Running head: PRE-PRANDIAL INSULIN ADMINISTRATION FINAL REPORT Pre-prandial Insulin Administration Clinical Project Final Report Ngoc Quyen T. Bui Arizona State University 1 Running head: PRE-PRANDIAL INSULIN ADMINISTRATION FINAL REPORT 2 Abstract Diabetes mellitus (DM) is a detrimental disease that afflicts approximately 23.6 million Americans and costs $176 billion dollars annually in direct medical expenses (American Diabetes Association [ADA], 2015). Approximately 208,000 children and adolescents with diabetes are under the age of 20 years (ADA, 105; CDC, 2014). Currently, the standard of medical practice in school-aged children and adolescents with type 1 diabetes is to administer insulin after the child or teen has eaten. The most current evidence has demonstrated a decrease hemoglobin A1C (HbA1c) and preference for pre-prandial insulin administration (Cobry et al., 2010; Danne et al., 2003; DePalma et al., 2011; Enander et al., 2012; Luijf et al., 2010; Scaramuzza et al., 2010). This Doctor of Nursing Practice (DNP) project delivered an educational program for parents of school age children and adolescents with type 1 diabetes and instituted pre-prandial insulin administration as the standard of care in an outpatient pediatric endocrine clinic. Education was delivered in both verbal and written formats. Data collection included weekly blood glucose reports and HbA1c at initial and follow-up sessions. Descriptive statistics were utilized to analyze the data. No post intervention data was able to be collected due to participant drop out. Future directions to promote this practice change are discussed. PRE-PRANDIAL INSULIN ADMINISTRATION 3 Background and Significance According to the United States (U.S.) Department of Health and Human Services (2014), diabetes mellitus (DM) affects approximately 23.6 million people and is the seventh leading cause of death in the U.S. The total cost for direct medical expenses due to DM in 2012 was 176 billion dollars (ADA, 2015). Data from the Center of Disease Control and Prevention (CDC) and the American Diabetes Association (ADA) in 2008-2009, estimated 208,000 individuals with diabetes are under the age of 20 years, and roughly 18,436 children are diagnosed with type 1 DM (ADA, 2015; CDC, 2014). The prevalence of diabetes is higher in Hispanic, African American, Asian, Pacific Islander, and American Indians ethnicities (CDC, 2015). Type 1 DM is a condition resulting from a defective or failure of pancreatic beta cells to secrete insulin (ADA, 2016). Without insulin, glucose cannot enter the cells to be turned into energy and this impairs the body’s ability to metabolize carbohydrate, protein, and fat correctly which results in hyperglycemia or high blood glucose (Burns et al., 2013). Prolonged uncontrolled blood glucose can have detrimental health sequelae in adulthood such as hypertension, amputations, blindness, stroke, and renal disease (ADA, 2014; NDEP, 20014). Currently, the standard of care for insulin administration is to dose insulin pre-prandial. However, this type of administration can be difficult in young children due to their unpredictable appetite and oral intake. This creates a barrier in preventing adequate control of blood glucose (BG) and subsequently hemoglobin A1c (HbA1c) levels. Purpose and Rationale The goal of diabetes management is to decrease health sequelae and improve quality of life. One way to achieve these goals is through improved management of BG and HbA1c. Therefore, the purpose of this Doctor of Nursing Practice (DNP) project is to implement an PRE-PRANDIAL INSULIN ADMINISTRATION 4 insulin administration practice change which is demonstrating efficacy in the most recent scientific literature. According to the most current evidence, school-aged children and adolescents with Type 1 DM will benefit from changing insulin administration from a postprandial insulin administration to a pre-prandial insulin administration. The evidence suggests that this timing of insulin administration contributes to better current and future health. Internal Evidence Horizon View Medical Center (HVMC) is an outpatient pediatric endocrine clinic in Las Vegas, Nevada. At this clinic, it has been noted that approximately 50% of the daily pediatric patient visits are related to DM. Currently, all of the children who are insulin dependent are administering insulin at the post-prandial time point which is the opposite practice from what this author observed when working as a Registered Nurse on an adult medical-surgical floor. When the healthcare providers at the clinic were questioned about this practice, the reply was simply because some children do not know how much carbohydrate they will consume at each meal in order to correctly compensate pre-prandial insulin administration. Problem Statement It is imperative to monitor BG and HbA1c to better manage DM (Chase, 2011; Valent et al., 2010; World Health Organization, 2011). In a cohort study by Samahy, Elbarbary, and Elmorsi (2015), poor glycemic control was detrimental and caused acute complications such as diabetic ketoacidosis (DKA) or severe