kjhp Korean Journal of Health Promotion Korean J Health Promot 2234-2141 2093-5676 The Korean Society of Health Promotion and Disease Prevention 10.15384/kjhp.2017.17.2.47 kjhp-17-47 Original Article Serum Ferritin Levels Are Associated with the Higher Risk of Diabetes Mellitus in Men and Postmenopausal Women, Based on the 2010-2012 KNHANES KimJoo-Yeon 1 KangHee-Taik 1 2 LeeYong-Jae 3 KimJin-Young 1 KimTae-Jong 1 LimHyoung-Ji 1 LeeJae-Woo 1 Department of Family Medicine, Chungbuk National University Hospital, Cheongju, Korea Department of Family Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Corresponding author : Hee-Taik Kang, MD Department of Family Medicine, College of Medicine, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju 28644, Korea Tel: +82-43-269-6301, Fax: +82-43-269-6675 E-mail: kanght0818@gmail.com 012017 19012017 17247 53 03042017 13062017 Copyright © 2017 The Korean Society of Health Promotion and Disease Prevention 2017 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Background:

The aim of this study was to investigate the relationship between serum ferritin and diabetes mellitus (DM) in the Korean population.

 Methods:

This cross-sectional study included 9,576 subjects (4,264 men, 2,394 premenopausal women, and 2,918 postmenopausal women) older than 19 years using data from the 2010-2012 Korean National Health and Nutrition Examination Survey. DM was defined as fasting plasma glucose ≥126 mg/dL, glycosylated hemoglobin ≥6.5%, or use of any glucose-lower medication including insulin therapy.

 Results:

The overall prevalence of DM was 12.0, 3.6, and 17.3% in men, premenopausal women, and post-menopausal women, respectively. DM prevalence was greater with ferritin levels from Q1 to Q4: 10.3, 10.2, 12.7, and 14.8% in men; 2.0, 2.8, 2.8, and 6.4% in premenopausal women; and 13.9, 14.4, 18.1, and 22.9% in post-menopausal women, respectively. Compared with participants in Q1, the odds ratios (95% confidence intervals) for DM among participants in Q4 were 1.67 (1.20-2.32) in men, 2.06 (0.91-4.66) in premenopausal women, and 1.60 (1.09-2.35) in post-menopausal women after adjusting for age and other covariates.

 Conclusion:

Serum ferritin concentration was positively associated with a higher risk of DM in adult men and post-menopausal women.

 Diabetes mellitus Ferritin Insulin resistance REFERENCESBeat diabetes: an urgent call for global action Lancet 201638710027 1483 Korean Diabetes Association Korean Diabetes Fact Sheet 2016 [Internet] Seoul Korean Diabetes Association 2016 [Accessed May 3, 2017]. Available from: http://www.diabetes.or.kr/temp/KDA_fact_sheet%202016.pdf American Diabetes Association Economic costs of diabetes in the U.S. in 2007 Diabetes Care 2008313 596615 Peyrin-Biroulet L Williet N Cacoub P Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review Am J Clin Nutr 20151026 158594 Gabay C Kushner I Acute-phase proteins and other systemic responses to inflammation N Engl J Med 19993406 44854 Opara EC Role of oxidative stress in the etiology of type 2 diabetes and the effect of antioxidant supplementation on glycemic control J Investig Med 2004521 1923 Evans JL Maddux BA Goldfine ID The molecular basis for oxidative stress-induced insulin resistance Antioxid Redox Signal 200577-8 104052 Pradhan AD Manson JE Rifai N Buring JE Ridker PM C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus JAMA 20012863 32734 Rajpathak SN Wylie-Rosett J Gunter MJ Negassa A Kabat GC Rohan TE Biomarkers of body iron stores and risk of developing type 2 diabetes Diabetes Obes Metab 2009115 4729 Hotamisligil GS Inflammation and metabolic disorders Nature 20064447121 8607 Wilson JG Lindquist JH Grambow SC Crook ED Maher JF Potential role of increased iron stores in diabetes Am J Med Sci 20033256 3329 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 20042916 7117 Lee BK Kim Y Kim YI Association of serum ferritin with metabolic syndrome and diabetes mellitus in the South Korean general population according to the Korean National Health and Nutrition Examination Survey 2008 Metabolism 20116010 141624 Kim S Park SK Ryoo JH Choi JM Hong HP Park JH Incidental risk for diabetes according to serum ferritin concentration in Korean men Clin Chim Acta 2015451Pt B 1659 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 2011603 41420 Park RJ Moon JD Low transferrin saturation is associated with impaired fasting glucose and insulin resistance in the South Korean adults: the 2010 Korean National Health and Nutrition Examination Survey Diabet Med 2015325 6738 Kim I Yetley EA Calvo MS Variations in iron-status measures during the menstrual cycle Am J Clin Nutr 1993585 7059 Powell LW Seckington RC Deugnier Y Haemochromatosis Lancet 201638810045 70616 Fernández-Real JM Ricart-Engel W Arroyo E Balançá R Casamitjana-Abella R Cabrero D Serum ferritin as a component of the insulin resistance syndrome Diabetes Care 1998211 628 Evans JL Maddux BA Goldfine ID The molecular basis for oxidative stress-induced insulin resistance Antioxid Redox Signal 200577-8 104052 Davis RJ Corvera S Czech MP Insulin stimulates cellular iron uptake and causes the redistribution of intracellular transferrin receptors to the plasma membrane J Biol Chem 1986261 19 870811 Tables

