Associations of Arginine with Gestational Diabetes Mellitus in a Follow-Up Study

Abstract

In the reported study we applied the targeted metabolomic profiling employing high pressure liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC–MS/MS) to understand the pathophysiology of gestational diabetes mellitus (GDM), early identification of women who are at risk of developing GDM, and the differences in recovery postpartum between these women and normoglycemic women. We profiled the peripheral blood from patients during the second trimester of pregnancy and three months, and one year postpartum. In the GDM group Arg, Gln, His, Met, Phe and Ser were downregulated with statistical significance in comparison to normoglycemic (NGT) women. From the analysis of the association of all amino acid profiles of GDM and NGT women, several statistical models predicting diabetic status were formulated and compared with the literature, with the arginine-based model as the most promising of the screened ones (area under the curve (AUC) = 0.749). Our research results have shed light on the critical role of arginine in the development of GDM and may help in precisely distinguishing between GDM and NGT and earlier detection of GDM but also in predicting women with the increased type 2 diabetes mellitus (T2DM) risk.

Early markers of gestational diabetes mellitus

“…They play a role in cellular systems and are associated with vascular disease and cancer. Their concentrations, determined by high-performance liquid chromatography (HPLC) and HPLC-MS/MS, differ in pregnant women with GDM compared to healthy pregnant women; cysteine concentrations are higher in GDM, whereas methionine concentrations are lower, and the results for homocysteine concentrations are conflicting ( 18 , 40 , 41 ).…”

Comparison of Diagnostic Values of Maternal Arginine Concentration for Different Pregnancy Complications: A Systematic Review and Meta-Analysis

“…Despite the fact that the associations of several amino acids, such as branched-chain amino acids [ 60 ], methionine [ 61 ], and phenylalanine [ 45 ], with GDM risk have been widely described, the crucial role of arginine in the pathogenesis of GDM and its potential to be a good predictor in the earlier detection of this disease has attracted increasing attention. A recent systematic screening conducted in the GDM pregnancies with targeted metabonomics found that an arginine-based model showed the best prediction performance for diabetic status [ 13 ], which was further confirmed by a consensus multivariate analysis showing that urine arginine concentration in the first trimester has the highest accuracy in predicting GDM cases [ 62 ]. These findings have shed light on the critical role of arginine in the development of GDM.…”

“…The association between the maternal arginine concentration and GDM was reported in 14 case–control studies [ 13 , 19 , 20 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ], comprising 416 patients and 736 normal pregnancies. A meta-analysis indicated that the appearance of GDM was accompanied by a higher maternal arginine concentration (SMD: 0.46; 95% CI: 0.11, 0.81; I 2 = 82.3%, Figure 4 A).…”

“…On the other hand, there has been increasing attention paid to the role of arginine in promoting insulin secretion and improving insulin sensitivity [ 11 , 12 ]. A recent systematic screening of biomarkers for GDM according to the targeted metabolomic profiling revealed that an arginine-based model is most promising for predicting diabetic status [ 13 ]. The above findings suggest that plasma arginine concentration has the potential to be a predictor or biomarker for the development of several pregnancy complications.…”

Pathogenesis of Pregnancy-Related Complications 1.0 and 2.0

“…Burzynska-Pedziwiatr et al [ 20 ] performed the targeted metabolomic profiling in patients with GDM during gestation and postpartum period and revealed that the downregulation of arginine played a critical role in the development of GDM and in addition may also predict increased risk of type 2 diabetes mellitus.…”