Hubungan Stres Oksidatif dan Akumulasi Advanced Glycation End-Products (AGEs) terhadap Komplikasi Mikrovaskular Diabetes: Systematic Review

Sri Octa Handayani, Khorina Fatin Bilqis, Shellya Puti Sudesty

Abstract

Abstrak

Komplikasi mikrovaskular diabetes melitus (DM), termasuk retinopati, nefropati, dan neuropati, merupakan penyebab utama morbiditas kronik pada penderita diabetes secara global. Stres oksidatif dan akumulasi advanced glycation end-products (AGEs) melalui jalur biokimia akibat hiperglikemia berperan penting dalam patogenesis komplikasi tersebut. Systematic review ini bertujuan menganalisis bukti ilmiah terkini terkait hubungan mekanistik antara stres oksidatif dan AGEs terhadap komplikasi mikrovaskular diabetes. Pencarian literatur dilakukan pada basis data PubMed, Scopus, ScienceDirect, dan MDPI dalam rentang tahun 2018–2026 menggunakan kata kunci terkontrol. Dari 1.847 artikel yang teridentifikasi, sebanyak 32 artikel memenuhi kriteria inklusi. Hasil kajian menunjukkan bahwa hiperglikemia kronik memicu peningkatan produksi spesies oksigen reaktif (ROS) melalui beberapa jalur utama, termasuk aktivasi NADPH oksidase, disfungsi rantai transport elektron mitokondria, dan jalur poliol. AGEs yang terbentuk berikatan dengan reseptor RAGE, mengaktivasi jalur NF-κB yang memperburuk inflamasi kronik, disfungsi endotel, serta perubahan struktur jaringan mikrovaskular. Sebanyak 28 dari 32 studi menunjukkan korelasi signifikan antara kadar AGEs dan derajat keparahan komplikasi. Intervensi yang menargetkan stres oksidatif dan jalur AGEs–RAGE menunjukkan potensi dalam memperlambat progresi komplikasi, menegaskan pentingnya pendekatan terapi berbasis mekanisme biokimia. Temuan ini juga menyoroti perlunya penelitian lanjutan berbasis uji klinis untuk mengevaluasi efektivitas intervensi antioksidan dan inhibitor AGEs dalam praktik klinik sehari-hari yang lebih luas populasi.

Kata Kunci: Advanced Glycation End-Products; Diabetes Melitus; Komplikasi Mikrovaskular; Stres Oksidatif; RAGE

Oxidative Stress and Accumulation of Advanced Glycation End-Products (AGEs) in Relation to Diabetic Microvascular Complications: A Systematic Review

Abstract

Microvascular complications of diabetes mellitus (DM), including retinopathy, nephropathy, and neuropathy, are major causes of chronic morbidity worldwide. Oxidative stress and the accumulation of advanced glycation end-products (AGEs), driven by hyperglycemia-related biochemical pathways, play key roles in the pathogenesis of these complications. This systematic review aims to analyze current scientific evidence regarding the mechanistic relationship between oxidative stress and AGEs in diabetic microvascular complications. Literature searches were conducted in PubMed, Scopus, ScienceDirect, and MDPI databases from 2018 to 2026 using controlled keywords. Of 1,847 identified articles, 32 met the inclusion criteria. The findings indicate that chronic hyperglycemia increases the production of reactive oxygen species (ROS) through several major pathways, including NADPH oxidase activation, mitochondrial electron transport chain dysfunction, and the polyol pathway. AGEs interact with their receptor (RAGE), activating the NF-κB pathway, which exacerbates chronic inflammation, endothelial dysfunction, and structural changes in microvascular tissues. A total of 28 out of 32 studies reported a significant correlation between AGE levels and the severity of complications. Interventions targeting oxidative stress and the AGEs–RAGE pathway show promise in slowing disease progression, highlighting the importance of mechanism-based therapeutic strategies. These findings also underscore the need for further clinical trials to evaluate the effectiveness of antioxidant and AGE-inhibiting therapies in broader clinical settings.

Keyword: Advanced Glycation End-Products; Diabetes Mellitus; Microvascular Complications; Oxidative Stress; RAGE