Immune dysfunction in developmental programming of type 2 diabetes mellitus

Intrauterine growth restriction (IUGR) is a common complication of pregnancy and increases the risk of the offspring developing type 2 diabetes mellitus (T2DM) later in life. Alterations in the immune system are implicated in the pathogenesis of IUGR-induced T2DM. The development of the fetal immune system is a delicate balance as it must remain tolerant of maternal antigens whilst also preparing for the post-birth environment. In addition, the fetal immune system is susceptible to an altered intrauterine milieu caused by maternal and placental inflammatory mediators or secondary to nutrient and oxygen deprivation. Pancreatic-resident macrophages populate the pancreas during fetal development, and their phenotype is dynamic through the neonatal period. Furthermore, macrophages in the islets are instrumental in islet development as they influence beta-cell proliferation and islet neogenesis. In addition, cytokines, derived from beta-cells and macrophages, are important to islet homeostasis in the fetus and adult and, when perturbed, can cause islet dysfunction. Several activated immune pathways have been identified in the islets of people who experienced IUGR, with alternations in the levels of IL-1 beta and IL-4 as well as changes in TGF beta signalling. Leptin levels are also altered. Immunomodulation has shown therapeutic benefit in T2DM and might be particularly useful in IUGR-induced T2DM.

Automated summary

Intrauterine growth restriction (IUGR) is a common complication of pregnancy that increases the risk of type 2 diabetes mellitus (T2DM) later in life for the offspring. The development and balance of the fetal immune system, the role of pancreatic-resident macrophages, and cytokines derived from beta-cells and macrophages play key roles in islet development and function. Therapeutic immunomodulation may be beneficial for treating T2DM, particularly in cases induced by IUGR.