Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions

• DOI: 10.1016/j.redox.2025.103516
• Publication Date: 2025-01-28T17:17:23Z
• Authors: Julia Cacace; Clara Luna-Marco; Alberto Hermo-Arg...; Catherine Pesante...; Omar A. Hernández...; María Pelechá-Sal...; Celia Bañuls; Nadezda Apostolova; Luis de Miguel-Ro...; Carlos Morillas; Milagros Rocha; Susana Rovira-Llopis; Víctor M. Víctor
• Keywords: Inflammation; Medicine (General); HbA1c; R5-920; QH301-705.5; Type 2 diabetes; Biology (General); OXPHOS; Mitochondria

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.