Association between higher urinary normetanephrine and insulin resistance in a Japanese population

PLoS One. 2020 Feb 13;15(2):e0228787. doi: 10.1371/journal.pone.0228787. eCollection 2020.


Since activation of the sympathetic nervous system is associated with both impaired insulin secretion and insulin resistance, or namely with diabetes, evaluation of such activation in ordinary clinical settings may be important. Therefore, we evaluated the relationships between urinary concentrations of the catecholamine metabolites, urinary normetanephrine (U-NM) and urinary metanephrine (U-M), and glucose metabolism in a general population. From 1,148 participants in the 2016 population-based Iwaki study of Japanese, enrolled were 733 individuals (gender (M/F): 320/413; age: 52.1±15.1), who were not on medication affecting serum catecholamines, not diabetic, and had complete data-set and blood glucose levels appropriate for the evaluation of insulin secretion and resistance, using homeostasis model assessment (HOMA-β and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-β, but adjustment for multiple factors correlated with HOMA indices abolished these (β = -0.031, p = 0.499, and β = -0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (β = 0.132, p<0.001) remained significant even after these adjustments (β = 0.107, p = 0.007), whereas U-M did not correlate with HOMA-R. Furthermore, use of the optimal cut-off value of U-NM for the prediction of insulin resistance (HOMA-R >1.6) determined by ROC analysis (0.2577 mg/gCr) showed that individuals at risk had an odds ratio of 2.65 (confidence interval: 1.42-4.97) after adjustment for the same factors used above. Higher U-NM concentrations within the physiologic range are a significant risk factor for increased insulin resistance in a general Japanese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Blood Glucose / analysis
  • Case-Control Studies
  • Female
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Japan
  • Linear Models
  • Male
  • Metanephrine / urine
  • Middle Aged
  • Normetanephrine / urine*
  • Odds Ratio
  • ROC Curve
  • Risk Factors


  • Blood Glucose
  • Insulin
  • Normetanephrine
  • Metanephrine

Grant support

The Japan Science and Technology Agency.