title: Comorbidity affects the relationship between glycemic control and cardiovascular outcomes in diabetes: a cohort study.
abstract: BACKGROUND
  Recent studies have shown mixed results regarding the effectiveness of intensive glucose-lowering therapy in reducing risk for cardiovascular events.
  
  
  OBJECTIVE
  To determine whether attaining hemoglobin A(1c) (HbA(1c)) targets of 6.5% or less or 7.0% or less for glycemic control at baseline provides differential benefits for patients with high versus low-to-moderate levels of comorbidity.
  
  
  METHODS
  5-year longitudinal observational study of patients with type 2 diabetes. Patients were categorized into high and low-to-moderate comorbidity subgroups by using the Total Illness Burden Index (TIBI), a validated patient-reported measure of comorbidity.
  
  
  METHODS
  101 diabetes outpatient clinics and 103 general practitioners' clinics in Italy.
  
  
  METHODS
  2613 (83%) of 3074 patients with type 2 diabetes, sampled randomly from diabetes outpatient clinic rosters and recruited consecutively from general practitioners' clinics, who completed the baseline questionnaire.
  
  
  METHODS
  TIBI score, total mortality, and incident cardiovascular events. Hazard ratios (HRs) were adjusted for age and sex.
  
  
  RESULTS
  Attaining an HbA(1c) level of 6.5% or less at baseline was associated with lower 5-year incidence of cardiovascular events in the low-to-moderate comorbidity subgroup (adjusted HR, 0.60 [95% CI, 0.42 to 0.85]; P = 0.005) but not in the high comorbidity subgroup (adjusted HR, 0.92 [CI, 0.68 to 1.25]; P = 0.61; P for subgroup by HbA(1c) interaction = 0.048). Similarly, attaining a baseline HbA(1c) level of 7.0% predicted fewer cardiovascular events in the low-to-moderate comorbidity subgroup (adjusted HR, 0.61 (CI, 0.44 to 0.83; P = 0.001) but not in the high comorbidity subgroup (adjusted HR, 0.88 [CI, 0.66 to 1.17]; P = 0.38; P for subgroup by HbA(1c) interaction = 0.093).
  
  
  CONCLUSIONS
  The observational nature of the study does not allow causal inference. The length of the data collection period was limited. Information on clinical management was not available.
  
  
  CONCLUSIONS
  Patients with the high levels of comorbidity common in type 2 diabetes may receive diminished cardiovascular benefit from intensive blood glucose control. Comorbidity should be considered when tailoring glucose-lowering therapy in patients with type 2 diabetes.
  
  
  BACKGROUND
  Pfizer of Italy.
authors.affiliation: University of California Irvine, Irvine, California, USA. sgreenfi@uci.edu
authors.forename: Sheldon
authors.initials: S
authors.lastname: Greenfield
authors.forename: John
authors.initials: J
authors.lastname: Billimek
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Monica
authors.initials: M
authors.lastname: Franciosi
authors.forename: Giorgia
authors.initials: G
authors.lastname: De Berardis
authors.forename: Antonio
authors.initials: A
authors.lastname: Nicolucci
authors.forename: Sherrie H
authors.initials: SH
authors.lastname: Kaplan
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D015897:Comorbidity; D017281:Cost of Illness; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin