S, Tumino, R, Sacerdote, C, Mattiello, A, Spijkerman, AMW, van der A, DL, Beulens, JWJ, van Dieren, S, Nilsson, PM, Groop, LC, Franks, PW, Rolandsson, O, Bueno-de-Mesquita, B & Nöthlings, U 2012, 'HbA 1c measured in stored erythrocytes is positively linearly associated with mortality in individuals with diabetes mellitus', PLoS One, vol. 7, no. 6, e38877. https://doi.org/10.1371/journal.pone.0038877
Sluik, Diewertje ; Boeing, Heiner ; Montonen, Jukka ; Kaaks, Rudolf ; Lukanova, Annekatrin ; Sandbaek, Annelli ; Overvad, Kim ; Arriola, Larraitz ; Ardanaz, Eva ; Saieva, Calogero ; Grioni, Sara ; Tumino, Rosario ; Sacerdote, Carlotta ; Mattiello, Amalia ; Spijkerman, Annemieke M W ; van der A, Daphne L. ; Beulens, Joline W J ; van Dieren, Susan ; Nilsson, Peter M. ; Groop, Leif C. ; Franks, Paul W. ; Rolandsson, Olov ; Bueno-de-Mesquita, Bas ; Nöthlings, Ute. / HbA 1c measured in stored erythrocytes is positively linearly associated with mortality in individuals with diabetes mellitus. In: PLoS One. 2012 ; Vol. 7, No. 6.
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T1 - HbA 1c measured in stored erythrocytes is positively linearly associated with mortality in individuals with diabetes mellitus

AU - Sluik, Diewertje

AU - Boeing, Heiner

AU - Montonen, Jukka

AU - Kaaks, Rudolf

AU - Lukanova, Annekatrin

AU - Sandbaek, Annelli

AU - Overvad, Kim

AU - Arriola, Larraitz

AU - Ardanaz, Eva

AU - Saieva, Calogero

AU - Grioni, Sara

AU - Tumino, Rosario

AU - Sacerdote, Carlotta

AU - Mattiello, Amalia

AU - Spijkerman, Annemieke M W

AU - van der A, Daphne L.

AU - Beulens, Joline W J

AU - van Dieren, Susan

AU - Nilsson, Peter M.

AU - Groop, Leif C.

AU - Franks, Paul W.

AU - Rolandsson, Olov

AU - Bueno-de-Mesquita, Bas

AU - Nöthlings, Ute

PY - 2012/6/13

Y1 - 2012/6/13

N2 - Introduction: Observational studies have shown that glycated haemoglobin (HbA 1c) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA 1c measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. Methods: Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA 1c was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA 1c in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. Results: After a median follow-up of 9.3 years, 460 participants died. Higher HbA 1c was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity =0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA 1c and medication. Conclusion: This prospective study showed that persons with lower HbA 1c had better survival than those with higher HbA 1c. The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA 1c appears to be associated with reduced mortality risk.

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