Haemoglobin A1c variability is a strong, independent predictor of all-cause mortality in patients with type 2 diabetes

Emanuela Orsi, Anna Solini, Enzo Bonora, Cecilia Fondelli, Roberto Trevisan, Monica Vedovato, Franco Cavalot, Gabriella Gruden, Susanna Morano, Antonio Nicolucci, Giuseppe Penno, Giuseppe Pugliese

Research output: Contribution to journalArticle

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Abstract

Aims: To evaluate various measures of haemoglobin (Hb) A1c variability, compared with average HbA1c, as independent predictors of mortality. Materials and Methods: The Renal Insufficiency And Cardiovascular Events Italian multicentre study enroled 15733 patients with type 2 diabetes from 19 diabetes clinics during 2006-2008. A total of 3 to 5 HbA1c measures, obtained during the 2-year period before enrolment, were available from 9 centres (8290 patients) and were used to calculate average HbA1c (HbA1c -MEAN) and HbA1c variability, measured as intra-individual standard deviation (HbA1c-SD), SD adjusted for the number of HbA1c assessments (HbA1c-AdjSD) and coefficient of variation (HbA1c-CV), that is, the HbA1c-SD to HbA1c-MEAN ratio. Vital status on October 31, 2015 was retrieved for 8252 patients (99.5%). Results: The measures of HbA1c variability increased according to quartiles of HbA1c-MEAN and vice versa. HbA1c-MEAN and measures of HbA1c variability were associated with all-cause mortality; however, the strength of association of HbA1c-MEAN was lower than that of HbA1c -SD, HbA1c-CV or HbA1c-AdjSD, and disappeared after adjusting for confounders and any of the measures of HbA1c variability. Mortality increased with quartiles of HbA1c-MEAN, HbA1c -SD, HbA1c-CV and HbA1c-AdjSD, but only the association with HbA1c variability measures remained after adjustment for confounders and/or each other measure. In the fully adjusted model, mortality risk was lower for HbA1c-SD below the median and higher for HbA1c-SD above the median, regardless of whether HbA1c-MEAN was below or above the median. Conclusions: HbA1c variability is a strong, independent predictor of all-cause mortality in type 2 diabetes and appears to be even more powerful than average HbA1c in predicting mortality.

Original languageEnglish
Pages (from-to)1885-1893
JournalDiabetes, Obesity and Metabolism
Volume20
Issue number8
DOIs
Publication statusPublished - 2018

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Type 2 Diabetes Mellitus
Hemoglobins
Mortality
Multicenter Studies
Renal Insufficiency

Keywords

  • All-cause mortality
  • Cardiovascular risk factors
  • Complications
  • HbA1c
  • Type 2 diabetes
  • Variability

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Haemoglobin A1c variability is a strong, independent predictor of all-cause mortality in patients with type 2 diabetes. / Orsi, Emanuela; Solini, Anna; Bonora, Enzo; Fondelli, Cecilia; Trevisan, Roberto; Vedovato, Monica; Cavalot, Franco; Gruden, Gabriella; Morano, Susanna; Nicolucci, Antonio; Penno, Giuseppe; Pugliese, Giuseppe.

In: Diabetes, Obesity and Metabolism, Vol. 20, No. 8, 2018, p. 1885-1893.

Research output: Contribution to journalArticle

Orsi, E, Solini, A, Bonora, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Gruden, G, Morano, S, Nicolucci, A, Penno, G & Pugliese, G 2018, 'Haemoglobin A1c variability is a strong, independent predictor of all-cause mortality in patients with type 2 diabetes', Diabetes, Obesity and Metabolism, vol. 20, no. 8, pp. 1885-1893. https://doi.org/10.1111/dom.13306
Orsi, Emanuela ; Solini, Anna ; Bonora, Enzo ; Fondelli, Cecilia ; Trevisan, Roberto ; Vedovato, Monica ; Cavalot, Franco ; Gruden, Gabriella ; Morano, Susanna ; Nicolucci, Antonio ; Penno, Giuseppe ; Pugliese, Giuseppe. / Haemoglobin A1c variability is a strong, independent predictor of all-cause mortality in patients with type 2 diabetes. In: Diabetes, Obesity and Metabolism. 2018 ; Vol. 20, No. 8. pp. 1885-1893.
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abstract = "Aims: To evaluate various measures of haemoglobin (Hb) A1c variability, compared with average HbA1c, as independent predictors of mortality. Materials and Methods: The Renal Insufficiency And Cardiovascular Events Italian multicentre study enroled 15733 patients with type 2 diabetes from 19 diabetes clinics during 2006-2008. A total of 3 to 5 HbA1c measures, obtained during the 2-year period before enrolment, were available from 9 centres (8290 patients) and were used to calculate average HbA1c (HbA1c -MEAN) and HbA1c variability, measured as intra-individual standard deviation (HbA1c-SD), SD adjusted for the number of HbA1c assessments (HbA1c-AdjSD) and coefficient of variation (HbA1c-CV), that is, the HbA1c-SD to HbA1c-MEAN ratio. Vital status on October 31, 2015 was retrieved for 8252 patients (99.5{\%}). Results: The measures of HbA1c variability increased according to quartiles of HbA1c-MEAN and vice versa. HbA1c-MEAN and measures of HbA1c variability were associated with all-cause mortality; however, the strength of association of HbA1c-MEAN was lower than that of HbA1c -SD, HbA1c-CV or HbA1c-AdjSD, and disappeared after adjusting for confounders and any of the measures of HbA1c variability. Mortality increased with quartiles of HbA1c-MEAN, HbA1c -SD, HbA1c-CV and HbA1c-AdjSD, but only the association with HbA1c variability measures remained after adjustment for confounders and/or each other measure. In the fully adjusted model, mortality risk was lower for HbA1c-SD below the median and higher for HbA1c-SD above the median, regardless of whether HbA1c-MEAN was below or above the median. Conclusions: HbA1c variability is a strong, independent predictor of all-cause mortality in type 2 diabetes and appears to be even more powerful than average HbA1c in predicting mortality.",
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AU - Solini, Anna

