Endocrine Abstracts (2019) 65 P176 | DOI: 10.1530/endoabs.65.P176

Brain derived neurotrophic factor (BDNF) methylation in patients with impaired glucose regulation: implications progression to type 2 diabetes mellitus (T2DM)

Helene Fachim1,2, Kirk Siddals1,2, Nagaraj Malipatil1, Gabriela Cortes3, Rachelle Donn2, Caroline Dalton4, Gavin Reynolds4, Martin Gibson1,2 & Adrian Heald1,2

1Salford Royal Foundation Trust, Salford, UK; 2The University of Manchester, Manchester, UK; 3High Speciality Regional Hospital of Ixtapaluca, Ixtapaluca, Mexico; 4Sheffield Hallam University, Sheffield, UK

Introduction: There is growing evidence of external factors modulating epigenetic modifications and their contribution to the development of obesity and T2DM. One of the epigenetic signatures is DNA methylation. We investigated whether a lifestyle intervention could influence DNA methylation of Brain derived neurotrophic factor (BDNF) in individuals with IGR, as BDNF is thought to play an important role in glucose metabolism.

Methods: IGR participants (n=20) were recruited and underwent anthropometric measurements/fasting blood tests and adipose tissue biopsy pre/post-lifestyle (6 months) intervention. Genomic DNA was extracted from adipose tissue, bisulphite converted and pyrosequencing was used to determine methylation levels in the IV exon of the BDNF gene.

Results: The intervention did not result in differences within the 4 CpGs methylation (comparing baseline and after intervention). However we found positive Pearson correlations at the baseline between CpG1 and weight (r = 0.462, P= 0.04); CpG1 and hip–waist ratio (r = 0.494, P = 0.027); also negative correlations between CpG3 and BMI (r = −0.886, P = 0.003); and CpG3 and triglycerides levels (r = −0.536, P = 0.022). Considering those patients who lost 3% or more of weight after intervention, we found a negative correlation at baseline between CpG3 and BMI (r = −0.707, P = 0.05). Considering the data after the intervention we found a positive correlation between CpG2 and insulin levels (r = 0.590, P = 0.006). Regarding those individuals who lost 3% of weight or more we found a positive correlation between CpG3 and HOMAS (r = 0.802, P = 0.05); and negative correlation between CpG4 and HOMAB (r = −0.869, P = 0.05).

Conclusion: Observed associations between BDNF DNA methylation patterns across different glucose metabolic states suggest that BDNF may be involved in the pathophysiological process of insulin resistance and type 2 diabetes.