Iron metabolism is prospectively associated with insulin resistance and glucose intolerance over a 7-year follow-up period: the CODAM study

N. Wlazlo, M.M.J. van Greevenbroek, I. Ferreira, E.H.J.M. Jansen, E.J.M. Feskens, C.J.H. van der Kallen, C.G. Schalkwijk, B. Bravenboer, C.D.A. Stehouwer

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Abstract

Objectives Several markers of iron metabolism have been associated with insulin resistance (IR) and type 2 diabetes mellitus in cross-sectional studies. However, prospective data on these associations are scarce, and it is currently unclear in which tissues iron metabolism may contribute to IR. Therefore, we investigated whether markers of iron metabolism were associated with IR in muscle, liver, and adipocytes, and with glucose intolerance over a 7-year follow-up period. Design and methods Serum ferritin, transferrin, total iron, non-transferrin-bound iron, and transferrin saturation were determined at baseline of a prospective cohort study in 509 individuals (60 % men, age 59 ± 6.9 years, body mass index 28.5 ± 4.3). Both at baseline and after a 7-year follow-up (n = 386), measures of glucose, insulin (during glucose tolerance tests), and non-esterified fatty acids were obtained. Using generalized estimating equations, we investigated associations between baseline iron markers and indices of muscle, liver, and adipocyte insulin resistance (adipocyte IR), as well as glucose intolerance, over the 7-year period. Results Over a 7-year period, baseline serum ferritin (per 10 µg/L increase) was positively associated with homeostasis model assessment insulin resistance (HOMA2-IR) [ß = 0.77 % (95 % CI 0.50–1.03)], hepatic insulin resistance (hepatic IR) [ß = 0.39 % (0.23–0.55)], adipocyte IR [ß = 1.00 % (0.65–1.35)], and AUCglucose [ß = 0.32 % (0.18–0.46)] after adjustment for several covariates, including inflammatory markers (all p <0.001). Similarly, serum transferrin (per 0.1 g/L) was associated with HOMA2-IR [ß = 2.66 % (1.55–3.78)], hepatic IR [ß = 1.16 % (0.47–1.85)], adipocyte IR [ß = 3.75 % (2.27–5.25)], and AUCglucose [ß = 1.35 % (0.74–1.96)] over 7 years. Conclusions Iron metabolism and related factors may contribute to IR in muscle, liver, and adipocytes, eventually leading to impaired glucose metabolism and hyperglycaemia.
Original languageEnglish
Pages (from-to)337-348
JournalActa Diabetologica
Volume52
Issue number2
DOIs
Publication statusPublished - 2015

Fingerprint

Glucose Intolerance
Insulin Resistance
Iron
Adipocytes
Transferrin
Liver
Ferritins
Muscles
Glucose
Glucose Tolerance Test
Serum
Hyperglycemia
Type 2 Diabetes Mellitus
Body Mass Index
Homeostasis
Cohort Studies
Fatty Acids
Cross-Sectional Studies

Keywords

  • beta-cell function
  • serum ferritin
  • diabetes-mellitus
  • syndrome desir
  • fatty liver
  • risk
  • transferrin
  • stores
  • men
  • inflammation

