Elevated Acetoacetate and Monocyte Chemotactic Protein-1 Levels in Cord Blood of Infants of Diabetic Mothers

Abstract

Background: Infants of diabetic mothers (IDMs) are at increased risk for metabolic complications. Type 1 and some type 2 diabetic patients have elevated levels of the ketone bodies acetoacetate (AA) and β-hydroxybutyrate (BHB). Objective: The aim of this study was to examine how hyperketonemia in diabetic mothers affects markers of inflammation and oxidative stress in their offspring. Methods: Blood was obtained from 23 diabetic mothers and 13 healthy mothers and their infants’ umbilical cords at delivery. Interleukin-8, monocyte chemotactic protein-1 (MCP-1) and protein carbonyl (protein oxidation) levels were determined by ELISA. U937 human monocyte cell culture was used to examine the effect of AA and BHB on secretion of MCP-1. Results: There was a significant increase in the levels of AA in cord blood of IDMs compared with cord blood of infants of healthy mothers. A significant increase in the levels of protein oxidation (p < 0.05) and MCP-1 levels (p < 0.05) was observed in the cord blood of IDMs. The level of MCP-1 correlated significantly (r = 0.51, p = 0.01) with the concentration of AA in the IDMs. In further experiments with cultured monocytes treated with exogenous AA (0–4 mM), a significant increase in MCP-1 secretion was observed in AA- but not BHB-treated monocytes. Conclusion: Blood levels of AA and MCP-1 are elevated in IDMs, which may contribute to the development of the metabolic complications seen in IDMs.