Increased Plasma Levels of ACE and Ang II in Prediabetes May Contribute to Adipose Tissue Dysfunction

Abstract

Adipose tissue is essential for the regulation of insulin sensitivity and cytokine production, which are key processes in maintaining metabolic homeostasis. Previous studies have shown a link between the renin-angiotensin system (RAS) and adipose tissue dysfunction in type 2 diabetes (T2D); however, the role of RAS in prediabetes remains underexplored. This study aimed to analyze the association between RAS components and adipose tissue dysfunction in the prediabetic state. This observational, cross-sectional study was conducted between 21/05/21 and 20/05/24 and analyzed RAS markers in plasma samples. This study was conducted at King Edward Hospital, focusing on individuals from outpatient clinics. The study included non-prediabetic (NPD), prediabetic (PD), and T2D individuals (n = 40 per group) aged 25-45 years. The participants were selected based on fasting blood glucose levels and HbA1c criteria. Plasma RAS markers and adipose function markers were measured in each participant. Primary outcomes included HOMA-IR, HbA1c, and plasma levels of ACE1, Ang II, ACE2, Ang 1-7, adiponectin, adipsin, MCP-1, and HDL. PD participants had significantly altered glycaemic control (HOMA-IR: 2.1 ± 0.4 vs. 3.9 ± 0.8; HbA1c: 4.9 ± 0.4 vs. 5.9 ± 0.6) compared to NPD. Plasma ACE1 (162.0 ± 10.55 vs. 180.3 ± 7.546) and Ang II (20.26 ± 2.404 vs. 25 ± 1.752) were elevated, while adiponectin (29.08 ± 5.72 vs. 23.22 ± 4.93) and HDL (1.01 ± 0.11 vs. 0.67 ± 0.11) were reduced in PD. Alterations in RAS manifest early in prediabetes and are associated with adipose tissue dysfunction. These findings suggest that RAS dysregulation contributes to early metabolic disturbances in prediabetes.