Decreased plasma neuregulin 4 concentration is associated with increased high-sensitivity C-reactive protein in newly diagnosed type 2 diabetes mellitus patients: a cross-sectional study

Acta Diabetol. 2017 Dec;54(12):1091-1099. doi: 10.1007/s00592-017-1044-4. Epub 2017 Sep 16.

Abstract

Aims: Inflammation has been reported to be involved in the pathogenesis of atherosclerosis. This principal objective of this study was to investigate if the secretion of neuregulin 4 (Nrg4), a soluble protein associated with metabolic syndrome and subclinical cardiovascular disease, is correlated with the inflammation marker high-sensitivity C-reactive protein (hs-CRP) in patients with newly diagnosed type 2 diabetes mellitus (nT2DM).

Methods: A study group of 311 nT2DM patients was divided into three subgroups based on hs-CRP tertiles. Multiple linear regression was conducted to explore the association between plasma Nrg4 and hs-CRP levels.

Results: The nT2DM patients with the highest hs-CRP levels (>2.46 mg/L) exhibited higher atherogenic coefficients and atherogenic index of plasma (AIP) levels, but lower levels of plasma Nrg4, as compared to those with the lowest hs-CRP levels (<0.63 mg/L). Plasma Nrg4 levels were inversely associated with white blood cell count, hs-CRP, and AIP and positively associated with high-density lipoprotein cholesterol (HDL-C), before and after adjustment for age, gender, body mass index (BMI), and body fat percentage (P < 0.01 or P < 0.05). hs-CRP was the factor most strongly associated with plasma Nrg4 levels.

Conclusions: These results indicate that lower plasma Nrg4 levels may be associated with elevated hs-CRP in nT2DM patients. It generates the hypothesis that decreased levels of Nrg4 may trigger the development of atherosclerosis through its proinflammatory effects. These findings need to be confirmed by further prospective studies.

Keywords: Atherosclerosis; High-sensitivity C-reactive protein; Inflammation; Neuregulin 4; Newly diagnosed type 2 diabetes mellitus.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Body Mass Index
  • C-Reactive Protein / metabolism*
  • Cholesterol, HDL / blood
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Female
  • Humans
  • Leukocyte Count
  • Male
  • Metabolic Syndrome / metabolism
  • Middle Aged
  • Neuregulins / blood*

Substances

  • Biomarkers
  • Cholesterol, HDL
  • Neuregulins
  • neuregulin-4
  • C-Reactive Protein