Diabetes Mellitusta Metabolik Hafızanın Rolü

Yıl 2022, Cilt: 11 Sayı: 3, 1257 - 1264, 27.09.2022

Hürmet Küçükkatırcı , Zeynep Caferoğlu , Nihal Hatipoğlu

https://doi.org/10.37989/gumussagbil.975209

Öz

Diabetes Mellitus, morbidite ve mortalitenin artmasına neden olan, önemli bir halk sağlığı problemidir. Diyabete spesifik hiperglisemi, çeşitli ilaçlar veya ekzojen insülin uygulaması yolu ile klinik olarak kontrol edilmeye çalışılmaktadır fakat gerek tedavi gerekse takipteki gelişmelere rağmen diyabetli birçok hastada vasküler komplikasyon gelişme durumunun önüne hâlen tam anlamı ile geçilememiştir. Çeşitli epidemiyolojik ve geniş kapsamlı çalışmalar, erken ve yoğun hiperglisemi kontrolünün diyabet ile ilişkili komplikasyon riskini azalttığını göstermiştir ve ilgili çalışmaların tamamı, erken glisemik kontrolün gerekliliğini vurgulamaktadır. Erken dönemdeki hiperglisemi kontrolü yakın zamanda “metabolik hafıza” olarak tanımlanmıştır. Mitokondri ve endotel hücrelerinde serbest oksijen radikallerinin aşırı üretimi, mitokondriyal deoksiribonükleik asit (DNA) hasarı, protein kinaz C aktivasyonu, poliol ve hekzoamin yolağı aktivasyonu, ileri glikozilasyon son ürünlerinin ve reseptörlerinin artışı gibi birçok mekanizma metabolik hafıza patogenezinde önemli rol oynamaktadır. Bu mekanizmalar, gen ekspresyonunu kalıcı olarak indükleyerek epigenetik değişikliklere neden olmaktadır. Metabolik hafıza; histon modifikasyonu, DNA metilasyonu ve mikro-ribonükleik asit (RNA) ile ilişkili mekanizmalar gibi epigenetik değişiklikler ile gerçekleşir. Klinik açıdan değerlendirildiğinde ise metabolik hafıza teorisi, metabolik kontrolü en kısa sürede sağlamak için erken ve yoğun tedavi rejiminin gerekliliğini vurgulamaktadır. Uzun süreli diyabetik komplikasyonları en aza indirgemek amacıyla erken ve yoğun hiperglisemi kontrolünün yanı sıra, reaktif oksijen türleri ve glikozilasyonu azaltabilen terapötik ajanlardan ve/veya epigenetik tedaviden de yararlanılabilir. Bu derlemede; metabolik hafıza teorisine, metabolik hafızanın tanımı ve patogenezine, epigenetik mekanizmalara ve terapötik yaklaşımlara yer verilmiştir.

Anahtar Kelimeler

Diabetes Mellitus, Diyabetik komplikasyonlar, Epigenetik, Metabolik hafıza

The Role of Metabolic Memory in Diabetes Mellitus

Öz

Diabetes Mellitus, is an important public health problem that causes increased morbidity and mortality. Hyperglycemia, specific sign of diabetes; tried to be controlled clinically exogenous insulin administration or various drugs however, despite developments treatment and follow-up, development of vascular complications hasn’t been completely prevented in many diabetic patients. Several epidemiological, comprehensive studies have shown that early-intensive control of hyperglycemia reduces risk of diabetes-related complications. These studies emphasize need for early glycemic control. Early control of hyperglycemia has recently been defined as "metabolic memory". Different mechanisms, such as overproduction of free oxygen radicals in mitochondria and endothelial cells, mitochondrial deoxyribonucleic acid (DNA) damage, protein kinase C activation, polyol-hexosamine pathway activation, increased production of advanced glycation end products (AGEs) and AGE receptor overexpression play an important role in metabolic memory pathogenesis. These mechanisms induce gene expression permanently and causing epigenetic changes. Metabolic memory occurs through epigenetic changes such as histone modification, DNA methylation and micro-ribonucleic acid (RNA)-related mechanisms. From a clinical point of view, metabolic memory theory emphasizes necessity of an early-intensive treatment regimen to achieve metabolic control as soon as possible. In addition to early intensive hyperglycemia control, therapeutic agents or epigenetic therapy can reduce reactive oxygen species and glycosylation also be used in order to minimize long-term diabetic complications. In this review, metabolic memory theory, definition and pathogenesis of metabolic memory, epigenetic mechanisms and therapeutic approaches are evaluated.

Anahtar Kelimeler

Diabetes Mellitus, Diabetic complications, Epigenetics, Metabolic memory

Kaynakça

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