Peripartum changes in the orexigenic CNS peptide neuropeptide-Y in gestational diabetics

Background: Development of relative insulin resistance during pregnancy is a normal physiologic change related to placental lactogen and pregnancy-associated elevated lipid concentrations. Several studies have investigated the role of tissue response, tyrosine kinase insulin receptor phosphorylation, and other cytokines that might contribute to development of such resistance. In this study, we specifically investigate the accompanying changes in concentrations of the orexigenic neurotransmitter neuropeptide Y (NPY) during pregnancy with the development and resolution of insulin resistance in gestational diabetics. Given that increased NPYergic activity is associated with increased eating behavior and body weight, we hypothesize levels of the central nervous system (CNS) peptide NPY will shift, along with other factors such as adiponectin, leptin, and ghrelin, in the development and resolution of gestational diabetes mellitus. Methods: Antepartum and postpartum plasma concentrations of NPY, leptin, ghrelin, tumor necrosis factor-alpha, glucose, and insulin were measured in gravid patients that were healthy (N=22), class A1 and A2 gestational diabetics (N=8), or type 2 diabetics (N=4). Homeostatic Model Assessment of insulin resistance was also calculated. Data was analyzed using a t-test and considered significant with p<0.05. Results: We demonstrate that during the third trimester, class A2 gestational diabetics display an elevated NPY concentration. This elevated NPY begins to resolve immediately postpartum, normalizing by the patient’s 6 week postpartum visit. The associated Homeostatic Model Assessment of insulin resistance index (HOMA) is consistent with these observations showing a concomitant elevation of HOMA intrapartum with improved insulin resistance within 24 hours postpartum. Discussion: Collectively, these results suggest a role for central nervous system involvement in the development of insulin resistance during gestational diabetes. Additionally, rising NPY levels during pregnancy may warrant routine patient surveillance for the development of occult insulin resistance and the obstetrical management of the same.