Cite this

Wlazlo, N., van Greevenbroek, M. M. J., Ferreira, I., Jansen, E. H. J. M., Feskens, E. J. M., van der Kallen, C. J. H., ... Stehouwer, C. D. A. (2015). Iron metabolism is prospectively associated with insulin resistance and glucose intolerance over a 7-year follow-up period: the CODAM study. Acta Diabetologica, 52(2), 337-348. https://doi.org/10.1007/s00592-014-0646-3
Wlazlo, N. ; van Greevenbroek, M.M.J. ; Ferreira, I. ; Jansen, E.H.J.M. ; Feskens, E.J.M. ; van der Kallen, C.J.H. ; Schalkwijk, C.G. ; Bravenboer, B. ; Stehouwer, C.D.A. / Iron metabolism is prospectively associated with insulin resistance and glucose intolerance over a 7-year follow-up period: the CODAM study. In: Acta Diabetologica. 2015 ; Vol. 52, No. 2. pp. 337-348.
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title = "Iron metabolism is prospectively associated with insulin resistance and glucose intolerance over a 7-year follow-up period: the CODAM study",
abstract = "Objectives Several markers of iron metabolism have been associated with insulin resistance (IR) and type 2 diabetes mellitus in cross-sectional studies. However, prospective data on these associations are scarce, and it is currently unclear in which tissues iron metabolism may contribute to IR. Therefore, we investigated whether markers of iron metabolism were associated with IR in muscle, liver, and adipocytes, and with glucose intolerance over a 7-year follow-up period. Design and methods Serum ferritin, transferrin, total iron, non-transferrin-bound iron, and transferrin saturation were determined at baseline of a prospective cohort study in 509 individuals (60 {\%} men, age 59 ± 6.9 years, body mass index 28.5 ± 4.3). Both at baseline and after a 7-year follow-up (n = 386), measures of glucose, insulin (during glucose tolerance tests), and non-esterified fatty acids were obtained. Using generalized estimating equations, we investigated associations between baseline iron markers and indices of muscle, liver, and adipocyte insulin resistance (adipocyte IR), as well as glucose intolerance, over the 7-year period. Results Over a 7-year period, baseline serum ferritin (per 10 µg/L increase) was positively associated with homeostasis model assessment insulin resistance (HOMA2-IR) [{\ss} = 0.77 {\%} (95 {\%} CI 0.50–1.03)], hepatic insulin resistance (hepatic IR) [{\ss} = 0.39 {\%} (0.23–0.55)], adipocyte IR [{\ss} = 1.00 {\%} (0.65–1.35)], and AUCglucose [{\ss} = 0.32 {\%} (0.18–0.46)] after adjustment for several covariates, including inflammatory markers (all p <0.001). Similarly, serum transferrin (per 0.1 g/L) was associated with HOMA2-IR [{\ss} = 2.66 {\%} (1.55–3.78)], hepatic IR [{\ss} = 1.16 {\%} (0.47–1.85)], adipocyte IR [{\ss} = 3.75 {\%} (2.27–5.25)], and AUCglucose [{\ss} = 1.35 {\%} (0.74–1.96)] over 7 years. Conclusions Iron metabolism and related factors may contribute to IR in muscle, liver, and adipocytes, eventually leading to impaired glucose metabolism and hyperglycaemia.",
keywords = "beta-cell function, serum ferritin, diabetes-mellitus, syndrome desir, fatty liver, risk, transferrin, stores, men, inflammation",
author = "N. Wlazlo and {van Greevenbroek}, M.M.J. and I. Ferreira and E.H.J.M. Jansen and E.J.M. Feskens and {van der Kallen}, C.J.H. and C.G. Schalkwijk and B. Bravenboer and C.D.A. Stehouwer",
year = "2015",
doi = "10.1007/s00592-014-0646-3",
language = "English",
volume = "52",
pages = "337--348",
journal = "Acta Diabetologica",
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Wlazlo, N, van Greevenbroek, MMJ, Ferreira, I, Jansen, EHJM, Feskens, EJM, van der Kallen, CJH, Schalkwijk, CG, Bravenboer, B & Stehouwer, CDA 2015, 'Iron metabolism is prospectively associated with insulin resistance and glucose intolerance over a 7-year follow-up period: the CODAM study', Acta Diabetologica, vol. 52, no. 2, pp. 337-348. https://doi.org/10.1007/s00592-014-0646-3

Iron metabolism is prospectively associated with insulin resistance and glucose intolerance over a 7-year follow-up period: the CODAM study. / Wlazlo, N.; van Greevenbroek, M.M.J.; Ferreira, I.; Jansen, E.H.J.M.; Feskens, E.J.M.; van der Kallen, C.J.H.; Schalkwijk, C.G.; Bravenboer, B.; Stehouwer, C.D.A.

In: Acta Diabetologica, Vol. 52, No. 2, 2015, p. 337-348.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Iron metabolism is prospectively associated with insulin resistance and glucose intolerance over a 7-year follow-up period: the CODAM study

AU - Wlazlo, N.

AU - van Greevenbroek, M.M.J.

AU - Ferreira, I.

AU - Jansen, E.H.J.M.

AU - Feskens, E.J.M.

AU - van der Kallen, C.J.H.

AU - Schalkwijk, C.G.

AU - Bravenboer, B.

AU - Stehouwer, C.D.A.

