Advanced Glycation End Products (AGEs) and Oxidative Stress are Increased in Individuals with Charcot
Effrosyni Blathra1, Ioanna A Anastasiou1,2, Ioanna Eleftheriadou1
1Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Abstract:
AimsCharcot neuro-osteoarthropathy (CN) is a rare but severe diabetes-related complication characterized by neuropathy, inflammation, and progressive bone and joint destruction. Advanced glycation end products (AGEs) may contribute to diabetes complications through protein glycation and activation of AGE-receptor for AGE (RAGE)-associated inflammatory and oxidative-stress pathways. This cross-sectional case-control study compared AGEs, soluble RAGE (sRAGE), and oxidative-stress markers among individuals with diabetes and CN (DM/CN), individuals with diabetes without CN (DM/noCN), and healthy controls.Research Design and MethodsThis was a case-control study on 15 people with active or chronic DM/CN, 33 individuals with DM/noCN and 26 age-matched healthy controls. Subjects underwent thorough clinical evaluation; AGEs were measured in lens via autofluorescence and in serum samples. Serum levels of sRAGE and reactive oxygen markers were also determined.ResultsParticipants with DM/CN had higher lens and serum AGE levels and oxidative stress than those with DM/noCN. Both diabetes groups had higher AGEs, sRAGE, and oxidative-stress levels than healthy controls. AGEs, sRAGE, and oxidative stress were associated with peripheral neuropathy, and CN was independently associated with higher circulating AGE concentrations after adjustment for HbA1c and BMI.ConclusionsIndividuals with diabetes and CN exhibit increased AGE accumulation and oxidative stress compared with individuals with diabetes without CN. These findings support a potential role for AGE-associated inflammatory and oxidative-stress pathways in the pathophysiology of CN. Larger prospective studies are needed to determine the clinical and prognostic value of AGEs, sRAGE, and oxidative-stress markers in CN.
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