Advanced glycation end products via skin autofluorescence as potential marker of carotid atherosclerosis in patients with type 2 diabetes.

BACKGROUND AND AIMS: Advanced glycation end products (AGEs) are reported to be correlated with diabetic vascular complications. This study aimed to investigate the association between AGEs and carotid atherosclerosis (CAS) as a surrogate marker of cardiovascular disease (CVD). METHODS AND RESULTS: A total of 1006 patients with type 2 diabetes were included. CAS was defined as the presence of carotid arterial atherosclerotic plaque in any of bilateral carotid artery segments measured by ultrasonography. AGEs were measured by the noninvasive skin autofluorescence method. AGEage index was calculated as AGEs × age/100. Patients with CAS showed a significantly higher AGEage (P < 0.01), and the prevalence of CAS increased with ascending AGEage levels (P for trend < 0.001). Logistic regression analysis revealed that AGEage was significantly positively associated with odds of CAS, and the odds ratios of the presence of CAS across quartiles of AGEage were 1.00, 3.00 [95% confidence interval (CI) 1.90-4.74], 4.04 (95%CI 2.50-6.53) and 4.99 (95%CI 2.97-8.40) for the multivariable-adjusted model (P for trend <0.001), respectively. In the fully adjusted model, each 5.0 increase in AGEage was associated with a 0.019 mm increment in carotid intima-media thickness. Furthermore, AGEage presented an acceptable predictive value for CAS, with an optimal cutoff point of 43.2, and the sensitivity, specificity and area under the curve (AUC) were 74.5% (95%CI 70.7-78.1%), 61.9% (95%CI 57.2-66.4%) and 0.735 (0.706-0.762), respectively. CONCLUSION: AGEage, the noninvasive measurement of AGEs combined with age is a promising approach for triaging patients at high risk of CVDs.

Association of Advanced Glycation End Products With Lower-Extremity Atherosclerotic Disease in Type 2 Diabetes Mellitus.

Aims: Advanced glycation end products (AGEs) were reported to be correlated with the development of diabetes, as well as diabetic vascular complications. Therefore, this study aimed at investigating the association between AGEs and lower-extremity atherosclerotic disease (LEAD). Methods: A total of 1,013 type 2 diabetes patients were enrolled. LEAD was measured through color Doppler ultrasonography. The non-invasive skin autofluorescence method was performed for AGEs measurement. Considering that age plays an important role in both AGEs and LEAD, age-combined AGEs, i.e., AGEage index (define as AGEs × age/100) was used for related analysis. Results: The overall prevalence of LEAD was 48.9% (495/1,013). Patients with LEAD showed a significantly higher AGEage (p < 0.001), and the prevalence of LEAD increased with ascending AGEage levels (p for trend < 0.001). Logistic regression analysis revealed that AGEage was significantly positively associated with risk of LEAD, and the odds ratios of presence of LEAD across quartiles of AGEage were 1.00, 1.72 [95% confidence interval (CI) = 1.14-2.61], 2.72 (95% CI = 1.76-4.22), 4.29 (95% CI = 2.69-6.85) for multivariable-adjusted model (both p for trend < 0.001), respectively. The results were similar among patients of different sexes, body mass index, and with or without diabetes family history. Further, AGEage presented a better predictive value for LEAD than glycated hemoglobin A1c (HbA1c), with its sensitivity, specificity, and area under the curve of 75.5% (95% CI = 71.6-79.2%), 59.3% (95% CI = 54.9-63.6%), and 0.731 (0.703-0.758), respectively. Conclusion: AGEage, the non-invasive measured skin AGEs combined with age, seems to be a more promising approach than HbA1c in identifying patient at high risk of LEAD.

Association of advanced glycation end products with diabetic retinopathy in type 2 diabetes mellitus.

AIMS: Advanced glycation end products (AGEs) were reported to be associated with diabetes development and diabetes related complications when accumulated in high levels. This study investigated the association between AGEs and diabetic retinopathy (DR). METHODS: A total of 1,471 patients with type 2 diabetes were enrolled. Fundus radiography was used for DR measurement. AGEs were detected through non-invasive skin autofluorescence method. RESULTS: Patients with more advanced DR showed a much higher AGEs, and the prevalence of DR (based on the severity) increase with ascending AGEs quartiles (all P for trend < 0.001). The multivariable-adjusted odds ratios of any DR across AGEs quartiles were 1.00, 1.69 (95% confidence interval [CI] 1.16-2.47), 1.58 (95%CI 1.06-2.37) and 1.60 (95%CI 1.05-2.44) (P for trend = 0.044), respectively. Similar results were found in vision-threatening DR (VTDR) subgroup (P for trend = 0.009). When AGEs was considered as a continuous variable by using restricted cubic splines, a graded positive association of AGEs with the odds of any presence of DR was observed (P for trend < 0.001). Further, we found that AGEs presented the similar predictive value for any DR with glycated hemoglobin A1c (HbA1c). When it comes to VTDR, AGEs showed a significantly higher efficacy in early screening than HbA1c (P = 0.002). With a cut-off point of 77.1, the sensitivity, specificity and area under the curve of AGEs were 90.0% (95%CI 76.3-97.2%), 49.4% (95%CI 46.8-52.0%), and 0.728 (95%CI 0.704-0.750), respectively. CONCLUSION: Non-invasive measured skin AGEs, associated with the prevalence of all stages of DR, might be a more suitable indicator than HbA1c for mimicking the poor prognosis of hyperglycemia.