Serum Ferritin as a Component of the Insulin Resistance Syndrome

OBJECTIVE In epidemiological studies, serum ferritin was the second-strongest determinant of blood glucose (after BMI) in regression models and the third-strongest determinant of serum insulin (after BMI and age). Its concentration also correlated positively with plasma triglycerides and apolipoprotein B concentrations, and negatively with HDL₂ cholesterol. We hypothesized that serum ferritin could be a marker of insulin resistance.

RESEARCH DESIGN AND METHODS Oral glucose tolerance and insulin sensitivity (S_I, minimal model method) were prospectively evaluated in 36 healthy subjects. The relationship between serum ferritin and metabolic control (as measured by HbA_1c levels) was also studied in 76 consecutive NIDDM patients.

RESULTS In healthy subjects, log-transformed serum ferritin (LOGFER) correlated with basal serum glucose (r = 0.44, P = 0.007), but not with BMI, age, systolic or diastolic blood pressure, total cholesterol, VLDL cholesterol, HDL cholesterol, total triglycerides, VLDL triglycerides, serum insulin, or HbA_1c (all P = NS). Identical results were obtained when the two lowest quartiles of serum ferritin were evaluated separately. However, in the two highest quartiles, LOGFER correlated with BMI (0.50, P = 0.02), diastolic blood pressure (r = 0.8, P < 0.0001), serum LDL cholesterol (r = 0.57, P = 0.01), VLDL cholesterol (r = 0.48, P = 0.03), total cholesterol and HDL₂ and HDL₃ subtractions of HDL cholesterol (r = −0.68, −0.76, −0.55, P = 0.001. < 0.0001, and 0.01, respectively), total triglycerides (r = 0.60, P = 0.006), HDL₂/HDL₃ quotient (P = −0.71, P = 0.001), VLDL triglycerides (r = 0.65, P = 0.004), and serum uric acid (r = 0.51, P = 0.03), but not with systolic blood pressure (r = 0.38, P = 0.15). After adjusting for BMI, only the correlations between LOGFER and diastolic blood pressure (r = 0.7, P = 0.002) and HDL₂/HDL₃ quotient (r = −0.63, P = 0.01) remained significant. Strong correlations between LOGFER and glucose area under the curve during oral glucose tolerance test (Pearson's r = 0.73, P = 0.001) and S₁ (r = −0.68, P = 0.001), which remained significant after controlling for BMI, were observed. LOGFER (β = −0.44, P = 0.01) and BMI (β = −0.52, P = 0.004) constituted independent predictors of insulin sensitivity in a multivariate analysis (R² = 0.68). In 76 consecutive NIDDM outpatients, serum glucose (P < 0.00001) and LOGFER (P = 0.03) independently predicted the value of HbA_1c (R² = 0.40) in a multiple linear regression analysis.

CONCLUSIONS The correlations among serum ferritin and diastolic blood pressure, HDL quotient, glucose area under the curve, and S₁ suggest that serum ferritin could be a marker of the insulin resistance syndrome. Serum ferritin may also be an independent determinant of poor metabolic control in the diabetic patient.