title: Low hemoglobin A(1c) in nondiabetic adults: an elevated risk state?
abstract: OBJECTIVE
  To identify predictors of low hemoglobin A(1c) (HbA(1c)) (<5.0%) and to investigate the association of low HbA(1c) with cause-specific mortality and risk of liver disease hospitalization.
  
  
  METHODS
  Prospective cohort study of 13,288 participants in the Atherosclerosis Risk in Communities Study. Logistic regression was used to identify cross-sectional correlates of low HbA(1c), and Cox proportional hazards models were used to estimate the association of low HbA(1c) with cause-specific mortality.
  
  
  RESULTS
  Compared with participants with HbA(1c) in the normal range (5.0 to <5.7%), participants with low HbA(1c) were younger, less likely to smoke, had lower BMI, lower white cell count and fibrinogen levels, and lower prevalence of hypercholesterolemia and history of coronary heart disease. However, this group was more likely to have anemia and had a higher mean corpuscular volume. In adjusted Cox models with HbA(1c) of 5.0 to <5.7% as the reference group, HbA(1c) <5.0% was associated with a significantly increased risk of all-cause mortality (hazard ratio [HR]: 1.32, 95% CI: 1.13-1.55) and of cancer death (1.47, 95% CI: 1.16-1.84). We also noted nonsignificant trends toward increased risk of death from cardiovascular causes (1.27, 95% CI: 0.93-1.75) and respiratory causes (1.42, 95% CI: 0.78-2.56). There was a J-shaped association between HbA(1c) and risk of liver disease hospitalization.
  
  
  CONCLUSIONS
  No single cause of death appeared to drive the association between low HbA(1c) and total mortality. These results add to evidence that low HbA(1c) values may be a generalized marker of mortality risk in the general population.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Colorado (Anschutz Medical Campus), Aurora, Colorado, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Aggarwal
authors.forename: Andrea L C
authors.initials: AL
authors.lastname: Schneider
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006760:Hospitalization; D006801:Humans; D008107:Liver Diseases / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk
chemical_list: D006442:Glycated Hemoglobin