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

Abstract

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.

Keywords

• Type 2 diabetes mellitus
• Malnutrition
• Famine
• Epigenetic

Erken Yaşamda Yetersiz Beslenmenin Tip 2 Diyabetes Mellitus Gelişim Riskine Etkisi

Abstract

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

Keywords

• tip 2 diyabet
• yetersiz beslenme
• kıtlık
• epigenetik

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