hypoglycemia. In addition, the following chronic conditions in pediatric patients were the result of uncontrolled BG: neuropathy 6.3%, retinopathy 1.8%, and microalbuminuria 6.8% (Samahy et al., 2015). Timely insulin administration is both necessary and imperative to adequately control post-prandial BG, episodes of nocturnal hypoglycemia, and HbA1c (Cobry et al., 2010; Danne et PRE-PRANDIAL INSULIN ADMINISTRATION 5 al., 2003; Scaramuzza et al., 2010). According to Scaramuzza et al. (2010), pre-prandial insulin administration, either 15 minutes or immediately prior to a meal, was more effective than postprandial administration in keeping BG stable and closer to therapeutic levels. A randomized control study by, Enander, Gundevall, Stromgren, Chaplin, and Hanas (2012), showed a significant reduction by 0.5% in HbA1c in participants who administered pre-prandial insulin based on counting their carbohydrate consumption. Another randomized study on pre- versus post insulin administration by Ratner, Wynne, Nakhle, Brusco, Vlajnic, and Rendel (2011) did not find a significant difference in HbA1c level. However, they did find fewer symptoms and episodes of nocturnal hypoglycemia. It appears that there is a growing body of evidence supporting pre-prandial insulin administration to better control BG and HbA1c. The emerging evidence of the effectiveness of pre-prandial insulin administration has led to the clinically relevant PICOT question: In diabetic school-aged children (P), how does preprandial insulin administration (I), versus standard of care (C), affect HbA1c (O) over three months (T). Search Strategy In order to answer the aforementioned PICOT question, a comprehensive literature search was conducted via the following databases: Cochrane Library, PubMed, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). A combination of the following keywords were used within each database: school-aged children(s), pediatric(s), adolescent(s), children(s), youth(s), diabetes, diabetic(s), pre-prandial, before meal(s), post-prandial, after meal(s), blood sugar, blood glucose, HbA1c, HgA1c, A1c, insulin administration, insulin injection, meal dosing, meal time injection, and timing of meal injection/administration. PRE-PRANDIAL INSULIN ADMINISTRATION 6 Boolean connectors AND, OR, IN, and FOR were used in various places within the search as well. In addition, an ancestry and cross reference search was identified through relevant articles. PubMed Initially, the search in PubMed yielded 148 articles. When searched using "timing of insulin administration AND children AND blood sugar", the search yielded 30 articles. In limiting publication dates to the last five years and the human species, nine articles were found but only two were applicable and retained for further review. CINAHL The search in CINAHL resulted in 28 articles with the following terms: timing of insulin administration AND children AND blood sugar. The search was refined to include the English language, within the last five years, all child, and publications for pediatric diabetes which resulted in 10 studies. Boolean phrases used were: Blood glucose/AND OR Diabetes Mellitus. The search was further broken down into major headings using BG yielding a final result of three articles. Two studies were retained for further evaluation. Cochrane Library The search for pre-prandial insulin administration in the Cochrane Library yielded 10 studies. Using the MeSH term hemoglobin A, and Glycosylated (HbA1), the search yielded 20 Cochrane reviews. Other MeSH terms used included: Diabetes Mellitus and BG self-monitoring. The search phrase “pre-prandial insulin injection” and limiting the search to articles from 2010 to 2015 yielded 12 articles. Of the 12 articles, four were included for further review. After this exhaustive literature search, eleven studies were chosen for further review and critically appraised in order to place the salient points in an evaluation table. The studies consisted of five randomized cross over studies, one non-randomized cross over study, one PRE-PRANDIAL INSULIN ADMINISTRATION 7 randomized controlled trial, one non-randomized controlled trial, two pilot studies, and one systematic literature review. Articles pertaining to the adult population and older than five years were included due to limited number of studies performed on the subject and conducted with the pediatric population. However, these studies had significant findings supporting pre-prandial insulin administration. Some studies were excluded because it did not pertain to insulin timing comparison. Critical Appraisal and Synthesis of Evidence Overall, the studies chosen for further review were strong, good quality studies consisting of one level I, seven level II, and three level III studies using Fineout-Overholt & Melnyk (2006), rapid appraisal for RCT's. Seven studies were performed within the last five years and four were more dated due to limited studies on the subject matter in the pediatric population. The majority of the studies were randomized crossover studies. The remainder were nonrandomized cross