Cutaneous microangiopathy in patients with type 2 diabetes: Impaired vascular endothelial growth factor expression and its correlation with neuropathy, retinopathy and nephropathy. Issue 5 (2nd April 2019)

• Record Type: Journal Article
• Authors: Sugimoto, Kazuhiro; Murakami, Hiroshi; Deguchi, Takahisa; Arimura, Aiko; Daimon, Makoto; Suzuki, Susumu; Shimbo, Takuro; Yagihashi, Soroku
• Is Part Of: Journal of diabetes investigation. Volume 10:Issue 5(2019)
• Page Start: 1318
• Page End: 1331
• Publication Date: 2019-04-02
• Subjects: Microangiopathy -- Skin -- Vascular endothelial growth factor; Diabetes -- Periodicals; Diabetes -- Research -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462005
• DOI: 10.1111/jdi.13020
• Languages: English
• ISSNs: 2040-1116

Abstract

Abstract: Aims/Introduction: To examine the three‐dimensional morphology and vascular endothelial growth factor (VEGF) expression of skin microvasculature in patients with type 2 diabetes in relation to neuropathy, retinopathy and nephropathy. Materials and Methods: The present study enrolled 17 individuals with type 2 diabetes and 16 without. Skin sections were double‐immunostained for type IV collagen and VEGF‐A or protein gene product 9.5. Projected images from confocal microscopy served to quantify the occupancy rate of subepidermal type IV collagen‐immunoreactive microvascular basement membrane area (OR‐T4MBM), subepidermal VEGF‐A‐immunoreactive area and the VEGF/T4MBM ratio, as well as the protein gene product 9.5‐immunoreactive 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. Results: 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‐T4MBM 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. Conclusions: 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 2 diabetes. Abstract : Individuals with type 2 diabetes showed subepidermal microvascular proliferation associated with impaired vascular endothelial growth factor A expression compared with those without. These microvascular changes of the skin appeared before development of neuropathy, retinopathy or nephropathy. This is the first report to provide pathological evidence for the emergence of cutaneous microangiopathy with impaired vascular endothelial growth factor A expression in the absence of overt chronic microvascular complications in individuals with type 2 diabetes.