Association of elevated serum ferritin concentration with insulin resistance and impaired glucose metabolism in Korean men and women
Introduction
Iron is a transition metal that can convert poorly reactive free radicals (eg, H2O2) into highly reactive moieties (eg, the hydroxyl radical), which can cause oxidative damage to cells and tissues [1], [2]. Increased accumulation of iron in patients with hemochromatosis or hematologic diseases affects the synthesis and secretion of insulin by the pancreas [3], [4] and compromises insulin action in target tissues [5], [6], [7]. Recent reports have linked increased serum ferritin concentrations in nonpathologic conditions, reflecting subclinical iron overload, to insulin resistance [8], [9], [10], [11] and an increased risk of type 2 diabetes mellitus (DM) [12], [13].
Serum ferritin concentrations differ significantly according to sex and ethnicity. Asian men and women were reported to have higher adjusted mean serum ferritin concentrations compared with their white counterparts [14]. A study examining the association of diabetes with serum ferritin concentration in 6 racial/ethnic groups found that serum ferritin concentrations were significantly higher in women with diabetes than in women without diabetes in all racial/ethnic groups, but serum ferritin concentrations were significantly lower in Asian men with diabetes than in those without diabetes [15]. As serum ferritin concentrations differ significantly between men and women, it is thought that ferritin plays a different role in insulin resistance in each sex [16]. However, conflicting data have been reported with regard to the relationship between iron overload and glucose metabolism in Asian men and women [16], [17], [18], [19], [20]. The relationships between serum ferritin concentrations and insulin resistance [16] and risk of diabetes [19] have been reported in Chinese women, but not in men. Another Chinese study [17] found that serum ferritin concentrations of healthy, glucose-tolerant, first-degree relatives of type 2 DM patients were significantly higher than those of healthy control subjects in men, but not in women. However, Sun and colleagues [20] showed a strong positive association between elevated serum ferritin concentration and the risks of type 2 DM, impaired fasting glucose (IFG), and metabolic syndrome in both men and women aged 50 to 70 years. Therefore, the role played by ferritin in insulin resistance in men and women, particularly in Asian populations, remains poorly understood. Few studies have examined the relationship between serum ferritin concentration and glucose regulation status in large numbers of subjects with normal fasting glucose (NFG), IFG, and type 2 DM. The present study was performed to examine the association of serum ferritin concentrations with glucose metabolism abnormalities and insulin resistance and to determine if the association differed between men and women in a Korean population of varied glucose regulation status.
Section snippets
Subjects
Clinical and laboratory data were collected from 13 848 adults (47% women) who visited the Health Promotion Center at Asan Medical Center (Seoul, Korea) for regular health checkups in 2008. The health checkup recipients came voluntarily from all over South Korea; but most of them were middle-aged office workers, professionals, or housewives living in Seoul or the nearby urban area of Gyeonggi province. Each subject completed a standard questionnaire that detailed medical history, family history
Results
Among the 12 090 subjects, 1054 had type 2 DM, 3783 had an IFG level, and 7253 had an NFG concentration. The average serum concentration of ferritin was much higher in men (167 ± 103 ng/mL) than in women (65 ± 51 ng/mL). Ferritin concentrations were highest in the DM group, followed by the IFG group and the NFG group, in both men and women (186 ± 127, 176 ± 108, and 156 ± 92 ng/mL, respectively, in men; 85 ± 62, 75 ± 55, and 59 ± 47 ng/mL, respectively, in women) (Table 1). Table 2 shows the
Discussion
Our findings confirm that serum ferritin concentrations are significantly increased in prediabetic subjects as well as in type 2 DM patients and that serum ferritin concentration is positively associated with components of metabolic syndrome in both Korean men and women. However, men and women differ with regard to the role of ferritin in insulin resistance and glucose regulation. Specifically, increased serum concentrations of ferritin were associated with insulin resistance, metabolic
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The study protocol was approved by the Institutional Review Board of the Asan Medical Center, Seoul, Korea.