Adams Jeremy N, Martelle Susan E, Raffield Laura M, Freedman Barry I, Langefeld Carl D, Hsu Fang-Chi, Maldjian Joseph A, Williamson Jeff D, Hugenschmidt Christina E, Carr J Jeffery, Cox Amanda J, Bowden Donald W
Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston - Salem, NC, USA.
Department of Internal Medicine, Nephrology, Wake Forest School of Medicine, Winston - Salem, NC, USA.
J Diabetes Complications. 2016 Mar;30(2):262-8. doi: 10.1016/j.jdiacomp.2015.11.025. Epub 2015 Nov 30.
Human studies of links between advanced glycation end-products (AGEs) and disease phenotypes are less common than studies of animal and cell models. Here, we examined the association of total AGEs with diabetes risk factors in a predominately type 2 diabetes (T2D) affected cohort.
AGEs were measured using an enzyme linked immunosorbant assay in 816 individuals from the DHS Mind Study (n=709 T2D affected), and association analyses were completed.
Total AGEs were associated with estimated glomerular filtration rate (p=0.0054; β=-0.1291) and coronary artery calcification (p=0.0352; β=1.1489) in the entire cohort. No significant associations were observed when individuals with T2D were analyzed separately. In individuals without T2D, increased circulating AGEs were associated with increased BMI (p=0.02, β=0.138), low density lipoproteins (p=0.046, β=17.07) and triglycerides (p=0.0004, β=0.125), and decreased carotid artery calcification (p=0.0004, β=-1.2632) and estimated glomerular filtration rate (p=0.0018, β=-0.1405). Strong trends were also observed for an association between AGEs and poorer cognitive performance on the digit symbol substitution test (p=0.046, β=-6.64) and decreased grey matter volume (p=0.037, β=-14.87).
AGEs may play an important role in a number of phenotypes and diseases, although not necessarily in interindividual variation in people with T2D. Further evaluation of specific AGE molecules may shed more light on these relationships.
与动物和细胞模型研究相比，关于晚期糖基化终产物（AGEs）与疾病表型之间联系的人体研究较少见。在此，我们在一个主要受2型糖尿病（T2D）影响的队列中，研究了总AGEs与糖尿病风险因素之间的关联。
使用酶联免疫吸附测定法对来自DHS Mind研究的816名个体（n = 709名受T2D影响）进行AGEs测量，并完成关联分析。
在整个队列中，总AGEs与估计肾小球滤过率（p = 0.0054；β = -0.1291）和冠状动脉钙化（p = 0.0352；β = 1.1489）相关。单独分析T2D个体时未观察到显著关联。在无T2D的个体中，循环AGEs升高与体重指数增加（p = 0.02，β = 0.138）、低密度脂蛋白升高（p = 0.046，β = 17.07）和甘油三酯升高（p = 0.0004，β = 0.125）相关，与颈动脉钙化降低（p = 0.0004，β = -1.2632）和估计肾小球滤过率降低（p = 0.0018，β = -0.1405）相关。在数字符号替换测试中，AGEs与较差的认知表现（p = 0.046，β = -6.64）以及灰质体积减少（p = 0.037，β = -14.87）之间的关联也观察到了强烈趋势。
AGEs可能在多种表型和疾病中起重要作用，尽管不一定在T2D患者的个体间差异中起作用。对特定AGE分子的进一步评估可能会更清楚地揭示这些关系。
