Accepted Manuscript Markers of iron metabolism and metabolic syndrome in Swiss adults N. Kilani , G. Waeber , P. Vollenweider , P. Marques-Vidal PII:
S0939-4753(14)00171-9
DOI:
10.1016/j.numecd.2014.04.018
Reference:
NUMECD 1301
To appear in:
Nutrition, Metabolism and Cardiovascular Diseases
Received Date: 5 March 2014 Revised Date:
29 April 2014
Accepted Date: 30 April 2014
Please cite this article as: Kilani N, Waeber G, Vollenweider P, Marques-Vidal P, Markers of iron metabolism and metabolic syndrome in Swiss adults, Nutrition, Metabolism and Cardiovascular Diseases (2014), doi: 10.1016/j.numecd.2014.04.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Markers of iron metabolism and metabolic syndrome in Swiss adults Running title: Iron metabolism and metabolic syndrome Kilani N 1; Waeber G 1; Vollenweider P 1 and Marques-Vidal P 1,2 Department of Internal Medicine, Internal Medicine, Lausanne University Hospital, Lausanne,
RI PT
1
Switzerland and 2 Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland
SC
Address for correspondence and reprints Pedro Marques-Vidal
BH 10 - 642
M AN U
Département de Médecine Interne
Centre Hospitalier Universitaire Vaudois Rue du Bugnon 21 1011 Lausanne Switzerland Phone : +41 21 314 09 34
TE D
Email : [email protected]
EP
Word count: 419 (excluding references and table). References: 8
AC C
Keywords: Metabolic syndrome; ferritin; transferrin; TIBC; iron metabolism; epidemiology; Switzerland.
ACCEPTED MANUSCRIPT
Several population-based studies have shown an association between moderately elevated serum ferritin levels and metabolic syndrome (MS) (1, 2). Although the association between ferritin levels and MS is well described, less is known regarding the relationship between MS
RI PT
and other markers of iron metabolism such as serum iron, serum transferrin, total iron binding capacity (TIBC) or transferrin saturation (TSAT) (3). We aimed at assessing the associations between different markers of iron metabolism and MS. Data from CoLaus, a cross-sectional,
SC
population-based study, were used (4). The study has been approved by the Ethics Committee of the Canton Vaud, and all participants provided written informed consent. MS was defined
M AN U
according to the National Cholesterol Education Program Adult Panel III guidelines (5). The following markers of iron metabolism were assessed: serum iron, ferritin, transferrin, TIBC and TSAT. Statistical analysis was stratified on gender, with a further stratification on menopausal status in women.
TE D
Of the initial 6,733 participants, 1235 (18%) were excluded because of missing data for the variables of interest or for possible non-diagnosed haemochromatosis, (TSAT >50%). Of the remaining 5,498 participants (mean age±SD: 53±11 years), 2,596 were men, 1,285
EP
premenopausal and 1,617 postmenopausal women. The prevalence of MS was 29.4% in men,
AC C
8.3% in premenopausal and 25.5% in postmenopausal women. In all groups, the highest prevalence of MS occurred in the highest quartiles of serum ferritin, transferrin and TIBC, and in the lowest quartile of TSAT. The results of the multivariate analysis are summarized in the table. Among men and postmenopausal women, being in the highest quartile of serum ferritin, transferrin and TIBC was associated with a higher risk of MS. , while being in the highest quartile of TSAT was associated with a lower risk of MS. No association was found between markers of iron metabolism and MS in premenopausal women.
ACCEPTED MANUSCRIPT
The mechanisms by which inadequate iron homeostasis is associated with MS are poorly understood. The increased inflammatory status among subjects with MS (6) could explain the increased levels of markers of iron metabolism in MS. Other studies have suggested that ferritin
RI PT
and iron may damage muscle, hepatic and adipose tissue cells, leading to insulin resistance (6). Iron-induced liver damages could also impair lipid homeostasis, leading to hypertriglyceridaemia (6). Iron metabolism could also influence MS via adiponectin (7) or osteocalcin (8), both of
SC
which are related with insulin sensitivity, but the precise mechanisms remain to be identified.
M AN U
We conclude that several markers of iron metabolism, but not serum iron itself, are independently associated with MS in men and postmenopausal women. References 1.
Kang HT, Linton JA, Shim JY. Serum ferritin level is associated with the prevalence of
TE D
metabolic syndrome in Korean adults: the 2007-2008 Korean National Health and Nutrition Examination Survey. Clin Chim Acta. 2012 Mar 22;413(5-6):636-41. PubMed PMID: 22212623. Epub 2012/01/04. eng.
Li J, Wang R, Luo D, Li S, Xiao C. Association between Serum Ferritin Levels and Risk
EP
2.
of the Metabolic Syndrome in Chinese Adults: A Population Study. PLoS One.
