- Email: [email protected]
68: Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long- term neurologic morbidity of the offspring
Oral Concurrent Session 5
DIABETES, FETAL PROGRAMMING AND METABOLISM
ajog.org
had higher peak glucose and area under the IPGTT curve, compared with CTR (Figures 1A&B), and higher mean arterial pressure compared to CTR (Figure 1C). Female FRC offspring were heavier and had higher % VAT (Figure 1D), liver fat infiltrates, HOMA-IR scores, insulin area under the IPGTT curve, serum concentrations of leptin, and lower concentrations of adiponectin compared to female CTR offspring (Table). No significant differences in these parameters were noted in male offspring. Serum concentrations of TG or TC were not different between the 2 groups for either gender. CONCLUSION: Maternal intake of high fructose leads to fetal programming of adult obesity, hypertension and metabolic dysfunction, all risk factors for CVD. This fetal programming is more pronounced in female offspring. Limiting intake of high fructose enriched diets in pregnancy may have significant impact on long term health.
67 High fructose diet in pregnancy leads to fetal programming of hypertension, insulin resistance and obesity in adult offspring Antonio Saad1, Joshua Disckerson1, Phyllis Gamble1, Huaizhi Yin1, Talar Kechichian1, Ashley Salazar1, Igor Patrikeev2, Massoud Motamedi2, George Saade1, Maged Costantine1 1
UTMB Galveston, Galveston, TX, 2UTMB Center of Biomedical Engineering, Galveston, TX
OBJECTIVE: Consumption of fructose rich diets in the U.S is on the
rise and thought to be associated with obesity and cardio-metabolic diseases. Our objective was to determine the effects of antenatal exposure to high fructose diet on offspring’s development of metabolic syndrome-like phenotype and other cardiovascular disease (CVD) risk factors later in life. STUDY DESIGN: Pregnant C57BL/6J dams were randomly allocated to fructose solution (FRC, 10% W/V, n¼10) as only drinking fluid or water (CTR, n¼10) from day 1 of pregnancy until delivery. Pups were then started on regular chow, and evaluated at 1 year of life. We measured % visceral adipose tissue (VAT) and liver fat infiltrates using computed tomography (CT), and blood pressure using CODA/non-invasive monitor. Intraperitoneal glucose tolerance testing (IPGTT), with corresponding insulin concentrations were obtained. Serum concentrations of glucose, insulin, triglycerides (TG), total cholesterol (TC), leptin, and adiponectin were measured in duplicate using standardized assays. Fasting homeostatic model assessment (HOMA-IR) was also calculated to assess insulin resistance. RESULTS: Maternal weight, pup number and average weight at birth were similar between the two groups. Male and female FRC offspring
68 Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long- term neurologic morbidity of the offspring Kira D. Nahum Sacks1, Michael Friger1, Efrat Spiegel2, Hanaa Abokaf2, Ruslan Sergienko1, Daniella Landau2, Eyal Sheiner2 1
Ben Gurion University of the Negev, Beer Sheva, Israel, 2Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel
OBJECTIVE: To assess whether in utero exposure to gestational diabetes mellitus (GDM) increases the risk of long- term neurologic morbidity in the offspring. STUDY DESIGN: A retrospective population-based cohort study compared the incidences of hospitalization due to neurologic disease between singletons exposed and unexposed to GDM. Deliveries occurred between the years 1991-2014 in a regional tertiary medical center. Mothers with pre-gestational diabetes and children with congenital malformations were excluded from the study. KaplanMeier survival curve was used to estimate cumulative incidence of neurologic morbidity. A multivariate generalized estimating
S48 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2016
ajog.org
DIABETES, FETAL PROGRAMMING AND METABOLISM
equation (GEE) logistic regression model analysis was used to control for confounders and for maternal clusters. RESULTS: During the study period 256,270 deliveries met the inclusion criteria; 5.0% of mothers were diagnosed with GDM (n¼12,889), of which 4.0% with GDMA1 (n¼10,241) and 1.0% with GDMA2 (n¼2648). During the follow-up period, a significant linear association was noted between the severity of the GDM (no GDM, GDMA1, GDMA2) and neurologic disease of the offspring (1.0%, vs. 1.4% vs. 1.7% respectively, p<0.001). Children born to women with GDM had higher cumulative incidence of neurologic morbidity (Kaplan-Meier survival curves; figure). Using a GEE multivariable logistic regression model controlling for time-to-event, maternal age, gestational age at delivery, and birth-weight, maternal GDM was found to be an independent risk factor for long-term neurologic disease of the offspring (GDMA1; adjusted OR ¼2.1; 95% CI 1.7-2.4, GDMA2; adjusted OR ¼1.9; 95% CI 1.4-2.6). In utero exposure to GDM imposed an especially high risk for autism of the offspring (GDMA1; adjusted OR ¼3.4; 95% CI 1.0-11.7, GDMA2; adjusted OR ¼8.1; 95% CI 1.8-36.6). CONCLUSION: Exposure to maternal GDM is an independent risk factor for long-term neurologic morbidity in the offspring.
