Correlation between the accumulation of skin glycosylation end products and the development of type 2 diabetic peripheral neuropathy

Abstract

Background The accumulation of advanced glycation end products (AGEs) occurring in skin tissues can be measured by AGE Reader. Here, we assessed the correlation between AGEs values and the development of type 2 diabetic peripheral neuropathy (DPN). Methods The basic clinical information of 560 patients with T2DM was collected through an electronic system. AGEs and diabetic complication risk score was measured by AGE Reader, a non-invasive optical signal detector. All of the participants were classified into 4 groups based on Dyck criteria: grade 0 (non-DPN group), grade 1 (early stage group), grade 2 (middle stage group) and grade 3 (advanced group). Pearson correlation analysis and Spearman correlation analysis were used to evaluate the correlation between AGEs and other indexes. The sensitivity and specificity of glycosylated products were evaluated by ROC curve. Results With the increase of DPN severity, the accumulative AGEs showed an increasing trend. Significant differences (P = 0.000) of AGEs were found among grades 0, 1, 2, and 3 of DPN, and significant differences (P = 0.000) of AGEs were found between grades 1 and 3. There were significant differences in DPN risk score between grades 0, 1, 2, and 3, between grades 1, 2, and 3, and between grades 2 and 3 (P < 0.01 or P < 0.05). AGEs were positively correlated with age, blood uric acid, disease course, systolic blood pressure, the risk scores of the four major complications of diabetes, renal function indicators (serum creatinine, Cystatin C, homocysteine, the ratio of urinary albumin and creatinine, urinary microalbumin, α-microglobulin, urinary transferrin, urinary immunoglobulin), inflammatory indicators (white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, C-reactive protein), and TCSS score. However, it was negatively correlated with BMI,fasting insulin, insulin 1–3 h postprandial, lymphocyte count, HOMA insulin resistance index and estimated glomerular filtration rate. The area under the AGEs cumulant and neuropathy risk score curve was 0.769 and 0.743, respectively. The confidence intervals were (71.2–82.6%) and (68.8–79.9%), respectively. The maximum Youden’s index of AGEs cumulant was 0.440, and the corresponding AGEs cumulant value was 77.65. The corresponding sensitivity and specificity were 0.731 and 0.709, respectively. Furthermore, the maximum Youden’s index of neuropathy risk score was 0.385, and the corresponding neuropathy risk score was 66.25. The corresponding sensitivity and the specificity were 0.676 and 0.709, respectively. Conclusion The cumulative amount of skin AGEs can be used as the diagnostic index and the prediction and evaluation index of DPN severity. Moreover, the diabetic peripheral neuropathy risk score can predict the risk of DPN in patients with T2DM.

Non-apoptotic programmed cell deaths in diabetic pulmonary dysfunction: the new side of advanced glycation end products

“…Abnormal glucose metabolism is closely related to DM, which involves complex organic reactions and the production of AGEs. These products have long been validated to be associated with various diabetic complications ( 29 , 30 ). Specifically, the produced AGEs further accumulate and cause various lesions and tissue damage ( 29 ).…”

“…These products have long been validated to be associated with various diabetic complications ( 29 , 30 ). Specifically, the produced AGEs further accumulate and cause various lesions and tissue damage ( 29 ). The lung is a possible target organ of AGEs due to its rich constitution of capillaries, collagen, and elastin fibers that are prone to deposit AGEs ( 31 , 32 ).…”

Relationship between neutrophil to lymphocyte ratio and diabetic peripheral neuropathy: a systematic review and meta-analysis

“…Initially, 486 records were identified through a combination of database searches and a manual review of article citations. Following the removal of duplicate entries and irrelevant records, a total of 15 studies [3,5,[16][17][18][19][20][21][22][23][24][25][26][27][28] were deemed suitable for inclusion in the systematic review and subsequent meta-analysis. These studies collectively encompassed 4575 patients diagnosed with type 2 diabetes, of which 1708 individuals developed DPN.…”

“…This meta-analysis included 15 studies, of whom seven were conducted in East Asia [3,17,18,20,[26][27][28], three in Egypt [5,16,22], three in India [21,23,25], and two in turkey [19,24]. Regarding the language used in the documents, they were all authored in the English language.…”

“…Thus, analyzing the relationship between NLR and diabetic neuropathy makes sense. Recent studies have reported significant elevated Neutrophil to lymphocyte ratio (NLR) levels in DPN patients compared to T2D patients without DPN [3,5,[16][17][18][19][20][21][22][23][24][25][26][27][28]. NLR has been used as a novel biomarker and diagnostic tool to test for chronic inflammation.…”