Hyperferritinemia Is a Predictor of Onset of Diabetes in Japanese Males Independently of Decreased Renal Function and Fatty Liver: A Fifteen-Year Follow-Up Study

Background: Type 2 diabetes is an important health concern worldwide. The disease etiology may depend on multiple environmental and genetic factors that cause insulin resistance, including dysregulation of iron storage. The goal of this study was to examine the relationship of the serum ferritin concentration with onset of diabetes over a long period. Methods: Correlations of serum ferritin and metabolic markers with onset of diabetes mellitus were examined over 15 years in 150 males participating in a health screening program. Results: HOMA-β showed a gradual significant decrease in the first 4 years in subjects with ferritin > 190 ng/mL (group H) compared to those with ferritin < 190 ng/mL, but there was no difference in HO-MA-R between these groups. A significant number of cases with onset of diabetes was observed over 15 years (hazard ratio (HR): 3.97), and obesity, fasting blood glucose level, hemoglobin A1c (HbA1c), HOMA-R, fasting immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) were all significant in univariate comparison between non-diabetes and diabetes-onset groups. In multivariate analysis, ferritin in group H (HR: 3.25), fatty liver (HR: 3.38), estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m² (HR: 3.48) and high-density lipoprotein (HDL) < 40 mg/dL (HR: 2.61) were sig- nificant predictive factors for onset of type 2 diabetes mellitus. Conclusions: These results suggest that the serum ferritin level is an important index for priority intervention in preventive medicine for reduction of onset of diabetes.