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

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.

Soluble CD163 levels are elevated in cerebrospinal fluid and serum in people with Type 2 diabetes mellitus and are associated with impaired peripheral nerve function.

AIMS: To measure soluble CD163 levels in the cerebrospinal fluid and serum of people with Type 2 diabetes, with and without polyneuropathy, and to relate the findings to peripheral nerve function. METHODS: A total of 22 people with Type 2 diabetes and 12 control subjects without diabetes were included in this case-control study. Participants with diabetes were divided into those with neuropathy (n = 8) and those without neuropathy (n = 14) based on clinical examination, vibratory perception thresholds and nerve conduction studies. Serum and cerebrospinal fluid soluble CD163 levels were analysed using an enzyme-linked immunosorbent assay. RESULTS: Soluble CD163 levels were significantly higher in the cerebrospinal fluid and serum of the participants with Type 2 diabetes compared with the control participants [cerebrospinal fluid: median (range) 107 (70-190) vs 84 (54-115) µg/l, P < 0.01 and serum: 2305 (920-7060) vs 1420 (780-2740) µg/l, P < 0.01). Cerebrospinal fluid soluble CD163 was positively related to impaired peripheral nerve conduction (nerve conduction study rank score: r = 0.42; P = 0.0497) and there was a trend for higher levels of soluble CD163 in the cerebrospinal fluid and serum in participants with neuropathy than in those without neuropathy [cerebrospinal fluid: median (range) 131 (86-173) vs 101 (70-190) µg/l, P = 0.08 and serum: 3725 (920-7060) vs 2220 (1130-4780), P = 0.06). CONCLUSIONS: Cerebrospinal fluid soluble CD163 level is associated with impaired peripheral nerve function. Higher levels of soluble CD163 in people with diabetic polyneuropathy suggest that inflammation plays a role in the development of neural impairment. The relationship between cerebrospinal fluid soluble CD163 level and peripheral nerve conduction indicates that soluble CD163 may be a potential biomarker for the severity of diabetic polyneuropathy.