Simultaneous Consideration of HbA1c and Insulin Resistance Improves Risk Assessment in White Individuals at Increased Risk for Future Type 2 Diabetes

Type 2 diabetes (T2D) prevalence increases unabated even as interventions focused on individuals at high risk can prevent T2D (1). Best approaches to identify individuals at high risk continue to be refined. Current risk assessment focuses on elevated glycemia, commonly estimated by fasting glucose (FG) and HbA1c levels, despite imperfect sensitivity and specificity (2). We previously showed that risk for T2D increases progressively as HbA1c increases, independently and in addition to increasing FG (3,4). As risk assessment for T2D depends on more than glycemia alone, simultaneous consideration of another physiological axis may improve biomarker-based diagnostic precision. Here, we test the hypothesis that simultaneous consideration of HbA1c and insulin resistance (IR), assessed with fasting insulin as HOMA of IR (HOMA-IR), can substantially improve risk assessment for T2D. We have previously detailed our statistical approach, IR and T2D diagnostic criteria, and particulars of the Framingham Heart Study (FHS) (3). Using the same FHS data and excluding those with T2D at baseline, we categorized individuals according to HbA1c <5.7% or 5.7–6.49% and into HOMA-IR tertiles and followed them for a mean (SD) of 16.4 (4.5) years for incident T2D. Age- and sex-adjusted T2D incidence rates and counts of subjects are shown in Fig. 1 A for all …