Elsevier

Metabolism

Volume 60, Issue 3, March 2011, Pages 414-420
Metabolism

Association of elevated serum ferritin concentration with insulin resistance and impaired glucose metabolism in Korean men and women

https://doi.org/10.1016/j.metabol.2010.03.007Get rights and content

Abstract

Increased serum ferritin concentrations in nonpathologic conditions, reflecting subclinical iron overload, have been reported to be associated with insulin resistance and an increased risk of type 2 diabetes mellitus (DM). However, serum ferritin concentrations differ significantly according to sex and ethnicity; and data concerning the relationship between serum ferritin concentrations and glucose metabolism abnormalities in Asian men and women are conflicting. This cross-sectional study investigated the association of serum ferritin concentrations with insulin resistance and impaired glucose metabolism in a large number of subjects with normal fasting glucose (NFG) level, impaired fasting glucose (IFG) level, or type 2 DM. We analyzed clinical and laboratory data from 12 090 subjects (6378 men and 5712 women; age, 20-89 years) who underwent general medical checkups. The study population included 1054 subjects with type 2 DM, 3783 subjects with IFG level, and 7253 subjects with NFG level. Serum ferritin, hemoglobin A1c, fasting glucose, lipid, and insulin levels were measured. Insulin resistance and β-cell function indices were derived from a homeostasis model assessment. Serum 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). After adjustment for other variables using multiple regression analysis, homeostasis model assessment of insulin resistance was independently associated with serum ferritin concentration in men, but not in women. When the fourth quartile of ferritin was compared with the first quartile, the age-adjusted odds ratio (OR) for type 2 DM was 1.71 (95% confidence interval, 1.38-2.12) in men and 1.50 (1.05-2.13) in women. The OR in men was attenuated to 1.27 (1.01-1.60) but remained significant after adjustment for body mass index (BMI), waist circumference, blood pressure, serum lipids, liver enzymes, and high-sensitivity C-reactive protein (hsCRP). In nondiabetic subjects, the age-adjusted OR for IFG in the fourth quartile of ferritin was 1.82 (1.56-2.13) in men and 1.68 (1.40-2.02) in women. The OR was attenuated to 1.31 (1.11-1.55) in men and 1.45 (1.19-1.78) in women after adjustment for BMI, waist circumference, blood pressure, serum lipids, liver enzymes, and hsCRP. In NFG subjects, the age-adjusted OR for metabolic syndrome in the fourth quartile of ferritin concentration was 2.85 (1.99-4.07) in men and 1.21 (0.82-1.79) in women. In men, the OR was attenuated to 1.58 (1.06-2.37) after adjustment for BMI, liver enzymes, and hsCRP. Increased serum concentrations of ferritin are associated with insulin resistance, type 2 DM, IFG, and metabolic syndrome in men, but only with IFG in women. These results suggest that iron overload is associated with insulin resistance in men, but not in 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.

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