over, crossover, or pilot studies. The eleven studies exhibited a moderate to strong degree of homogeneity in diagnosis, insulin dependence, and major variables as shown in the synthesis Table 2 (Appendix F). However, heterogeneity was observed in the demographics because studies on adults were included (Appendix E). The population age ranges from two to 82 years of age. Although the population age ranged widely across the lifespan, nine of the studies included participants within the targeted age group (Corby et al., 2010; Danne et al., 2003; Danne et al., 2007; DePalma et al., 2011; Enander et al., 2012; Fullerton et al., 2014; Luijf et al., 2010; Scaramuzza et al., 2010; Schernthaner et al., 2004). Four studies were conducted in a hospital setting and six were in an outpatient setting. Although eight studies were conducted outside the U.S., the findings can likely be generalized as they focused on the same diagnosis and utilized similar inclusion and PRE-PRANDIAL INSULIN ADMINISTRATION 8 exclusion criteria. There was strong homogeneity in the variables of interest amongst the eleven studies. Nine of eleven studies had post-prandial BG as the independent variable and timing of insulin administration as the dependent variable. Seven out of eleven studies measured postprandial BG differences between the timing of insulin administration. The majority of the studies utilized the following statistical analysis: level of significance (p), ANOVA, and t-test. Other statistical analyses that were used in less than three studies include: 95% confidence interval (CI), trapezoidal method for area under the curve (AUC), standard deviations (SD), Pearson's correlation coefficient, degree of power, Fisher's exact test, 7-point blood glucose profile, and Wilcoxon's test. The statistical analysis aids the reader to extrapolate significant results in order to take action (Kellar and Kelvin, 2013). The brand of glucose monitor used were not consistent in all eleven studies, however, quality controls were performed in most studies to ensure accuracy of the monitors utilized. The measurement tools used to measure BG was not consistent throughout the eleven studies. Six out of eleven studies received funding from various drug and medical equipment companies raising the suspicion for bias, however all authors denied any potential bias. Conclusion of Evidence Overall, the eleven studies had a similar conclusion: pre-prandial insulin administration is the preferred practice over post-prandial insulin administration. Improved post-prandial BG, less glucose excursions, greater patient satisfaction, and decreasing BMI also were found as a result of pre-prandial insulin administration. Therefore, this proposed Doctor of Nursing Practice (DNP) project plans to develop and deliver an educational program for parents of type 1 schoolaged and adolescents with diabetes and institute pre-prandial insulin administration as the standard of care in an outpatient pediatric endocrine clinic. PRE-PRANDIAL INSULIN ADMINISTRATION Chapter 2 The purpose of this DNP project is to critically analyze the literature for supporting evidence to guide nursing practice in order to promote health. However, translating evidence into practice is an arduous task. The use of theory and models were utilized to assist and guide this DNP project. John Hopkins Evidence-Based Model The John Hopkins Evidence Based Practice (JHNEBP) model was chosen to guide this DNP practice change project. The model involves three major process: practice question, evidence, and translation (Newhouse et al., 2007). The practice question is the evidence-based practice (EBP) question and assigning roles. The second process involves identifying internal and external evidence, appraising the evidence, and developing recommendations based on strength of evidence (Newhouse et al., 2007). The final process is translation, which involves determining feasibility, creating an action plan, implementing change, evaluating outcomes, identifying next steps, and communicating findings (Newhouse et al., 2007). The JHNEBP model is fitting to guide the proposed DNP project which will lead to a practice change because it recommends in-depth investigation of evidence, risks, harms, applicability, and outcomes. In following each step of the process, the model clearly gives guidance to find solutions to clinical problems in need of a practice change. Step 1 of the model was depicted through the identification of the PICOT question. Step 2 involves gathering evidence both in practice and from the literature to support or dismiss the practice change (i.e., pre-prandial insulin administration). In appraising the evidence, strength and applicability of a study can be identified and used to determine the reliability and validity of the results. Lastly, the model suggest that a plan of action be implemented in practice that is based on the evidence which 9 PRE-PRANDIAL INSULIN ADMINISTRATION 10 supports pre-prandial insulin administration in pediatric patients. The goal is to educate parents and children and eventually mainstream pre-prandial insulin administration