1352-P: Among Those with Normoglycemia (NG), Insulin Resistance Risk Score (IRRS) Elevation Is Observed Up to Three Years prior to Diagnosis of Diabetes (T2D) or Prediabetes (PD)

Introduction and Objective: The prevalence of PD and T2D has been steadily increasing. Thus, early risk markers for PD and T2D in individuals with NG are critically important. We asked whether Insulin Resistance Risk Score (IRRS) could be an early risk marker for future PD or T2D. Methods: Individuals with NG (FPG <100 mg/dL and HbA1c <5.7%) were followed-up for 3 years for incident composite events of PD or T2D. IRRS was assessed from intact insulin and C-peptide levels in fasting participants at baseline and in the first 2 of 3 follow-up years. Results: Participants (n=16,333, 69% women) had mean (SD) age of 44 (12) years and median (IQR) IRRS of 12% (6 - 28). 23.5% (n =3,838) had incident events (IE) (n=865 in the bottom tertile of IRRS, 1269 in middle tertile, and 1704 in the top tertile, P <0.001). IE increased across the entire range of IRRS (Figure 1A). Participants with IEs had higher median IRRS at baseline and a greater rate of IRRS increase than those who did not (P interaction < 0.001). IRRS elevation was observed up to 3 years prior to IEs. Participants without IEs had a consistent low IRRS during follow-up (Figure 1B). Conclusion: IRRS elevation was observed early and increased more rapidly in participants with IEs. Those who maintained low IRRS levels did not experience events during a 3-year follow up. Disclosure J.Z. Louie: None. D. Shiffman: Other Relationship; Quest Diagnostics. O. Melander: None. F. Abbasi: None. L.A. Bare: Employee; Quest Diagnostics. J.B. Meigs: Consultant; Quest Diagnostics. M.J. McPhaul: Consultant; Quest Diagnostics.