Low brain-derived neurotrophic factor protein levels and single-nucleotide polymorphism Val66Met are associated with peripheral neuropathy in type II diabetic patients

Acta Diabetol. 2020 Jul;57(7):891-898. doi: 10.1007/s00592-020-01508-6. Epub 2020 Mar 2.


Background: Studies by our group demonstrated brain-derived neurotrophic factor (BDNF) levels in blood and BDNF-Val66met-SNP as potential biomarkers in chemotherapy-induced peripheral neuropathy. Here, we evaluate symptoms of peripheral neuropathy (PN) and depression in patients with type II diabetes mellitus in search of an association with serum BDNF levels and the Val66Met-SNP.

Methods: In total, 90 patients enrolled in the study; 23 (25.6%) had known PN, as determined by nerve conduction studies (NCS-PN), and 67 (74.4%) were not diagnosed with PN (U-PN). PN symptoms were assessed and graded in these groups using the total neuropathy score (TNSr) and DN4 scales. Small nerve fiber testing of sensitivity thresholds to cold, warm and hot pain signals was performed using the Q-sense device. Depression was assessed using the PHQ9 questionnaire. BDNF protein levels and Val66Met-SNP were determined with ELISA and Sanger sequencing, respectively.

Results: NCS-PN patients showed lower serum BDNF levels alongside significantly higher TNSr, DN4 and PHQ9 scores and lower hot pain sensitivity thresholds as compared to U-PN patients. Patients with Met-BDNF-SNP showed increased TNSr scores and lower hot pain sensitivity thresholds as compared to patients with Val-BDNF-SNP. Depression showed a weaker correlation with sensitivity thresholds to hot pain signals as compared to TNSr and DN4 scores.

Conclusions: Diminished peripheral BDNF resources and Met-BDNF-SNP genotype are associated with augmented symptoms of PN in patients with type II diabetes mellitus. Sensitivity thresholds to hot pain signals may be less influenced by depression and possibly more accurately detect PN symptoms in diabetic patients.

Keywords: Brain-derived neurotrophic factor (BDNF); Peripheral neuropathy (PN); Val66Met-SNP.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • Biomarkers / blood
  • Brain-Derived Neurotrophic Factor / blood*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetic Neuropathies / blood*
  • Diabetic Neuropathies / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Methionine / genetics
  • Middle Aged
  • Peripheral Nervous System Diseases / blood
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / genetics
  • Polymorphism, Single Nucleotide*
  • Valine / genetics


  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human
  • Methionine
  • Valine