in school-aged children in an outpatient pediatric endocrine clinic. Imogene King’s theory of goal attainment also was used to guide this project. This midrange theory incorporates the following concepts: stress, personal space, self, perception, time, growth and development, communication, interaction, transaction, and role (Parker and Smith, 2010). The transaction process model is a universal model that can be applied to just about any scenario involving at least two persons (Parker and Smith, 2010). It is through this interaction that goals are set and obtained. Using the transaction process model, a goal was set with patient and parent. The dyad received education regarding pre-prandial insulin administration and agreed to change their practice of administering insulin after eating. The goal is to improve BG and HbA1c in children with type 1 diabetics through pre-prandial insulin administration. Closer blood glucose control may prevent detrimental future sequelae such as neuropathy, blindness, and amputations. Methods Ethical Approval Online training Collaborative Institutional Training Initiative (CITI) was completed prior to beginning the DNP project. Modules were completed for informed consent, the Health Insurance Portability and Accountability Act (HIPAA), basic IRB regulation and review process, vulnerable subjects, conflict of interest in research involving human subjects, assessing risks, privacy and confidentiality, and data management. A certificate of completion was obtained after completing the modules and exam. In addition, approval from Arizona State University’s IRB was granted on January 3, 2016 (Appendix G). PRE-PRANDIAL INSULIN ADMINISTRATION 11 Participants and Setting Horizon View Medical Center’s (HVMC) outpatient pediatric endocrinology office was chosen for the location for this DNP project due to access of the targeted population. A letter of support can be viewed in Appendix H. Recruitment and data collection were performed during routine office visits. All parents with children who have type 1 diabetes were given an explanatory introduction letter from the medical assistant at check-in (Appendix J). The inclusion criteria to participate in the project included: children ages six to 18 years, diagnosed with type 1 diabetes, English speaking, diagnosed for three or more years, have a hemoglobin A1c (HbA1c) of at least eight percent since last visit, and who are medically stable on their current insulin regimen. Procedure If parents were interested in participating and met the inclusion criteria, Ngoc Quyen Bui, Doctor of Nursing Practice (DNP) student answered questions or concerns that the parent and child may have. Informed consent, assent, and pre-survey questionnaires were completed during the initial visit by parents and children. The parent created a four digit identification (ID) number with the last four digits of their phone number to ensure confidentiality (Appendix K). Information regarding weekly blood glucose reports and blood results for blood glucose and HbA1c were obtained via electronic medical records. In addition, teaching was done in both verbal and a written format during the initial visit (Appendix L). Verbal teaching regarding insulin injection sites, rotation of sites, rotation techniques, when to change the insulin cartridge, and sick days were reinforced with parent and child during the initial visit. Common injection sites were: abdominal region, lower back side, thigh, and back of arms. The W, M, or circle method can be used for site rotation to prevent scar tissue buildup. Sites should be rotated every PRE-PRANDIAL INSULIN ADMINISTRATION 12 3 days along with the insulin cartridge change. Parents were reinforced to substitute carbohydrates with sugary drinks or soft foods when the child cannot tolerate solids during a gastrointestinal or other minor acute illness. The parents also were taught to check blood glucose more frequently (every 2-3 hours) and urine for ketones when the child was ill. The teaching handout contained information on the sliding scale with different BG levels and time for administration. Parents were instructed to always carry glucose tablets and intramuscular glucagon for hypoglycemic episodes. For medical emergency, parents were advised to call 9-1-1 then notify the endocrinology’s office per office routine. The pre-questionnaires contained questions regarding family and child demographics, general diabetes care, and current practice (Appendix M). The follow-up survey was administered at the routine three month visit (Appendix N). Outcome measures Content validity of pre and post surveys and educational handout was determined by Dr. Saad and Trisha Briones, CPNP at HVMC. The pre and post surveys utilized a Likert type scale, fill in the blank, multiple choice, and open ended questions. Data was analyzed using the Wilcoxson paired t-test and descriptive statistics. Data collection The data was be stored on a password protected computer to ensure that only the authorized users can access the information. Authorized users were Ms. Bui and Dr. Jacobson. Hard copies