Maternal plasma protein profiles in response to oral 50-gram glucose load in mid-pregnancy: a pilot study

Accumulating evidence documents the initiation of diverse physiologic and biochemical response subsequent to an oral glucose load. However, significant gaps in knowledge exist in the understanding of consequences of glucose load during pregnancy, a state of insulin resistance. Using high dimensional protein arrays, we conducted a pilot proof-of-concept and feasibility study to investigate profiles of 120 plasma proteins in pre- and post- 50-gram oral glucose challenge samples. Participants (N = 10) were selected from among women enrolled in a pregnancy cohort. Differences in plasma protein concentrations between pre- and post-glucose load challenge samples were evaluated using Student's T-test (paired) and mean fold change comparisons. Multiple testing adjusted p-values (i.e., false discovery rate q values) were computed using Benjamini-Hochberg (BH) corrections. Plasma haptoglobulin, epidermal growth factor, hemoglobin, thrombospondin-1, and S100 protein concentrations were two to five fold higher in post-glucose load compared with pre-glucose load samples (all q-values <0.05). Among women aged >31 years (above median), post-load S100 protein was elevated 9.92-fold above pre-load concentrations, while it was elevated 4.10-fold among women aged <31 years (below median). Similarly, among women with post-load glucose concentrations <101mg/dl (below median), S100 was elevated 8.26-fold while it was elevated 3.28 fold among women with post-load glucose concentrations >101mg/dl (above median). Our study findings suggest that post-glucose load changes in plasma biomarkers represent a diverse set of cellular responses including receptor for advanced glycation end products (RAGE), inflammation, oxidative stress and adipogenesis, during mid-pregnancy. Future studies of larger populations and longer periods of follow-up are warranted.