Background: T2D risk assessment is typically based on fasting glucose (FG) and HbA1c levels. We tested the hypothesis that HbA1c-based T2D risk assessment is improved by also considering another physiological axis, insulin resistance (IR), assessed using a fasting insulin (FI) homeostasis model (HOMA-IR).

Methods: We followed 2,205 white individuals from the Framingham Heart Study without T2D (medication use or FG >=126 mg/dL) at baseline for a mean of 16 years. We used age-sex adjusted regression to model incident T2D as a function of baseline HbA1c and IR tertile of HOMA-IR (FI x FG/22.5).

Results: Of 266 incident T2D cases, 205 (77%) were in HOMA-IR tertile 3, and of these, 135 (66% of 205) had HbA1c <5.7 (Table). Individuals in HOMA-IR tertile 3 had 16-year T2D CI rates of 20-35%. Both HbA1c and IR were independently associated with elevated incident T2D risk. We saw similar patterns in the 1,583 individuals with baseline FG <100 mg/dL.

Conclusion: HbA1c and fasting insulin are commonly available clinical diagnostic tests. Combined consideration of high levels of both identifies the great majority of white individuals at highly increased risk for future T2D.


J.B. Meigs: Consultant; Self; Quest Diagnostics. B.C. Porneala: None. A. Leong: None. D. Shiffman: Employee; Self; Quest Diagnostics. J. Devlin: Employee; Self; Quest Diagnostics. M.J. McPhaul: Employee; Self; Quest Diagnostics.

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