Cacace Julia, Luna-Marco Clara, Hermo-Argibay Alberto, Pesantes-Somogyi Catherine, Hernández-López Omar A, Pelechá-Salvador María, Bañuls Celia, Apostolova Nadezda, de Miguel-Rodríguez Luis, Morillas Carlos, Rocha Milagros, Rovira-Llopis Susana, Víctor Víctor M
Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain.
Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain; Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, Spain.
Redox Biol. 2025 Apr;81:103516. doi: 10.1016/j.redox.2025.103516. Epub 2025 Jan 28.
The mitochondrial electron transport chain becomes overloaded in type 2 diabetes (T2D), which increases ROS (Reactive Oxygen Species) production and impairs mitochondrial function. Peripheral blood mononuclear cells (PBMCs) are critical players in the inflammatory process that underlies T2D. Poor glycaemic control in T2D is closely linked to the development of comorbidities. Our aim was to evaluate if glycaemic control in T2D has an impact on the oxygen consumption rates (OCR) of PBMC, OXPHOS complexes and inflammation. We recruited 181 subjects, consisting of 79 healthy controls, 64 patients with T2D and good glycaemic control (HbA1c<7 %), and 38 T2D patients with poor glycaemic control (HbA1c>7 %). We found a decrease in the basal OCR of PBMCs from patients with HbA1c>7 % with respect to controls (p < 0.05). Maximal OCR and spare respiratory capacity were lower in patients with HbA1c>7 % than in controls and patients with HbA1c<7 % (p < 0.05 for all). Mitochondrial ROS levels were higher in T2D patients, and particularly in the HbA1c > 7 group (p < 0.05 HbA1c<7 % vs control, p < 0.001 HbA1c>7 % vs control; p < 0.001 HbA1c > 7 vs HbA1c < 7). With respect to controls, poor glycaemic control in T2D patients was associated with a decrease in mitochondrial complex III and V (p < 0.05 and p < 0.01, respectively) and enhanced neutrophil-endothelial interactions (p < 0.001 vs controls). MPO levels were enhanced in T2D patients in general (p < 0.05 vs controls), and ICAM-1 and VCAM-1 were specifically increased in HbA1c > 7 patients vs controls (p < 0.01 and p < 0.001, respectively). Negative low-to-moderate correlations were found between HbA1c and basal respiration (r = -0.319, p < 0.05), maximal respiration (r = -0.350, p < 0.01) and spare respiratory capacity (r = -0.295, p < 0.05). Our findings suggest that poor glycaemic control during the progression of T2D compromises mitochondrial respiration and OXPHOS complex content in PBMCs. These alterations occur in parallel to enhanced neutrophil-endothelial interactions and adhesion molecule levels, leaving T2D patients with poor glycaemic control at a higher risk of developing vascular diseases.
在2型糖尿病（T2D）中，线粒体电子传递链会超负荷运转，这会增加活性氧（ROS）的产生并损害线粒体功能。外周血单核细胞（PBMCs）是T2D潜在炎症过程中的关键参与者。T2D患者血糖控制不佳与合并症的发生密切相关。我们的目的是评估T2D患者的血糖控制是否会对PBMC的氧消耗率（OCR）、氧化磷酸化复合物和炎症产生影响。我们招募了181名受试者，包括79名健康对照者、64名血糖控制良好（糖化血红蛋白<7%）的T2D患者以及38名血糖控制不佳（糖化血红蛋白>7%）的T2D患者。我们发现，糖化血红蛋白>7%的患者PBMC的基础OCR相对于对照组有所下降（p<0.05）。糖化血红蛋白>7%的患者的最大OCR和备用呼吸能力低于对照组以及糖化血红蛋白<7%的患者（所有p值均<0.05）。T2D患者的线粒体ROS水平较高，尤其是在糖化血红蛋白>7%的组中（糖化血红蛋白<7%与对照组相比，p<0.05；糖化血红蛋白>7%与对照组相比，p<0.001；糖化血红蛋白>7%与糖化血红蛋白<7%相比，p<0.001）。与对照组相比，T2D患者血糖控制不佳与线粒体复合物III和V的减少相关（分别为p<0.05和p<0.01），并且中性粒细胞与内皮细胞的相互作用增强（与对照组相比，p<0.001）。一般而言，T2D患者的髓过氧化物酶（MPO）水平升高（与对照组相比，p<0.05），并且与对照组相比，糖化血红蛋白>7%的患者的细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）特异性增加（分别为p<0.01和p<0.001）。糖化血红蛋白与基础呼吸之间存在低至中度的负相关（r=-0.319，p<0.05）、最大呼吸（r=-0.350，p<0.01）和备用呼吸能力（r=-0.295，p<0.05）。我们的研究结果表明，T2D进展过程中血糖控制不佳会损害PBMC中的线粒体呼吸和氧化磷酸化复合物含量。这些改变与中性粒细胞-内皮细胞相互作用增强和黏附分子水平升高同时发生，使血糖控制不佳的T2D患者发生血管疾病的风险更高。
