The possible impact of advanced glycation end products on pregnancy outcome in women with diabetes mellitus type 1.

Diabetes mellitus (DM) is a group of metabolic disorders of carbohydrate metabolism in which glucose is underutilized, resulting in hyperglycemia. Reproductive impairment in poorly controlled diabetes mellitus type 1 (T1DM) results from a combined effect of insulin deficiency and hyperglycemia that disrupt the functioning of metabolic signals participating in the regulation of the reproductive system. Good metabolic control as a result of intensive insulin therapy has a great impact on the fertility and childbearing possibilities in the T1DM females. Advanced glycation end products (AGEs) are formed by nonenzymatic modification of proteins, lipids, and nucleic acids by glucose. The formation and accumulation of AGEs are known to progress at an accelerated rate in diabetes. AGEs either act on the pro-inflammatory cell surface receptors called RAGE or bind to the circulating anti-inflammatory sRAGE that prevents activation of cell-surface RAGE by AGEs and other proinflammatory ligands. Pregnancy has been found to induce a significant increase in RAGE protein levels in both myometrium and omental vasculature. This review will focus on the role of AGEs and RAGE in pregnancy complicated by DM type 1 as well as ways to reduce the rate of congenital malformations in the offspring of diabetic type 1 women.