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Advanced Glycation Endproducts in Diabetic Foot Patient:Measurement/Positioning,Clinical Meaning and Speculated Inflammation Mechanisms

Author: HuXing
Tutor: HanChunMao
School: Zhejiang University
Course: Surgery
Keywords: Foot ulcers Diabetes Diabetic foot disease AGEs Detection index Diabetic rats Chronic complications glycation Neuropathy diabetic Ankle-brachial index Vascular disease Control blood sugar Immunohistochemical staining E -glycoside Diabetes Inflammation diabetes Skin tissue Wound
CLC: R587.2
Type: PhD thesis
Year: 2013
Downloads: 105
Quote: 0
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Abstract

AimAdvanced glycation endproducts (AGEs) were reported to play key role in the development of vascular/pripheral complications and chronic wound in diabetic patients. The characteristic fluorescence spectrum of AGEs at440nm, upon excitation at370nm, has been used to determine tissue AGE accumulation. In the year2004, Meerwaldt et al developed AGE reader based on this character, designed to non-invasively and rapidly measure skin auto-fluorescence and therefore AGE accumulation. Several following studies have shown that skin auto-fluorescence measured by AFR is strongly related to AGE accumulation in healthy subjects, diabetic and hemodialysis patients over a broad age range, and related with diabetic chronic complications. However, literatures about the quantitative relationship between skin AF value and AGEs accumulation within patient’s deep key tissues, and the screening and prognostic value of skin AF on foot complications in diabetic patient were insufficient. This study was designed to evaluate the association between skin AF, risk of diabetic foot complecations,and quantitative/positional distribution of major contents of AGEs in deep key tissues.Material and methodIn the first stage of clinical investigation (2009-02-2010-10),195Chinese diabetic subjects were examined. Skin AF and foot screening (according to the IWGDF guidline) were performed. After that, one-year follow up were performed for the patients who agreed. In the second stage (2010-09-2011-09),33patients who received lower limb amputation (including diabetic foot/arteriosclerosis obliterans/healthy traffic accident victims) were enrolled. After informed consent, the deep key tissue (artery, nerve and skin) were harvested during amputation surgery, and AGEs contents were quantitatively measured with HPLC-MS, and positioned by immuonohistochemistry staining. CRP/IL-6staining was also peformed to investigate the underlying inflammation mechanism.ResultsThe mean values of skin AF were:2.29±0.47for subjects without foot ulcers and2.80±0.69for those with foot ulcers, a significant difference(P<0.05). Skin AF was strongly correlated with age and duration of diabetes. After adjusting for these factors, multivariate logistic regression showed that Skin AF was independently associated with foot ulcerations. Glycosylated hemoglobin (Hb1Ac) levels was markedly declined, and high-density lipoprotein (HDL) cholesterol levels and VPT were significantly increased, after follow-up (P<0.05). Moreover, there were no significant changes in AF value and ABI during follow-up. HPLC-MS results indicated that skin AF and AGEs contents in key tissues of diabetic patients and ASO patients were higher than healthy patients, however, besides skin AF, other contents between three groups do not have significant difference. AGEs contents in different tissue were strongly correlated with each other; regression data showed that skin AF was strongly affected by AGEs contents in these tissues. IHC figures showed that different AGEs contents deposition in the same tissue were similar; in ASO and diabetic patients’tissue, AGEs deposition were accompanied with inflammation marker CRP and IL-6.ConclusionSkin AF had significant, direct association with diabetic foot ulcerations. It might provide useful information for risk screening of diabetic patients. Although diabetic patients followed strict traditional therapies controlled their blood glucose well, their foot screening results and AF level still worsed. Quantitatively, all AGEs levels were strongly correlated with each other; AF level were strongly affected by key tissue AGEs; AGEs contents depositions were accompanied with key tissue inflammation. In conclusion, measurement of skin AF could help evaluate diabetic foot risk; could assess the deep key tissue AGEs accumulation and deposition,and help assess the inflammation level within key tissues.

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