Early life factors and type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and its aetiology involves a complex interplay between genetic, epigenetic, and environmental factors. In recent years, evidences from both human and animal experiments have correlated early life factors with programming diabetes risk in adult life. Fetal and neonatal period is crucial for organ development. Many maternal factors during pregnancy may increase the risk of diabetes of offsprings in later life, which include malnutrition, healthy (hyperglycemia and obesity), behavior (smoking, drinking, and junk food diet), hormone administration, and even stress. In neonates, catch-up growth, lactation, glucocorticoids administration, and stress have all been found to increase the risk of insulin resistance or T2DM. Unfavorable environments (socioeconomic situation and famine) or obesity also has long-term negative effects on children by causing increased susceptibility to T2DM in adults. We also address the potential mechanisms that may underlie the developmental programming of T2DM. Therefore, it might be possible to prevent or delay the risk for T2DM by improving pre- and/or postnatal factors.

Figure 1

Prenatal factors mentioned in recent years that might correlate with insulin resistance and/or T2DM. Data from human and animal studies have shown that malnutrition or overnutrition, metabolic disorders, exposure to hypoxia, some chemicals and hormones, and unhealthy lifestyle such as smoking and alcohol drinking during pregnancy might predispose detrimental long-term effects on offspring, leading to increased risk of insulin resistance or T2DM. TFA: transfatty acids; BPA: biophenol A.

Figure 2

The effect of low protein diet during pregnancy on postnatal β cell. Low protein diet during pregnancy may lead to increased oxidative stress, fibrosis, decreased HNF4a expression, defected mitochondriogenesis, and mitochondria dysfunction, and increased cell differentiation instead of proliferation was found in β cell of adult animal offspring, which may participate in β-cell dysfunction and consequently increase the incidence of T2DM.

Figure 3

Lactation and insulin resistance. It has been found that both early weaning and overfeeding by more milk intake may lead to insulin resistance in later life. Maternal stress, obesity, hyperglycemia, and even smoking during lactation might also cause reduced insulin sensitivity in the offspring, which suggest that the breast milk can be the “agent,” transferring altered levels of hormones, insulin, or fatty acid contents from maternal circulation to neonate.