A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women

Simin Liu, Lesley Tinker, Yiqing Song, Nader Rifai, Denise E. Bonds, Nancy R. Cook, Gerardo Heiss, Barbara V. Howard, Gokhan S. Hotamisligil, Frank B. Hu, Lewis H. Kuller, Jo Ann E. Manson

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Background: Inflammatory cytokines, including tumor necrosis factor α, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations. Methods: Among 82 069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's Health Initiative Observational Study, we prospectively examined the relationships of plasma levels of tumor necrosis factor α receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-up period of 5.9 years, 1584 women who had clinical diabetes were matched by age, ethnicity, clinical center, time of blood draw, and duration of follow-up to 2198 study participants who were free of the disease. Results: After adjustment for matching factors and known diabetes risk factors, all 3 markers were significantly associated with increased diabetes risk; the estimated relative risks comparing the highest with the lowest quartiles were 1.47 (95% confidence interval [CI], 1.10-1.97) for tumor necrosis factor α receptor 2, 3.08 (95% CI, 2.25-4.23) for IL-6, and 3.46 (95% CI, 2.50-4.80) for hsCRP (P for trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and hsCRP remained significant in each ethnic group. While no statistically significant interactions were observed between ethnicity and these biomarkers on diabetes risk, there were consistent trends for the associations of hsCRP and IL-6 with increased diabetes risk in all ethnic groups. Conclusion: These prospective data showed that elevated levels of IL-6 and hsCRP were consistently and significantly associated with an increased risk of clinical diabetes in postmenopausal women.

Original languageEnglish (US)
Pages (from-to)1676-1685
Number of pages10
JournalArchives of Internal Medicine
Volume167
Issue number15
DOIs
StatePublished - Aug 13 2007
Externally publishedYes

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C-Reactive Protein
Interleukin-6
Diabetes Mellitus
Prospective Studies
Cytokines
Receptors, Tumor Necrosis Factor, Type II
Confidence Intervals
Ethnic Groups
Type 2 Diabetes Mellitus
Biomarkers
Women's Health
Observational Studies
Insulin Resistance
Cardiovascular Diseases
Tumor Necrosis Factor-alpha
Population

ASJC Scopus subject areas

  • Internal Medicine

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A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women. / Liu, Simin; Tinker, Lesley; Song, Yiqing; Rifai, Nader; Bonds, Denise E.; Cook, Nancy R.; Heiss, Gerardo; Howard, Barbara V.; Hotamisligil, Gokhan S.; Hu, Frank B.; Kuller, Lewis H.; Manson, Jo Ann E.

In: Archives of Internal Medicine, Vol. 167, No. 15, 13.08.2007, p. 1676-1685.

Research output: Contribution to journalArticle

Liu, S, Tinker, L, Song, Y, Rifai, N, Bonds, DE, Cook, NR, Heiss, G, Howard, BV, Hotamisligil, GS, Hu, FB, Kuller, LH & Manson, JAE 2007, 'A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women', Archives of Internal Medicine, vol. 167, no. 15, pp. 1676-1685. https://doi.org/10.1001/archinte.167.15.1676
Liu, Simin ; Tinker, Lesley ; Song, Yiqing ; Rifai, Nader ; Bonds, Denise E. ; Cook, Nancy R. ; Heiss, Gerardo ; Howard, Barbara V. ; Hotamisligil, Gokhan S. ; Hu, Frank B. ; Kuller, Lewis H. ; Manson, Jo Ann E. / A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women. In: Archives of Internal Medicine. 2007 ; Vol. 167, No. 15. pp. 1676-1685.
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abstract = "Background: Inflammatory cytokines, including tumor necrosis factor α, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations. Methods: Among 82 069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's Health Initiative Observational Study, we prospectively examined the relationships of plasma levels of tumor necrosis factor α receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-up period of 5.9 years, 1584 women who had clinical diabetes were matched by age, ethnicity, clinical center, time of blood draw, and duration of follow-up to 2198 study participants who were free of the disease. Results: After adjustment for matching factors and known diabetes risk factors, all 3 markers were significantly associated with increased diabetes risk; the estimated relative risks comparing the highest with the lowest quartiles were 1.47 (95{\%} confidence interval [CI], 1.10-1.97) for tumor necrosis factor α receptor 2, 3.08 (95{\%} CI, 2.25-4.23) for IL-6, and 3.46 (95{\%} CI, 2.50-4.80) for hsCRP (P for trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and hsCRP remained significant in each ethnic group. While no statistically significant interactions were observed between ethnicity and these biomarkers on diabetes risk, there were consistent trends for the associations of hsCRP and IL-6 with increased diabetes risk in all ethnic groups. Conclusion: These prospective data showed that elevated levels of IL-6 and hsCRP were consistently and significantly associated with an increased risk of clinical diabetes in postmenopausal women.",
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T1 - A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women

