title: The hemoglobin glycation index identifies subpopulations with harms or benefits from intensive treatment in the ACCORD trial.
abstract: OBJECTIVE
  This study tested the hypothesis that intensive treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial disproportionately produced adverse outcomes in patients with diabetes with a high hemoglobin glycation index (HGI = observed HbA1c - predicted HbA1c).
  
  
  METHODS
  ACCORD was a randomized controlled trial of 10,251 patients with type 2 diabetes assigned to standard or intensive treatment with HbA1c goals of 7.0% to 7.9% (53 to 63 mmol/mol) and less than 6% (42 mmol/mol), respectively. In this ancillary study, a linear regression equation (HbA1c = 0.009 × fasting plasma glucose [FPG] [mg/dL] + 6.8) was derived from 1,000 randomly extracted participants at baseline. Baseline FPG values were used to calculate predicted HbA1c and HGI for the remaining 9,125 participants. Kaplan-Meier and Cox regression were used to assess the effects of intensive treatment on outcomes in patients with a low, moderate, or high HGI.
  
  
  RESULTS
  Intensive treatment was associated with improved primary outcomes (composite of cardiovascular events) in the low (hazard ratio [HR] 0.75 [95% CI 0.59-0.95]) and moderate (HR 0.77 [95% CI 0.61-0.97]) HGI subgroups but not in the high HGI subgroup (HR 1.14 [95% CI 0.93-1.40]). Higher total mortality in intensively treated patients was confined to the high HGI subgroup (HR 1.41 [95% CI 1.10-1.80]). A high HGI was associated with a greater risk for hypoglycemia in the standard and intensive treatment groups.
  
  
  CONCLUSIONS
  HGI calculated at baseline identified subpopulations in ACCORD with harms or benefits from intensive glycemic control. HbA1c is not a one-size-fits-all indicator of blood glucose control, and taking this into account when making management decisions could improve diabetes care.
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center and Children's Hospital Research Institute for Children, New Orleans, LA jhempe@chnola-research.org.
authors.forename: James M
authors.initials: JM
authors.lastname: Hempe
authors.affiliation: Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA.
authors.forename: Shuqian
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.
authors.forename: Leann
authors.initials: L
authors.lastname: Myers
authors.affiliation: Research Division of Biostatistics and Study Methodology, Children's National Medical Center, Washington, DC.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McCarter
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.affiliation: Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Fonseca
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D016757:Death, Sudden, Cardiac / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000401:mortality / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000097:blood / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D012307:Risk Factors; D020521:Stroke / Q000209:etiology
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents