- Email: [email protected]
252: TNF alpha has a direct inhibitory effect on Ca2+ responses necessary for eNOS activation in primary HUVEC
www.AJOG.org
Diabetes, Labor, Medical-Surgical-Disease, Obstetric Quality & Safety, Prematurity, Ultrasound-Imaging
Poster Session II
252 TNF alpha has a direct inhibitory effect on Ca2ⴙ responses necessary for eNOS activation in primary HUVEC Heather Bankowski1, Fu Xian Yi2, Derek Boeldt3, Dinesh Shah4, Ian Bird5 1 University of Wisconsin, Obstetrics and Gynecology, Maternal Fetal Medicine, Madison, WI, 2University of Wisconsin, Obstetrics and Gynecology, Madison, WI, 3University of WI School of Medicine and Public Health, Obstetrics and Gynecology, Madison, WI, 4 University of WI School of Medicine and Public Health, Obstetrics and Gynecology, Maternal Fetal Medicine, Madison, WI, 5University of WI School of Medicine and Public Health, Obstetrics and Gynecology & Pediatrics, Madison, WI
251 Numeracy and literacy in pregnant women with pregestational diabetes Etoi Garrison1, Cornelia Graves2, Rebecca Gregory3, Russell Rothman4, James Slaughter5, Sarah Fletcher5, Kelly A. Bennett6 1 Vanderbilt University School of Medicine, Obstetrics and Gynecology, Nashville, TN, 2St. Thomas Health-Baptist Hospital, Obstetrics and Gynecology, Nashville, TN, 3Vanderbilt University Medical Center, Eskind Diabetes Center, Nashville, TN, 4Vanderbilt University School of Medicine, Medicine, Nashville, TN, 5Vanderbilt University School of Medicine, Biostatistics, Nashville, TN, 6Vanderbilt University School of Medicine, Obstetrics and Gynecology, Nashville, TN
OBJECTIVE: Numeracy is defined as the ability to use numbers and math in daily life. Diabetes-related numeracy skills may be used to perform diabetes-related tasks for self-management of Type 1 and Type 2 diabetes. Inadequate health literacy and poor diabetes-related numeracy have been found to be independently associated with poor glycemic control among nonpregnant adult diabetics. This association in diabetes during pregnancy has not been well studied. We investigated this association in a defined pregnant diabetic population. STUDY DESIGN: Subjects were prospectively enrolled and administered validated measures of literacy (REALM), diabetes-related numeracy (DNT), and perceived self-efficacy (PDSMS). Glucose meter readings and A1C data were collected at baseline enrollment and prior to delivery. Univariate analyses were conducted. RESULTS: Fifty-eight subjects were recruited, 52% (n⫽30) with Type 1 and 48 % (n⫽28) with Type 2 diabetes. Subjects were high school educated, but 8% had less than 9th grade literacy skills. Mean baseline A1C was 7.0%, mean DNT score was 84 out of 100. Thirty-three percent could not use a food label to determine caloric content based upon serving size. Seventy-one percent of the Type 2 diabetics and 41 % of the Type 1 diabetics were unable to use a nutrition label to calculate carbohydrate grams based upon serving size. Eighteen percent of the Type 2 diabetics could not use numerical hierarchy to determine which glucose values were above or below a normal reference range. Health literacy and DNT scores were negatively and significantly associated with HgBA1C (r2 0.08 p 0.04; r2 0.11, p 0.01), respectively. Every 14% increase in DNT score was associated with a 0.35 (Type I) and 0.52 (Type II) decrease in HgBA1C (p⫽0.04). CONCLUSION: In this defined group, health literacy and numeracy-dependent diabetes self-management skills were significantly associated with better glycemic control. This data may be useful in the development of targeted diabetes education tools in pregnancy.
OBJECTIVE: Evidence suggests that the pathologic metabolic state of diabetes mellitus(DM)results in oxidative stress. Tumor necrosis factor alpha (TNF␣) has been shown to induce intracellular reactive oxygen species formation and is proposed to be a significant perpetrator of insulin resistance in gestational diabetes mellitus (GDM). Previously we have shown in DM HUVEC in vivo ROS damage to eNOS protein. Even in GDM patients, there is a overall decrease in NO production consistent with ROS damage of functional eNOS protein, despite maintenance of eNOS protein levels. It is known that sustained Ca2⫹ elevation is also required for eNOS activity. Could TNF␣ also inhibit NO production at the level of Ca2⫹ signaling? Hypothesis: The decrease in agonist stimulated NO production due to TNF␣ stimulated ROS production may not only occur through damage to eNOS protein in DM HUVEC but may also involve direct impairment of Ca2⫹ signaling mechanisms necessary for eNOS activation. STUDY DESIGN: HUVEC cells from a combined pool of control patients were prepared at a density of 95%. HUVEC underwent acute (30 minutes)and chronic (16 hours) treatments with 50, 10 or 1 ng/ml TNF␣ prior to imaging using Fura-2 to detect Ca2⫹ in real time in response to 30 minute stimulation with ATP (100 uM). RESULTS: There were statistically significant reductions (P⫽ⱕ0.05) in burst numbers in cells in the acute and chronic TNF␣ treatment groups (Fig. 1). The decrease in Ca2⫹ bursts was dose dependent in each case. In addition to the damaged eNOS protein itself, there is an acute, direct effect of TNF to directly inhibit eNOS activation by also impairing sustained Ca2⫹ signaling in the form of repetitive bursts. These in vitro findings compliment our prior observations on in vivo ROS damage to eNOS in DM HUVEC. CONCLUSION: Ultimately, such improved understanding of the inhibitory role of TNF␣ and other inflammatory cytokines will lead to a therapeutic strategy to reduce oxidative stress and development of macro and micro-vascular complications in pregnancies complicated by DM.
Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology
S123
Poster Session II
Diabetes, Labor, Medical-Surgical-Disease, Obstetric Quality & Safety, Prematurity, Ultrasound-Imaging
www.AJOG.org
253 Comparing daily versus less frequent blood glucose monitoring in patients with mild gestational diabetes Hector Mendez-Figueroa1, Julie Daley1, Vrishali V. Lopes1, Donald R. Coustan1 1 Women & Infants Hospital of RI and the Warren Alpert Medical School of Brown University, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Providence, RI
OBJECTIVE: In recent years the prevalence of GDM has risen 122%. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommended the 75 gram 2-hr oral glucose tolerance test (OGTT) for the diagnosis of GDM with the number of abnormal values required decreasing from two to one. This will increase the number of patients diagnosed with GDM. We therefore evaluated different frequencies in blood glucose (BG) monitoring in order to establish a more cost-effective approach while still detecting patients requiring therapy in a timely fashion STUDY DESIGN: This retrospective chart review analyzed data from the diabetes in pregnancy clinic. Mild GDM was defined as meeting Carpenter and Coustan criteria but with fasting plasma glucose (FPG) less than 95 mg/dl on the 3-hour 100-g OGTT. Only women requiring therapy were included. Three data sets were constructed from each patients self BG monitoring log: The first had all the BG values available and served as control; the second had every other days BG blocked and unavailable for review; and the third had only every third days BG available for review. In order to avoid bias, at a 4:1 ratio we matched 30 patients for both age and year of diagnosis of mild GDM, but who did not receive treatment and included them in the pool. The two data sets containing blocked BG values were compared to control data. RESULTS: Two blinded investigators reviewed all BG logs with instructions to start therapy when at least one third of values for a given time of day in a given week exceeded targets. A total of 121 subjects were included. Table 1 shows the mean difference expressed in days between the date therapy would have started with BG monitoring done daily, every other day and every third day. Subgroup analysis revealed that this strategy can be applied to all patient subgroups. CONCLUSION: BG monitoring in patients with mild gestational diabetes can be extended to every other day or every third day. This change in monitoring does not lead to a delay of therapy of greater than 1 week. This approach would allow for a more efficient use of our limited health resources.
S124
254 Changes in basal and bolus insulin pump dosing across gestation in women with well-controlled Type 1 diabetes Gladys Ramos1, Hilary Roeder1, Thomas Moore1 1 University of California San Diego, Department of Reproductive Medicine, San Diego, CA
OBJECTIVE: Use of the insulin pump in Type 1 diabetes mellitus (T1DM) improves glycemic control and reduces hypoglycemia. Our objective was to characterize the changes in insulin basal and bolus pump dosing required to maintain excellent glucose control (HbA1c ⬍6.5) across gestation. STUDY DESIGN: A retrospective cohort study was performed in women with T1DM with preconceptional HbA1c ⬍7.4. The primary outcome was the absolute and percentage change of basal and bolus insulin requirements from preconception to delivery. Secondary outcomes included gestational age at which insulin requirements peaked and changes in basal and bolus insulin rates during specific time segments during the day. RESULTS: Nine women with T1DM were studied. All were using an insulin pump at initiation of prenatal care; the PC mean HbA1c was 6.4⫹/⫺0.5. By the end of pregnancy, total daily dose of insulin (TDI) almost tripled, from 33.3 ⫹/⫺7.8 to 93.5 ⫹/⫺ 27.9 U/day. However, basal insulin rates rose only modestly (50% increase, from 16.2 ⫹/⫺ 6.5 to 24.0 ⫹/⫺ 9 U/day) while bolus insulin doses quadrupled from 17.1 ⫹ /⫺6.1 to 69.5 /⫺ 29.6 U/day (p⫽0.0001). Basal and bolus insulin requirements peaked at 33.2⫹/⫺2.7 and 34.6⫹/⫺2.3 weeks respectively (p⫽0.23). Total units of insulin per kilogram of maternal body weight increased from PC (0.6 U/kg) reaching a maximum of 1.3U/kg at 36 weeks. Bolus insulin increased from approximately 50% of TDI at PC to 75% of TDI at 36 weeks GA (Figure 1). The time segment during the day requiring the highest increase across gestation
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012
Diabetes, Labor, Medical-Surgical-Disease, Obstetric Quality & Safety, Prematurity, Ultrasound-Imaging
Poster Session II
252 TNF alpha has a direct inhibitory effect on Ca2ⴙ responses necessary for eNOS activation in primary HUVEC Heather Bankowski1, Fu Xian Yi2, Derek Boeldt3, Dinesh Shah4, Ian Bird5 1 University of Wisconsin, Obstetrics and Gynecology, Maternal Fetal Medicine, Madison, WI, 2University of Wisconsin, Obstetrics and Gynecology, Madison, WI, 3University of WI School of Medicine and Public Health, Obstetrics and Gynecology, Madison, WI, 4 University of WI School of Medicine and Public Health, Obstetrics and Gynecology, Maternal Fetal Medicine, Madison, WI, 5University of WI School of Medicine and Public Health, Obstetrics and Gynecology & Pediatrics, Madison, WI
251 Numeracy and literacy in pregnant women with pregestational diabetes Etoi Garrison1, Cornelia Graves2, Rebecca Gregory3, Russell Rothman4, James Slaughter5, Sarah Fletcher5, Kelly A. Bennett6 1 Vanderbilt University School of Medicine, Obstetrics and Gynecology, Nashville, TN, 2St. Thomas Health-Baptist Hospital, Obstetrics and Gynecology, Nashville, TN, 3Vanderbilt University Medical Center, Eskind Diabetes Center, Nashville, TN, 4Vanderbilt University School of Medicine, Medicine, Nashville, TN, 5Vanderbilt University School of Medicine, Biostatistics, Nashville, TN, 6Vanderbilt University School of Medicine, Obstetrics and Gynecology, Nashville, TN
