2. Biomedic Investigation Unit (IBC). Hospital Clínico Universitario de Valladolid. Department of Medicine, University of Valladolid. Valladolid, Spain.
Institutional addresses: Avda. Ramón y Cajal, 3; 47005; Valladolid, Spain.
Background: Metabolic syndrome and insulin resistance may hamper the beneficial effect of intravenous thrombolysis in acute ischemic stroke. We investigated the temporal profile and prognostic value of 11 circulating biomarkers of insulin resistance in acute ischemic stroke patients treated with intravenous thrombolysis.
Methods: We performed a prospective study in acute ischemic stroke patients with a middle cerebral artery (MCA) occlusion who received intravenous tissue plasminogen activator (tPA). Measurement of C-Peptide, Ghrelin, Gastricinhibitory- polypeptide (GIP), Glucagon-like-peptide-1 (GLP-1), Glucagon, Insulin, Leptin, Resistin, Visfatin, Interleukin-6 (IL-6) and Tumor-necrosis-factor-alpha (TNF-α) was performed in three time-points: before tPA-bolus, right after tPAinfusion and at 24h. Long term clinical outcome, early neurological recovery, MCA-recanalization, infarct volume and hemorrhagic transformation were outcome variables.
Results: Fifty-two patients were included (61%women, mean-age75). Three months after stroke onset, 24 (47%) patients were functionally independent. In a multivariate adjusted regression model, GIP level at 1h≥109.51 pg/ml (OR 13.78 [1.38-137.31], p=0.02) and GIP level at 24h≥82.19 pg/ml (OR 28.46 [1.09-739.82], p=0.04) emerged as independent predictors of good outcome. Baseline GIP and 0-1 h increment in IL-6 and TNF-α were associated with early neurological course. Ghrelin level at 1h and 0-24h increment in Leptin level were independently associated with a larger infarct volume.
Conclusions: Blood concentration of several molecules reflecting a more pronounced insulin resistance status was associated with a worse outcome in acute ischemic stroke patients treated with intravenous thrombolysis. Noteworthy, a higher GIP level at 1h and 24 h after tPA treatment predicted good long-term outcome.
Key words: Insulin resistance, acute stroke, cytokines.