Increased levels of inflammatory mediators and proinflammatory monocytes in patients with type I diabetes mellitus and nephropathy

• Published in: Journal of diabetes and its complications 2017-01, Vol.31 (1), p.245-252
• Main Authors: Kolseth, Ingrid Benedicte Moss, Reine, Trine Marita, Parker, Krystina, Sudworth, Amanda, Witczak, Bartlomiej J, Jenssen, Trond Geir, Kolset, Svein Olav
• Format: Article
• Language: English
• Subjects: Biomarkers - blood; Body mass index; Cardiovascular disease; Cells, Cultured; Cholesterol; Diabetes; Diabetes Mellitus, Type 1 - complications; Diabetic Angiopathies - blood; Diabetic Angiopathies - immunology; Diabetic Angiopathies - metabolism; Diabetic Angiopathies - pathology; Diabetic Nephropathies - blood; Diabetic Nephropathies - immunology; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Disease Progression; Endocrinology & Metabolism; Endothelial dysfunction; Endothelium; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Female; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - immunology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hypertension; Inflammation; Inflammation Mediators - blood; Inflammation Mediators - metabolism; Intercellular Adhesion Molecule-1 - blood; Intercellular Adhesion Molecule-1 - metabolism; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - immunology; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - pathology; Laboratories; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Male; Middle Aged; Monocyte; Monocytes - immunology; Monocytes - metabolism; Monocytes - pathology; Mortality; Nephropathy; Patients; Plasminogen Activator Inhibitor 1 - blood; Plasminogen Activator Inhibitor 1 - metabolism; Renal Insufficiency - complications; Renal Insufficiency - immunology; Renal Insufficiency - metabolism; Renal Insufficiency - pathology; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - immunology; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - pathology; Rodents; Severity of Illness Index; Type 1 diabetes mellitus; Up-Regulation
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2016.06.029

Abstract Aims To investigate and describe the relationship between diabetic nephropathy and systemic inflammation in patients with type 1 diabetes mellitus (T1DM). Methods Patients with T1DM, with or without reduced renal function due to diabetic nephropathy, were included. Differences in inflammatory mediators, adhesion molecules, markers of endothelial dysfunction and subsets of monocytes were studied in patients with mean disease duration of 31 years. Results Patients with T1DM with and without renal failure were compared. Patients with nephropathy had increased plasma levels of proinflammatory monocytes, as well as circulatory PAI-1, syndecan-1, VEGF, IL-1β, IL-1Ra and CCL4. Peripheral blood mononuclear cells from patients with nephropathy numerically increased soluble ICAM and PAI-1 in co-culture with primary endothelial cells compared to cells from patients without nephropathy. Conclusions T1DM patients with kidney failure have higher levels of proinflammatory monocytes and circulatory inflammatory mediators compared to patients with T1DM alone. The results highlight the importance of inflammation and endothelial dysfunction in diabetic nephropathy with reduced GFR.