Diabetes Care, Vol 21, Issue 1 62-68, Copyright © 1998 by American Diabetes Association

ARTICLES

Serum ferritin as a component of the insulin resistance syndrome

JM Fernandez-Real, W Ricart-Engel, E Arroyo, R Balanca, R Casamitjana-Abella, D Cabrero, M Fernandez-Castaner and J Soler
Section of Endocrinology, Hospital de Girona, Spain. hosptrueta@comgir.com

OBJECTIVE: In epidemiological studies, serum ferritin was the second-strongest determinant of blood glucose (after BMI) in regression models and the third-strongest determinant of serum insulin (after BMI and age). Its concentration also correlated positively with plasma triglycerides and apolipoprotein B concentrations, and negatively with HDL2 cholesterol. We hypothesized that serum ferritin could be a marker of insulin resistance. RESEARCH DESIGN AND METHODS: Oral glucose tolerance and insulin sensitivity (SI, minimal model method) were prospectively evaluated in 36 healthy subjects. The relationship between serum ferritin and metabolic control (as measured by HbA1c levels) was also studied in 76 consecutive NIDDM patients. RESULTS: In healthy subjects, log-transformed serum ferritin (LOGFER) correlated with basal serum glucose (r = 0.44, P = 0.007), but not with BMI, age, systolic or diastolic blood pressure, total cholesterol, VLDL cholesterol, HDL cholesterol, total triglycerides, VLDL triglycerides, serum insulin, or HbA1c (all P = NS). Identical results were obtained when the two lowest quartiles of serum ferritin were evaluated separately. However, in the two highest quartiles, LOGFER correlated with BMI (0.50, P = 0.02), diastolic blood pressure (r = 0.8, P < 0.0001), serum LDL cholesterol (r = 0.57, P = 0.01), VLDL cholesterol (r = 0.48, P = 0.03), total cholesterol and HDL2 and HDL3 subtractions of HDL cholesterol (r = -0.68, -0.76, -0.55, P = 0.001. < 0.0001, and 0.01, respectively), total triglycerides (r = 0.60, P = 0.006), HDL2/HDL3 quotient (P = -0.71, P = 0.001), VLDL triglycerides (r = 0.65, P = 0.004), and serum uric acid (r = 0.51, P = 0.03), but not with systolic blood pressure (r = 0.38, P = 0.15). After adjusting for BMI, only the correlations between LOGFER and diastolic blood pressure (r = 0.7, P = 0.002) and HDL2/HDL3 quotient (r = -0.63, P = 0.01) remained significant. Strong correlations between LOGFER and glucose area under the curve during oral glucose tolerance test (Pearson's r = 0.73, P = 0.001) and SI (r = -0.68, P = 0.001), which remained significant after controlling for BMI, were observed. LOGFER (beta = -0.44, P = 0.01) and BMI (beta = -0.52, P = 0.004) constituted independent predictors of insulin sensitivity in a multivariate analysis (R2 = 0.68). In 76 consecutive NIDDM outpatients, serum glucose (P < 0.00001) and LOGFER (P = 0.03) independently predicted the value of HbA1c (R2 = 0.40) in a multiple linear regression analysis. CONCLUSIONS: The correlations among serum ferritin and diastolic blood pressure, HDL quotient, glucose area under the curve, and SI suggest that serum ferritin could be a marker of the insulin resistance syndrome. Serum ferritin may also be an independent determinant of poor metabolic control in the diabetic patient.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Dongiovanni, L. Valenti, A. Ludovica Fracanzani, S. Gatti, G. Cairo, and S. Fargion Iron Depletion by Deferoxamine Up-Regulates Glucose Uptake and Insulin Signaling in Hepatoma Cells and in Rat Liver Am. J. Pathol., March 1, 2008; 172(3): 738 - 747. [Abstract] [Full Text] [PDF]

				I. S. Vari, B. Balkau, A. Kettaneh, P. Andre, J. Tichet, F. Fumeron, E. Caces, M. Marre, B. Grandchamp, P. Ducimetiere, et al. Ferritin and Transferrin Are Associated With Metabolic Syndrome Abnormalities and Their Change Over Time in a General Population: Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) Diabetes Care, July 1, 2007; 30(7): 1795 - 1801. [Abstract] [Full Text] [PDF]

				M. L. Jehn, E. Guallar, J. M. Clark, D. Couper, B. B. Duncan, C. M. Ballantyne, R. C. Hoogeveen, Z. L. Harris, and J. S. Pankow A Prospective Study of Plasma Ferritin Level and Incident Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study Am. J. Epidemiol., May 1, 2007; 165(9): 1047 - 1054. [Abstract] [Full Text] [PDF]

				J. M. Fernandez-Real, J. M. Moreno, B. Chico, A. Lopez-Bermejo, and W. Ricart Circulating Visfatin Is Associated With Parameters of Iron Metabolism in Subjects With Altered Glucose Tolerance Diabetes Care, March 1, 2007; 30(3): 616 - 621. [Abstract] [Full Text] [PDF]

				X. Chen, T. O. Scholl, and T. P. Stein Association of Elevated Serum Ferritin Levels and the Risk of Gestational Diabetes Mellitus in Pregnant Women: The Camden Study Diabetes Care, May 1, 2006; 29(5): 1077 - 1082. [Abstract] [Full Text] [PDF]

