Kallistatin as a Potential Marker of Therapeutic Response During Alpha-Lipoic Acid Treatment in Diabetic Patients with Sensorimotor Polyneuropathy

Int J Mol Sci. 2024 Dec 11;25(24):13276. doi: 10.3390/ijms252413276.

Abstract

Diabetic sensorimotor neuropathy (DSPN) is strongly associated with the extent of cellular oxidative stress and endothelial dysfunction in type 2 diabetes (T2DM). Alpha-lipoic acid (ALA) attenuates the progression of DSPN through its antioxidant and vasculoprotective effects. Kallistatin has antioxidant and anti-inflammatory properties. We aimed to evaluate changes in kallistatin levels and markers of endothelial dysfunction in patients with T2DM and DSPN following six months of treatment with 600 mg/day of ALA. A total of 54 patients with T2DM and DSPN and 24 control patients with T2DM but without neuropathy participated in this study. The serum concentrations of kallistatin, ICAM-1, VCAM-1, oxLDL, VEGF, ADMA, and TNF-alpha were measured by an ELISA. Peripheral sensory neuropathy was assessed with neuropathy symptom questionnaires and determination of the current perception threshold. After ALA treatment, the level of kallistatin significantly decreased, as well as the levels of TNF-alpha and ADMA. Changes in kallistatin levels were positively correlated with changes in oxLDL. The improvement in DSPN symptoms following ALA treatment showed a positive correlation with changes in kallistatin, VEGF, oxLDL, and ADMA levels. Based on our results, kallistatin could represent a potential new biomarker for assessing therapeutic response during ALA treatment in patients with DSPN.

Keywords: alpha-lipoic acid; diabetic sensorimotor neuropathy; endothelial dysfunction; kallistatin; oxidative stress; type 2 diabetes.

MeSH terms

  • Adult
  • Aged
  • Antioxidants / metabolism
  • Antioxidants / therapeutic use
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Arginine / therapeutic use
  • Biomarkers* / blood
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Neuropathies* / blood
  • Diabetic Neuropathies* / drug therapy
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Lipoproteins, LDL / blood
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Serpins* / blood
  • Thioctic Acid* / therapeutic use
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Cell Adhesion Molecule-1 / blood
  • Vascular Endothelial Growth Factor A* / blood
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Thioctic Acid
  • kallistatin
  • Serpins
  • Biomarkers
  • Vascular Endothelial Growth Factor A
  • Tumor Necrosis Factor-alpha
  • Lipoproteins, LDL
  • Arginine
  • oxidized low density lipoprotein
  • Intercellular Adhesion Molecule-1
  • N,N-dimethylarginine
  • Vascular Cell Adhesion Molecule-1
  • Antioxidants