OBJECTIVE: Numeracy is defined as the ability to use numbers and math in daily life. Diabetes-related numeracy skills may be used to perform diabetes-related tasks for self-management of Type 1 and Type 2 diabetes. Inadequate health literacy and poor diabetes-related numeracy have been found to be independently associated with poor glycemic control among nonpregnant adult diabetics. This association in diabetes during pregnancy has not been well studied. We investigated this association in a defined pregnant diabetic population. STUDY DESIGN: Subjects were prospectively enrolled and administered validated measures of literacy (REALM), diabetes-related numeracy (DNT), and perceived self-efficacy (PDSMS). Glucose meter readings and A1C data were collected at baseline enrollment and prior to delivery. Univariate analyses were conducted. RESULTS: Fifty-eight subjects were recruited, 52% (n⫽30) with Type 1 and 48 % (n⫽28) with Type 2 diabetes. Subjects were high school educated, but 8% had less than 9th grade literacy skills. Mean baseline A1C was 7.0%, mean DNT score was 84 out of 100. Thirty-three percent could not use a food label to determine caloric content based upon serving size. Seventy-one percent of the Type 2 diabetics and 41 % of the Type 1 diabetics were unable to use a nutrition label to calculate carbohydrate grams based upon serving size. Eighteen percent of the Type 2 diabetics could not use numerical hierarchy to determine which glucose values were above or below a normal reference range. Health literacy and DNT scores were negatively and significantly associated with HgBA1C (r2 0.08 p 0.04; r2 0.11, p 0.01), respectively. Every 14% increase in DNT score was associated with a 0.35 (Type I) and 0.52 (Type II) decrease in HgBA1C (p⫽0.04). CONCLUSION: In this defined group, health literacy and numeracy-dependent diabetes self-management skills were significantly associated with better glycemic control. This data may be useful in the development of targeted diabetes education tools in pregnancy.
OBJECTIVE: Evidence suggests that the pathologic metabolic state of diabetes mellitus(DM)results in oxidative stress. Tumor necrosis factor alpha (TNF␣) has been shown to induce intracellular reactive oxygen species formation and is proposed to be a significant perpetrator of insulin resistance in gestational diabetes mellitus (GDM). Previously we have shown in DM HUVEC in vivo ROS damage to eNOS protein. Even in GDM patients, there is a overall decrease in NO production consistent with ROS damage of functional eNOS protein, despite maintenance of eNOS protein levels. It is known that sustained Ca2⫹ elevation is also required for eNOS activity. Could TNF␣ also inhibit NO production at the level of Ca2⫹ signaling? Hypothesis: The decrease in agonist stimulated NO production due to TNF␣ stimulated ROS production may not only occur through damage to eNOS protein in DM HUVEC but may also involve direct impairment of Ca2⫹ signaling mechanisms necessary for eNOS activation. STUDY DESIGN: HUVEC cells from a combined pool of control patients were prepared at a density of 95%. HUVEC underwent acute (30 minutes)and chronic (16 hours) treatments with 50, 10 or 1 ng/ml TNF␣ prior to imaging using Fura-2 to detect Ca2⫹ in real time in response to 30 minute stimulation with ATP (100 uM). RESULTS: There were statistically significant reductions (P⫽ⱕ0.05) in burst numbers in cells in the acute and chronic TNF␣ treatment groups (Fig. 1). The decrease in Ca2⫹ bursts was dose dependent in each case. In addition to the damaged eNOS protein itself, there is an acute, direct effect of TNF to directly inhibit eNOS activation by also impairing sustained Ca2⫹ signaling in the form of repetitive bursts. These in vitro findings compliment our prior observations on in vivo ROS damage to eNOS in DM HUVEC. CONCLUSION: Ultimately, such improved understanding of the inhibitory role of TNF␣ and other inflammatory cytokines will lead to a therapeutic strategy to reduce oxidative stress and development of macro and micro-vascular complications in pregnancies complicated by DM.
Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology
S123
Poster Session II
Diabetes, Labor, Medical-Surgical-Disease, Obstetric Quality & Safety, Prematurity, Ultrasound-Imaging
www.AJOG.org
253 Comparing daily versus less frequent blood glucose monitoring in patients with mild gestational diabetes Hector Mendez-Figueroa1, Julie Daley1, Vrishali V. Lopes1, Donald R. Coustan1 1 Women & Infants Hospital of RI and the Warren Alpert Medical School of Brown University, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Providence, RI
OBJECTIVE: In recent years the prevalence of GDM has risen 122%. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommended the 75 gram 2-hr oral glucose tolerance test (OGTT) for the diagnosis of GDM with the number of abnormal values required decreasing from two to one. This will increase the number of patients diagnosed with GDM. We therefore evaluated different frequencies in blood glucose (BG) monitoring in order to establish a more cost-effective approach while still detecting patients requiring therapy in a timely fashion STUDY DESIGN: This retrospective chart review analyzed data from the diabetes in pregnancy clinic. Mild GDM was defined as meeting Carpenter and Coustan criteria but with fasting plasma glucose (FPG) less than 95 mg/dl on the 3-hour 100-g OGTT. Only women requiring therapy were included. Three data sets were constructed from each patients self BG monitoring log: The first had all the BG values available and served as control; the second had every other days BG blocked and unavailable for review; and the third had only every third days BG available for review. In order to avoid bias, at a 4:1 ratio we matched 30 patients for both age and year of diagnosis of mild GDM, but who did not receive treatment and included them in the pool. The two data sets containing blocked BG values were compared to control data. RESULTS: Two blinded investigators reviewed all BG logs with instructions to start therapy when at least one third of values for a given time of day in a given week exceeded targets. A total of 121 subjects were included. Table 1 shows the mean difference expressed in days between the date therapy would have started with BG monitoring done daily, every other day and every third day. Subgroup analysis revealed that this strategy can be applied to all patient subgroups. CONCLUSION: BG monitoring in patients with mild gestational diabetes can be extended to every other day or every third day. This change in monitoring does not lead to a delay of therapy of greater than 1 week. This approach would allow for a more efficient use of our limited health resources.
S124
254 Changes in basal and bolus insulin pump dosing across gestation in women with well-controlled Type 1 diabetes Gladys Ramos1, Hilary Roeder1, Thomas Moore1 1 University of California San Diego, Department of Reproductive Medicine, San Diego, CA
OBJECTIVE: Use of the insulin pump in Type 1 diabetes mellitus (T1DM) improves glycemic control and reduces hypoglycemia. Our objective was to characterize the changes in insulin basal and bolus pump dosing required to maintain excellent glucose control (HbA1c ⬍6.5) across gestation. STUDY DESIGN: A retrospective cohort study was performed in women with T1DM with preconceptional HbA1c ⬍7.4. The primary outcome was the absolute and percentage change of basal and bolus insulin requirements from preconception to delivery. Secondary outcomes included gestational age at which insulin requirements peaked and changes in basal and bolus insulin rates during specific time segments during the day. RESULTS: Nine women with T1DM were studied. All were using an insulin pump at initiation of prenatal care; the PC mean HbA1c was 6.4⫹/⫺0.5. By the end of pregnancy, total daily dose of insulin (TDI) almost tripled, from 33.3 ⫹/⫺7.8 to 93.5 ⫹/⫺ 27.9 U/day. However, basal insulin rates rose only modestly (50% increase, from 16.2 ⫹/⫺ 6.5 to 24.0 ⫹/⫺ 9 U/day) while bolus insulin doses quadrupled from 17.1 ⫹ /⫺6.1 to 69.5 /⫺ 29.6 U/day (p⫽0.0001). Basal and bolus insulin requirements peaked at 33.2⫹/⫺2.7 and 34.6⫹/⫺2.3 weeks respectively (p⫽0.23). Total units of insulin per kilogram of maternal body weight increased from PC (0.6 U/kg) reaching a maximum of 1.3U/kg at 36 weeks. Bolus insulin increased from approximately 50% of TDI at PC to 75% of TDI at 36 weeks GA (Figure 1). The time segment during the day requiring the highest increase across gestation
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012