J Lipid Atheroscler.  2013 Dec;2(2):69-76. 10.12997/jla.2013.2.2.69.

Serum Ferritin Level is an Independent Predictor of Insulin Resistance in Non-diabetic Men Aged Between 30-69 Years: Korean National Health and Nutrition Examination Survey 2008-2010

• Koo BK
• Kim SW
• Yi KH
• Moon MK

• KMID: 1845571
• DOI: http://doi.org/10.12997/jla.2013.2.2.69

Abstract

OBJECTIVE
We investigated predictors of insulin resistance in Korean population from the Korean National Health and Nutrition Examination Surveys.
METHODS
Adults aged between 30-69 years without anemia were selected for the analysis. Fat mass was measured by dual-energy X-ray absorptiometry, and 24-hour nutritional information was obtained by interview from study subjects. Insulin resistance and beta cell function were calculated from homeostatic model assessment.
RESULTS
6,256 men and 8,003 women were included in the the study. Among participants, 9.8 (standard error [SE] 0.4) % of men and 6.8 (SE 0.4) % of women had diabetes mellitus (DM); moreover, serum ferritin level was higher in the DM patients compared to the non-DM subjects both in men and women (p<0.001). Serum ferritin levels correlated significantly with insulin resistance (age and body mass index adjusted p<0.001) in men, but not in women. Serum ferritin levels also correlated with total body fat (p=0.009), triglyceride levels (p<0.001), alanine aminotransferase (ALT) levels (p<0.001) and leukocyte count (p<0.001), but not with iron or fat intake. Multivariate analysis showed that serum ferritin level was an independent predictor of insulin resistance even after adjusting body fat, ALT levels, triglyceride levels and leukocyte count (beta=0.027, p=0.027). Beta cell function was not associated with ferritin levels both in men and women.
CONCLUSION
Elevated serum ferritin was a risk factor for DM by increasing insulin resistance rather than affecting beta cell function. Serum ferritin level was an independent predictor of insulin resistance even after adjusting body fat or systemic inflammation in men.

Keyword

Ferritin; Insulin resistance; Diabetes mellitus

MeSH Terms

Absorptiometry, Photon
Adipose Tissue
Adult
Alanine Transaminase
Anemia
Body Mass Index
Diabetes Mellitus
Female
Ferritins*
Humans
Inflammation
Insulin Resistance*
Insulin*
Iron
Leukocyte Count
Male
Multivariate Analysis
Nutrition Surveys*
Risk Factors
Triglycerides
Alanine Transaminase
Ferritins
Insulin
Iron

Reference

1. Haidari M, Javadi E, Sanati A, Hajilooi M, Ghanbili J. Association of increased ferritin with premature coronary stenosis in men. Clin Chem. 2001; 47:1666–1672.

2. Williams MJ, Poulton R, Williams S. Relationship of serum ferritin with cardiovascular risk factors and inflammation in young men and women. Atherosclerosis. 2002; 165:179–184.

3. Piperno A, Trombini P, Gelosa M, Mauri V, Pecci V, Vergani A, et al. Increased serum ferritin is common in men with essential hypertension. J Hypertens. 2002; 20:1513–1518.

4. Ford ES, Cogswell ME. Diabetes and serum ferritin concentration among U.S. adults. Diabetes Care. 1999; 22:1978–1983.

5. Kim CH, Kim HK, Bae SJ, Park JY, Lee KU. Association of elevated serum ferritin concentration with insulin resistance and impaired glucose metabolism in Korean men and women. Metabolism. 2011; 60:414–420.

6. Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB. Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA. 2004; 291:711–717.

7. de Jager J, Dekker JM, Kooy A, Kostense PJ, Nijpels G, Heine RJ, et al. Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn Study. Arterioscler Thromb Vasc Biol. 2006; 26:1086–1093.

8. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006; 17:4–12.

9. Park SK, Ryoo JH, Kim MG, Shin JY. Association of serum ferritin and the development of metabolic syndrome in middle-aged Korean men: a 5-year follow-up study. Diabetes Care. 2012; 35:2521–2526.

10. Fernández-Real JM, Ricart-Engel W, Arroyo E, Balançá R, Casamitjana-Abella R, Cabrero D, et al. Serum ferritin as a component of the insulin resistance syndrome. Diabetes Care. 1998; 21:62–68.

