Hyperglycemia Affects the Expression of Inflammatory Genes in Peripheral Blood Mononuclear Cells of Patients with Type 2 Diabetes

ABSTRACT

Objective: Innate immune system dysregulation and chronic low-grade inflammation are associated with the pathogenesis of type 2 diabetes (T2D). The aim of this study was to investigate the effect of hyperglycemia on mRNA expression of four inflammatory genes in peripheral blood mononuclear cells (PBMCs) of pre-diabetic and diabetic individuals.

Methods: In a case-control study, quantitative real-time PCR was used to analyze changes in IL-1β, IL1R1, IL-6, and IL6ST gene expression in PBMCs of 30 T2D patients with high blood glucose levels, 24 diabetic and nondiabetic individuals with moderately high blood glucose levels and 30 controls with normal blood glucose levels.

Results: In T2D patients with high blood glucose, IL-1β expression showed a 2.69-fold increase (p = 0.0380), while IL-6 expression levels were 3.45 fold lower (p = 0.0045) versus control subjects. Moreover, compared with control group the expression of IL1R1 and IL-6 genes both were downregulated in individuals with moderately high blood glucose levels by 2.38 (p = 0.0365) and 4.34 fold (p = 0.0027), respectively. In addition, hemoglobin A1C (A1C) levels were positively correlated with IL-1β expression and fasting plasma glucose (FPG) levels showed a positive correlation with IL-1β and a negative correlation with IL-6 expression.

Conclusion: The observed changes in both IL-1β and IL-6 mRNA levels in PBMCs may contribute to the development of inflammatory processes involved in the pathogenesis of T2D. Downregulation of IL1R1 in individuals with mild hyperglycemia may indicate an attempt to reduce the pro-inflammatory effects of IL-1β via auto-stimulation.

KEYWORDS:

• Hyperglycemia
• IL-1β
• IL-6
• inflammation
• Type 2 diabetes

Author’s Contribution

MA carried out the experiments, analyzed the data, and wrote the paper. VH-Z designed the project, helped to analyze the data, and wrote the paper.

Acknowledgments

We thank Iranian Society of Diabetes and the clinics of the University of Tehran for providing us with blood samples.

Declaration of interest

There is no conflict of interest to declare. We have full control of all primary data and we agree to allow the journal to review our data if requested.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Iran National Science Foundation [94000647].