Insulin Resistance Is Associated With a Poor Response to Intravenous Thrombolysis in Acute Ischemic Stroke

Abstract

OBJECTIVEInsulin resistance (IR) may not only increase stroke risk, but could also contribute to aggravate stroke prognosis. Mainly through a derangement in endogenous fibrinolysis, IR could affect the response to intravenous thrombolysis, currently the only therapy proved to be efficacious for acute ischemic stroke. We hypothesized that high IR is associated with more persistent arterial occlusions and poorer long-term outcome after stroke thrombolysis.RESEARCH DESIGN AND METHODSWe performed a prospective, observational, longitudinal study in consecutive acute ischemic stroke patients presenting with middle cerebral artery (MCA) occlusion who received intravenous thrombolysis. Patients with acute hyperglycemia (≥155 mg/dL) receiving insulin were excluded. IR was determined during admission by the homeostatic model assessment index (HOMA-IR). Poor long-term outcome, as defined by a day 90 modified Rankin scale score ≥3, was considered the primary outcome variable. Transcranial Duplex-assessed resistance to MCA recanalization and symptomatic hemorrhagic transformation were considered secondary end points.RESULTSA total of 109 thrombolysed MCA ischemic stroke patients were included (43.1% women, mean age 71 years). The HOMA-IR was higher in the group of patients with poor outcome (P = 0.02). The probability of good outcome decreased gradually with increasing HOMA-IR tertiles (80.6%, 1st tertile; 71.4%, 2nd tertile; and 55.3%, upper tertile). A HOMA-IR in the upper tertile was independently associated with poor outcome when compared with the lower tertile (odds ratio [OR] 8.54 [95% CI 1.67–43.55]; P = 0.01) and was associated with more persistent MCA occlusions (OR 8.2 [1.23–54.44]; P = 0.029).CONCLUSIONSHigh IR may be associated with more persistent arterial occlusions and worse long-term outcome after acute ischemic stroke thrombolysis.

Post–Glucose Load Measures of Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke

“…The association between insulin resistance and prognosis of patients with ischemic stroke has rarely been studied. Recent results from Calleja et al8 (n=109) and Bas et al9 (n=108) showed that insulin resistance was associated with worse outcome in patients with acute ischemic stroke who were treated with intravenous thrombolysis. A preliminary report from Hishinuma et al including 32 patients with stroke without history of diabetes mellitus showed that 3 of 4 patients with recurrent events had insulin resistance 10.…”

“…Previous studies have shown that insulin resistance is associated with an increased risk of coronary heart disease and stroke in the nondiabetic population 3, 4, 5, 6, 7. Recent studies have also shown that insulin resistance is associated with worse outcomes in patients with acute ischemic stroke who are treated with intravenous thrombolysis 8, 9. Few studies, however, have focused on the clinical outcome of general ischemic stroke 10.…”

“…Insulin resistance in previous studies was assessed mostly by the homeostasis model assessment of insulin resistance (HOMA‐IR), a measurement based on fasting plasma glucose and insulin levels 8, 9, 10. A previous study showed greater risk of cardiovascular disease associated with an increase in 2‐hour plasma glucose levels compared with an increase in fasting plasma glucose levels 12.…”

Blood biomarkers of insulin resistance in acute stroke patients treated with intravenous thrombolysis: Temporal profile and prognostic value

“…Hyperglycemia is known to be a strong determinant of poor outcome in stroke patients in general [27], and also in ischemic stroke patients treated with intravenous thrombolysis [28]. In this context, not only admission's glycemia predicts stroke outcome, but hyperglycemia observed at any time within the first 48 hours may have a deleterious effect on stroke patients (5,6). In order to explain the independent association found between GIP and outcome, we hypothesize that GIP expression in the setting of acute ischemic stroke might be a part of an insulin-sensitizing response aimed to reduce glucose level, thus counteracting the adverse effect of acute hyperglucemia on stroke outcome.…”

“…Our group previously reported that insulin resistance, the proposed key pathophysiological mechanism underlying metabolic syndrome [5], is associated with a worse response to intravenous thrombolysis in acute ischemic stroke [6]. In that study, insulin resistance was measured by means of the HOMA index calculated during admission.…”