ABSTRACT
OBJECTIVE: Our objective was to investigate the association between maternal outcomes and twin chorionicity in a large, contemporary obstetric population. STUDY DESIGN: Retrospective cohort study was conducted at a single, large tertiary care center. Prenatal and inpatient records for all individuals with twin gestations were reviewed from 2000 to 2016. Patients with monoamniotic twins, higher-order multiples reduced to twins, multiple sets of twins in the study period, or undetermined chorionicity were excluded. Patients with monochorionic twins were compared with those with dichorionic twins. The co-primary outcomes were gestational diabetes mellitus and hypertensive disorders of pregnancy. Secondary outcomes included cesarean delivery, preterm delivery, postpartum hemorrhage, and other maternal outcomes. Bivariate and multivariate analyses were performed to assess associations of chorionicity with maternal outcomes. RESULTS: Of the 2,979 patients eligible for inclusion, 2,627 (88.2%) had dichorionic twin gestations and 352 (11.8%) had monochorionic twin gestations. Patients with monochorionic twins were less likely to self-identify as non-Hispanic White and to have conceived via assisted reproductive technology but were more likely to be publicly insured, multiparous and have prenatal care with a maternal-fetal medicine provider. Neither gestational diabetes mellitus (6.8% monochorionic vs. 6.2% dichorionic, p = 0.74; adjusted odds ratio [OR] 1.06, 95% confidence interval (CI) 0.60-1.86) nor hypertensive disorders of pregnancy (21.9% monochorionic vs. 26.3% dichorionic, p = 0.09; adjusted OR 0.99, 95% CI, 0.71-1.38) differed by chorionicity. Of the secondary maternal outcomes, patients with monochorionic twins experienced a lower frequency of cesarean delivery (46.0 vs. 61.8%, p < 0.001), which persisted after multivariate analyses (adjusted OR 0.60, 95% CI 0.46-0.80). There were no differences in preterm delivery, preterm premature rupture of membranes, hemorrhage, hysterectomy, or intrahepatic cholestasis of pregnancy. CONCLUSION: The odds of gestational diabetes mellitus and hypertensive disorders of pregnancy do not appear to differ by twin chorionicity. KEY POINTS: · Hypertensive disorders of pregnancy do not differ by twin chorionicity.. · Gestational diabetes mellitus does not differ by twin chorionicity.. · Maternal outcomes are similar for individuals with monochorionic and dichorionic twin gestations..
ABSTRACT
Adiponectin is a hormone that lowers glucose production by increasing liver insulin sensitivity. Insulin blocks the generation of biochemical intermediates for glucose production by inhibiting autophagy. However, autophagy is stimulated by an essential mediator of adiponectin action, AMPK. This deadlock led to our hypothesis that adiponectin inhibits autophagy through a novel mediator. Mass spectrometry revealed a novel protein that we call suppressor of glucose by autophagy (SOGA) in adiponectin-treated hepatoma cells. Adiponectin increased SOGA in hepatocytes, and siRNA knockdown of SOGA blocked adiponectin inhibition of glucose production. Furthermore, knockdown of SOGA increased late autophagosome and lysosome staining and the secretion of valine, an amino acid that cannot be synthesized or metabolized by liver cells, suggesting that SOGA inhibits autophagy. SOGA decreased in response to AICAR, an activator of AMPK, and LY294002, an inhibitor of the insulin signaling intermediate, PI3K. AICAR reduction of SOGA was blocked by adiponectin; however, adiponectin did not increase SOGA during PI3K inhibition, suggesting that adiponectin increases SOGA through the insulin signaling pathway. SOGA contains an internal signal peptide that enables the secretion of a circulating fragment of SOGA, providing a surrogate marker for intracellular SOGA levels. Circulating SOGA increased in parallel with adiponectin and insulin activity in both humans and mice. These results suggest that adiponectin-mediated increases in SOGA contribute to the inhibition of glucose production.
