Low Adiponectin Concentration in Pregnancy Predicts Postpartum Beta-Cell Dysfunction: Pathophysiologic Implications for the Link between Gestational Diabetes (GDM) and Future Type 2 Diabetes (T2DM)
Abstract Number: 1007-P
Authors: RAVI RETNAKARAN, YING QI, PHILIP W. CONNELLY, MATHEW SERMER, ANTHONY J. HANLEY, BERNARD ZINMAN
Institutions: Toronto, ON, Canada
Results: The postpartum period following GDM is characterized by subtle metabolic defects, including underlying beta-cell dysfunction that is believed to mediate the increased future risk of T2DM in this patient population. Recently, low circulating levels of the adipokine adiponectin and increased levels of the inflammatory marker C-reactive protein (CRP) have emerged as novel risk factors for T2DM, although their relevance to GDM and subsequent T2DM has not been studied. Since hypoadiponectinemia and subclinical inflammation during pregnancy are indeed features of GDM, we hypothesized that adiponectin and CRP in pregnancy may relate to the pathophysiology linking GDM with T2DM in the postpartum. In this context, we performed metabolic characterization, including OGTT, in 487 women in late 2nd/early 3rd trimester and again at 3-months postpartum. This study population reflected the full spectrum of glucose tolerance in pregnancy, ranging from normal glucose tolerance (n=259) to gestational impaired glucose tolerance (n=91) to GDM (n=137). As expected, adiponectin (r=0.40, p<0.0001) and CRP (r=-0.28, p<0.0001) in pregnancy were both associated with postpartum insulin sensitivity (ISOGTT). Intriguingly, adiponectin was also related to postpartum beta-cell function (insulinogenic index/HOMA-IR) (r=0.16, p=0.0009). Indeed, on multiple linear regression analyses, adiponectin in pregnancy independently predicted both postpartum insulin sensitivity (t=3.93, p<0.0001) and beta-cell function (t=2.34, p=0.019), even after adjustment for GDM. Moreover, adiponectin emerged as a significant negative independent determinant of postpartum fasting glucose (t=-2.98, p=0.0031). In summary, hypoadiponectinemia in pregnancy is an independent predictor of postpartum metabolic dysfunction, including insulin resistance, beta-cell dysfunction, and increased fasting glucose. In particular, its relationship with beta-cell dysfunction implicates hypoadiponectinemia as a potential factor in the pathophysiology linking GDM with future T2DM.