The available data are contradictory. Studies using biochemical techniques to measure GAG content in the intima of the aorta of patients with type 2 diabetes mellitus have observed a reduction of HS , suggesting that the abnormalities in HS metabolism are not necessarily restricted to the kidney, although there has not been any examination of any possible relationship with coexistent diabetic nephropathy. The staining of skin basement membranes by JM-403, the monoclonal antibody that reacts with HS-GAG side chains, was significantly reduced in type 1 diabetic patients with diabetic nephropathy, as compared to patients with long-standing diabetes without nephropathy . However, similar findings were observed also in patients with ESRD of non-
diabetic origin . The more recently discovered anomalies in HS-PG seem to be restricted, at least in type 2 diabetes, to the kidney taking into account the observation of the tissue distribution of agrin , of the finding that increased microvascular permeability in human diabetic retinopathy is not associated with changes in expression of agrin and perlecan , and the HS disaccharide unit IdUA(2S)a1^4GlcN(3S) . Moreover, findings on the expression and regulation of N-deacetylase/N-sulfotransferase enzymes  at least demonstrate that alterations in HS-PG metabolism in type 2 diabetic patients with nephropathy are not generalized.
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