of the completed surveys were identified only with an identification (ID) number that the parent created with the last four digit of their phone number during the initial visit. The de-identified data is to be stored for 6 months. Hard copies of the surveys were shredded immediately upon completion of data analysis. Ngoc Quyen Bui RN, DNP student and Diana PRE-PRANDIAL INSULIN ADMINISTRATION 13 Jacobson PhD, RN, PPCNP-BC, PMHS, FAANP had full access to the data. Ms. Bui obtained the weekly blood glucose readings from the child’s medical record after receiving consent from the parents. Ms. Bui had full access to the medical records to obtain blood glucose, hemoglobin A1c, and weekly blood glucose report from January to May 2016. After this period, no future data was collected. De-identified data is planned to be presented to Horizon View Medical Center medical and nursing health care providers at the completion of the project. Budget It was projected that the project would cost less than $30 to complete and the cost met this expectation. The only foreseeable cost incurred was to print the pre- and post- survey questionnaires, consents, educational handouts, introduction letter, instructions, time, and cost for gasoline to travel to the endocrine clinic (Appendix I). However, the providers at HVMC agreed to have the questionnaires printed in the office to help offset the cost. There were no compensation offered for the participants. In addition, the project took place during routine office visits with blood tests ordered and obtained at the clinic with the patient’s insurance covering this cost. Therefore, there were no extra costs incurred by the participants to participate in this DNP project. Writing implements were available in every exam room for the participants to complete the questionnaires. Estimated total time and cost for travel to the clinic was six hours and $30 for gasoline. Actual cost of the project was roughly $35 dollars for printing services and gasoline. Results Although 20 participants were anticipated to be recruited, this was not achieved due to the following circumstances: child’s HbA1c was less than 8%, the parent did not speak English, or the child was not ready to commit to a change in insulin administration. A higher number of PRE-PRANDIAL INSULIN ADMINISTRATION 14 participants could have been recruited if the criteria allowed for Spanish speaking dyads and a longer time frame was allowed for recruitment. A total of seven participating dyads that met all the inclusion criteria were included in the project. Demographics The participant age ranged from eight to 17 years. There were four females and, 3 males. The race/ethnicity of the participants included three African Americans, three Hispanics, and one Hispanic/Caucasian. Means The participant’s average age was 13.9 years and average age at diagnosis was 10 years. The mean HbA1c recorded from the initial session was 10.33%. Three month follow-up appointments were scheduled for late March 2016 or early April 2016. A Wilcoxson paired ttest and descriptive statistics were used to analyze the data. First Visit Child Survey Five participants reported their current practice as only administering insulin after meals; one reported administering insulin after meals at school and before meals at home; and one participant administered insulin before meals only. All participants were comfortable with insulin administration but only five knew their insulin to carbohydrate ratio. All seven participants were aware of at least one of four options for treating hypoglycemia and could name at least two out of three potential sites for insulin administration. Pre-assessment Parental Survey Three parents thought that pre-prandial insulin administration would help lower their child’s blood glucose; three did not know; and one reported only sometimes they think it does. Not every parent was comfortable with insulin administration. In fact, only two reported being PRE-PRANDIAL INSULIN ADMINISTRATION 15 comfortable all the time; three were comfortable most of the time; and two were somewhat comfortable. However, all seven parents had knowledge of their child’s current insulin to carbohydrate ratio, site of insulin administration, insulin practice, and what to do on sick days. Post-data No post-data information was available. Three patients did not keep follow-up appointments. Spoke with two parents via telephone and sent post-survey via email. Parents were also reminded to send blood glucose reports from the past 3 months. Unfortunately, no data was received. Therefore, post intervention data analysis was unable to be completed. Limitations and Implications Although results from data analysis is not yet available, it is expected that the results would mirror that of evidence synthesis from the literature. This DNP project has the potential to lower BG and HbA1c for patients and help providers at HVMC to better manage type 1 DM. Anticipating a positive outcome, it is vital to sustain the pre-prandial insulin administration practice. The biggest limitation of this project was the sample size