Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes

Whitehall II prospective cohort study

Maren Carstensen, Christian Herder, Mika Kivimäki, Markus Jokela, Michael Roden, Martin J. Shipley, Daniel R. Witte, Eric J. Brunner, A. Tabák

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE - Although interleukin-1 receptor antagonist (IL-1Ra) treatment is associated with improved β-cell function and glycemic control in patients with type 2 diabetes, its role in the development of type 2 diabetes remains unclear. We used repeated measurements to characterize IL-1Ra trajectories in individuals who developed type 2 diabetes. RESEARCH DESIGN AND METHODS - This case-cohort study, nested within the Whitehall II cohort, was based on 335 incident type 2 diabetes cases and 2,475 noncases. We measured serum IL-1Ra levels at up to three time points per individual and estimated retrospective trajectories of IL-1Ra before diabetes diagnosis (case subjects) or end of follow-up (control subjects) using multilevel analysis. Models were adjusted for age, sex, and ethnicity. RESULTS - IL-1Ra levels were already higher in the case than control subjects 13 years before diabetes diagnosis/end of follow-up (mean [95% CI] 302 [290-314] vs. 244 [238-249] pg/ml). In control subjects, IL-1Ra levels showed a modest linear increase throughout the study period. In case subjects, IL-1Ra trajectories were parallel to those in control subjects until 6 years (95% CI 7.5- 4.5) before diagnosis and then rose steeply to 399 (379-420) pg/ml at the time of diagnosis (P <0.0001 for slope difference). Adjustment for BMI and waist circumference as time-varying covariates had little impact on these trajectories. CONCLUSIONS - We show elevated IL-1Ra levels for 13 years and an accelerated increase during the last 6 years before type 2 diabetes diagnosis, indicating the presence of an anti-inflammatory response that may act to counterbalance the metabolic and immunologic disturbances that precede type 2 diabetes.

Original languageEnglish
Pages (from-to)1222-1227
Number of pages6
JournalDiabetes
Volume59
Issue number5
DOIs
Publication statusPublished - May 2010

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Interleukin-1 Receptors
Type 2 Diabetes Mellitus
Cohort Studies
Prospective Studies
Serum
Multilevel Analysis
Waist Circumference
Anti-Inflammatory Agents
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes : Whitehall II prospective cohort study. / Carstensen, Maren; Herder, Christian; Kivimäki, Mika; Jokela, Markus; Roden, Michael; Shipley, Martin J.; Witte, Daniel R.; Brunner, Eric J.; Tabák, A.

In: Diabetes, Vol. 59, No. 5, 05.2010, p. 1222-1227.

Research output: Contribution to journalArticle

Carstensen, M, Herder, C, Kivimäki, M, Jokela, M, Roden, M, Shipley, MJ, Witte, DR, Brunner, EJ & Tabák, A 2010, 'Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study', Diabetes, vol. 59, no. 5, pp. 1222-1227. https://doi.org/10.2337/db09-1199
Carstensen, Maren ; Herder, Christian ; Kivimäki, Mika ; Jokela, Markus ; Roden, Michael ; Shipley, Martin J. ; Witte, Daniel R. ; Brunner, Eric J. ; Tabák, A. / Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes : Whitehall II prospective cohort study. In: Diabetes. 2010 ; Vol. 59, No. 5. pp. 1222-1227.
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AU - Carstensen, Maren

AU - Herder, Christian

AU - Kivimäki, Mika

AU - Jokela, Markus

AU - Roden, Michael

AU - Shipley, Martin J.

AU - Witte, Daniel R.

AU - Brunner, Eric J.

AU - Tabák, A.

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N2 - OBJECTIVE - Although interleukin-1 receptor antagonist (IL-1Ra) treatment is associated with improved β-cell function and glycemic control in patients with type 2 diabetes, its role in the development of type 2 diabetes remains unclear. We used repeated measurements to characterize IL-1Ra trajectories in individuals who developed type 2 diabetes. RESEARCH DESIGN AND METHODS - This case-cohort study, nested within the Whitehall II cohort, was based on 335 incident type 2 diabetes cases and 2,475 noncases. We measured serum IL-1Ra levels at up to three time points per individual and estimated retrospective trajectories of IL-1Ra before diabetes diagnosis (case subjects) or end of follow-up (control subjects) using multilevel analysis. Models were adjusted for age, sex, and ethnicity. RESULTS - IL-1Ra levels were already higher in the case than control subjects 13 years before diabetes diagnosis/end of follow-up (mean [95% CI] 302 [290-314] vs. 244 [238-249] pg/ml). In control subjects, IL-1Ra levels showed a modest linear increase throughout the study period. In case subjects, IL-1Ra trajectories were parallel to those in control subjects until 6 years (95% CI 7.5- 4.5) before diagnosis and then rose steeply to 399 (379-420) pg/ml at the time of diagnosis (P <0.0001 for slope difference). Adjustment for BMI and waist circumference as time-varying covariates had little impact on these trajectories. CONCLUSIONS - We show elevated IL-1Ra levels for 13 years and an accelerated increase during the last 6 years before type 2 diabetes diagnosis, indicating the presence of an anti-inflammatory response that may act to counterbalance the metabolic and immunologic disturbances that precede type 2 diabetes.

AB - OBJECTIVE - Although interleukin-1 receptor antagonist (IL-1Ra) treatment is associated with improved β-cell function and glycemic control in patients with type 2 diabetes, its role in the development of type 2 diabetes remains unclear. We used repeated measurements to characterize IL-1Ra trajectories in individuals who developed type 2 diabetes. RESEARCH DESIGN AND METHODS - This case-cohort study, nested within the Whitehall II cohort, was based on 335 incident type 2 diabetes cases and 2,475 noncases. We measured serum IL-1Ra levels at up to three time points per individual and estimated retrospective trajectories of IL-1Ra before diabetes diagnosis (case subjects) or end of follow-up (control subjects) using multilevel analysis. Models were adjusted for age, sex, and ethnicity. RESULTS - IL-1Ra levels were already higher in the case than control subjects 13 years before diabetes diagnosis/end of follow-up (mean [95% CI] 302 [290-314] vs. 244 [238-249] pg/ml). In control subjects, IL-1Ra levels showed a modest linear increase throughout the study period. In case subjects, IL-1Ra trajectories were parallel to those in control subjects until 6 years (95% CI 7.5- 4.5) before diagnosis and then rose steeply to 399 (379-420) pg/ml at the time of diagnosis (P <0.0001 for slope difference). Adjustment for BMI and waist circumference as time-varying covariates had little impact on these trajectories. CONCLUSIONS - We show elevated IL-1Ra levels for 13 years and an accelerated increase during the last 6 years before type 2 diabetes diagnosis, indicating the presence of an anti-inflammatory response that may act to counterbalance the metabolic and immunologic disturbances that precede type 2 diabetes.

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