AC C
2013;8(9):e74168. PubMed PMID: 24066115. Pubmed Central PMCID: 3774625. Epub 2013/09/26. eng. 3.
Alissa EM, Ahmed WH, Al-Ama N, Ferns GA. Relationship between indices of iron status and coronary risk factors including diabetes and the metabolic syndrome in Saudi subjects without overt coronary disease. J Trace Elem Med Biol. 2007;21(4):242-54. PubMed PMID: 17980815. Epub 2007/11/06. eng.
ACCEPTED MANUSCRIPT
4.
Firmann M, Mayor V, Vidal PM, Bochud M, Pecoud A, Hayoz D, et al. The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome. BMC Cardiovasc Disord. 2008;8:6.
5.
RI PT
PubMed PMID: 18366642. Pubmed Central PMCID: 2311269. Epub 2008/03/28. eng. National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Third Report of the National Cholesterol Education Program
SC
(NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-
6.
M AN U
421. PubMed PMID: 12485966. Epub 2002/12/18. eng.
Leiva E, Mujica V, Sepulveda P, Guzman L, Nunez S, Orrego R, et al. High levels of iron status and oxidative stress in patients with metabolic syndrome. Biol Trace Elem Res. 2013 Jan;151(1):1-8. PubMed PMID: 23079936. Epub 2012/10/20. eng. Gabrielsen JS, Gao Y, Simcox JA, Huang J, Thorup D, Jones D, et al. Adipocyte iron
TE D
7.
regulates adiponectin and insulin sensitivity. J Clin Invest. 2012 Oct 1;122(10):3529-40. PubMed PMID: 22996660. Pubmed Central PMCID: 3461897. Epub 2012/09/22. eng.
EP
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 Oct;60(10):1416-24.
AC C
8.
PubMed PMID: 21489582. Epub 2011/04/15. eng.
ACCEPTED MANUSCRIPT
Table: Association between quartiles of iron metabolism markers and presence of metabolic syndrome, stratified by gender and
RI PT
menopausal status. First
Second
Third
Fourth
p-value §
p-value §§
p-value §§§
Iron
1 (ref.)
0.91 (0.69-1.21)
0.98 (0.74-1.30)
0.92 (0.68-1.26)
0.75
0.47
0.76
Ferritin
1 (ref.)
0.90 (0.67-1.23)
1.04 (0.78-1.41)
1.44 (1.07-1.94)
S0939-4753(14)00171-9
DOI:
10.1016/j.numecd.2014.04.018
Reference:
NUMECD 1301
To appear in:
Nutrition, Metabolism and Cardiovascular Diseases
Received Date: 5 March 2014 Revised Date:
29 April 2014
Accepted Date: 30 April 2014
Please cite this article as: Kilani N, Waeber G, Vollenweider P, Marques-Vidal P, Markers of iron metabolism and metabolic syndrome in Swiss adults, Nutrition, Metabolism and Cardiovascular Diseases (2014), doi: 10.1016/j.numecd.2014.04.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Markers of iron metabolism and metabolic syndrome in Swiss adults Running title: Iron metabolism and metabolic syndrome Kilani N 1; Waeber G 1; Vollenweider P 1 and Marques-Vidal P 1,2 Department of Internal Medicine, Internal Medicine, Lausanne University Hospital, Lausanne,
RI PT
1
Switzerland and 2 Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland
SC
Address for correspondence and reprints Pedro Marques-Vidal
BH 10 - 642
M AN U
Département de Médecine Interne
Centre Hospitalier Universitaire Vaudois Rue du Bugnon 21 1011 Lausanne Switzerland Phone : +41 21 314 09 34
TE D
Email : [email protected]
EP
Word count: 419 (excluding references and table). References: 8
AC C
Keywords: Metabolic syndrome; ferritin; transferrin; TIBC; iron metabolism; epidemiology; Switzerland.
ACCEPTED MANUSCRIPT
Several population-based studies have shown an association between moderately elevated serum ferritin levels and metabolic syndrome (MS) (1, 2). Although the association between ferritin levels and MS is well described, less is known regarding the relationship between MS
RI PT
and other markers of iron metabolism such as serum iron, serum transferrin, total iron binding capacity (TIBC) or transferrin saturation (TSAT) (3). We aimed at assessing the associations between different markers of iron metabolism and MS. Data from CoLaus, a cross-sectional,
SC
population-based study, were used (4). The study has been approved by the Ethics Committee of the Canton Vaud, and all participants provided written informed consent. MS was defined
M AN U
according to the National Cholesterol Education Program Adult Panel III guidelines (5). The following markers of iron metabolism were assessed: serum iron, ferritin, transferrin, TIBC and TSAT. Statistical analysis was stratified on gender, with a further stratification on menopausal status in women.
