Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity and Metformin Treatment in Adult Patients With Type 2 Diabetes Mellitus

Can J Diabetes. 2019 Feb;43(1):19-26. doi: 10.1016/j.jcjd.2018.01.014. Epub 2018 Feb 3.


Objectives: The aim of this study was to investigate the association of serum brain-derived neurotrophic factor (BDNF) levels with platelet reactivity and antidiabetes treatment, as well as serum adipocytokine concentrations.

Methods: This observational, open-label study enrolled 149 patients. Serum BDNF, hematologic, biochemical parameters and platelet reactivity were measured. Blood samples were taken after the last acetylsalicylic acid dose.

Results: Patients with high BDNF levels were younger (65.60±8.956 vs. 68.59±8.516) and smoked cigarettes more frequently (14.6% vs. 4.1%); they were more commonly being treated by metformin (77.3% vs. 54%); had higher platelet counts (245.81±68.85 103/mm3 vs. 206.61±44.48 103/mm3); had shorter collagen-adenosine diphosphate closure time (CADP-CT) values (104.88±69.73 s vs. 140.93±86.63 s); had higher triglyceride concentrations (140.73±67.5 vs. 121.76±60.49) and had higher concentrations of serum thromboxane B2 (0.938±1.59 vs. 0.364±0.76). In univariate linear regression analyses, predictive factors for serum BDNF levels above the median were metformin treatment, current smoking, platelet count, triglyceride concentration, total cholesterol concentration and CADP-CT >74 s. In multivariate backward stepwise analysis CADP-CT >141 s; adiponectin concentration >4.22 µg/mL; total cholesterol and low-density lipoprotein levels were independently associated with serum BDNF levels above the median.

Conclusions: Our results suggest that BDNF may be associated with lipid metabolism and that increased production of BDNF may be related to metformin treatment. Moreover, we showed an association between BDNF levels and platelet reactivity; we found that serum BDNF levels in patients with type 2 diabetes who had high platelet reactivity were higher than in subjects with normal platelet reactivity despite antiplatelet therapy.

Keywords: adiponectin; adiponectine; aspirin; aspirine; diabetes mellitus; diabète sucré; metformin; metformine; plaquette; platelet.

Publication types

  • Multicenter Study
  • Observational Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aspirin / pharmacology
  • Aspirin / therapeutic use
  • Biomarkers / blood
  • Brain-Derived Neurotrophic Factor / blood*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / pharmacology
  • Metformin / therapeutic use*
  • Middle Aged
  • Platelet Activation / drug effects*
  • Platelet Activation / physiology
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prospective Studies
  • Treatment Outcome


  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Hypoglycemic Agents
  • Platelet Aggregation Inhibitors
  • BDNF protein, human
  • Metformin
  • Aspirin