Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases

Abstract

Gestational diabetes mellitus (GDM) is defined as the presence of high blood glucose levels with the onset, or detected for the first time during pregnancy, as a result of increased insulin resistance. GDM may be induced by dysregulation of pancreatic β-cell function and/or by alteration of secreted gestational hormones and peptides related with glucose homeostasis. It may affect one out of five pregnancies, leading to perinatal morbidity and adverse neonatal outcomes, and high risk of chronic metabolic and cardiovascular injuries in both mother and offspring. Currently, GDM diagnosis is based on evaluation of glucose homeostasis at late stages of pregnancy, but increased age and bodyweight , and familiar or previous occurrence of GDM, may conditionate this criteria. In addition, an earlier and more specific detection of GDM with associated metabolic and cardiovascular risk could improve GDM development and outcomes. In this sense, 1st-2nd trimester-released biomarkers found in maternal plasma including adipose tissue-derived factors such as adiponectin, visfatin, omentin-1, fatty acid-binding protein-4 and retinol binding-protein-4 have shown correlations with GDM development. Moreover, placenta-related factors such as sex hormone-binding globulin, afamin, fetuin-A, fibroblast growth factors-21/23, ficolin-3 and follistatin, or specific micro-RNAs may participate in GDM progression and be useful for its recognition. Finally, urine-excreted metabolites such as those related with serotonin system, non-polar amino-acids and ketone bodies, may complete a predictive or earlydiagnostic panel of biomarkers for GDM.

Preconception air pollution exposure and glucose tolerance in healthy pregnant women in a middle income country

“…The change in methylation patterns affects glucose concentration by altering peripheral insulin sensitivity during pregnancy [44,45]. Finally, changes in glucose homeostasis in healthy pregnant women might be due to the metabolic induction change in the hypothalamus [46,47]. Our results of the associations between tra c indicators as well as PMs exposures and glucose intolerance could be explained by one or all of the above mechanisms.…”

Prognostic utility of heart-type fatty acid-binding protein in patients with stable coronary artery disease and impaired glucose metabolism: a cohort study

“…Several studies have provided the evidence of myocardial damage in the early asymptomatic period among patients with IGM [12][13][14]. Additionally, some reports also indicated that diabetic patients could have heart damage in results of its complications like diabetic cardiomyopathy [15, 16]. Therefore, a further understanding of the cardiovascular risk associated with IGM will help to risk stratification and preventive strategies in pre-diabetic patients.…”

“…Besides, diabetic patients could have structural and/or functional modifications in the myocardial tissue such as lacking of insulin sensitivity and glucose assimilation. As a compensatory mechanism, H-FABP may increase when fatty acid uptake increases in heart to supply more adenosine triphosphate (ATP) [15,16]. On the other hand, there is evidence that abnormal of cardiac microvascular circulation caused by metabolic disorders might induce cardiomyocyte injury and impair cardiac function [32].…”

“…Additionally, besides the atherosclerosis of large arteries can be easily induced by impaired glucose metabolism (IGM), previous studies have also provided the evidence supporting the relation of IGM to myocardial injury and silent ischemia among patients with IGM [12][13][14]. Furthermore, previous studies have also revealed that diabetic patients might suffer from cardiac dysfunction due to its complications such as diabetic cardiomyopathy or diabetic vasculopathy [15,16].…”

Epicardial adipose tissue thickness as a potential predictor of gestational diabetes mellitus: a prospective cohort study

“…We propose that there are two mechanisms that might be responsible for the increased EAT thickness in GDM patients. Firstly, the higher levels of retinol-binding protein 4 and lower levels of adiponectin secreted by adipose tissue, including EAT, prior to 16 GW [25,26], could cause insulin resistance (IR), the main mechanisms underlying GDM [27]. Secondly, during the first-second trimester, EAT releases higher levels of pro-inflammatory adipokines (RBP4, hs-CRP, fatty acid-binding protein-4, leptin, and visfatin), and lower levels of anti-inflammatory adipokines (omentin-1 and adiponectin); these may participate in the chronic low-grade state of inflammation that has previously been confirmed to be associated with GDM [26,28].…”