Oral Concurrent Session 5
STUDY DESIGN: Female heterozygous eNOS-/+ with moderate hy-
pertension were placed on HFD for 4 weeks to induce a MLS phenotype. They were bred with wild type (WT) males, and on gestational day 1 (GD1), dams were randomly allocated to receive either a mixture of MI/DCI in water (7.02/0.18 mg/ml respectively, based on previous studies) or water (placebo). At term, (GD18), maternal weight, systolic blood pressure (SBP) by tail-cuff and glucose tolerance test (GTT) were obtained. Dams were then sacrificed; pups and placentas were weighed, maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin) were measured by multiplex elisa assay (Bio-Rad). RESULTS: Mean SBP was significantly lower in the group supplemented with MI/DCI compared to placebo (Fig. 1; P¼0.04). Pregnant mice with MLS phenotype treated with MI/DCI showed significantly lower GTT compared to placebo at all time periods (Fig. 2). Leptin serum levels were lower in the pregnant MI/DCI treated mice compared with the placebo treated group (MI/DCI: 16985 976.4 pg/dl vs. placebo: 24181.9 3128.2 pg/dl, p¼0.05). No other differences were seen in any of the remaining serum metabolic biomarkers studied. There were no differences between the MI/DCI group and the control group respectively in maternal weight gain (11.53 0.9 vs 11.6 0.7 in g), fetal weights (0.9 0.01 vs 0.88 0.01 in g) or placental weights (0.11 0.02 vs 0.11 0.01 in g). CONCLUSION: This is the first study to investigate MI/DCI effects in pregnancies complicated by MS showing that Inositols supplementation improves glucose tolerance and blood pressure profiles. Further studies are warranted to evaluate MI/DCI supplementation benefits in pregnancy complicated by MS.
69 Maternal inositol supplementation improves metabolic profile and blood pressure in pregnancies complicated by metabolic syndrome Francesca Ferrari1, Fabio Facchinetti2, Robyn P. Roberts1, Yongsheng Lan1, Mia M. Saade1, Sean C. Blackwell1, Jerrie S. Refuerzo1, Monica Longo1 1
UT Health - University of Texas Medical School at Houston, Houston, TX, Obstetrics & Gynecology, University of Modena and Reggio Emilia, Modena, Italy 2
OBJECTIVE: Myoinositol (MI) and D-chiro-inositol (DCI) improve
insulin resistance in women with gestational diabetes and postmenopausal women with metabolic syndrome (MS). We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase (eNOS) and fed high fat diet (HFD) develop metabolic like syndrome (MLS) phenotype. Our hypothesis is that a mixture of MI/DCI supplementation during pregnancy will decrease the severity of MS in a pregnant mouse model of MLS. Supplement to JANUARY 2016 American Journal of Obstetrics & Gynecology
S49
DIABETES, FETAL PROGRAMMING AND METABOLISM
ajog.org
had higher peak glucose and area under the IPGTT curve, compared with CTR (Figures 1A&B), and higher mean arterial pressure compared to CTR (Figure 1C). Female FRC offspring were heavier and had higher % VAT (Figure 1D), liver fat infiltrates, HOMA-IR scores, insulin area under the IPGTT curve, serum concentrations of leptin, and lower concentrations of adiponectin compared to female CTR offspring (Table). No significant differences in these parameters were noted in male offspring. Serum concentrations of TG or TC were not different between the 2 groups for either gender. CONCLUSION: Maternal intake of high fructose leads to fetal programming of adult obesity, hypertension and metabolic dysfunction, all risk factors for CVD. This fetal programming is more pronounced in female offspring. Limiting intake of high fructose enriched diets in pregnancy may have significant impact on long term health.
