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541: Investigating the mechanisms leading to improved metabolic profile by inositol in pregnancy complicated by metabolic syndrome
ajog.org
Poster Session III (MS). Our aim was to investigate the underlying mechanisms responsible for these findings. STUDY DESIGN: Heterozygous endothelial nitric oxide synthase mice (eNOS-/+) fed high fed diet lead to a well characterized murine model of MS. Females eNOS-/+ with MS were bred with WT males. On gestational day 1 (GD1), dams were allocated to receive either a mixture of INO in water (MI/DCI: 7.2/0.18 mg/ml) or water as control. Four groups of pregnant dams were obtained: WT, WT-INO, eNOS-/+ and eNOS-/+INO. At term gestation, mice were sacrificed and placentas collected for protein extraction and quantitative western blot analysis. Placental proteins involved in inflammatory and metabolic pathways were evaluated: inducible nitric oxide synthase (iNOS), IkB kinase (inhibitor of kappa B), Glucose transporter type 4 (GLUT4), Glucose transporter type 1 (GLUT1), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1), and placental growth factor (PLGF). RESULTS: Placental weights were similar among groups. iNOS placenta expression was lower in the eNOS-/+ group compared to the WT group; treatment with INO increased iNOS expression in eNOS-/+INO placentas to a level similar to WT (Fig 1, P¼0.04). No differences in IkB kinase protein expression was seen among the groups. GLUT4 was lower in placentas from eNOS-/+ compared with WT; and treatment with INO increased GLUT4 expression in the eNOS-/+ placentas (Fig 2, P¼0.001); whereas GLUT1 was not different among groups. VEGF expression was lower in the eNOS-/+ placentas (0.090.002) vs WT one (0.10.003; P¼0.03), and INO treatment did not change its expression level. PLGF was lower in the eNOS-/+ placentas compared to WT controls (0.180.01 vs. WT 0.220.01 respectively, P¼0.04) and INO treatment did not change its expression level. CONCLUSION: In this pregnant murine model of metabolic syndrome, INO treatment increases placental expression of iNOS and GLUT4, modulating inflammatory and metabolic pathways. This mechanism could explained the benefit of INO treatment in improving metabolic syndrome during pregnancy.
541 Investigating the mechanisms leading to improved metabolic profile by inositol in pregnancy complicated by metabolic syndrome
Monica Longo1, Arun Mani1, Fangxian Lu1, Francesca Ferrari2, Fabio Facchinetti2, Jerrie S. Refuerzo1, Baha M. Sibai1, Sean C. Blackwell1 1 2
Dept. of OB/GYN, McGovern Medical School at UTHealth, Houston, TX, Dept. of OB/GYN, University of Modena and Reggio Emilia, Modena, Italy
OBJECTIVE: Myoinositol (MI) and D-chiro-inositol (DCI) improve
insulin resistance in women with GDM. We have previously shown that Inositol (INO) supplementation improved blood pressure and metabolic profile in a pregnant mouse model of metabolic syndrome
Supplement to JANUARY 2017 American Journal of Obstetrics & Gynecology
S319
ajog.org
Poster Session III
543 A novel approach to assist with the diagnosis of gestational diabetes Jennifer Caruso, James Hole, Carlos Roberts WellSpan York Hospital, York, PA
OBJECTIVE: Although a one-step approach to the diagnosis of
542 Association between cord c-peptide and markers of oxidative stress and inflammation in children born to women with glucose intolerance Ramkumar Menon Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, Bethesda, MD
OBJECTIVE: Cord c-peptide, a marker of fetal pancreatic beta-cell
function, is related to fetal glucose levels. Our objective was to evaluate the association between cord c-peptide, a marker of fetal pancreatic beta-cell function, and oxidative stress and inflammation in children later in life. STUDY DESIGN: Secondary analysis of children followed at 5-10 years after birth to mothers enrolled during pregnancy in a randomized trial of mild GDM treatment vs. usual care, or born to women with lesser degrees of glucose intolerance (abnormal blood glucose screen but normal oral glucose tolerance test). We excluded children born to pregnancies complicated by anomalies, preeclampsia, gestational hypertension, abruption, preterm birth weeks, small for gestational age, or receipt of steroids. At follow-up, children provided fasting blood samples for leukocyte DNA telomere length, High Mobility Group Box-1 (HMGB-1, a marker of inflammation and nuclear injury), 8-Oxo-2’-deoxyguanosine (8-OXODG) and 8-isoprostane (two markers of oxidative stress induced tissue damage), and the antioxidant superoxide dismutase. Multivariable linear regression models adjusted for maternal age, race/ethnicity, child sex, and study group evaluated the association between cord c-peptide and log values of the markers. RESULTS: 233 children were evaluated at a mean age of 71 years. Overall, after adjusting for potentially confounding factors, increasing cord c-peptide was associated with increasing HMGB-1 (p¼.02), but not with any of the other markers evaluated (table). CONCLUSION: Susceptible fetuses, as measured by cord c-peptide, may have higher tissue injury and inflammation later in life, independent of markers of oxidative stress measured by this study. This altered fetal programming is likely initiated by in utero exposure to hyperglycemia, which in turn leads to increased pancreatic secretion of insulin and c-peptide. Our results support the fetal origin of adult diseases.
