PAPP-A activity is increased in cerebrospinal fluid from patients with diabetic polyneuropathy and correlates with peripheral nerve impairment

M. Kallestrup*, J. Frystyk, U. Espelund, R. Hjortebjerg, H. Tankisi, H. Andersen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalGrowth Hormone and IGF Research
Volume48-49
Pages (from-to)53-59
ISSN1096-6374
DOIs
Publication statusPublished - 1. Oct 2019

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Pregnancy-Associated Plasma Protein-A
Diabetic Neuropathies
Peripheral Nerves
Cerebrospinal Fluid
Insulin-Like Growth Factor Binding Protein 4
Type 2 Diabetes Mellitus
Serum
Insulin-Like Growth Factor II
Neuroprotective Agents
Insulin-Like Growth Factor I

Keywords

  • Diabetes
  • IGF
  • PAPP-A
  • Polyneuropathy

Cite this

@article{8e41ef3e07fa43ffa9c7ffb7efda032d,
title = "PAPP-A activity is increased in cerebrospinal fluid from patients with diabetic polyneuropathy and correlates with peripheral nerve impairment",
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.",
keywords = "Diabetes, IGF, PAPP-A, Polyneuropathy",
author = "M. Kallestrup and J. Frystyk and U. Espelund and R. Hjortebjerg and H. Tankisi and H. Andersen",
year = "2019",
month = "10",
day = "1",
doi = "10.1016/j.ghir.2019.10.001",
language = "English",
volume = "48-49",
pages = "53--59",
journal = "Growth Hormone & I G F Research",
issn = "1096-6374",
publisher = "Churchill Livingstone",

}

PAPP-A activity is increased in cerebrospinal fluid from patients with diabetic polyneuropathy and correlates with peripheral nerve impairment. / Kallestrup, M.; Frystyk, J.; Espelund, U.; Hjortebjerg, R.; Tankisi, H.; Andersen, H.

In: Growth Hormone and IGF Research, Vol. 48-49, 01.10.2019, p. 53-59.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - PAPP-A activity is increased in cerebrospinal fluid from patients with diabetic polyneuropathy and correlates with peripheral nerve impairment

AU - Kallestrup, M.

AU - Frystyk, J.

AU - Espelund, U.

AU - Hjortebjerg, R.

AU - Tankisi, H.

AU - Andersen, H.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - Diabetes

KW - IGF

KW - PAPP-A

KW - Polyneuropathy

U2 - 10.1016/j.ghir.2019.10.001

DO - 10.1016/j.ghir.2019.10.001

M3 - Journal article

C2 - 31670029

AN - SCOPUS:85073680819

VL - 48-49

SP - 53

EP - 59

JO - Growth Hormone & I G F Research

JF - Growth Hormone & I G F Research

SN - 1096-6374

ER -