AU - Bonora, Enzo

AU - Fondelli, Cecilia

AU - Trevisan, Roberto

AU - Vedovato, Monica

AU - Cavalot, Franco

AU - Gruden, Gabriella

AU - Morano, Susanna

AU - Nicolucci, Antonio

AU - Penno, Giuseppe

AU - Pugliese, Giuseppe

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N2 - Aims: To evaluate various measures of haemoglobin (Hb) A1c variability, compared with average HbA1c, as independent predictors of mortality. Materials and Methods: The Renal Insufficiency And Cardiovascular Events Italian multicentre study enroled 15733 patients with type 2 diabetes from 19 diabetes clinics during 2006-2008. A total of 3 to 5 HbA1c measures, obtained during the 2-year period before enrolment, were available from 9 centres (8290 patients) and were used to calculate average HbA1c (HbA1c -MEAN) and HbA1c variability, measured as intra-individual standard deviation (HbA1c-SD), SD adjusted for the number of HbA1c assessments (HbA1c-AdjSD) and coefficient of variation (HbA1c-CV), that is, the HbA1c-SD to HbA1c-MEAN ratio. Vital status on October 31, 2015 was retrieved for 8252 patients (99.5%). Results: The measures of HbA1c variability increased according to quartiles of HbA1c-MEAN and vice versa. HbA1c-MEAN and measures of HbA1c variability were associated with all-cause mortality; however, the strength of association of HbA1c-MEAN was lower than that of HbA1c -SD, HbA1c-CV or HbA1c-AdjSD, and disappeared after adjusting for confounders and any of the measures of HbA1c variability. Mortality increased with quartiles of HbA1c-MEAN, HbA1c -SD, HbA1c-CV and HbA1c-AdjSD, but only the association with HbA1c variability measures remained after adjustment for confounders and/or each other measure. In the fully adjusted model, mortality risk was lower for HbA1c-SD below the median and higher for HbA1c-SD above the median, regardless of whether HbA1c-MEAN was below or above the median. Conclusions: HbA1c variability is a strong, independent predictor of all-cause mortality in type 2 diabetes and appears to be even more powerful than average HbA1c in predicting mortality.

AB - Aims: To evaluate various measures of haemoglobin (Hb) A1c variability, compared with average HbA1c, as independent predictors of mortality. Materials and Methods: The Renal Insufficiency And Cardiovascular Events Italian multicentre study enroled 15733 patients with type 2 diabetes from 19 diabetes clinics during 2006-2008. A total of 3 to 5 HbA1c measures, obtained during the 2-year period before enrolment, were available from 9 centres (8290 patients) and were used to calculate average HbA1c (HbA1c -MEAN) and HbA1c variability, measured as intra-individual standard deviation (HbA1c-SD), SD adjusted for the number of HbA1c assessments (HbA1c-AdjSD) and coefficient of variation (HbA1c-CV), that is, the HbA1c-SD to HbA1c-MEAN ratio. Vital status on October 31, 2015 was retrieved for 8252 patients (99.5%). Results: The measures of HbA1c variability increased according to quartiles of HbA1c-MEAN and vice versa. HbA1c-MEAN and measures of HbA1c variability were associated with all-cause mortality; however, the strength of association of HbA1c-MEAN was lower than that of HbA1c -SD, HbA1c-CV or HbA1c-AdjSD, and disappeared after adjusting for confounders and any of the measures of HbA1c variability. Mortality increased with quartiles of HbA1c-MEAN, HbA1c -SD, HbA1c-CV and HbA1c-AdjSD, but only the association with HbA1c variability measures remained after adjustment for confounders and/or each other measure. In the fully adjusted model, mortality risk was lower for HbA1c-SD below the median and higher for HbA1c-SD above the median, regardless of whether HbA1c-MEAN was below or above the median. Conclusions: HbA1c variability is a strong, independent predictor of all-cause mortality in type 2 diabetes and appears to be even more powerful than average HbA1c in predicting mortality.

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