1. PAPP-A activity is increased in cerebrospinal fluid from patients with diabetic polyneuropathy and correlates with peripheral nerve impairment.
- Author
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Kallestrup M, Frystyk J, Espelund U, Hjortebjerg R, Tankisi H, and Andersen H
- Subjects
- Adult, Aged, Biomarkers blood, Case-Control Studies, Diabetic Neuropathies cerebrospinal fluid, Diabetic Neuropathies etiology, Female, Humans, Male, Middle Aged, Polyneuropathies cerebrospinal fluid, Polyneuropathies etiology, Prognosis, Biomarkers cerebrospinal fluid, Diabetes Mellitus, Type 2 complications, Diabetic Neuropathies diagnosis, Polyneuropathies diagnosis, Pregnancy-Associated Plasma Protein-A cerebrospinal fluid
- Abstract
Objective: Insulin-like growth factors (IGFs) have neuroprotective effects. IGF activity is partly controlled by pregnancy-associated plasma protein-A (PAPP-A), an enzyme which enhances IGF-action by cleavage of IGF-binding protein-4 (IGFBP-4). To study the role of PAPP-A and the IGF system in diabetic polyneuropathy (DPN), we measured immunoreactive (total) concentrations of IGF-I and IGF-II, bioactive IGF by cell-based bioassay, PAPP-A, as well as intact and PAPP-A-cleaved IGFBP-4 in cerebrospinal fluid (CSF) and serum from patients with type 2 diabetes (T2D) with and without DPN., Design: Twenty-three patients with T2D were included. Based on clinical examination, vibratory perception thresholds and nerve conduction studies, patients were diagnosed with (n = 9) or without (n = 14) DPN., Results: In CSF, PAPP-A activity, as estimated by IGFBP-4 fragment levels, was higher in patients with than without DPN (34.57 vs 13.79 μg/L, p = .003) and concentrations correlated with peripheral nerve impairment measures (r = 0.73, p < .01). Furthermore, serum bioactive IGF was lower in patients with than without DPN (0.8 vs 1.3 μg/L, p = .006) and correlated inversely to the severity of DPN (r = -0.67, p < .01)., Conclusions: In both CSF and serum, members of the IGF system correlated with measures of peripheral nerve impairment in patients with T2D. This supports a relationship between the IGF system and the development of DPN. Further studies are needed to clarify if these changes are causally linked to the pathogenesis of DPN., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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