Influence of dyslipidaemia on monocyte inflammatory profile in diabetes and diabetic wound healing.

Abstract

Diabetes often presents with many severe complications. Diabetic foot ulcers (DFUs), a common manifestation of peripheral arterial disease and neuropathy in diabetes, impose significantly impaired healing, resulting in limb amputations and mortality. Chronic inflammation is the underlying mechanism, where monocytes and macrophages are crucial. Macrophage M1 inflammatory and M2 anti-inflammatory imbalance is noted in diabetic wounds, along with some monocyte changes in diabetes. Monocyte changes are linked to altered lipids in healthy people and CVD. This study investigates monocyte inflammatory profiles in diabetes with and without foot ulcers, their link to lipid profiles, and their association with DFU healing outcomes. This study was conducted across generally healthy individuals (HC), people with diabetes (DM) and diabetic foot ulcers (DFU) to determine monocyte M1/M2 profiles and their associations with blood lipids and healing outcomes. DFU participants were monitored for 12 weeks, with ulcer outcomes classified as healed, healing or nonhealing. This study highlighted immune suppression in people with DFU, with reduced M2 (CD163) and M1 (CD86, TLR2 and TLR4) markers, associated with poor glycaemic control. Suppression of both M1 and M2 markers in DFU suggests a reduced ability of monocytes to elicit appropriate immune responses. A typically altered lipid profile with low HDL-C, Apo A1, and high triglycerides was observed in DM and DFU and showed subtle links with the monocyte profile. Well-managed LDL-C levels in DFU likely reduce monocyte inflammation by regulating cellular lipid homeostasis and lipid rafts but did not enhance monocyte anti-inflammatory potential. Despite the overall reduction in the monocyte inflammatory profile in DFU, the monocyte inflammatory state was associated with healing success. Increased CD120b and CD120b/CD163 ratio in nonhealing DFUs indicates CD120b as a potential biomarker for healing outcomes in addition to HDL-C and Apo A1.