title: Dipeptidyl peptidase-4 activity might be a link between tumour necrosis factor alpha and insulin resistance in type 1 diabetes.
abstract: Tumour necrosis factor alpha (TNF α) leads to β cell damage in type 1 diabetes (T1DM) but also causes insulin resistance (IR). It modulates dipeptidyl peptidase-4 (DPP-4) activity, adipokine linked with both IR and T1DM. We were interested if there is an association of TNF α in conjunction with DPP-4 and IR in T1DM. DPP-4 activity, TNF α concentration measurements, and insulin sensitivity calculation using estimated glucose disposal rate (eGDR) equation were performed in 70 T1DM patients. They were divided into two groups according to eGDR median. The group with higher IR had higher value of DPP-4 activity (27.57 ± 1.77 vs. 18.33 ± 1.14, p < 0.001) and TNF α concentration (12.91 ± 0.83 vs. 6.72 ± 0.36, p < 0.001). TNF α concentration and DPP-4 activity negatively correlated with eGDR (r = -0.616, p < 0.001 and r = -0.643, p < 0.001) while correlating positively with each other (r = 0.422; p = 0.001). The linear regression showed that eGDR decreases for 0.166 mg kg(-1) min(-1) by TNF α concentration increase of 1 pg/mL (p < 0.001) and for 0.090 mg kg(-1) min(-1) by DPP-4 activity increase of 1 U/L (p = 0.001) when adjusted for age, gender disease duration, glycated haemoglobin, body mass index and waist-to-hip ratio. eGDR decreased by additional 0.60 mg kg(-1) min(-1) (B = -0.150, p < 0.001) when DPP-4 activity was additionally adjusted for TNF α. TNF α concentration is associated with IR, correlates with its severity and increases the drop in insulin sensitivity modulated by DPP-4 activity. Whether TNF α involvement in the insulin signalling pathway is mediated by DPP-4 activity needs to be further evaluated.
authors.affiliation: Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, 10000, Zagreb, Croatia.|School of Medicine, University of Zagreb, 10000, Zagreb, Croatia.
authors.forename: Lea
authors.initials: L
authors.lastname: Duvnjak
authors.affiliation: Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, 10000, Zagreb, Croatia. kblaslov@gmail.com.
authors.forename: Kristina
authors.initials: K
authors.lastname: Blaslov
authors.affiliation: Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, 10000, Zagreb, Croatia.
authors.forename: Matea Nikolac
authors.initials: MN
authors.lastname: Perković
authors.affiliation: Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, 10000, Zagreb, Croatia.
authors.forename: Jadranka Knežević
authors.initials: JK
authors.lastname: Ćuća
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D006442:Glycated Hemoglobin; D014409:Tumor Necrosis Factor-alpha; C042807:DPP4 protein, human
keywords: Dipeptidyl peptidase-4; Insulin sensitivity; Tumour necrosis factor alpha; Type 1 diabetes