Mkhize Bongeka Cassandra, Mosili Palesa, Ngubane Phikelelani Sethu, Sibiya Ntethelelo Hopewell, Khathi Andile
School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban 3629, KwaZulu-Natal, South Africa.
Department of Human Physiology, University of KwaZulu-Natal, Westville 4000, KwaZulu-Natal, South Africa.
Int J Mol Sci. 2025 Jun 9;26(12):5517. doi: 10.3390/ijms26125517.
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.
脂肪组织对于调节胰岛素敏感性和细胞因子生成至关重要，而这是维持代谢稳态的关键过程。先前的研究表明，肾素-血管紧张素系统（RAS）与2型糖尿病（T2D）中的脂肪组织功能障碍之间存在联系；然而，RAS在糖尿病前期的作用仍未得到充分研究。本研究旨在分析糖尿病前期状态下RAS成分与脂肪组织功能障碍之间的关联。这项观察性横断面研究于2021年5月21日至2024年5月20日进行，分析了血浆样本中的RAS标志物。本研究在爱德华国王医院开展，重点关注门诊患者。该研究纳入了年龄在25至45岁之间的非糖尿病前期（NPD）、糖尿病前期（PD）和T2D个体（每组n = 40）。参与者根据空腹血糖水平和糖化血红蛋白（HbA1c）标准进行选择。测量了每位参与者的血浆RAS标志物和脂肪功能标志物。主要结局包括稳态模型评估的胰岛素抵抗（HOMA-IR）、HbA1c以及血管紧张素转换酶1（ACE1）、血管紧张素II（Ang II）、血管紧张素转换酶2（ACE2）、血管紧张素1-7（Ang 1-7）、脂联素、脂肪酶、单核细胞趋化蛋白-1（MCP-1）和高密度脂蛋白（HDL）的血浆水平。与NPD相比，PD参与者的血糖控制显著改变（HOMA-IR：2.1±0.4 vs. 3.9±0.8；HbA1c：4.9±0.4 vs. 5.9±0.6）。PD患者的血浆ACE1（162.0±10.55 vs. 180.3±7.546）和Ang II（20.26±2.404 vs. 25±1.752）升高，而脂联素（29.08±5.72 vs. 23.22±4.93）和HDL（1.01±0.11 vs. 0.67±0.11）降低。RAS的改变在糖尿病前期早期就已出现，并与脂肪组织功能障碍相关。这些发现表明，RAS失调导致糖尿病前期早期的代谢紊乱。
