P C M van Poppel1, M S Gresnigt2, P Smits3, M G Netea2, C J Tack4. 1. Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Electronic address: p.vanpoppel@aig.umcn.nl. 2. Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands. 3. Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 4. Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Abstract
AIMS: The enzyme dipeptidyl peptidase-4 (DPP-4) is a key player in the degradation of incretin hormones that are involved in glucose metabolism. DPP-4 is also expressed on immune cells and is associated with several immunological functions. Some studies have reported increased rates of infections in patients treated with DPP-4 inhibitors. We therefore assessed whether treatment with the DPP-4 inhibitor vildagliptin affected cytokine production and T-cell differentiation. METHODS:Patients with type 2 diabetes were treated with vildagliptin or an active comparator, acarbose, for four weeks, in a randomized cross-over trial. Blood was sampled at the end of each treatment period and peripheral blood mononuclear cells were isolated and stimulated with a broad spectrum of pattern recognition receptor agonists. RESULTS:Serum cytokine concentrations and ex vivo cytokine production (both monocyte and T-cell derived) did not differ during treatment with vildagliptin compared to acarbose. Similarly, ex vivo relative upregulation of mRNA transcription of T-cell lineage specific transcription factors was unaffected by vildagliptin treatment. CONCLUSIONS: These data show that a four-week treatment with vildagliptin in patients with type 2 diabetes mellitus does not result in a significant modulation of cytokine responses. This observation suggests that inhibition of DDP-4 does not lead to an increased risk of infection by diminishing cytokine production.
RCT Entities:
AIMS: The enzyme dipeptidyl peptidase-4 (DPP-4) is a key player in the degradation of incretin hormones that are involved in glucose metabolism. DPP-4 is also expressed on immune cells and is associated with several immunological functions. Some studies have reported increased rates of infections in patients treated with DPP-4 inhibitors. We therefore assessed whether treatment with the DPP-4 inhibitor vildagliptin affected cytokine production and T-cell differentiation. METHODS:Patients with type 2 diabetes were treated with vildagliptin or an active comparator, acarbose, for four weeks, in a randomized cross-over trial. Blood was sampled at the end of each treatment period and peripheral blood mononuclear cells were isolated and stimulated with a broad spectrum of pattern recognition receptor agonists. RESULTS: Serum cytokine concentrations and ex vivo cytokine production (both monocyte and T-cell derived) did not differ during treatment with vildagliptin compared to acarbose. Similarly, ex vivo relative upregulation of mRNA transcription of T-cell lineage specific transcription factors was unaffected by vildagliptin treatment. CONCLUSIONS: These data show that a four-week treatment with vildagliptin in patients with type 2 diabetes mellitus does not result in a significant modulation of cytokine responses. This observation suggests that inhibition of DDP-4 does not lead to an increased risk of infection by diminishing cytokine production.
Authors: Hermine Muniangi-Muhitu; Elina Akalestou; Victoria Salem; Shivani Misra; Nicholas S Oliver; Guy A Rutter Journal: Front Endocrinol (Lausanne) Date: 2020-10-08 Impact factor: 5.555