Journal List > Korean J Health Promot > v.17(2) > 1089932

TOOLS
Serum Ferritin Levels Are Associated with the Higher Risk of Diabetes Mellitus in Men and Postmenopausal Women, Based on the 2010-2012 KNHANES
Original Article

Korean J Health Promot 2017;17(2):47-53.

Published online: 19 January 2017

DOI: https://doi.org/10.15384/kjhp.2017.17.2.47

Serum Ferritin Levels Are Associated with the Higher Risk of Diabetes Mellitus in Men and Postmenopausal Women, Based on the 2010-2012 KNHANES

Joo-Yeon Kim1, Hee-Taik Kang1, 2, Yong-Jae Lee3, Jin-Young Kim1, Tae-Jong Kim1, Hyoung-Ji Lim1, Jae-Woo Lee1

1Department of Family Medicine, Chungbuk National University Hospital, Cheongju, Korea

2Department of Family Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea

3Department 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

Received 3 April 2017       Accepted 13 June 2017

Copyright © 2017 The Korean Society of Health Promotion and Disease Prevention

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.

Abstract

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.

Keywords: Diabetes mellitus, Ferritin, Insulin resistance

REFERENCES

1.Beat diabetes: an urgent call for global action. Lancet. 2016. 387(10027):1483.
2.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.
3.American Diabetes Association. Economic costs of diabetes in the U.S. in 2007. Diabetes Care. 2008. 31(3):596–615.
4.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. 2015. 102(6):1585–94.
crossref
5.Gabay C., Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999. 340(6):448–54.
crossref
6.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. 2004. 52(1):19–23.
crossref
7.Evans JL., Maddux BA., Goldfine ID. The molecular basis for oxidative stress-induced insulin resistance. Antioxid Redox Signal. 2005. 7(7-8):1040–52.
crossref
8.Pradhan AD., Manson JE., Rifai N., Buring JE., Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001. 286(3):327–34.
crossref
9.Rajpathak SN., Wylie-Rosett J., Gunter MJ., Negassa A., Kabat GC., Rohan TE, et al. Biomarkers of body iron stores and risk of developing type 2 diabetes. Diabetes Obes Metab. 2009. 11(5):472–9.
crossref
10.Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006. 444(7121):860–7.
crossref
11.Wilson JG., Lindquist JH., Grambow SC., Crook ED., Maher JF. Potential role of increased iron stores in diabetes. Am J Med Sci. 2003. 325(6):332–9.
crossref
12.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(6):711–7.
crossref
13.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. 2011. 60(10):1416–24.
crossref
14.Kim S., Park SK., Ryoo JH., Choi JM., Hong HP., Park JH, et al. Incidental risk for diabetes according to serum ferritin concentration in Korean men. Clin Chim Acta. 2015. 451(Pt B):165–9.
crossref
15.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(3):414–20.
crossref
16.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. 2015. 32(5):673–8.
crossref
17.Kim I., Yetley EA., Calvo MS. Variations in iron-status measures during the menstrual cycle. Am J Clin Nutr. 1993. 58(5):705–9.
crossref
18.Powell LW., Seckington RC., Deugnier Y. Haemochromatosis. Lancet. 2016. 388(10045):706–16.
crossref
19.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(1):62–8.
crossref
20.Evans JL., Maddux BA., Goldfine ID. The molecular basis for oxidative stress-induced insulin resistance. Antioxid Redox Signal. 2005. 7(7-8):1040–52.
crossref
21.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. 1986. 261(19):8708–11.
crossref

Table 1.
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.

Table 2.
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.

Table 3.
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.

a Model 1 was not adjusted.

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

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

TOOLS
Similar articles