67 High fructose diet in pregnancy leads to fetal programming of hypertension, insulin resistance and obesity in adult offspring Antonio Saad1, Joshua Disckerson1, Phyllis Gamble1, Huaizhi Yin1, Talar Kechichian1, Ashley Salazar1, Igor Patrikeev2, Massoud Motamedi2, George Saade1, Maged Costantine1 1
UTMB Galveston, Galveston, TX, 2UTMB Center of Biomedical Engineering, Galveston, TX
OBJECTIVE: Consumption of fructose rich diets in the U.S is on the
rise and thought to be associated with obesity and cardio-metabolic diseases. Our objective was to determine the effects of antenatal exposure to high fructose diet on offspring’s development of metabolic syndrome-like phenotype and other cardiovascular disease (CVD) risk factors later in life. STUDY DESIGN: Pregnant C57BL/6J dams were randomly allocated to fructose solution (FRC, 10% W/V, n¼10) as only drinking fluid or water (CTR, n¼10) from day 1 of pregnancy until delivery. Pups were then started on regular chow, and evaluated at 1 year of life. We measured % visceral adipose tissue (VAT) and liver fat infiltrates using computed tomography (CT), and blood pressure using CODA/non-invasive monitor. Intraperitoneal glucose tolerance testing (IPGTT), with corresponding insulin concentrations were obtained. Serum concentrations of glucose, insulin, triglycerides (TG), total cholesterol (TC), leptin, and adiponectin were measured in duplicate using standardized assays. Fasting homeostatic model assessment (HOMA-IR) was also calculated to assess insulin resistance. RESULTS: Maternal weight, pup number and average weight at birth were similar between the two groups. Male and female FRC offspring
68 Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long- term neurologic morbidity of the offspring Kira D. Nahum Sacks1, Michael Friger1, Efrat Spiegel2, Hanaa Abokaf2, Ruslan Sergienko1, Daniella Landau2, Eyal Sheiner2 1
Ben Gurion University of the Negev, Beer Sheva, Israel, 2Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel
OBJECTIVE: To assess whether in utero exposure to gestational diabetes mellitus (GDM) increases the risk of long- term neurologic morbidity in the offspring. STUDY DESIGN: A retrospective population-based cohort study compared the incidences of hospitalization due to neurologic disease between singletons exposed and unexposed to GDM. Deliveries occurred between the years 1991-2014 in a regional tertiary medical center. Mothers with pre-gestational diabetes and children with congenital malformations were excluded from the study. KaplanMeier survival curve was used to estimate cumulative incidence of neurologic morbidity. A multivariate generalized estimating
S48 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2016
ajog.org
DIABETES, FETAL PROGRAMMING AND METABOLISM
equation (GEE) logistic regression model analysis was used to control for confounders and for maternal clusters. RESULTS: During the study period 256,270 deliveries met the inclusion criteria; 5.0% of mothers were diagnosed with GDM (n¼12,889), of which 4.0% with GDMA1 (n¼10,241) and 1.0% with GDMA2 (n¼2648). During the follow-up period, a significant linear association was noted between the severity of the GDM (no GDM, GDMA1, GDMA2) and neurologic disease of the offspring (1.0%, vs. 1.4% vs. 1.7% respectively, p<0.001). Children born to women with GDM had higher cumulative incidence of neurologic morbidity (Kaplan-Meier survival curves; figure). Using a GEE multivariable logistic regression model controlling for time-to-event, maternal age, gestational age at delivery, and birth-weight, maternal GDM was found to be an independent risk factor for long-term neurologic disease of the offspring (GDMA1; adjusted OR ¼2.1; 95% CI 1.7-2.4, GDMA2; adjusted OR ¼1.9; 95% CI 1.4-2.6). In utero exposure to GDM imposed an especially high risk for autism of the offspring (GDMA1; adjusted OR ¼3.4; 95% CI 1.0-11.7, GDMA2; adjusted OR ¼8.1; 95% CI 1.8-36.6). CONCLUSION: Exposure to maternal GDM is an independent risk factor for long-term neurologic morbidity in the offspring.
