Prior treatment with dipeptidyl peptidase 4 inhibitors is associated with better functional outcome and lower in-hospital mortality in patients with type 2 diabetes mellitus admitted with acute ischaemic stroke
Abstract:It is unclear whether prior antidiabetic treatment affects stroke severity and outcome. To evaluate this association, we prospectively studied all patients who were admitted in our Department with acute ischaemic stroke (n = 378, mean age = 78.8 ± 6.5 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale. The outcome was assessed with the modified Rankin Scale at discharge and with in-hospital mortality. A total of 123 patients had type 2 diabetes mellitus… Show more
“…A recent prospective human study has shown that prior treatment with gliptins is associated with better functional outcome and lower mortality in stroke patients with T2D . This observation is supported by recent preclinical results that have shown a strong neuroprotective action of the gliptin linagliptin in normal mice and mice with T2D, where chronic DPP‐4 inhibition before (4 weeks) and after (3 weeks) experimental stroke reduced brain damage .…”
Gliptins are anti-type 2 diabetes (T2D) drugs that regulate glycaemia by preventing endogenous glucagon-like peptide-1 (GLP-1) degradation. Chronically administered gliptins before experimental stroke can also induce neuroprotection, and this effect is potentially relevant for reducing brain damage in patients with T2D and high risk of stroke. It is not known, however, whether acute gliptin treatment after stroke (mimicking a post-hospitalization treatment) is neuroprotective or whether gliptin-mediated neuroprotection occurs via GLP-1-receptor (GLP-1R) activation. To answer these two questions, wild-type and glp-1r(-/-) mice were subjected to transient middle cerebral artery occlusion (MCAO). Linagliptin was administered acutely (50 mg/kg intravenously), at MCAO time or chronically (10 mg/kg orally) for 4 weeks before and 3 weeks after MCAO. Neuroprotection was assessed by stroke volume measurement and quantification of NeuN-positive surviving neurons. Plasma/brain GLP-1 levels and dipeptidyl peptidase-4 activity were also measured. The results show that the linagliptin-mediated neuroprotection against stroke requires chronic pretreatment and does not occur via GLP-1R. The findings provide essential new knowledge with regard to the potential clinical use of gliptins against stroke, as well as a strong impetus to identify gliptin-mediated neuroprotective mechanisms.
“…A recent prospective human study has shown that prior treatment with gliptins is associated with better functional outcome and lower mortality in stroke patients with T2D . This observation is supported by recent preclinical results that have shown a strong neuroprotective action of the gliptin linagliptin in normal mice and mice with T2D, where chronic DPP‐4 inhibition before (4 weeks) and after (3 weeks) experimental stroke reduced brain damage .…”
Gliptins are anti-type 2 diabetes (T2D) drugs that regulate glycaemia by preventing endogenous glucagon-like peptide-1 (GLP-1) degradation. Chronically administered gliptins before experimental stroke can also induce neuroprotection, and this effect is potentially relevant for reducing brain damage in patients with T2D and high risk of stroke. It is not known, however, whether acute gliptin treatment after stroke (mimicking a post-hospitalization treatment) is neuroprotective or whether gliptin-mediated neuroprotection occurs via GLP-1-receptor (GLP-1R) activation. To answer these two questions, wild-type and glp-1r(-/-) mice were subjected to transient middle cerebral artery occlusion (MCAO). Linagliptin was administered acutely (50 mg/kg intravenously), at MCAO time or chronically (10 mg/kg orally) for 4 weeks before and 3 weeks after MCAO. Neuroprotection was assessed by stroke volume measurement and quantification of NeuN-positive surviving neurons. Plasma/brain GLP-1 levels and dipeptidyl peptidase-4 activity were also measured. The results show that the linagliptin-mediated neuroprotection against stroke requires chronic pretreatment and does not occur via GLP-1R. The findings provide essential new knowledge with regard to the potential clinical use of gliptins against stroke, as well as a strong impetus to identify gliptin-mediated neuroprotective mechanisms.
“…Despite these promising results of preclinical studies, there are very few data regarding the role of DPP-4 inhibitors in improving the outcome of patients with acute ischemic stroke. In a small study ( n = 123), we reported that patients who were hospitalized with acute ischemic stroke and were treated with DPP-4 inhibitors prior to stroke had a trend for less severe stroke at admission and also had better functional outcome and lower in-hospital mortality than patients treated with other antihyperglycemic agents [ 50 ].…”
Section: Dpp-4 Inhibitors and Acute Ischemic Strokementioning
Diabetes mellitus (DM) is a major risk factor for ischemic stroke. Moreover, patients with DM suffer more severe strokes and have worse functional outcome following an acute stroke than patients without DM. In this context, data from animal studies and emerging evidence from clinical studies suggest that incretin-based antihyperglycemic agents might exert beneficial effects in patients with DM who suffer ischemic stroke. It appears that these agents exert neuroprotective actions that might both reduce infarct size and promote recovery. The present review summarizes the evidence on the potential role of incretin-based antihyperglycemic agents in the management of acute ischemic stroke.
“…Rat models showed that PEDF induces the production of inflammatory chemokines such as MIP-2 and MIP-3 α in microglia [136]. The myokine dipeptidyl-peptidase 4 (DPP4) has recently come in the spotlight because its inhibition, as well as the use of glucagon-like receptor 1 (GLP-1) agonists, leads to an antistroke effect [137, 138] and a cardioprotective role [139]. During physical exercise, DPP4 inhibitors improve mitochondrial biogenesis and muscle activity through the activation of GLP-1 signaling [140].…”
Section: Bone-skeletal Muscle Biomarkers In Strokementioning
Since the increasing update of the biomolecular scientific literature, biomarkers in stroke have reached an outstanding and remarkable revision in the very recent years. Besides the diagnostic and prognostic role of some inflammatory markers, many further molecules and biological factors have been added to the list, including tissue derived cytokines, growth factor-like molecules, hormones, and microRNAs. The literatures on brain derived growth factor and other neuroimmune mediators, bone-skeletal muscle biomarkers, cellular and immunity biomarkers, and the role of microRNAs in stroke recovery were reviewed. To date, biomarkers represent a possible challenge in the diagnostic and prognostic evaluation of stroke onset, pathogenesis, and recovery. Many molecules are still under investigation and may become promising and encouraging biomarkers. Experimental and clinical research should increase this list and promote new discoveries in this field, to improve stroke diagnosis and treatment.
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