{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T05:30:45Z","timestamp":1792474245311,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>To examine the three\u2010dimensional morphology and vascular endothelial growth factor (VEGF) expression of skin microvasculature in patients with type\u00a02 diabetes in relation to neuropathy, retinopathy and nephropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The present study enrolled 17 individuals with type\u00a02 diabetes and 16 without. Skin sections were double\u2010immunostained for type\u00a0IV collagen and VEGF\u2010A or protein gene product\u00a09.5. Projected images from confocal microscopy served to quantify the occupancy rate of subepidermal type\u00a0IV collagen\u2010immunoreactive microvascular basement membrane area (OR\u2010T4MBM), subepidermal VEGF\u2010A\u2010immunoreactive area and the VEGF\/T4MBM ratio, as well as the protein gene product\u00a09.5\u2010immunoreactive intraepidermal nerve fiber density. Reduced intraepidermal nerve fiber density was applied for the diagnosis of neuropathy, fundic ophthalmoscopy and fluorescein angiography for retinopathy, and microalbuminuria or persistent proteinuria for nephropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 12 patients with diabetes had neuropathy, 10 had retinopathy and eight had nephropathy. Regardless of the presence or absence of neuropathy, retinopathy or nephropathy, OR\u2010T4MBM was significantly increased in patients with diabetes compared with individuals without diabetes. In contrast, VEGF\/T4MBM ratio was significantly decreased in those with neuropathy and retinopathy, as well as in those with and without nephropathy, whereas a trend toward a decreased VEGF\/T4MBM ratio was seen in patients without retinopathy, as compared with individuals without diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study is the first report to show that cutaneous microangiopathy, as indicated by subepidermal microvascular proliferation and impaired VEGF expression, appears to occur before the development of overt clinical neuropathy, retinopathy or nephropathy in patients with type\u00a02 diabetes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13020","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T10:47:39Z","timestamp":1549363659000},"page":"1318-1331","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cutaneous microangiopathy in patients with type\u00a02 diabetes: Impaired vascular endothelial growth factor expression and its correlation with neuropathy, retinopathy and nephropathy"],"prefix":"10.1111","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4928-2443","authenticated-orcid":false,"given":"Kazuhiro","family":"Sugimoto","sequence":"first","affiliation":[{"name":"Diabetes Center Ohta Nishinouchi Hospital Koriyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Deguchi","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrine Medicine Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima 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