Laura Smith University of Cincinnati. June 7 th, 2012

Transcription

1 Laura Smith University of Cincinnati June 7 th, 2012

2 1. Background 2. Grant 3. Research Strategy

3 Background

4 Practical /Relevant Useful skill Filled a need

5 25.8 million in the U.S. (2011) A leading cause of: heart disease, stroke, kidney disease, neuropathy, amputation, blindness etc. Medication (insulin and oral), diet and monitoring blood glucose are standards of care Daily blood glucose: 3-4 x per day HbA1C: 2 x a year (or more if necessary)

6 Test Target Blood Glucose Fasting Before Meals 1-2 hours After Meals mg/dl (5-7mmol/L) mg/dl (4-7mmol/L) <180 mg/dl (10mmol/L) HbA1C < 6.5%

7 Diabetes is more complex during pregnancy as there is a risk of adverse maternal and neonatal outcomes Hypo- and hyperglycemic states are known to be associated with type-i diabetes during pregnancy Higher rates of adverse outcomes in type-i diabetic pregnancies than non-diabetic pregnancies Includes maternal, neonatal and offspring outcomes Preeclampsia, premature labor, premature delivery, infection. abnormal birth weight, minor congenital malformation, hypoglycemia. Obesity, insulin resistance, beta cell dysfunction and diabetes, renal and cardiovascular dysfunction, altered neurocognitive function.

8 Regardless of that Women with pre-gestation type- I diabetes continue have considerably higher proportions of adverse maternal and neonatal outcomes than non-diabetic pregnancies This indicates a gap!

9 Previous studies have examined glucose control during pregnancy, however. Used mean glucose concentrations How to identify problem periods w/ mean data? Used short term continuous monitoring Inconvenience, QoL

10 Diabetes in Pregnancy Program Project Grant (PPG) Jane Khoury et al NIH Funded UC and CCHMC women; 439 pregnancies

11 The purpose of the PPG was to: Collect maternal glucose control data Collect neonatal weight and blood glucose Daily capillary blood glucose monitoring (CBGM) 4-6 x per day Glycohemoglobin (HbA 1 ) Monthly

12 Instructed to measure their glucose: before each meal, 90-minutes after each meal, at bedtime and at 3am throughout pregnancy Managed with intensive insulin therapy, involving a split mixed-dose regimen of three to four injections per day using short- and intermediateacting insulin combined with dietary regulation Goals of glycemic control were: less than 5.55 mmol/l for fasting less than 7.77 mmol/l for 90 minute postprandial

13 Follow-up studies: 1. Use of functional data analysis (semiparametric regression) to compare maternal and neonatal outcome data from PPG Assessed time specific differences in glycemic profiles Identified the first and third trimesters as periods of gestation where maternal glucose concentrations differ for large for gestational age (LGA) (90%) and appropriate for age (AGA) fetuses

14 Follow-up studies (cont): 2. Pilot study to track the offspring of women from the PPG Assess the effect of level of maternal glucose control during pregnancy on long-term outcome of the offspring, by assessing the ability to locate and recruit the offspring 19 participated Glucose tolerance testing, BMI, dual x-ray absorptiometry and blood pressure

15 Grant

16 R-21 NIH Exploratory/Developmental Research Grant Award Encourages new, exploratory and developmental research projects by providing support for the early stages of project development 2 years $275K Cost effective

17 Secondary Analysis in Obesity, Diabetes and Digestive Kidney Diseases (PA ) the goal of this program is to facilitate research that explores innovative hypotheses through the use of existing data sets. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) $275,000 for 2 years Posted March 19 th, 2012 Opened May 16 th, 2012 PA

18 Encourages applications that are: Innovative Explore existing data sets Analysis that shapes/informs future studies Novel approaches/methodologies Interventions

