Risk Factors for Insulin Resistance, Metabolic Syndrome, and Diabetes in 248 HFE C282Y Homozygotes Identified by Population Screening in the HEIRS Study.

BACKGROUND

We sought to identify risk factors for insulin resistance, metabolic syndrome (MetS), and diabetes mellitus in 248 non-Hispanic white HFE C282Y homozygotes identified by population screening.

METHODS

We analyzed observations obtained prospectively in a postscreening examination: age; sex; body mass index (BMI); systolic/diastolic blood pressure; metacarpophalangeal (MP) joint hypertrophy; hepatomegaly; complete blood counts; alanine/aspartate aminotransferase levels; elevated C-reactive protein (>0.5 mg/dL); transferrin saturation; serum ferritin; homeostasis model assessment-insulin resistance (HOMA-IR); and MetS.

RESULTS

Twenty-six participants (10.5%) had diabetes diagnoses. A significant trend across HOMA-IR quartiles was observed only for blood neutrophils. Logistic regression on HOMA-IR fourth quartile revealed positive associations: age (P = 0.0002); male sex (P = 0.0022); and BMI (P < 0.0001). HOMA-IR fourth quartile predicted MetS (P < 0.0001). Logistic regression on diabetes revealed positive associations: age (P = 0.0012); male sex (P = 0.0068); MP joint hypertrophy (P = 0.0167); neutrophils (P = 0.0342); and MetS (P = 0.0298). Serum ferritin did not predict HOMA-IR fourth quartile, MetS, or diabetes.

CONCLUSIONS

In screening C282Y homozygotes, age, male sex, and BMI predicted HOMA-IR fourth quartile. HOMA-IR fourth quartile alone predicted MetS. Diabetes was associated with greater age, male sex, MP joint hypertrophy, greater blood neutrophil counts, and MetS.