# Thiamine and METTL14 in Diabetes Management with Intensive Insulin Therapy

## TL;DR

This study explores how thiamine and METTL14, an epigenetic regulator, may improve diabetes treatment when combined with intensive insulin therapy.

## Contribution

The study identifies METTL14's role in regulating metabolic genes and shows thiamine's potential to enhance insulin therapy outcomes.

## Key findings

- METTL14 regulates genes like TPK1, IPMK, and PIK3R1, which are linked to metabolic pathways in diabetes.
- Thiamine levels correlate with TPK1 expression, and thiamine combined with insulin reduces glucose and triglyceride levels.
- m6A modification levels decrease after insulin therapy, suggesting METTL14's involvement in metabolic regulation.

## Abstract

Background/Objectives: Epigenetic regulation plays a critical role in diabetes research, with N6-methyladenosine (m6A) modification emerging as a key factor in disease progression. METTL14, an essential epigenetic regulator, may influence the effects of thiamine on intensive insulin therapy in diabetic patients. Methods: Blood samples from twenty diabetic patients were collected before and after intensive insulin therapy for MeRIP-seq and RNA-seq analysis. Genes with m6A modifications and corresponding mRNAs were identified and functionally analyzed using Gene Ontology (GO) and KEGG pathway analysis. RT-qPCR was used to confirm the overexpression of METTL14, PIK3R1, TPK1, and IPMK, while METTL14 overexpression was further validated in THP1 cells. Results: GO analysis revealed a significant enrichment of overlapping genes in metabolic pathways. A reduction in m6A modification levels was observed post intensive insulin therapy, indicating METTL14’s involvement in regulating TPK1, IPMK, and PIK3R1 expression. TPK1 levels showed a positive correlation with thiamine levels. Clinical validation demonstrated that combining thiamine with insulin therapy significantly reduced glucose and triglyceride levels compared to insulin alone. Conclusions: Thiamine supplementation alongside intensive insulin therapy offers therapeutic potential by downregulating TPK1 expression and mitigating lipid-related complications in diabetic patients. These findings highlight the pivotal role of METTL14-mediated m6A modification in regulating key metabolic genes during diabetes treatment.