Circulating Cytokines Predict the Development of Insulin Resistance in a Prospective Finnish Population Cohort

J Clin Endocrinol Metab. 2016 Sep;101(9):3361-9. doi: 10.1210/jc.2016-2081. Epub 2016 Jun 30.

Abstract

Context: Metabolic inflammation contributes to the development of insulin resistance (IR), but the roles of different inflammatory and other cytokines in this process remain unclear.

Objective: We aimed at analyzing the value of different cytokines in predicting future IR.

Design, setting, and participants: We measured the serum concentrations of 48 cytokines from a nationwide cohort of 2200 Finns (the Cardiovascular Risk in Young Finns Study), and analyzed their role as independent risk factors for predicting the development of IR 4 years later.

Main outcome measures: We used cross-sectional regression analysis adjusted for known IR risk factors (high age, body mass index, systolic blood pressure, triglycerides, smoking, physical inactivity, and low high-density lipoprotein cholesterol), C-reactive protein and 37 cytokines to find the determinants of continuous baseline IR (defined by homeostatic model assessment). A logistic regression model adjusted for the known risk factors, baseline IR, and 37 cytokines was used to predict the future IR.

Results: Several cytokines, often in a sex-dependent manner, remained as independent determinants of current IR. In men, none of the cytokines was an independent predictive risk marker of future IR. In women, in contrast, IL-17 (odds ratio, 1.42 for 1-SD change in ln-transformed IL-17) and IL-18 (odds ratio, 1.37) were independently associated with the future IR. IL-17 levels also independently predicted the development of incident future IR (odds ratio, 1.48).

Conclusions: The systemic levels of the T helper 1 cell cytokine IL-18 and the T helper 17 cell cytokine IL-17 thus may have value in predicting future insulin sensitivity in women independently of classical IR risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Cross-Sectional Studies
  • Cytokines / blood*
  • Female
  • Finland / epidemiology
  • Follow-Up Studies
  • Humans
  • Inflammation / blood*
  • Inflammation / diagnosis
  • Inflammation / epidemiology
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Risk Factors

Substances

  • Biomarkers
  • Cytokines