Plasma cyclic glycine proline/IGF-1 ratio predicts clinical outcome and recovery in stroke patients

Ann Clin Transl Neurol. 2019 Feb 27;6(4):669-677. doi: 10.1002/acn3.743. eCollection 2019 Apr.

Abstract

Objective: Many stroke patients make a partial recovery in function during the first 3 months, partially through promoting insulin-like growth factor-1 (IGF-1) function. A prognostic biomarker that associates with IGF-1 function may predict clinical outcome and recovery of stroke. This study evaluated plasma concentrations of IGF-1, IGF binding protein (IGFBP)-3 and cyclic-glycine-proline (cGP) and their associations with clinical outcome in stroke patients.

Methods: Thirty-four patients were recruited within 3 days of stroke. Clinical assessments included the National Institutes of Health Stroke Scale (NIHSS) within 3 days (baseline), and at days 7 and 90; the modified Rankin Scale (mRS) and Fugl-Meyer Upper-Limb Assessment Scale (FM-UL) at days 7 and 90. Plasma samples were collected from the patients at the baseline, days 7 and 90. Fifty age-matched control participants with no history of stroke were also recruited and provided plasma samples. IGF-1, IGFBP-3, and cGP concentrations were analyzed using ELISA or HPLC-MS.

Results: Baseline concentrations of IGFBP-3, cGP, and cGP/IGF-1 ratio were lower in stroke patients than the control group. The neurological scores of stroke patients were improved and plasma cGP and cGP/IGF-1 ratio increased over time. Baseline cGP/IGF-1 ratio was correlated with the NIHSS scores at day 90 and the changes in NIHSS scores from the baseline to 90 days.

Interpretation: Low cGP concentrations and cGP/IGF-1 ratio in stroke patients suggest an impaired IGF-1 function. The cGP/IGF-1 ratio at admission maybe further developed as a prognostic biomarker for stroke recovery.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Ischemia / blood
  • Female
  • Glycine / blood*
  • Humans
  • Insulin-Like Growth Factor I / biosynthesis
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Middle Aged
  • Peptides, Cyclic / blood*
  • Plasma / metabolism
  • Proline / blood
  • Stroke / blood*
  • Young Adult

Substances

  • IGF1 protein, human
  • Peptides, Cyclic
  • cyclic glycine-proline
  • Insulin-Like Growth Factor I
  • Proline
  • Glycine

Grants and funding

This work was funded by Brain Research New Zealand ‐ A Centre of Research Excellence, New Zealand grants BRNZ 371526 and BRNZ 3709482; Vitality New Zealand, Christchurch, New Zealand grant UniServices 36423.