Human Plasma Proteomics to Identify Predictive Biomarkers for the Onset of Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. The untreated GDM affects both the baby and mother during gestation as well as presents the risk of subsequent development of diabetes type II to mothers and babies. The standard tests such as fasting glucose and hemoglobin (HbA1c) for hyperglycemia in diabetes, are not recommended for the diagnosis/screening of GDM. Instead an oral glucose tolerance test (OGTT) is specifically recommended, which is time-consuming, invasive and not easily accessible to at-risk women. The aim of present study is, therefore, to determine the effect of GDM on plasma proteomics as variable plasma proteins can be secreted by the cells at the pathological sites and can serve as biomarker of the disease. For this purpose, blood samples were taken from 400 pregnant women at early second trimester (16-20 week of gestation) and then followed them for the development of GDM. Out of 400, 42 pregnant women developed GDM in third trimester (24-28 week of gestation) at which time blood samples were taken again. These Forty-two pregnant women were grouped as GDM I and GDM II, before and after the development of gestational diabetes, respectively. An equivalent number (n=42) of healthy pregnant women who did not develop GDM was randomly selected from first sampling during second trimester and referred to as control I. The same subjects were sampled again during 3 rd trimester to serve as control II. Blood samples from all the groups were subjected to 2D gel electrophoresis. Nineteen protein spots were differently expressed between GDM and control group, five of which were further identified by LC/MS as Transthyretin, Retinol ii binding protein A4 (RBP4), Haptoglobin alpha chain, Fibrinogen gamma chain and Apolipoprotein A1. Four proteins, Haptoglobin alpha chain, Fibrinogen gamma chain, Transthyretin, Retinol binding protein A4 (RBP4) were significantly higher in GDM I women as compared to normal pregnant women (Control I) in early second trimester. Moreover, the levels of these four proteins remained high in third trimester in GDM II as compared to control II. However, the level of apolipoprotein A1 was significantly lower in GDM I as compared to control I. Follow-up study of apolipoprotein A1 showed the same trend, its level remained low in third trimester in GDM II as compared to Control II. These five proteins can be used as predictive plasma biomarkers of GDM that might help in the identification of at-risk pregnancies, hence, providing the best opportunity for early treatment in order to prevent the onset or progression of the disease.