Participant characteristics by sex and menopausal status

  Men Women
    Premenopausal Postmenopausal
Unweighted N 4,264 2,394 2,918
Age, y 43.7±0.3 35.4±0.2 60.0±0.3
BMI, kg/m² 24.2±0.1 22.6±0.1 24.4±0.1
SBP, mmHg 119.9±0.3 108.4±0.3 124.4±0.5
DBP, mmHg 79.1±0.2 72.2±0.3 76.0±0.3
FPG, mg/dL 99.9±0.5 91.8±0.5 101.5±0.6
HbA1c, % 5.85±0.02 5.5±0.02 6.0±0.02
Hemoglobin, g/dL 15.5±0.02 13.3±0.02 13.4±0.02
Ferritin, ng/mL 128.1±1.9 34.9±0.8 68.6±1.2
Iron, μg/dL 134.1±1.0 110.9±1.2 105.2±0.7
TIBC, μg/dL 310.6±0.9 324.5±1.1 314.9±1.0
Cholesterol, mg/dL 188.5±0.8 180.9±0.8 202.5±0.8
Triglyceride, mg/dL 154.1±2.3 98.3±2.9 136.9±2.0
HDL-C, mg/dL 46.7±0.2 54.0±0.3 49.9±0.3
Creatinine, mg/dL 9 0.97±0.00 0.71±0.00 0.73±0.00
WBC, ×109/L 6.3±0.03 5.7±0.04 5.7±0.04
Regular drinker, % 38.9±0.9 13.1±0.8 6.1±0.6
Current smoker, % 44.4±1.0 8.6±0.8 4.9±0.5
Regular exerciser, % 41.2±1.0 37.3±1.2 32.7±1.1
Higher education, % 36.8±1.1 42.6±1.3 10.5±0.9
DM, % 12.0±0.7 3.6±0.4 17.3±1.0

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; TIBC, total iron binding capacity; HDL-C, high-density lipoprotein cholesterol; WBC, white blood cells; DM, diabetes mellitus. Values are presented as mean±standard error.