19 Research Strategy

20 Specific Aim 1. Using advanced statistical strategies, identify and characterize the degree and timing of gestational glycemic dysfunction on the risk of maternal complications and adverse neonatal and offspring outcomes Specific Aim 2. Evaluate the impact of adherence to glucose selfmonitoring on glycemic control measured as daily glucose concentration and monthly glycohemoglobin A1 Specific Aim 3. Develop HBM based pilot intervention to address the gestational time-specific associations of poor glucose adherence and adverse maternal, neonatal and offspring outcomes

21 SA #1: Functional data analysis Expansion of preliminary semi-parametric regression study using PPG data Type I diabetes Monitored glucose throughout pregnancy Delivered single, live fetus, > 32 weeks

22 SA #1: Functional data analysis Expected outcomes: expect that we will be able to once again identify crucial times during pregnancy associated with risks for maternal and neonatal morbidities association not causality

23 SA #2: Pilot Study Expansion Expand Pilot Study to include remaining offspring Waived consent Name, DOB, Phone number Electronic Medical Records (EMR) Diagnostic Codes growth, adiposity, fasting glucose, insulin levels (diabetes/renal) and cardiovascular status

24 SA #2: Pilot Study Expansion Expected outcomes: Offspring with successfully located codes will be associated with women from PPG who had uncontrolled glucose during gestation Elucidate impact of the importance of glucose monitoring adherence during pregnancy

25 SA #2: Pilot Study Expansion Potential problems: 1. Locating EMR 2. Connecting EMR to PPG mothers 3. Bias

26 SA # 3: Develop time-specific intervention Use of preliminary data, SAs #1 and #2 and the Health Belief Model (HBM) to develop pilot intervention Pilot intervention could be applied at time-specific periods of gestation as indicated from the semiparametric regression Forecasted use in a clinical setting

27 SA # 3: Develop time-specific intervention HBM Developed for health related behaviors 6 constructs perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action and selfefficacy Applications in Diabetes Adherence to medical therapy/metabolic control

28 SA # 3: Develop time-specific intervention Expected outcomes: Interim analysis will reveal the need for educational process for perceived severity, perceived benefits and self efficacy (minimum) Perceived barriers? Can these be changed? Successful development of a pilot intervention would allow for further study of glucose monitoring adherence on a new population of women with type I diabetes in pregnancy and eventual use in a clinical setting

29 Educational Constructs Behavioral Behavioral Process of HBM Objectives Outcome How to modify? Severity -mention negative consequences -personalize seriousness Benefits -positive benefits Self Efficacy -Use of small steps -demonstration -reinforcement

30 SA # 3: Develop time-specific intervention Potential Problems: Use of HBM in this setting Primary and Secondary prevention Long term behavior change Alternative Strategies: Use of a different theory if necessary?

31 2 year period beginning in September 2012 Apply for Institutional Review Board approval prior to the award announcement Data Analysis EMR Review Development of Pilot Intervention Results Conferences/Publications

32 Table 1. Grant Timetable Year 1 Year 2 Quarter of Year Early IRB approval x Weekly Team Meetings x x x x x x x x Interim Functional data analysis x x x x x Offspring EMR Chart review and follow up x x x x x Development of Pilot Intervention x x x x x Present early results at conferences x x Final Analysis x x Publications Ongoing after last year x x

33 Employee Role (% effort) Year 1 Salary Year 2 Salary Total PI PI (20%) $21,800 $22,500 $44,300 PI PI (10%) $13,500 $13,900 $27,400 Co-PI Co-I (5%) $9,200 $9,500 $18,700 Coordinator Co-I (40%) $17,500 $18,000 $35,500 Statistician Data Mgmt (10%) $9,300 $9,500 $18,800 Graduate Student GradStudent (100%) $36,200 $37,300 $73,500 = $218,200 Fringe $50,000 Travel $6,000 =$274,200

34 We anticipate that results from this proposal will enhance subsequent extramural applications Early identification of children at risk for morbidity, and potential intervention during early childhood Insights into later outcomes

35 Great learning experience! Teamwork Time management Writing skills

36 Dr. Liliana Rojas-Guyler Dr. Rebecca Vidorek Dr. Jane Khoury Dr. Rhonda VanDyke Dr. Jareen Meinzen-Derr

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