				T. Iwasaki, A. Nakajima, M. Yoneda, Y. Yamada, K. Mukasa, K. Fujita, N. Fujisawa, K. Wada, and Y. Terauchi Serum Ferritin Is Associated With Visceral Fat Area and Subcutaneous Fat Area Diabetes Care, October 1, 2005; 28(10): 2486 - 2491. [Abstract] [Full Text] [PDF]

				C. Bozzini, D. Girelli, O. Olivieri, N. Martinelli, A. Bassi, G. De Matteis, I. Tenuti, V. Lotto, S. Friso, F. Pizzolo, et al. Prevalence of Body Iron Excess in the Metabolic Syndrome Diabetes Care, August 1, 2005; 28(8): 2061 - 2063. [Full Text] [PDF]

				J. M. Fernandez-Real, A. Lopez-Bermejo, and W. Ricart Iron Stores, Blood Donation, and Insulin Sensitivity and Secretion Clin. Chem., July 1, 2005; 51(7): 1201 - 1205. [Abstract] [Full Text] [PDF]

				J. Chen, R. P. Wildman, L. L. Hamm, P. Muntner, K. Reynolds, P. K. Whelton, and J. He Association Between Inflammation and Insulin Resistance in U.S. Nondiabetic Adults: Results from the Third National Health and Nutrition Examination Survey Diabetes Care, December 1, 2004; 27(12): 2960 - 2965. [Abstract] [Full Text] [PDF]

				M. Jehn, J. M. Clark, and E. Guallar Serum Ferritin and Risk of the Metabolic Syndrome in U.S. Adults Diabetes Care, October 1, 2004; 27(10): 2422 - 2428. [Abstract] [Full Text] [PDF]

				Y. Song, J. E. Manson, J. E. Buring, and S. Liu A Prospective Study of Red Meat Consumption and Type 2 Diabetes in Middle-Aged and Elderly Women: The Women's Health Study Diabetes Care, September 1, 2004; 27(9): 2108 - 2115. [Abstract] [Full Text] [PDF]

				S. Ghosh, S. Hevi, and S. L. Chuck Regulated secretion of glycosylated human ferritin from hepatocytes Blood, March 15, 2004; 103(6): 2369 - 2376. [Abstract] [Full Text] [PDF]

				R. Jiang, J. E. Manson, J. B. Meigs, J. Ma, N. Rifai, and F. B. Hu Body Iron Stores in Relation to Risk of Type 2 Diabetes in Apparently Healthy Women JAMA, February 11, 2004; 291(6): 711 - 717. [Abstract] [Full Text] [PDF]

				R. Jiang, J. Ma, A. Ascherio, M. J Stampfer, W. C Willett, and F. B Hu Dietary iron intake and blood donations in relation to risk of type 2 diabetes in men: a prospective cohort study Am. J. Clinical Nutrition, January 1, 2004; 79(1): 70 - 75. [Abstract] [Full Text] [PDF]

				T. T. Lao, K.-Y. Tse, L. Y. Chan, K.-F. Tam, and L.-F. Ho HBsAg Carrier Status and the Association Between Gestational Diabetes With Increased Serum Ferritin Concentration in Chinese Women Diabetes Care, November 1, 2003; 26(11): 3011 - 3016. [Abstract] [Full Text] [PDF]

				J. M. Fernandez-Real, G. Penarroja, A. Castro, F. Garcia-Bragado, A. Lopez-Bermejo, and W. Ricart Blood Letting in High-Ferritin Type 2 Diabetes: Effects on vascular reactivity Diabetes Care, December 1, 2002; 25(12): 2249 - 2255. [Abstract] [Full Text] [PDF]

				J. B. Whitfield, G. Zhu, J. E. Nestler, A. C. Heath, and N. G. Martin Genetic Covariation between Serum {gamma}-Glutamyltransferase Activity and Cardiovascular Risk Factors Clin. Chem., September 1, 2002; 48(9): 1426 - 1431. [Abstract] [Full Text] [PDF]

				J. M. Fernandez-Real, A. Lopez-Bermejo, and W. Ricart Cross-Talk Between Iron Metabolism and Diabetes Diabetes, August 1, 2002; 51(8): 2348 - 2354. [Abstract] [Full Text] [PDF]

				J. M. Fernandez-Real, G. Penarroja, A. Castro, F. Garcia-Bragado, I. Hernandez-Aguado, and W. Ricart Blood Letting in High-Ferritin Type 2 Diabetes : Effects on Insulin Sensitivity and {beta}-Cell Function Diabetes, April 1, 2002; 51(4): 1000 - 1004. [Abstract] [Full Text] [PDF]

				J. P.S. Chern, K.-H. Lin, M.-Y. Lu, D.-T. Lin, K.-S. Lin, J.-D. Chen, and C.-C. Fu Abnormal Glucose Tolerance in Transfusion-Dependent {beta}-Thalassemic Patients Diabetes Care, May 1, 2001; 24(5): 850 - 854. [Abstract] [Full Text]

				A. Davalos, J. Castillo, J. Marrugat, J. M. Fernandez-Real, A. Armengou, P. Cacabelos, and R. Rama Body iron stores and early neurologic deterioration in acute cerebral infarction Neurology, April 25, 2000; 54(8): 1568 - 1574. [Abstract] [Full Text] [PDF]

				P. J. Garry, W. C. Hunt, and R. N. Baumgartner Effects of Iron Intake on Iron Stores in Elderly Men and Women: Longitudinal and Cross-Sectional Results J. Am. Coll. Nutr., April 1, 2000; 19(2): 262 - 269. [Abstract] [Full Text] [PDF]