AU - Liu, Simin

AU - Tinker, Lesley

AU - Song, Yiqing

AU - Rifai, Nader

AU - Bonds, Denise E.

AU - Cook, Nancy R.

AU - Heiss, Gerardo

AU - Howard, Barbara V.

AU - Hotamisligil, Gokhan S.

AU - Hu, Frank B.

AU - Kuller, Lewis H.

AU - Manson, Jo Ann E.

PY - 2007/8/13

Y1 - 2007/8/13

N2 - Background: Inflammatory cytokines, including tumor necrosis factor α, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations. Methods: Among 82 069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's Health Initiative Observational Study, we prospectively examined the relationships of plasma levels of tumor necrosis factor α receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-up period of 5.9 years, 1584 women who had clinical diabetes were matched by age, ethnicity, clinical center, time of blood draw, and duration of follow-up to 2198 study participants who were free of the disease. Results: After adjustment for matching factors and known diabetes risk factors, all 3 markers were significantly associated with increased diabetes risk; the estimated relative risks comparing the highest with the lowest quartiles were 1.47 (95% confidence interval [CI], 1.10-1.97) for tumor necrosis factor α receptor 2, 3.08 (95% CI, 2.25-4.23) for IL-6, and 3.46 (95% CI, 2.50-4.80) for hsCRP (P for trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and hsCRP remained significant in each ethnic group. While no statistically significant interactions were observed between ethnicity and these biomarkers on diabetes risk, there were consistent trends for the associations of hsCRP and IL-6 with increased diabetes risk in all ethnic groups. Conclusion: These prospective data showed that elevated levels of IL-6 and hsCRP were consistently and significantly associated with an increased risk of clinical diabetes in postmenopausal women.

AB - Background: Inflammatory cytokines, including tumor necrosis factor α, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations. Methods: Among 82 069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's Health Initiative Observational Study, we prospectively examined the relationships of plasma levels of tumor necrosis factor α receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-up period of 5.9 years, 1584 women who had clinical diabetes were matched by age, ethnicity, clinical center, time of blood draw, and duration of follow-up to 2198 study participants who were free of the disease. Results: After adjustment for matching factors and known diabetes risk factors, all 3 markers were significantly associated with increased diabetes risk; the estimated relative risks comparing the highest with the lowest quartiles were 1.47 (95% confidence interval [CI], 1.10-1.97) for tumor necrosis factor α receptor 2, 3.08 (95% CI, 2.25-4.23) for IL-6, and 3.46 (95% CI, 2.50-4.80) for hsCRP (P for trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and hsCRP remained significant in each ethnic group. While no statistically significant interactions were observed between ethnicity and these biomarkers on diabetes risk, there were consistent trends for the associations of hsCRP and IL-6 with increased diabetes risk in all ethnic groups. Conclusion: These prospective data showed that elevated levels of IL-6 and hsCRP were consistently and significantly associated with an increased risk of clinical diabetes in postmenopausal women.

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