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 Kim; Hee-Taik Kang; Yong-Jae Lee; Jin-Young Kim; Tae-Jong Kim; Hyoung-Ji Lim; Jae-Woo Lee

doi:10.15384/kjhp.2017.17.2.47

Korean J Health Promot > Volume 17(2); 2017 > Article

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 Journal of Health Promotion 2017;17(2):47-53.

Published online: January 19, 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 Kang^1,², 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 April 03, 2017 Accepted June 13, 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.

요약

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

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 1^a	1	0.99 (0.71-1.38)	1.27 (0.93-1.72)	1.52 (1.14-2.03)
Model 2^b	1	1.18 (0.82-1.69)	1.54 (1.10-2.16)	1.68 (1.22-2.31)
Model 3^c	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 1^a	1	1.41 (0.63-3.15)	1.41 (0.63-3.16)	3.29 (1.55-7.00)
Model 2^b	1	1.21 (0.51-2.86)	1.05 (0.43-2.57)	2.07 (0.94-4.56)
Model 3^c	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 1^a	1	1.04 (0.74-1.47)	1.36 (0.96-1.93)	1.83 (1.29-2.60)
Model 2^b	1	1.00 (0.68-1.46)	1.21 (0.84-1.74)	1.57 (1.07-2.30)
Model 3^c	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.

^aModel 1 was not adjusted.

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

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

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.

5.. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340(6):448-54.

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.

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.

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.

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.

10.. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444(7121):860-7.

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.

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.

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.

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.

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.

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.

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.

18.. Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet 2016;388(10045):706-16.

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.

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.

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.