Serum Ferritin as a Component of the Insulin Resistance Syndrome

Abstract

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 (SI, minimal model method) were prospectively evaluated in 36 healthy subjects. The relationship between serum ferritin and metabolic control (as measured by HbA1c 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 HbA1c (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 HbA1c (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.