Oral Concurrent Session 5
STUDY DESIGN: Female heterozygous eNOS-/+ with moderate hy-
pertension were placed on HFD for 4 weeks to induce a MLS phenotype. They were bred with wild type (WT) males, and on gestational day 1 (GD1), dams were randomly allocated to receive either a mixture of MI/DCI in water (7.02/0.18 mg/ml respectively, based on previous studies) or water (placebo). At term, (GD18), maternal weight, systolic blood pressure (SBP) by tail-cuff and glucose tolerance test (GTT) were obtained. Dams were then sacrificed; pups and placentas were weighed, maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin) were measured by multiplex elisa assay (Bio-Rad). RESULTS: Mean SBP was significantly lower in the group supplemented with MI/DCI compared to placebo (Fig. 1; P¼0.04). Pregnant mice with MLS phenotype treated with MI/DCI showed significantly lower GTT compared to placebo at all time periods (Fig. 2). Leptin serum levels were lower in the pregnant MI/DCI treated mice compared with the placebo treated group (MI/DCI: 16985 976.4 pg/dl vs. placebo: 24181.9 3128.2 pg/dl, p¼0.05). No other differences were seen in any of the remaining serum metabolic biomarkers studied. There were no differences between the MI/DCI group and the control group respectively in maternal weight gain (11.53 0.9 vs 11.6 0.7 in g), fetal weights (0.9 0.01 vs 0.88 0.01 in g) or placental weights (0.11 0.02 vs 0.11 0.01 in g). CONCLUSION: This is the first study to investigate MI/DCI effects in pregnancies complicated by MS showing that Inositols supplementation improves glucose tolerance and blood pressure profiles. Further studies are warranted to evaluate MI/DCI supplementation benefits in pregnancy complicated by MS.
69 Maternal inositol supplementation improves metabolic profile and blood pressure in pregnancies complicated by metabolic syndrome Francesca Ferrari1, Fabio Facchinetti2, Robyn P. Roberts1, Yongsheng Lan1, Mia M. Saade1, Sean C. Blackwell1, Jerrie S. Refuerzo1, Monica Longo1 1
UT Health - University of Texas Medical School at Houston, Houston, TX, Obstetrics & Gynecology, University of Modena and Reggio Emilia, Modena, Italy 2
OBJECTIVE: Myoinositol (MI) and D-chiro-inositol (DCI) improve
insulin resistance in women with gestational diabetes and postmenopausal women with metabolic syndrome (MS). We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase (eNOS) and fed high fat diet (HFD) develop metabolic like syndrome (MLS) phenotype. Our hypothesis is that a mixture of MI/DCI supplementation during pregnancy will decrease the severity of MS in a pregnant mouse model of MLS. Supplement to JANUARY 2016 American Journal of Obstetrics & Gynecology
S49