Immunometabolism mRNA expression phenotypes and reprogramming of CD14 in T2DM with or without CVD

Background/Aim: Type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) have a significant impact on the expression of genes in peripheral blood mononuclear cells (PBMCs). The primary objective of this study was to investigate the role of two signaling pathways, STAT1/6, and two important modulators of immunometabolism, leptin and PPARs, in the development of T2DM with and without CVD. Furthermore, the study aimed to assess the correlation between these factors and the dynamics of CD14 in PBMCs. This research was conducted within the context of a growing body of literature on the complex pathophysiology of T2DM and its association with CVD. Prior studies have indicated that T2DM is characterized by an imbalance in immunometabolism and the involvement of various signaling pathways. Materials and methods: Blood samples were collected from a total of 47 subjects, including 7 healthy volunteers, 20 individuals diagnosed with diabetes and cardiovascular disease (D.CVD) and another 20 individuals diagnosed with diabetes only (D). PBMCs were isolated from these samples, and the expression levels of leptin, PPAR gamma, PPAR alpha, and CD14 genes were measured using Real-Time PCR. Results: The most relevant result showed that diabetic patients with CVD had significantly higher levels of leptin expression, which was positively correlated with STAT1 (r = 0.7497, p = 0.0001). On the other hand, diabetic patients without CVD had elevated PPAR. expression, which was strongly correlated with STAT6 (r = 0.8437, p = 0.0001). Interestingly, we found a significant increase in the PPAR gamma/ PPAR alpha ratio in the D.CVD group compared to the D group (4.273 +/- 0.9531; 7.52 +/- 3.556, p = 0.0479). Moreover, CD14 expression was significantly reduced in this group compared to diabetic patients without CVD. Conclusion: These findings suggested that the immunometabolic imbalance in T2DM was driven by a STAT1/Leptin phenotype in diabetic patients with CVD and by a STAT6/PPAR gamma phenotype in diabetic patients without CVD. Taking into account STAT1/Leptin and STAT6/PPAR gamma profiling could help clinicians identify novel therapeutic targets for T2DM and other related diseases.

Automated summary

The study aimed to investigate the role of signaling pathways (STAT1/6) and immunometabolism regulators (leptin and PPARs) in the development of type 2 diabetes mellitus (T2DM) with and without cardiovascular diseases (CVD), as well as the correlation with CD14 dynamics in peripheral blood mononuclear cells (PBMCs). The results showed that T2DM patients with CVD had higher levels of leptin expression correlated with STAT1, while T2DM patients without CVD had elevated PPAR expression correlated with STAT6. Additionally, the ratio of PPAR gamma/PPAR alpha was higher in the T2DM with CVD group, and CD14 expression was significantly reduced. These findings suggest potential therapeutic targets for T2DM and related diseases.