PY - 2015

Y1 - 2015

N2 - Objectives Several markers of iron metabolism have been associated with insulin resistance (IR) and type 2 diabetes mellitus in cross-sectional studies. However, prospective data on these associations are scarce, and it is currently unclear in which tissues iron metabolism may contribute to IR. Therefore, we investigated whether markers of iron metabolism were associated with IR in muscle, liver, and adipocytes, and with glucose intolerance over a 7-year follow-up period. Design and methods Serum ferritin, transferrin, total iron, non-transferrin-bound iron, and transferrin saturation were determined at baseline of a prospective cohort study in 509 individuals (60 % men, age 59 ± 6.9 years, body mass index 28.5 ± 4.3). Both at baseline and after a 7-year follow-up (n = 386), measures of glucose, insulin (during glucose tolerance tests), and non-esterified fatty acids were obtained. Using generalized estimating equations, we investigated associations between baseline iron markers and indices of muscle, liver, and adipocyte insulin resistance (adipocyte IR), as well as glucose intolerance, over the 7-year period. Results Over a 7-year period, baseline serum ferritin (per 10 µg/L increase) was positively associated with homeostasis model assessment insulin resistance (HOMA2-IR) [ß = 0.77 % (95 % CI 0.50–1.03)], hepatic insulin resistance (hepatic IR) [ß = 0.39 % (0.23–0.55)], adipocyte IR [ß = 1.00 % (0.65–1.35)], and AUCglucose [ß = 0.32 % (0.18–0.46)] after adjustment for several covariates, including inflammatory markers (all p <0.001). Similarly, serum transferrin (per 0.1 g/L) was associated with HOMA2-IR [ß = 2.66 % (1.55–3.78)], hepatic IR [ß = 1.16 % (0.47–1.85)], adipocyte IR [ß = 3.75 % (2.27–5.25)], and AUCglucose [ß = 1.35 % (0.74–1.96)] over 7 years. Conclusions Iron metabolism and related factors may contribute to IR in muscle, liver, and adipocytes, eventually leading to impaired glucose metabolism and hyperglycaemia.

AB - Objectives Several markers of iron metabolism have been associated with insulin resistance (IR) and type 2 diabetes mellitus in cross-sectional studies. However, prospective data on these associations are scarce, and it is currently unclear in which tissues iron metabolism may contribute to IR. Therefore, we investigated whether markers of iron metabolism were associated with IR in muscle, liver, and adipocytes, and with glucose intolerance over a 7-year follow-up period. Design and methods Serum ferritin, transferrin, total iron, non-transferrin-bound iron, and transferrin saturation were determined at baseline of a prospective cohort study in 509 individuals (60 % men, age 59 ± 6.9 years, body mass index 28.5 ± 4.3). Both at baseline and after a 7-year follow-up (n = 386), measures of glucose, insulin (during glucose tolerance tests), and non-esterified fatty acids were obtained. Using generalized estimating equations, we investigated associations between baseline iron markers and indices of muscle, liver, and adipocyte insulin resistance (adipocyte IR), as well as glucose intolerance, over the 7-year period. Results Over a 7-year period, baseline serum ferritin (per 10 µg/L increase) was positively associated with homeostasis model assessment insulin resistance (HOMA2-IR) [ß = 0.77 % (95 % CI 0.50–1.03)], hepatic insulin resistance (hepatic IR) [ß = 0.39 % (0.23–0.55)], adipocyte IR [ß = 1.00 % (0.65–1.35)], and AUCglucose [ß = 0.32 % (0.18–0.46)] after adjustment for several covariates, including inflammatory markers (all p <0.001). Similarly, serum transferrin (per 0.1 g/L) was associated with HOMA2-IR [ß = 2.66 % (1.55–3.78)], hepatic IR [ß = 1.16 % (0.47–1.85)], adipocyte IR [ß = 3.75 % (2.27–5.25)], and AUCglucose [ß = 1.35 % (0.74–1.96)] over 7 years. Conclusions Iron metabolism and related factors may contribute to IR in muscle, liver, and adipocytes, eventually leading to impaired glucose metabolism and hyperglycaemia.

KW - beta-cell function

KW - serum ferritin

KW - diabetes-mellitus

KW - syndrome desir

KW - fatty liver

KW - risk

KW - transferrin

KW - stores

KW - men

KW - inflammation

U2 - 10.1007/s00592-014-0646-3

DO - 10.1007/s00592-014-0646-3

M3 - Article

VL - 52

SP - 337

EP - 348

JO - Acta Diabetologica

JF - Acta Diabetologica

SN - 0940-5429

IS - 2

ER -