Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes

April P. Carson, Caroline S. Fox, Darren K McGuire, Emily B. Levitan, Martin Laclaustra, Devin M. Mann, Paul Muntner

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Background: Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c. Methods and Results: National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76). Conclusions: In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.

Original languageEnglish (US)
Pages (from-to)661-667
Number of pages7
JournalCirculation: Cardiovascular Quality and Outcomes
Volume3
Issue number6
DOIs
StatePublished - Nov 2010

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Hemoglobins
Mortality
Confidence Intervals
Erythrocytes
Blood Pressure
Erythrocyte Indices
Nutrition Surveys
Liver
Ferritins
Blood Volume
Cell Size
Life Style
Iron
Cholesterol
Morbidity
Enzymes
Research

Keywords

  • Epidemiology
  • Hemoglobin A1c
  • Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes. / Carson, April P.; Fox, Caroline S.; McGuire, Darren K; Levitan, Emily B.; Laclaustra, Martin; Mann, Devin M.; Muntner, Paul.

In: Circulation: Cardiovascular Quality and Outcomes, Vol. 3, No. 6, 11.2010, p. 661-667.

Research output: Contribution to journalArticle

Carson, April P. ; Fox, Caroline S. ; McGuire, Darren K ; Levitan, Emily B. ; Laclaustra, Martin ; Mann, Devin M. ; Muntner, Paul. / Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes. In: Circulation: Cardiovascular Quality and Outcomes. 2010 ; Vol. 3, No. 6. pp. 661-667.
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AU - Carson, April P.

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AU - Laclaustra, Martin

AU - Mann, Devin M.

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N2 - Background: Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c. Methods and Results: National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76). Conclusions: In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.

AB - Background: Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c. Methods and Results: National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76). Conclusions: In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.

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KW - Hemoglobin A1c

KW - Mortality

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