Participant characteristics according to ferritin quartiles

Men Q1 Q2 Q3 Q4 P P for trend
Ferritin levels ≤68.4 68.4-104.6 104.7-158.5 >158.5    
Age, y 45.1±0.6 42.6±0.5 43.2±0.6 44.0±0. 6 0.008 0.290
BMI, kg/m² 23.6±0.1 24.0±0.1 24.3±0.1 25.0±0.2 <0.001 <0.001
SBP, mmHg 119.6±0.5 118.9±0.6 119.5±0.6 121.6±0.5 <0.001 0.05
DBP, mmHg 77.9±0.5 78.2±0.4 79.1±0.4 81.3±0.4 <0.001 <0.001
FPG, mg/dL 96.6±0.8 98.0±0.8 100.1±1.0 104.9±1.1 <0.001 <0.001
HbA1c, % 5.7±0.03 5.7±0.03 5.7±0.04 5.8±0.04 0.001 0.012
Hb, g/dL 15.2±0.1 15.5±0.04 15.5±0.04 15.7±0.04 <0.001 <0.001
Ferritin, ng/mL 45.2±0. 7 86.6±0.4 129.2±0.6 252.9±4.2 <0.001 <0.001
Iron, μg/dL 127.6±2.2 133.6±1.9 135.8±1.9 139.4±2.0 0.001 <0.001
TIBC, μg/dL 323.4±1.6 307.9±1.4 305.6±0.3 306.0±1.5 <0.001 <0.001
Cholesterol, mg/dL 182.9±1.3 186.1±1.3 191.1±1.4 193.8±1.3 <0.001 <0.001
Creatinine, mg/dL 0.96±0.00 0.97±0.01 0.97±0.00 0.96±0.00 0.069 0.765
WBC, ×109/L 6.1±0.1 6.3±0.1 6.3±0.05 6.4±0.05 0.003 <0.001
Regular drinker, % 27.2±1.7 37.0±1.9 39.7±1.8 51.6±2.0 <0.001 <0.001
Current smoker, % 39.0±2.0 44.4±2.0 47.2±1.8 47.0±2.0 <0.001 <0.001
Regular exerciser, % 45.2±2.0 40.9±1.9 42.6±2.0 35.9±1.9 <0.001 <0.001
Higher education, % 30.7±1.9 37.9±1.9 39.8±2.1 38.4±2.0 <0.001 <0.001
DM, % 10.3±1.1 10.2±1.1 12.7±1.3 14.8±1.3 <0.001 <0.001
Premenopausal women            
Ferritin levels ≤14.3 14.4-27.3 27.4-44.4 >44.4    
Age, y 35.5±0.5 35.1±0.5 34.8±0.5 36.1±0.5 0.231 0.530
BMI, kg/m² 22.0±0.2 22.6±0.2 22.8±0.2 23.1±0.2 0.001 <0.001
SBP, mmHg 108.4±0.6 107.4±0.6 107.9±0.6 109.7±0.7 0.064 0.105
DBP, mmHg 71.9±0.5 71.8±0.5 71.7±0.5 73.3±0.4 0.033 0.029
FPG, mg/dL 90.1±0.7 90.7±0.7 90.9±0.7 95.0±1.4 0.015 0.001
HbA1c, % 5.5±0.02 5.4±0.02 5.4±0.03 5.5±0.04 0.003 0.081
Hb, g/dL 13.0±0.03 13.3±0.03 13.4±0.04 13.5±0.04 <0.001 <0.001
Ferritin, ng/mL 8.7±0.2 20.5±0.2 35.4±0.2 72.1±1.8 <0.001 <0.001
Iron, μg/dL 96.4±2.3 111.2±2.2 115.4±2.1 120.1±2.2 <0.001 <0.001
TIBC, μg/dL 360.0±2.5 324.5±1.8 312.4±2.0 302.6±1.6 <0.001 <0.001
Cholesterol, mg/dL 181.3±1.6 179.0±1.6 177.9±1.6 185.2±1.8 0.011 0.168
Creatinine, mg/dL 0.72±0.01 0.71±0.00 0.71±0.01 0.71±0.00 0.548 0.160
WBC, ×109/L 5.5±0.1 5.7±0.1 5.8±0.1 5.8±0.1 0.008 0.001
Regular drinker, % 11.1±1.4 11.6±1.8 11.8±1.6 17.6±1.9 <0.001 <0.001
Current smoker, % 7.1±1.6 8.2±1.4 8.3±1.5 10.6±1.6 <0.001 <0.001
Regular exerciser, % 37.3±2.6 37.0±2.3 36.5±2.4 38.1±2.5 <0.001 <0.001
Higher education, % 42.4±2.4 44.5±2.7 44.4±2.4 39.3±2.5 <0.001 <0.001
DM, % 2.0±0.6 2.8±0.7 2.8±0.7 6.4±1.2 <0.001 <0.001
Post-menopausal women            
Ferritin levels ≤36.5 36.6-57.7 57.8-87.3 >87.3    
Age, y 57.4±0.8 60.2±0.5 60.4±0.5 61.8±0.6 <0.001 <0.001
BMI, kg/m² 24.0±0.1 24.2±0.2 24.7±0.2 24.8±0.2 <0.001 <0.001
SBP, mmHg 123.6±1.0 123.4±0.8 126.1±0.9 124.5±0.7 0.089 0.163
DBP, mmHg 76.1±0.5 75.4±0.5 76.8±0.5 75.7±0.5 0.140 0.969
FPG, mg/dL 97.9±1.0 99.2±1.0 101.8±1. 4 107.2±1.5 <0.001 <0.001
HbA1c, % 5.9±0.04 6.0±0.04 6.0±0.05 6.1±0.05 0.005 <0.001
Hb, g/dL 13.3±0.04 13.5±0.04 13.5±0.04 13.5±0.04 <0.001 <0.001
Ferritin, ng/mL 24.4±0.4 46.9±0.3 71.4±0.40 134.2±2.6 <0.001 <0.001
Iron, μg/dL 101.5±1.5 105.5±1.3 103.0±1.4 110.8±1.7 <0.001 0.001
TIBC, μg/dL 336.8±1.9 314.6±1.7 307.2±1.8 300.3±1.9 <0.001 <0.001
Cholesterol, mg/dL 199.6±1.6 203.3±1.7 203.4±1.7 203.7±1.7 0.250 0.087
Creatinine, mg/dL 0.72±0.01 0.72±0.01 0.73±0.01 0.74±0.01 0.239 0.069
WBC, ×109/L 5.6±0.1 5.6±0.1 5.6±0.1 5.7±0.1 0.614 0.270
Regular drinker, % 4.2±1.0 4.7±0.9 6.2±1.2 9.4±1.4 <0.001 <0.001
Current smoker, % 4.8±0.9 4.0±0.9 5.0±1.2 5.9±1.2 <0.001 <0.001
Regular exerciser, % 29.5±2.1 34.5±2.2 34.2±2.1 32.6±2.0 <0.001 <0.001
Higher education, % 15.0±1.9 9.4±1.6 7.6±1.3 9.9±1.6 <0.001 <0.001
DM, % 13.9±1.6 14.4±1.5 18.1±1.9 22.9±2.1 <0.001 <0.001

