ABSTRACT
Objective:To investigate the effects of gestational diabetes mellitus (GDM) on neonatal metabolites.Methods:This retrospective cohort study recruited 580 singleton newborns who were born to women with GDM from January 2018 to December 2018 in Foshan Maternal and Child Health Care Hospital as the GDM group. Another 580 counterparts born to non-GDM singleton mothers with matching age were selected as the non-GDM group with an allocation ratio of 1 to 1. Neonatal genetic metabolic disease screening was performed within 3-7 days after birth. Two independent sample t-test, and multiple linear regression model were used for statistical analysis. Results:There were significant differences in seven amino acids and 10 fatty acids levels between the GDM and non-GDM group. The serum levels of six amino acids and eight fatty acids were increased in the GDM group, while the levels of piperamide [(140.79±32.60) vs (150.26±35.46) μmol/L, t=－4.733, P<0.001], palmitoyl carnitine [(2.59±0.81) vs (2.73±0.82) μmol/L, t=－2.940, P=0.003], and carbamate [(0.066±0.022) vs (0.069±0.022) μmol/L, t=－1.937, P=0.042] were decreased compared with the non-GDM group. After adjusting for maternal gravidity, parity, neonatal birth weight, and gender, multivariate linear regression analysis showed that GDM was positively correlated with three amino acids levels, which were cysteine ( ?=0.012), homocysteine ( ?=0.263) and leucine ( ?=4.225); and was negatively correlated with glycine ( ?=－6.271) and piperamide level ( ?=－9.885). With regard to the fatty acids, GDM was positively correlated with the neonatal propionyl carnitine ( ?=0.214), butyryl carnitine ( ?=0.014), 3-hydroxybutyryl carnitine ( ?=0.006), isovaleryl carnitine ( ?=0.009), 3-hydroxyisovaleryl carnitine ( ?=0.024), hexadecanoyl carnitine ( ?=0.001), decadienoyl carnitine ( ?=0.045), octadecadienyl carnitine level ( ?=0.128), but was negatively correlated with palmitoyl carnitine ( ?=－0.119), and carbamate ( ?=－0.002) (all P<0.05). Conclusions:Correlations between maternal GDM and the levels of amino acids and fatty acids in neonates was noted in this study, suggesting that maternal GDM may affect the metabolism of amino acids and fatty acids in offspring at early stage of life.
ABSTRACT
Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I (DHP-I), was developed. In present study, the potential roles of renal organic anion transporters (OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated and in rabbits. Our results indicated that imipenem and cilastatin were substrates of hOAT1 and hOAT3. Cilastatin inhibited hOAT1/3-mediated transport of imipenem with IC values comparable to the clinical concentration, suggesting the potential to cause a clinical drug-drug interaction (DDI). Moreover, imipenem exhibited hOAT1/3-dependent cytotoxicity, which was alleviated by cilastatin and probenecid. Furthermore, cilastatin and probenecid ameliorated imipenem-induced rabbit acute kidney injury, and reduced the renal secretion of imipenem. Cilastatin and probenecid inhibited intracellular accumulation of imipenem and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells. Renal OATs, besides DHP-I, was also the target of interaction between imipenem and cilastatin, and contributed to the nephrotoxicity of imipenem. This therefore gives in part the explanation about the mechanism by which cilastatin protected against imipenem-induced nephrotoxicity. Thus, OATs can potentially be used as a therapeutic target to avoid the renal adverse reaction of imipenem in clinic.