A Longitudinal Cohort Study Of Gestational Diabetes Mellitus Urinary Metabolomics And Adiponectin +45 T/G Polymorphism Systematic Review

Background: Gestational diabetes mellitus(GDM) is a pathological state of glucose intolerance that could adversely affect pregnancy outcome and increases the risk of developing maternal type 2 diabetes. The underlying mechanism for this state is not fully understood. Adiponectin(ADIPOQ), involving in regulating glucose levels and fatty acid oxidation, plays key roles in the metabolic derangements, such as gestational diabetes mellitus(GDM). Previously, several studies have been conducted to assess the association between ADIPOQ +45 T/G polymorphism and risk of GDM. The results, however, are inconclusive. In this study, firstly, urine from a longitudinal cohort of normal pregnancies and pregnancies complicated by gestational diabetes was investigated. Secondly, we aimed to evaluate the effect of the polymorphism on the risk of GDM using a meta-analysis.Methods:1. Urinary metabolic profiling of GDM analysis. Normal pregnancies and pregnancies complicated by gestational diabetes(19-35 years old) were chosen in first affiliated Hospital of Chongqing Medical University and urinary samples were collected. The analytical challenges in urinary metabolic profiling were first investigated, with an aim to improve the precision of the measurements and to eliminate the heteroscedastic noise. Paired statistical approaches were used to eliminate individual variability. Unsupervised and multilevel supervised models successfully discriminated the GDM subjects from the controls.2. After databases searching, 8 records were identified. Pooled odds ratios(OR) with their corresponding 95% confidenceintervals(CI) were used to evaluate the association between ADIPOQ +45 T/G polymorphism and risk of GDM.Results: 1. among selected 61 pregnancies, 34 pregnancies entered into normal glucose tolerance group(control group) and 27 entered into lower glucose tolerance group(treated group). Because the urinary consisted amount of biological molecules, the urinary sample were greatly diluted. LC-MS analysis suggested that 40.7%GDM pregnancies had urinary concentration while in control group, only 19.4% had this state。A relative deficiency of Vitamin B5 was a cause of GDM. This suppressed the synthesis of acetyl-Co A and so the b-oxidation of fatty acids. Consumption of processed foods might contribute to the deficiency of Vitamin B5. The deficiency of Vitamin B5 shifted the tryptophan metabolism toward the kynurenine pathway and so the production of acetyl-Co A, consequently, the citric acid cycle was maintained. An effect of this shift in tryptophan catabolism led to an increased disposal of nitrogenous wastes(uric acid and creatinine).2. No significant association was observed between the ADIPOQ +45 T/G polymorphism and the risk of GDM(heterozygote comparison: OR=1.15, 95%CI, 0.70-1.89; homozygote comparison: OR=1.21, 95%CI, 0.48-3.03; dominant model: OR=0.86, 95%CI, 0.50-1.48, recessive model: OR=1.21, 95%CI, 0.62-2.33, and allele comparison: OR=1.17, 95%CI, 0.79-1.76, respectively). Apparent heterogeneity was detected. However, no evidence of publication bias was found.Conclusions: A relative deficiency of Vitamin B5 and further increases in steroid hormone level in the GDM subjects compared to the controls at the late pregnancy were strongly associated with GDM. This meta-analysis provides evidence that the ADIPOQ +45 T/G polymorphism was not related to the risk of GDM. Further multicentre, prospective studies with larger sample size are valuable to confirm the result.