and waiting three months for post data to be available. Discussion Most of the parents I have interacted with were excited and willing to participate in a DNP project that could potentially help their children. The medical assistants, healthcare providers, and dietician helped to identify potential participants for the project. Without the support and aid of the staff, it would not have been possible to complete the project. Ultimately, the goal of this DNP project was to help patients with type 1 DM gain better control of their condition by lowering their blood glucose and HbA1c changing their insulin administration time PRE-PRANDIAL INSULIN ADMINISTRATION 16 from post-prandial to pre-prandial. In turn, this practice change also assisted providers to provide evidence-based care to better manage their patients’ condition. Chapter 3 Although the project got a late start and did not achieve the planned 20 participants as anticipated, the recruiting process went smoothly. The project is low cost and can be easily replicated. Parents were willing to participate because the project had the potential to lower blood glucose and HbA1c. Current policies such as the Affordable Care Act and Children’s Health Insurance Program (CHIP) in Nevada helped ensure all children have access to medical care and financial support for medical services. These policies were important especially for children with chronic diseases, such as type 1 diabetes, that require closer monitoring. Impact of Health Policies Children of lower-income households are at a disadvantage when it comes to receiving the proper health care. However, with health care initiatives like the Affordable Care Act (ACA) which was enacted in 2010, it is possible. The goal of the ACA was to expand health coverage to all Americans, lower costs, and enhance quality of care (Medicaid, 2016). Under the ACA, revisions to improve the CHIP in Nevada was established. Some of the revisions include: yearround open enrollment and provision for minimum mandatory benefits to prevent and treat health conditions (Medicaid, 2016). This is especially important for low-income children with chronic conditions such as type 1 DM. These children are insulin dependent, require frequent follow-ups, and laboratory blood tests. Without coverage, these children will not have appropriate access to medical care and treatment. Leadership Role and Sustainability PRE-PRANDIAL INSULIN ADMINISTRATION 17 Prior to this DNP project, I had limited exposure to conducting a translational practice change project. As a first time project director, I had a lot of fear and doubt in completing this project. The topic of the project was changed several times mostly due to feasibility and site permission. Once the topic and site permission was approved, the next problem to tackle was getting Institutional Review Board (IRB). It was a long process but with the help of my mentor Dr. Diana Jacobson, IRB approval was obtained. Sustaining participants in the project proven more difficult than anticipated since the protocol required the collection of post intervention data to be at 3 months. Three months for post intervention follow up was chosen in order to be able to recognize changes in HbA1C. However, as a leader, I have learned how to overcome the challenges of designing and delivering a practice change intervention due to my ability to persevere and continue. Lessons from this project will help with future practice change endeavors. This is a cost-effective project that will not require any additional training, guidelines, and no additional human labor costs. The providers, in the future, will discuss pre-prandial insulin administration during scheduled visits. Weekly blood glucose reports will continue to be sent via email by the parents for necessary treatment adjustments and ensure the child’s safety per office protocol. Conclusion Both providers and parents were supportive of this DNP project. Limited resources both human and fiscal are needed to sustain this practice change. During scheduled visits, providers can reinforce the importance of pre-prandial insulin administration. When providers indicate that this practice change is evidence-based, it can help increase parental confidence and compliance. In addition, there are no additional costs to incur since there are no additional extra PRE-PRANDIAL INSULIN ADMINISTRATION 18 staff or materials required. Again, the only change is the timing that insulin is instructed to be given. The eleven studies selected for critical appraisal showed improved post-prandial BG, less glucose excursions, greater satisfaction, and decreasing BMI as a result of pre-prandial insulin administration. Although larger scale research is needed, specifically in the pediatric population, the evidence suggests pre-prandial insulin administration should be adopted for better glycemic control and management of type 1 diabetes in children. It was expected that the results of this DNP project would show a decrease in children’s BG and HbA1c as suggested by the literature. This DNP project has taught me the value of evidence-based