Two large epidemiological studies have recently reported a strong association between elevated serum ferritin concentration and increased risk for diabetes (1,2). Moreover, other studies have revealed the relationship among excess ferritin, coronary heart disease, and insulin resistance and have therefore renewed interest in ferritin as a risk factor for diabetes.
This study further investigates the association between ferritin metabolism and different status of glucose tolerance, including 121 type 2 diabetic subjects, 86 impaired glucose tolerant (IGT) subjects, 58 normal glucose tolerant (NGT) first-degree relatives in type 2 diabetic pedigrees, and 85 healthy control subjects. All patients underwent an oral glucose tolerance test (OGTT) and insulin release tests after 8 h of fasting, and blood levels of ferritin, HbA1c, glucose, insulin, C-peptide, and lipids were measured. Serum ferritin levels were measured with the radioimmunoassay kit (Beijing North Institute of Biological Technology). Normal ranges for ferritin concentration are ∼12–245 ng/ml for adult men and ∼5–130 ng/ml for women. We defined elevated concentrations of ferritin as ≥295 ng/ml for men and ≥155 ng/ml for women.
Levels of fasting and postprandial plasma glucose in the NGT group were remarkably higher than in the healthy control subjects. Fasting insulin concentrations in the NGT group were also higher than those of the other groups, while postprandial insulin concentrations increased significantly when compared with healthy control subjects. Ferritin concentrations were the highest in type 2 diabetic subjects, followed by the IGT group, the NGT group, and the healthy control group (412.88 ± 155.58, 354.19 ± 173.03, 231.31 ± 130.32 [P < 0.05 compared with healthy control subjects], and 164.69 ± 110.54 ng/ml, respectively). In the type 2 diabetic group, the newly diagnosed patients had higher ferritin concentrations than previously diagnosed (461.72 ± 132.41 vs. 354.19 ± 173.03 ng/ml, P < 0.05).
We also compared concentrations of serum ferritin in men and women for each group. In general, concentrations of ferritin in men were higher than in women (P < 0.05) except for in the healthy control group. In male subjects, ferritin concentrations of both newly and previously diagnosed type 2 diabetic, IGT, NGT, and healthy control groups showed the same trend as the whole group (494.30 ± 142.6, 425.01 ± 136.77, 390.07 ± 125.09, 284.74 ± 112.04 [P < 0.001 compared with the healthy control subjects], and 197.93 ± 110.41 ng/ml, respectively). However, in female subjects, ferritin concentrations in newly (425.65 ± 137.5 ng/ml) and previously (295.37 ± 150.98 ng/ml) diagnosed type 2 diabetes and IGT (330.72 ± 131.03 ng/ml) were higher than the NGT (174.06 ± 123.45 ng/ml) and healthy contol (137.28 ± 89.63 ng/ml) groups (P < 0.001). No significant difference was found between female NGT and female healthy control subjects. Moreover, in newly diagnosed type 2 diabetes, the concentrations of ferritin were significantly higher than in the previously diagnosed type 2 diabetic and IGT patients.
Using multiple regression analysis, we found an association between ferritin concentration and BMI, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure. HbA1c, FPG, 2-h plasma postprandial glucose, triglycerides, and total cholesterol were positively related to ferritin concentrations, while HDL cholesterol levels were inversely related to ferritin concentrations.
In recent years, the issue of the potential pathology of serum ferritin in type 2 diabetes has gained remarkable interest (3). In this study, we found that serum ferritin concentrations were remarkably increased in type 2 diabetes, especially in newly diagnosed patients. Subjects with higher concentrations of ferritin consequently had higher HbA1c, glucose, and insulin concentrations. These results further proved a positive association between type 2 diabetes and high plasma ferritin concentrations.
The exact mechanism through which elevated ferritin promotes the development of type 2 diabetes is unknown. Some investigations argued that abnormalities in ferritin metabolism might be a primary cause of type 2 diabetes (4–6). In our study, ferritin concentration in IGT subjects, the high-risk population for type 2 diabetes, already significantly increased when compared with normal control subjects, implying that hyperferritinemia occurs before elevation of plasma glucose concentrations. This observation was further substantiated by evidence that NGT first-degree relatives in the type 2 diabetic pedigrees had higher ferritin concentrations than normal control subjects.
