RESUMO
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 (nâ¯=â¯9) or without (nâ¯=â¯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⯵g/L, pâ¯=â¯.003) and concentrations correlated with peripheral nerve impairment measures (râ¯=â¯0.73, pâ¯<â¯.01). Furthermore, serum bioactive IGF was lower in patients with than without DPN (0.8 vs 1.3⯵g/L, pâ¯=â¯.006) and correlated inversely to the severity of DPN (râ¯=â¯-0.67, pâ¯<â¯.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.