Genome-Wide Transcriptome Analysis in Type 2 Diabetes Patients Treated by Sitagliptin

In this study, transcriptome sequencing was performed on patients with type 2 diabetes mellitus treated with different prognosis to explore the differential level genes of different hypoglycemic effects of sitagliptin.

Patients with newly diagnosed T2DM (within six months of diagnosis) were selected as the study subjects. Patients were given sitagliptin 100 mg once a day orally. After 12 weeks of regular drug therapy, the reduction in glycated hemoglobin was compared before and after drug administration. The patients were then divided into two groups: the significantly effective group (M) and the less effective group (N). High-throughput sequencing of the transcriptome was conducted to detect the differential expression levels of genes in peripheral blood mononuclear cells. Expanded sample size validation of the candidate differential genes was conducted using reverse transcription-polymerase chain reaction (RT-PCR).

After 12 weeks of treatment with sitagliptin, high-throughput sequencing of the transcriptome found that expression of the following genes was different when comparing the significantly effective group (M) and the less effective group (N): ghrelin (GHRL), insulin-like growth factor-1 receptor (IGF1R), mitogen-activated protein kinase-3 (MAPK3), phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta (PIK3CD), and the suppressor of cytokine signaling-3 (SOCS3). The validation results of RT-PCR showed that, in the significantly effective group (M), the expression of IGF1R was significantly increased (P = 0.034), the expression of MAPK3 was significantly reduced (P = 0.002), and the expression of SOCS3 was also significantly reduced (P < 0.001).

There was a significant difference in gene level between patients with significant hypoglycemic effect and patients with poor hypoglycemic effect, and the expression of IGF1R increased and the expression of MAPK3 and SOCS3 decreased.