RESUMEN
Importance: Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk. Objective: To examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcPo2) in individuals with type 2 diabetes and PAD. Design, Setting, and Participants: This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania "Luigi Vanvitelli," Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcPo2 between 30 and 49 mm Hg were included. Interventions: Patients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months. Main Outcomes and Measures: Coprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcPo2 from baseline in each group. Results: Fifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcPo2 of 40.3 (5.7) mm Hg. Transcutaneous Po2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P < .001). The 10% increase of TcPo2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P < .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (-0.4 mg/dL; 95% CI, -0.7 to -0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (-119.4 mg/g; 95% CI, -195.0 to -43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P < .001). Conclusions and Relevance: In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcPo2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes. Trial Registration: ClinicalTrials.gov Identifier: NCT04881110.
Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedad Arterial Periférica , Masculino , Humanos , Anciano , Femenino , Liraglutida/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Perfusión , Enfermedad Arterial Periférica/tratamiento farmacológico , Extremidad InferiorRESUMEN
BACKGROUND: Inflammatory microenvironment is an essential component of all tumors, including thyroid cancer. Autoimmune thyroid diseases are often associated with thyroid cancer. CD25, expressed in Treg cells and B cells, has been found to be associated with autoimmune thyroid diseases and the NFkB pathway is critical to tumor formation, regulating immune-related genes, and pro-inflammatory cytokine. METHODS: Protein expression of CD25 and NFkB and its phosphorylated form was analyzed by immunohistochemistry in 80 patients with thyroid cancer (10 cases of cancers with Hashimoto's thyroiditis and 70 cases without). RESULTS: CD25 was mainly detected in the nucleus of the inflammatory cells such as in the thyrocytes and neoplastic cells. Protein staining was detected in the T-lymphocytes of the outermost zone of the lymphoid follicles. Moreover, in all cancer alterations, there were a higher level of p-NFkB than in the surrounding tissues. Again, p-NFkB staining was evident in neoplastic cells but not evident in inflammatory cells. CONCLUSIONS: Strong inflammatory infiltrate in the tumor microenvironment is correlated with an invasive phenotype. CD25 and p-NFkB levels were statistically significantly overexpressed in cancer cells.