11. Alexander CM. The coming of age of the metabolic syndrome. Diabetes Care. 2003; 26:3180–3181.

12. Mlinar B, Marc J, Janez A, Pfeifer M. Molecular mechanisms of insulin resistance and associated diseases. Clin Chim Acta. 2007; 375:20–35.

13. Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood. 2003; 101:3359–3364.

14. Shi Z, Zhou M, Yuan B, Qi L, Dai Y, Luo Y, et al. Iron intake and body iron stores, anaemia and risk of hyperglycaemia among Chinese adults: the prospective Jiangsu Nutrition Study (JIN). Public Health Nutr. 2010; 13:1319–1327.

15. Igaki N, Takashima M, Ohyama M, Oh S, Kida A, Yanase K, et al. The beneficial effect of effective control of anemia on hyperinsulinemia and hypoxemia in a hemodialysis patient with corrected transposition of the great arteries. Clin Exp Nephrol. 2004; 8:163–167.

16. Shi Z, Hu X, Yuan B, Hu G, Pan X, Holmboe-Ottesen G. Coexistence of anaemia and the metabolic syndrome in adults in Jiangsu, China. Asia Pac J Clin Nutr. 2008; 17:505–513.

17. Gillum RF. Association of serum ferritin and indices of body fat distribution and obesity in Mexican American men--the Third National Health and Nutrition Examination Survey. Int J Obes Relat Metab Disord. 2001; 25:639–645.

18. Brogan D. Software for sample survey data, misuse of standard packages. In : Armitage P, Colton T, editors. Encyclopedia of biostatistics. New York (NY): John Wiley and Sons, Inc;1998.

19. Lim S, Shin H, Song JH, Kwak SH, Kang SM, Yoon JW, et al. Increasing prevalence of metabolic syndrome in Korea: the Korean National Health and Nutrition Examination Survey for 1998-2007. Diabetes Care. 2011; 34:1323–1328.

20. Choi YJ, Kim HC, Kim HM, Park SW, Kim J, Kim DJ. Prevalence and management of diabetes in Korean adults: Korea National Health and Nutrition Examination Surveys 1998-2005. Diabetes Care. 2009; 32:2016–2020.

21. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004; 27:1487–1495.

22. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005; 112:2735–2752.

23. Ministry of Health and Welfare. Korea Centers for Disease Control and Prevention. Korea Health Statistics 2010 : Korea National Health and Nutrition Examination Survey (KNHANES V-1). Cheongwon: Korea Centers for Disease Control and Prevention;2011.

24. Brudevold R, Hole T, Hammerstrøm J. Hyperferritinemia is associated with insulin resistance and fatty liver in patients without iron overload. PLoS One. 2008; 3:e3547.

25. Fernández-Real JM, Peñarroja G, Castro A, García-Bragado F, Hernández-Aguado I, Ricart W. Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and beta-cell function. Diabetes. 2002; 51:1000–1004.

26. Valenti L, Fracanzani AL, Dongiovanni P, Bugianesi E, Marchesini G, Manzini P, et al. Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case-control study. Am J Gastroenterol. 2007; 102:1251–1258.

27. Fargion S, Dongiovanni P, Guzzo A, Colombo S, Valenti L, Fracanzani AL. Iron and insulin resistance. Aliment Pharmacol Ther. 2005; 22:Suppl 2. 61–63.

28. Dongiovanni P, Ruscica M, Rametta R, Recalcati S, Steffani L, Gatti S, et al. Dietary iron overload induces visceral adipose tissue insulin resistance. Am J Pathol. 2013; 182:2254–2263.

29. Rahier J, Loozen S, Goebbels RM, Abrahem M. The haemochromatotic human pancreas: a quantitative immunohistochemical and ultrastructural study. Diabetologia. 1987; 30:5–12.

30. Pham NM, Nanri A, Yi S, Kurotani K, Akter S, Foo LH, et al. Serum ferritin is associated with markers of insulin resistance in Japanese men but not in women. Metabolism. 2013; 62:561–567.

31. Rushton DH, Dover R, Sainsbury AW, Norris MJ, Gilkes JJ, Ramsay ID. Why should women have lower reference limits for haemoglobin and ferritin concentrations than men? BMJ. 2001; 322:1355–1357.

32. de Oliveira Otto MC, Alonso A, Lee DH, Delclos GL, Bertoni AG, Jiang R, et al. Dietary intakes of zinc and heme iron from red meat, but not from other sources, are associated with greater risk of metabolic syndrome and cardiovascular disease. J Nutr. 2012; 142:526–533.