gestational diabetes (GDM) has been suggested, this method has not been adopted by ACOG which recommends a 1 hour glucose screen and 3 hour glucose tolerance test (GTT) evaluation. In a two-step study, we developed and validated a scoring tool that can be used to diagnose GDM. Initially, we evaluated the results of 312 patients’ 1 hour glucose screen as well as maternal age, BMI, race, family history of diabetes, and personal history of GDM, prior macrosomia or shoulder dystocia. Our goal was to identify a scoring system for the diagnosis of GDM based on risk factors that can be used when classic testing is not possible. During the second step of the study, we validated our tool in a random population of patients. STUDY DESIGN: Both steps were IRB approved. The initial step was a retrospective chart review of 312 patient charts who underwent testing for GDM between January 2013 and October 2013. 77 patients were diagnosed with GDM (abnormal 3 hour GTT), 133 screened positive but had a normal 3 hour GTT and 102 women had a negative glucose screen (no 3 hour GTT). Based on the results and using statistical principles, a scoring tool was developed. The second step was a retrospective cohort study of 186 patients who underwent a 3 hour GTT. The scoring tool was applied to these patients to identify those patients at risk for GDM thus validating our scoring system. RESULTS: Using a Chi-Square test, the 1 hour glucose screen, BMI, age, history of GDM, history of macrosomia and family history of DM were found to be significantly related to a diagnosis of GDM. Based on previous literature and clinical utility, each of these characteristics was assigned a point value. Using a ROC analysis, a cut point of 3 was used to diagnose GDM. Using this, the test has a sensitivity of 89.33% and a specificity of 64.81%. In an effort to validate our scoring system, a cut off of 3 was used diagnose GDM. Based on our retrospective cohort of 186 patients, results indicated a sensitivity of 94.7% and a specificity of 29.3%. The positive predictive value was 13.2% and the negative predictive value was 98%. CONCLUSION: This study validates our use of a scoring system to identify patients with GDM. This tool should be very useful in those women who are not candidates for or are unable to tolerate the 3 hour GTT (post bariatric surgery). We plan to implement this tool in these populations.
S320 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2017
Poster Session III (MS). Our aim was to investigate the underlying mechanisms responsible for these findings. STUDY DESIGN: Heterozygous endothelial nitric oxide synthase mice (eNOS-/+) fed high fed diet lead to a well characterized murine model of MS. Females eNOS-/+ with MS were bred with WT males. On gestational day 1 (GD1), dams were allocated to receive either a mixture of INO in water (MI/DCI: 7.2/0.18 mg/ml) or water as control. Four groups of pregnant dams were obtained: WT, WT-INO, eNOS-/+ and eNOS-/+INO. At term gestation, mice were sacrificed and placentas collected for protein extraction and quantitative western blot analysis. Placental proteins involved in inflammatory and metabolic pathways were evaluated: inducible nitric oxide synthase (iNOS), IkB kinase (inhibitor of kappa B), Glucose transporter type 4 (GLUT4), Glucose transporter type 1 (GLUT1), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1), and placental growth factor (PLGF). RESULTS: Placental weights were similar among groups. iNOS placenta expression was lower in the eNOS-/+ group compared to the WT group; treatment with INO increased iNOS expression in eNOS-/+INO placentas to a level similar to WT (Fig 1, P¼0.04). No differences in IkB kinase protein expression was seen among the groups. GLUT4 was lower in placentas from eNOS-/+ compared with WT; and treatment with INO increased GLUT4 expression in the eNOS-/+ placentas (Fig 2, P¼0.001); whereas GLUT1 was not different among groups. VEGF expression was lower in the eNOS-/+ placentas (0.090.002) vs WT one (0.10.003; P¼0.03), and INO treatment did not change its expression level. PLGF was lower in the eNOS-/+ placentas compared to WT controls (0.180.01 vs. WT 0.220.01 respectively, P¼0.04) and INO treatment did not change its expression level. CONCLUSION: In this pregnant murine model of metabolic syndrome, INO treatment increases placental expression of iNOS and GLUT4, modulating inflammatory and metabolic pathways. This mechanism could explained the benefit of INO treatment in improving metabolic syndrome during pregnancy.