Values are presented as mean±standard error. Their P value and P for trend are determined by general linear model for continuous variables and chi square test for categorical variables. Q indicates quartile.

ORs (95% CI) for diabetes according to sex and menopausal specific ferritin quartiles

  Q1 Q2 Q3 Q4
Men        
Ferritin, ng/mL ≤68.3 68.4-104.6 104.7-158.5 >158.5
Model 1a 1 0.99 (0.71-1.38) 1.27 (0.93-1.72) 1.52 (1.14-2.03)
Model 2b 1 1.18 (0.82-1.69) 1.54 (1.10-2.16) 1.68 (1.22-2.31)
Model 3c 1 1.17 (0.81-1.69) 1.51 (1.08-2.13) 1.67 (1.20-2.32)
Premenopausal women        
Ferritin, ng/mL ≤14.3 14.4-27.3 27.4-44.4 >44.4
Model 1a 1 1.41 (0.63-3.15) 1.41 (0.63-3.16) 3.29 (1.55-7.00)
Model 2b 1 1.21 (0.51-2.86) 1.05 (0.43-2.57) 2.07 (0.94-4.56)
Model 3c 1 1.20 (0.50-2.87) 1.12 (0.45-2.81) 2.06 (0.91-4.66)
Post- menopausal women Ferritin, ng/mL ≤36.5 36.6-57.7 57.8-87.3 >87.3
Model 1a 1 1.04 (0.74-1.47) 1.36 (0.96-1.93) 1.83 (1.29-2.60)
Model 2b 1 1.00 (0.68-1.46) 1.21 (0.84-1.74) 1.57 (1.07-2.30)
Model 3c 1 0.98 (0.67-1.45) 1.19 (0.83-1.72) 1.60 (1.09-2.35)

Abbreviations: OR, odds ratios; CI, confidence interval. The ORs were calculated using logistic regression analyses.

Model 1 was not adjusted.

Model 2 was adjusted for age, BMI, SBP, total cholesterol, WBC count.

Model 3 was adjusted for age, BMI, SBP, total cholesterol, WBC count, alcohol habit, smoking status, physical activity and education level.