Distinct cytokine profiles associated with malnutrition, dyslipidemia and kidney dysfunction in patients with diabetic foot ulcer

Abstract

Chronic nonspecific immune immunoinflammatory responses play a pivotal role in the progression of diabetic foot ulcers (DFUs). However, current clinical evidence regarding the associations between cytokines and metabolic disorders in DFU patients is limited. This study focused on common cytokines and immunoinflammatory markers to investigate their roles in patients’ metabolic disorders. A total of 85 DFU patients, 53 patients with diabetes mellitus, and 51 healthy controls were enrolled in this study. The serum levels of proteins, lipids, kidney biomarkers, cytokines, and immunoinflammatory markers were analyzed to explore the associations between three complications (kidney dysfunction, dyslipidemia, and malnutrition) and immune inflammation. Compared with the DM patients, the DFU patients presented higher prevalence of kidney dysfunction, dyslipidemia, and malnutrition (all P < 0.001), accompanied with overexpression of tumor necrosis factor α (TNFα) and 6 interleukins (ILs), including IL4, IL6, IL8, IL10, IL12P70, IL17. These overexpressed cytokines and common immunoinflammatory biomarkers demonstrated evident correlations with at least one biomarker related to kidney, lipid, or nutritional biomarkers (|ρ|>0.3, P < 0.05). IL10 demonstrated an independent (OR = 0.29, P = 0.027) and nonlinear (p for nonlinearity = 0.268) association with malnutrition, but an insignificant prediction role (P = 0.056). IL6 demonstrated an association with kidney dysfunction independently (OR = 1.01, P = 0.008) and linearly (p for overall = 0.029), with a sensitive prediction role (AUC = 0.707, Sensitivity = 91.9%, Specificity = 52.1) and risk threshold at 30.41 ng/L. Although IL12P70 also correlated with kidney dysfunction independently (OR = 0.23, P = 0.046) and nonlinearly (p for nonlinearity = 0.001) with protective range from 1.50 ng/L to 5.06 ng/L, it demonstrated an insignificant prediction role (P = 0.071). IL17 correlated with dyslipidemia independently (OR = 1.66, P = 0.025) and linearly (p for overall = 0.008), with a specific prediction role (AUC = 0.749, Sensitivity = 64.2%, Specificity = 94.4%) and risk threshold at 4.56 ng/L. Our study revealed an antagonistic effect between proinflammatory and anti-inflammatory factors on metabolic disorders in DFU patients. Clinical intervention may contribute to the management of metabolic disorders in these patients.