541 Investigating the mechanisms leading to improved metabolic profile by inositol in pregnancy complicated by metabolic syndrome
Monica Longo1, Arun Mani1, Fangxian Lu1, Francesca Ferrari2, Fabio Facchinetti2, Jerrie S. Refuerzo1, Baha M. Sibai1, Sean C. Blackwell1 1 2
Dept. of OB/GYN, McGovern Medical School at UTHealth, Houston, TX, Dept. of OB/GYN, University of Modena and Reggio Emilia, Modena, Italy
OBJECTIVE: Myoinositol (MI) and D-chiro-inositol (DCI) improve
insulin resistance in women with GDM. We have previously shown that Inositol (INO) supplementation improved blood pressure and metabolic profile in a pregnant mouse model of metabolic syndrome
Supplement to JANUARY 2017 American Journal of Obstetrics & Gynecology
S319
ajog.org
Poster Session III
543 A novel approach to assist with the diagnosis of gestational diabetes Jennifer Caruso, James Hole, Carlos Roberts WellSpan York Hospital, York, PA
OBJECTIVE: Although a one-step approach to the diagnosis of
542 Association between cord c-peptide and markers of oxidative stress and inflammation in children born to women with glucose intolerance Ramkumar Menon Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, Bethesda, MD
OBJECTIVE: Cord c-peptide, a marker of fetal pancreatic beta-cell
function, is related to fetal glucose levels. Our objective was to evaluate the association between cord c-peptide, a marker of fetal pancreatic beta-cell function, and oxidative stress and inflammation in children later in life. STUDY DESIGN: Secondary analysis of children followed at 5-10 years after birth to mothers enrolled during pregnancy in a randomized trial of mild GDM treatment vs. usual care, or born to women with lesser degrees of glucose intolerance (abnormal blood glucose screen but normal oral glucose tolerance test). We excluded children born to pregnancies complicated by anomalies, preeclampsia, gestational hypertension, abruption, preterm birth weeks, small for gestational age, or receipt of steroids. At follow-up, children provided fasting blood samples for leukocyte DNA telomere length, High Mobility Group Box-1 (HMGB-1, a marker of inflammation and nuclear injury), 8-Oxo-2’-deoxyguanosine (8-OXODG) and 8-isoprostane (two markers of oxidative stress induced tissue damage), and the antioxidant superoxide dismutase. Multivariable linear regression models adjusted for maternal age, race/ethnicity, child sex, and study group evaluated the association between cord c-peptide and log values of the markers. RESULTS: 233 children were evaluated at a mean age of 71 years. Overall, after adjusting for potentially confounding factors, increasing cord c-peptide was associated with increasing HMGB-1 (p¼.02), but not with any of the other markers evaluated (table). CONCLUSION: Susceptible fetuses, as measured by cord c-peptide, may have higher tissue injury and inflammation later in life, independent of markers of oxidative stress measured by this study. This altered fetal programming is likely initiated by in utero exposure to hyperglycemia, which in turn leads to increased pancreatic secretion of insulin and c-peptide. Our results support the fetal origin of adult diseases.
gestational diabetes (GDM) has been suggested, this method has not been adopted by ACOG which recommends a 1 hour glucose screen and 3 hour glucose tolerance test (GTT) evaluation. In a two-step study, we developed and validated a scoring tool that can be used to diagnose GDM. Initially, we evaluated the results of 312 patients’ 1 hour glucose screen as well as maternal age, BMI, race, family history of diabetes, and personal history of GDM, prior macrosomia or shoulder dystocia. Our goal was to identify a scoring system for the diagnosis of GDM based on risk factors that can be used when classic testing is not possible. During the second step of the study, we validated our tool in a random population of patients. STUDY DESIGN: Both steps were IRB approved. The initial step was a retrospective chart review of 312 patient charts who underwent testing for GDM between January 2013 and October 2013. 77 patients were diagnosed with GDM (abnormal 3 hour GTT), 133 screened positive but had a normal 3 hour GTT and 102 women had a negative glucose screen (no 3 hour GTT). Based on the results and using statistical principles, a scoring tool was developed. The second step was a retrospective cohort study of 186 patients who underwent a 3 hour GTT. The scoring tool was applied to these patients to identify those patients at risk for GDM thus validating our scoring system. RESULTS: Using a Chi-Square test, the 1 hour glucose screen, BMI, age, history of GDM, history of macrosomia and family history of DM were found to be significantly related to a diagnosis of GDM. Based on previous literature and clinical utility, each of these characteristics was assigned a point value. Using a ROC analysis, a cut point of 3 was used to diagnose GDM. Using this, the test has a sensitivity of 89.33% and a specificity of 64.81%. In an effort to validate our scoring system, a cut off of 3 was used diagnose GDM. Based on our retrospective cohort of 186 patients, results indicated a sensitivity of 94.7% and a specificity of 29.3%. The positive predictive value was 13.2% and the negative predictive value was 98%. CONCLUSION: This study validates our use of a scoring system to identify patients with GDM. This tool should be very useful in those women who are not candidates for or are unable to tolerate the 3 hour GTT (post bariatric surgery). We plan to implement this tool in these populations.
S320 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2017