title: Evidence of non-linearity in the association of glycemic control with influenza/pneumonia mortality: a study of 19 000 adults from the US general population.
abstract: BACKGROUND
  Diabetes is a major public health problem and thought to be a risk factor for infectious diseases, but pertinent epidemiological evidence is limited. This study aimed to analyse the associations of diabetes, disease duration and glycated haemoglobin levels (HbA1c) with infectious diseases mortality in the general population, including the investigation of potential non-linear relationships.
  
  
  METHODS
  An observational, prospective study of 19 783 subjects included in the Third National Health and Nutrition Examination Survey, representing the adult non-institutionalized population of the United States of America, was conducted. The analysis was done by multiple Cox regression and restricted cubic spline modelling.
  
  
  RESULTS
  Self-reported diabetes and diabetes duration were not significantly associated with the outcomes. However, there was evidence for a non-linear association of HbA1c with mortality from influenza, pneumonia or other acute lower respiratory infections. Spline regression suggested a roughly doubled risk of mortality beyond an HbA1c of 6.5% (48 mmol/mol) in reference to 5.2% (33 mmol/mol).
  
  
  CONCLUSIONS
  Future studies on diabetes and infections should adequately address potential non-linearity, which may be necessary to better understand and characterize more precisely the relationship of diabetes with infectious diseases.
authors.affiliation: Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.|Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Lutz P
authors.initials: LP
authors.lastname: Breitling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D048909:Diabetes Complications / Q000453:epidemiology / Q000401:mortality; D003920:Diabetes Mellitus / Q000097:blood / Q000628:therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006306:Health Surveys; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007251:Influenza, Human / Q000150:complications* / Q000453:epidemiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011014:Pneumonia / Q000150:complications* / Q000453:epidemiology / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: CDC; NHANES; dose-response; glycated haemoglobin; impaired glucose tolerance; infectiology; non-linearity