The Hemoglobin Glycation Index Identifies Subpopulations With Harms or Benefits From Intensive Treatment in the ACCORD Trial

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 HbA(1c) 2 predicted HbA(1c)). RESEARCH DESIGN AND METHODS ACCORD was a randomized controlled trial of 10,251 patients with type 2 diabetes assigned to standard or intensive treatment with HbA(1c) 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 (HbA(1c) = 0.009 x 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 HbA(1c) 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. HbA(1c) 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.