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Clinical Science| Volume 81, P52-62, April 2018

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Impact of systemic inflammation on the relationship between insulin resistance and all-cause and cancer-related mortality

  • Author Footnotes
    1 These authors contributed equally to this work.
    Da Young Lee
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Eun-Jung Rhee
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
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  • Yoosoo Chang
    Affiliations
    Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
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  • Chong Il Sohn
    Affiliations
    Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
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  • Ho-Cheol Shin
    Affiliations
    Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
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  • Seungho Ryu
    Correspondence
    Correspondence to: S. Ryu, Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Samsung Main Building B2, 250, Taepyung-ro 2ga, Jung-gu, Seoul 04514, South Korea.
    Affiliations
    Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
    Search for articles by this author
  • Won-Young Lee
    Correspondence
    Correspondence to: W.Y. Lee, Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, South Korea.
    Affiliations
    Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
Published:November 27, 2017DOI:https://doi.org/10.1016/j.metabol.2017.11.014

      Abstract

      Background

      Insulin resistance and inflammation play an important role in a variety of chronic diseases.

      Objective

      We investigated the influence of systemic inflammation on the relationship between insulin resistance and mortality risk in apparently healthy adults.

      Methods

      This study examined the mortality outcomes for 165,849 Koreans enrolled in a health-screening program. The subjects were divided into four groups according to their homeostatic model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP) levels: group 0, HOMA-IR <75% and hs-CRP <2.0 mg/L; group 1, HOMA-IR ≥75% and hs-CRP <2.0 mg/L; group 2, HOMA-IR <75% and hs-CRP ≥2.0 mg/L; and group 3, HOMA-IR ≥75% and hs-CRP ≥2.0 mg/L. The Cox proportional hazard models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease, and cancer-related mortality.

      Results

      During the follow-up period of 1,417,325.6 person-years, a total of 1316 deaths (182 from cardiovascular disease) occurred. The multivariate-adjusted HRs for all-cause mortality were significantly higher in groups 2 (HR 1.40; 95% CI: 1.19–1.64) and group 3 (HR 1.68; 95% CI: 1.34–2.10) than that in group 0. For cardiovascular mortality, the sex-adjusted hazards were also significantly higher in groups 2 and 3 than that in group 0; however, this increased risk disappeared during multivariate analysis. Groups 2 and 3 had significantly higher risk for cancer-related mortality than group 0, with multivariate-adjusted hazard ratios of 1.48 (95% CI: 1.18–1.86) and 1.84 (95% CI: 1.35–2.51), respectively.

      Conclusions

      Systemic inflammation can be used to stratify the subjects according to the all-cause and cancer-related mortality risks, irrespective of the insulin-resistance status. And this tendency is most pronounced in cancer-related mortality.

      Abbreviations:

      CVD (cardiovascular disease), BMI (body mass index), HOMA-IR (high homeostatic model assessment of insulin resistance), hs-CRP (high-sensitivity C-reactive protein), BP (blood pressure), SBP (systolic blood pressure), DBP (diastolic blood pressure), TC (total cholesterol), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), TG (triglycerides), AST (aspartate aminotransferase), ALT (alanine aminotransferase), GGT (gamma-glutamyl transferase), ICD-10 (the International Classification of Diseases, 10th revision), HR (hazard ratio), CI (confidence interval), JUPITER (Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), NHANES (the Third National Health and Examination Survey), IL (Interleukin), TNF-α (tumor necrosis factor-α), CHD (coronary heart disease), IGF-I (insulin-like growth factor I)

      Keywords

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