Circulating Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-3 predict Three-months Outcome after Ischemic Stroke

Abstract

Reports on neuroprotective effects of Insulin-like growth factor-1 (IGF-1) and Insulin-like growth factor binding protein-3 (IGFBP-3) in ischemic brain tissue are inconsistent. The aim of this study was to determine if plasma levels of IGF-1 and IGFBP-3 in acute stroke patients are indicative of 3 months functional outcome. Plasma levels were measured via chemiluminescence immunoassay in heparin blood samples of patients included in the EARLY trial (NCT00562588). Plasma samples were drawn on admission and 8 days post-stroke. Neurological deficits were assessed via modified Rankin Scale (mRS) 3 months post-stroke, resulting in favorable (mRS=0-2) or unfavorable (mRS=3-6) outcome. A multiple binary logistic regression including IGF-1 and IGFBP-3 levels and confounders was conducted. Out of 404 included patients, 89 patients had an unfavorable outcome. Mean mRS on admission as well as 3 months post-stroke was 2 (±1). Low IGF-1 levels (day 8) were independently associated with a decreased risk of an unfavorable outcome (OR 0.61; 95%CI 0.37-0.99; p=0.044). Low IGFBP-3 levels (day 8) were independently associated with an unfavorable outcome (OR 2.75; 95%CI 1.56-4.84; p<0.001). Low IGFBP-3 levels and high IGF-1 levels in the subacute phase are predictive of unfavorable outcome 3 months after stroke.

Monocyte Transmodulation: The Next Novel Therapeutic Approach in Overcoming Ischemic Stroke?

“…Therefore, much effort has been devoted to research new therapeutic methods to prevent the unfortunate outcomes of stroke (122,123). To discover novel methods of ischemic stroke therapy, factors related to inflammation in the brain, such as C-reactive protein (CRP) (124), hepatocyte growth factor (125), insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (126), factor XIII (127), brain-derived neurotrophic factor (128), and D-dimer (129), have been investigated.…”

Investigating the relationship between IGF-I, -II and IGFBP-3 concentrations and later-life cognition and brain volume

“…Several studies have implied the possibility of a beneficial association between IGFBP-3 and cerebral small vessel disease. High concentrations of circulating IGFBP-3 are associated with reduced risk of ischaemic stoke and improved functional outcomes following stroke events(41,48,49). In mice, IGFBP-3 was shown to protect retinal vasculature from hyperoxia-induced vessel regression and, in vitro , promoted differentiation of endothelial precursor cells to endothelial cells, indicating a potential pathway by which IGFBP-3 may reduce WMHV (5,50).…”

Association Between Levels of Serum Insulin-like Growth Factor I and Functional Recovery, Mortality, and Recurrent Stroke at a 7-year Follow-up

“…However, there is significantly better individual recovery, as evidenced by the ▶table 3 Data for the 3-month s-IGF-I levels and shifts in mRS scores for patients who were followed for 7 years (cases of recurrent strokes and death are excluded). Category of shifts in mRS scores, as analyzed by crude correlations (above); 2 Category of shifts in mRS scores, as analyzed by differences in the absolute s-IGF-I levels (below); 3 N/A, not applicable; 4 P-values obtained using Pearson correlation for mRS shift categories of deterioration vs. improvement or for initial mRS = 0, deterioration vs. no shift, with rho values (r) given; 5 P-values obtained using the Student's t-test (for mRS shift categories of deterioration vs. improvement or for initial mRS = 0, deterioration vs. no shift); 6 Data for the mRS score shift categories between 3 months and 7 years and between 2 and 7 years are shown. For comparison, the shifts in mRS scores for the period 3 months and 2 years period from 3 months to 2 years are shown with the same selection of patients; 7 CI, 95 % confidence interval.…”

“…Therefore, the present investigation focused on this more stabilized level of s-IGF-I. It may be of importance that s-IGF-I appears to be dynamically regulated in the post-stroke period [19,21], and this may explain why there are different associations with functional outcomes in different studies [4][5][6][7][8], depending on which post-stroke time-point was used for s-IGF-I sampling. Nevertheless, a stabilized 3-month level of s-IGF-I is independently associated with recovery (mRS shift categories) be-▶table 2 Data for 3-month s-IGF-I with regard to overall favorable mRS (0-2) and unfavorable mRS (3-6), deaths, and recurrent stroke at 2 and 7 years after the index ischemic stroke.…”

“…Specifically, s-IGF-I is lower in elderly subjects, in those with metabolic syndrome or malnutrition, whereas a high level of physical activity is associated with a higher level of s-IGF-I. With regard to clinical outcomes after ischemic stroke (IS), higher levels of circulating s-IGF-I have been variously associated with better outcomes 2-6 months after IS [4,5], with worse 3-month outcomes [6], and with neutral outcomes after 1 year [7]. Furthermore, the 3-month s-IGFI levels have been reported as being independently associated with individual improvements (i. e., changes in modified Rankin scale scores; ΔmRS) in outcome [8] after IS.…”