Abstract
Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies (‘natural experiments’). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world. Recent studies have highlighted the importance of epigenetic regulation of gene expression as a possible major contributor to the link between the early-life famine exposure and T2D in adulthood. Findings from these studies suggest that prenatal exposure to the famine may result in induction of persistent epigenetic changes that have adaptive significance in postnatal development but can predispose to metabolic disorders including T2D at the late stages of life. In this review, quasi-experimental data on the developmental programming of T2D are summarized and recent research findings on changes in DNA methylation that mediate these effects are discussed.
Highlights
Type 2 diabetes (T2D) is one of most common chronic diseases, constituting a serious social and economic problem in modern societies, both developed and developing
Findings from the Dutch Hunger Winter Study on the developmental origin of type 2 diabetes (T2D) were confirmed in populations of other countries such as Austria, which has been subjected to three massive famine episodes during the 20th century
The excess risk of T2D was practically absent in those Austrian provinces that were less affected by hunger
Summary
Type 2 diabetes (T2D) is one of most common chronic diseases, constituting a serious social and economic problem in modern societies, both developed and developing. In malnourished conditions when the foetus exhibits poor growth in utero (commonly referred to as intrauterine growth restriction, IUGR), the foetal adaptation to undernutrition is realized by a variety of mechanisms responsible for the energy and glucose metabolism, such as enhanced peripheral insulin sensitivity for glucose utilization, increased hepatic glucose production, lowered insulin sensitivity for protein synthesis in muscle, and impaired pancreatic development [9] All these mechanisms provide obvious survival benefit for the IUGR foetuses by promoting both energy uptake and utilization, reducing the demand for amino acids and anabolic hormone production, and elevating glucose production to maintain glucose supply to vital organs, primarily the heart and brain.
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