The Impact of Malnutrition in Early Life on the Risk of Development of Type 2 Diabetes Mellitus

Yıl 2021, Cilt: 5 Sayı: 3, 368 - 374, 30.12.2021

Ülger Kaçar Mutlutürk Zeynep Caferoğlu Nihal Hatipoğlu

https://doi.org/10.25048/tudod.929258

Öz

Type 2 diabetes mellitus (T2DM) is a multifactorial disease that has a complex interaction of genetic, epigenetic and environmental
factors. Type 2 diabetes mellitus has significant effects on global health and economic burden, moreover the increase of its worldwide
incidence suggests that this disease may be affected not only by genetic or adult environmental conditions, but also by adverse conditions
in early life. In recent years, evidence from both animal experiments and natural experiments such as famine show that insufficient
nutrient intake in early life has been associated with the risk of T2DM in adult life. There is evidence that growth restriction caused
by intrauterine inadequate nutrient intake may impair fetal development, thus causing fetal adipose tissue and pancreatic beta cell
dysfunction. As a result, continuous adaptive changes, including reduced capacity for insulin secretion and insulin resistance; may
occur. These changes can lead to an improved ability to store fat, so the individual may be prone to the development of T2DM in later
life. In this regard, epigenetic mechanisms such as DNA methylation, histone modification and microRNA interactions play a key role.
In this review, basic mechanisms and research findings showing the role of developmental epigenetic variation in T2DM pathogenesis
are summarized.

Anahtar Kelimeler

Type 2 diabetes mellitus, Malnutrition, Famine, Epigenetic

Erken Yaşamda Yetersiz Beslenmenin Tip 2 Diyabetes Mellitus Gelişim Riskine Etkisi

Öz

Tip 2 diyabetes mellitus (T2DM) genetik, epigenetik ve çevresel faktörlerin karmaşık bir etkileşimi olan çok faktörlü bir hastalıktır. Tip 2
diyabetes mellitusun küresel sağlık ve ekonomik yük üzerinde önemli etkileri vardır. Biriken kanıtlar doğrultusunda bu hastalığın dünya
genelinde insidansındaki artışı sadece genetik veya yetişkin çevresel koşullardan değil aynı zamanda yaşamın erken dönemlerindeki
olumsuz durumlardan etkilenebileceğini düşündürmektedir. Son yıllarda, hem hayvan deneyleri hem de kıtlık gibi doğal durumlardan
elde edilen kanıtlar, erken yaşamda yetersiz besin alımını, yetişkin yaşamındaki T2DM riski ile ilişkilendirmiştir. İntrauterin yetersiz
besin alımı ile ortaya çıkan büyüme kısıtlamasının, fetal gelişimi bozabileceği ve böylece fetal yağ dokusu ve pankreatik beta hücre
disfonksiyonuna neden olabileceğine dair kanıtlar vardır. Bunun sonucunda insülin sekresyon kapasitesinde azalma ve insülin direnci
de dâhil olmak üzere, glukoz-insülin metabolizmasında kalıcı adaptif değişiklikler meydana gelebilir. Bu değişiklikler artan bir yağ
depolama kabiliyetine yol açabilir, böylece birey daha sonraki yaşamda T2DM gelişimine yatkın hâle gelebilir. Bu ilişkide DNA
metilasyonu, histon modifikasyonu ve mikroRNA etkileşimleri gibi epigenetik mekanizmalar temel rol oynamaktadır. Bu derlemede,
T2DM patogenezinde gelişimsel epigenetik varyasyonun rolünü gösteren temel mekanizmalar ve araştırma bulguları özetlenmiştir

Anahtar Kelimeler

tip 2 diyabet, yetersiz beslenme, kıtlık, epigenetik

Kaynakça

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