TE D
Of the initial 6,733 participants, 1235 (18%) were excluded because of missing data for the variables of interest or for possible non-diagnosed haemochromatosis, (TSAT >50%). Of the remaining 5,498 participants (mean age±SD: 53±11 years), 2,596 were men, 1,285
EP
premenopausal and 1,617 postmenopausal women. The prevalence of MS was 29.4% in men,
AC C
8.3% in premenopausal and 25.5% in postmenopausal women. In all groups, the highest prevalence of MS occurred in the highest quartiles of serum ferritin, transferrin and TIBC, and in the lowest quartile of TSAT. The results of the multivariate analysis are summarized in the table. Among men and postmenopausal women, being in the highest quartile of serum ferritin, transferrin and TIBC was associated with a higher risk of MS. , while being in the highest quartile of TSAT was associated with a lower risk of MS. No association was found between markers of iron metabolism and MS in premenopausal women.
ACCEPTED MANUSCRIPT
The mechanisms by which inadequate iron homeostasis is associated with MS are poorly understood. The increased inflammatory status among subjects with MS (6) could explain the increased levels of markers of iron metabolism in MS. Other studies have suggested that ferritin
RI PT
and iron may damage muscle, hepatic and adipose tissue cells, leading to insulin resistance (6). Iron-induced liver damages could also impair lipid homeostasis, leading to hypertriglyceridaemia (6). Iron metabolism could also influence MS via adiponectin (7) or osteocalcin (8), both of
SC
which are related with insulin sensitivity, but the precise mechanisms remain to be identified.
M AN U
We conclude that several markers of iron metabolism, but not serum iron itself, are independently associated with MS in men and postmenopausal women. References 1.
Kang HT, Linton JA, Shim JY. Serum ferritin level is associated with the prevalence of
TE D
metabolic syndrome in Korean adults: the 2007-2008 Korean National Health and Nutrition Examination Survey. Clin Chim Acta. 2012 Mar 22;413(5-6):636-41. PubMed PMID: 22212623. Epub 2012/01/04. eng.
Li J, Wang R, Luo D, Li S, Xiao C. Association between Serum Ferritin Levels and Risk
EP
2.
of the Metabolic Syndrome in Chinese Adults: A Population Study. PLoS One.
AC C
2013;8(9):e74168. PubMed PMID: 24066115. Pubmed Central PMCID: 3774625. Epub 2013/09/26. eng. 3.
Alissa EM, Ahmed WH, Al-Ama N, Ferns GA. Relationship between indices of iron status and coronary risk factors including diabetes and the metabolic syndrome in Saudi subjects without overt coronary disease. J Trace Elem Med Biol. 2007;21(4):242-54. PubMed PMID: 17980815. Epub 2007/11/06. eng.
ACCEPTED MANUSCRIPT
4.
Firmann M, Mayor V, Vidal PM, Bochud M, Pecoud A, Hayoz D, et al. The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome. BMC Cardiovasc Disord. 2008;8:6.
5.
RI PT
PubMed PMID: 18366642. Pubmed Central PMCID: 2311269. Epub 2008/03/28. eng. National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Third Report of the National Cholesterol Education Program
SC
(NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-
6.
M AN U
421. PubMed PMID: 12485966. Epub 2002/12/18. eng.
Leiva E, Mujica V, Sepulveda P, Guzman L, Nunez S, Orrego R, et al. High levels of iron status and oxidative stress in patients with metabolic syndrome. Biol Trace Elem Res. 2013 Jan;151(1):1-8. PubMed PMID: 23079936. Epub 2012/10/20. eng. Gabrielsen JS, Gao Y, Simcox JA, Huang J, Thorup D, Jones D, et al. Adipocyte iron
TE D
7.
regulates adiponectin and insulin sensitivity. J Clin Invest. 2012 Oct 1;122(10):3529-40. PubMed PMID: 22996660. Pubmed Central PMCID: 3461897. Epub 2012/09/22. eng.
EP
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 Oct;60(10):1416-24.
AC C
8.
PubMed PMID: 21489582. Epub 2011/04/15. eng.
ACCEPTED MANUSCRIPT
Table: Association between quartiles of iron metabolism markers and presence of metabolic syndrome, stratified by gender and
RI PT
menopausal status. First
Second
Third
Fourth
p-value §
p-value §§
p-value §§§
Iron
1 (ref.)
0.91 (0.69-1.21)
0.98 (0.74-1.30)
0.92 (0.68-1.26)
0.75
0.47
0.76
Ferritin
1 (ref.)
0.90 (0.67-1.23)
1.04 (0.78-1.41)
1.44 (1.07-1.94)