practice (EBP). Learning about EBP in the classroom and actually seeing its potential impact in real life offers a new perspective in my future practice as an advanced practice nurse in pediatrics. Personally, this project has motivated me not to become complacent when practicing but always question and search for a better solution based on evidence! I hope there will be more data collected within this endocrine practice site with a greater number of participants but the inclusion of other outpatient endocrinology offices in Las Vegas or even statewide may demonstrate even future benefit. In addition, the creation of a national guideline for pediatric insulin administration with specific time frames in which the pre-prandial insulin should be administered should be developed. PRE-PRANDIAL INSULIN ADMINISTRATION 19 References American Diabetes Association (2014). Statistics about diabetes. Retrieved from http://www.diabetes.org/diabetes-basics/statistics/ Blazik, M., Pnkowska, E. (2010). The education of patients in prandial insulin dosing related to the structure of bolus calculators. Pediatric Endocrinology, Diabetes, and Metabolism, 16(4), 301-305. Center of Disease Control and Prevention (2014). Diabetes in youth. Retrieved from http://www.cdc.gov/diabetes/risk/age/youth.html Corby, E., McFann, K., Messer, L., Gage, V., VanderWel, B., Horton, L., Chase, P. (2010). Timing of meal insulin boluses to achieve optimal postprandial glycemic control in patient with type 1 diabetes. Diabetes technology and therapeutics, 12(3), 173-177. doi 10.1089/dia.2009.0112 De Palma, A., Giani, E., Iafusco, D., Bosetti, A., Macedoni, M., Gazzarri, A., Spiri, D., Scaramuzza, A., Zuccotti, G. V. (2011). Lowering postprandial glycemia in children with type 1 diabetes after Italian pizza "Marghertia" (TyBoDi2 Study). Diabetes Technology and Therapeutics, 13(4), 483-487. doi 10.1089/dia.2010.0163 Enander, R., Gundevall, C., Chaplin, J., Hanas, R. (2012). Carbohydrate counting with a bolus calculator improves post-prandial blood glucose levels in children and adolescents with type 1 diabetes using insulin pump. Pediatric Diabetes, 13, 545-551. doi 10.1111/j.1399-5448.2012.00883.x Fullerton, B., Jeitler, K., Seitz, M., Horvath, K., Berghold, A., Siebenhofer, A. (2014). Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus (Review). The Cochrane Collaboration, 1-152. PRE-PRANDIAL INSULIN ADMINISTRATION 20 Kellar, S. P., Kelvin, E. A. (2013). Munro’s statistical methods for health care research (6th ed.). Philadelphia: Lippincott, Williams & Wilkins. Liberty, I. F., Gelber, A., Novack, L., Novack, V., Boteach, E., Harman, Boehm, I. (2012). Timing of insulin bolus in patients with type 1 diabetes: Effect on glucose control and variability using CGMS. Practical Diabetes 29:10.1002/pdi.v29.3, 98-102c. Luijf, Y. M., Van Bon, A. C., Hoekstra, J. B., DeVries, J. H. (2010). Premeal injection of rapidacting insulin reduces postprandial glycemic excursions in type 1 diabetes. Diabetes Care 33, 2152-2155. Owens, D. R., Luzio, S. D., Sert-Langeron, C., Riddle, M. C. (2011). Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: A 6-month 'proof-of-concept' study. The Cochrane Collaboration, 1020-1027. doi 10.111/j.1463-1326.2011.01459.x Parker, M. E., & Smith, M. C., (2010). Nursing theories & nursing practice (3rd ed.). Philadelphia: Davis. Ratner, R., Wynne, A., Nakhle, S., Brusco, O., Vlajnic, A., Rendell, M. (2011). Influence of preprandial vs. postprandial insulin glulisine on weight and glycaemic control in patients initiating basal-bolus regimen for type 2 diabetes: A multicenter, randomized, parallel, openlabel study (NCT00135096). Diabetes, Obesity, and Metabolism, 13, 1142-1148. Samahy, M. H., Elbarbary, N. S., Elmorsi, H. M. (2015). Current status of diabetes management, glycemic control and complications in children and adolescents with diabetes in Egypt. Where do we stand now? And where do we go from here? Diabetes Research and Clinical Practice, 1-7. PRE-PRANDIAL INSULIN ADMINISTRATION 21 Scaramuzza, A., Zuccotti, G. V. (2011). Lowering postprandial glycemia in children with type 1 diabetes after Italian pizza "Marghertia" (TyBoDi2 Study). Diabetes Technology and Therapeutics, 13(4), 483-487. doi 10.1089/dia.2010.0163 Schernthaner, G., Wein, W., Shnawa, N., Bates, P. C., Birkett, M. A. (2004). Preprandial vs postprandial insulin lispro-a comparative crossover trial in patients with type 1 diabetes. Diabetes UK Diabetic Medicine, 21(3), 279-284. PRE-PRANDIAL INSULIN ADMINISTRATION Appendix A 22 PRE-PRANDIAL INSULIN ADMINISTRATION Appendix B 23 PRE-PRANDIAL INSULIN ADMINISTRATION Appendix C 24 PRE-PRANDIAL INSULIN ADMINISTRATION Appendix D 25 Running head: PRE-PRANDIAL INSULIN ADMINISTRATION FINAL REPORT 26 Appendix E Table 1 Evaluation Table Author Cobry (2010) Timing of meal insulin boluses to achieve optimal postprandial glycemic control in patients with type 1 diabetes L: Colorado, USA F: SanofiAventis C/B: NR Conceptual Framework Design/Purpose Sample/Setting PT Design: CO study n = 23 LOS: 3 days Demographics: Mean age (18.3) 11 females 12 males 11 < 18 y/o 12 (18-29 y/o) DV: PP BG Purpose: To determine optimal timing of insulin in relation to meal time to minimize post-prandial blood glucose in T1D. Setting: OP Major Variables Measurement M- Freestyle Flash Data Analysis/Stats Used Fisher's exact test AUC S- p < 0.05 IV: TIA GE IV1: PRE20 mins PRP IV2: STARTimmediately PRP BG max Study Findings GE @ 60 mins PP: PRE < START and POST - p = 0.001 BG @ 120 mins PP: PRE < START & POST - p = 0.0408 ATR: 0% IC: Diagnosed with T1D for average of 11 years, weighs ~52.3kg, and A1c ~ 7.5% EC: Digestive conditions, gastroparesis, and celiac disease IV3: POST20 mins PP PRE AUC < START (p = 0.0297) & POST (p = 0.0463) PRE BG max < START (p = 0.0039) & POST (p = 0.0027) PRE had less BG > 180 mg/dL vs. START ( Evidence/Strengths/Limitations /Confidence to Act LOE: III Strengths: Low risk Standardized frozen pre-packaged meals w/ <20g of fat and known carb. content 0% ATR Limitations: Small sample Confidence to Act: Yes, the study was well designed, low risk, pediatric population, low attrition rate, and easy to replicate. PRE-PRANDIAL INSULIN ADMINISTRATION Author Danne (2003) A comparison of postprandial and preprandial administration of insulin Aspart in children and adolescents with type 1 diabetes L: Germany F: NR Conceptual Framework PT Design/Purpose Design: ROLT & CO Purpose: To compare glycemic control of PRP vs PP in children and adolescents with T1D. Sample/Setting 27 Major Variables Measurement n = 76 LOS: 5 days A1c Demographics: Age range (6-17 y/o) 49%-males 55%-<=13 y/o DV: PP BG Serum fructosamine Setting: Hospital ATR: 7% IC: Diagnosed with T1D for average 4.4 y (range 1-9.4y) C/B: NR EC: TDID >= 1.8 IU/kg, taking oral antidiabetic agents, unaware/recurre nt hypoglycemia, IV: TIAIV1: PRE: Immediately before meal IV2: POST: Immediately after; 30 mins max after Data Analysis/Stats Used OSNIT for serum fructosamine Study Findings p < 0.0001) & POST (p < 0.0001) PP BG @ 120 mins. DV1 < DV2 - p = 0.016 7-PBGP for A1c Satisfaction with DV1 vs. DV2 CI 95% SAS 6.12 on UNIX platform Satisfaction with DV1 p < 0.01 Evidence/Strengths/Limitations /Confidence to Act LOE:II Strengths: Safety was discussed Exclusions discussed Low ATR Limitations: Small sample No blinding No discussion of exclusion criteria Standardized meals- not discussed Statistical analysis and numerical data not discussed Confidence to Act: Yes, it is applicable to target population and testing methods are easy to replicate. A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Danne et al. (2007) Parental preference of prandial insulin aspart compared with preprandial human insulin a basal-bolus scheme with NPH insulin in a 12-wk crossover study of preschool children with type 1 diabetes. Conceptual Framework PT Design/Purpose Design: RCO Purpose: To compare S&E + parental satisfaction of (IAsp + NPH insulin) v. (HI + NPH) Sample/Setting significant concomitant illness pregnant, may become pregnant, allergy to product, and noncompliance with trial procedures n = 26 nIAsp + NPH = 12 n HI + NPH = 14 Demographics: AA = 2.4-6.9 y/o Males: 17 Females: 9 MA: 5 +/- 1.3 y/o DD: 1.8 +/- 1 y A1c: 7.8 +/1.1% Setting: OP 28 Major Variables LOS: 12 weeks DV1: avg PP BG DV2: HbA1c DV3: fructosamin e, DV4: satisfaction IV: TIA & combo of insulinIV1: PRE Measurement Data Analysis/Stats Used Study Findings Avg PP BG, A1c, fructosamine, and satisfaction WHO DTSQ-Mto assess treatment satisfaction NS: avg PP BG, A1c, or fructosamin e of PRE vs. POST Seven-point BG profiles Evidence/Strengths/Limitations /Confidence to Act LOE: II Strengths: Randomized Discussion of search criteria Limitations: No blinding No homogeneity of meals and compliance Small sample sized No statistical method described Funding by Eli Lilly & Co Confidence to Act: Yes, the study was well designed and easy to replicate with minimal risks. A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Conceptual Framework Design/Purpose Sample/Setting L: Germany ATR: 15% F: Novo Nordisk A/S, Denmark IC: Treatment with insulin or insulin analog >= 6M A1c <= 12% Currently treated with short, intermediate, or long acting HI or insulin analogs or selfmixed >= 1M C/B: Yes De Palma (2011) Lowering postprandial glycemia in children with PT Design: PS EC: Investigational drug within last month Hypoglycemic unawareness Allergy nScreened = 56 n = 38 Purpose: To determine most effective Demographics: AA: 6-19 y/o n-boys = 23 29 Major Variables Measurement Data Analysis/Stats Used Study Findings Evidence/Strengths/Limitations /Confidence to Act (IAsp + NPH ) IV2: POST (HI + NPH) LOS: 4 days BG DV: PP BG AUC IV- TIA & method- Stat-graphics Plus 5.1 Trapezoidal method for AUC AUC 6h BG PP DV3 < DV2 - p = 0.01 LOE: III Strengths: IC & EC discussed Feasible to replicate No ATR A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author type 1 diabetes after Italian pizza "Marghertia" L: Italy F: None indicated C/B: No Conceptual Framework Design/Purpose Sample/Setting type and timing of bolus using insulin pump in children with T1D. n-girls = 15 DD 8.0 +/- 4.3 Mean BMI 21.9 +/- 4.3 m/kg2 ID: 0.83 +/0.30 U/k/day A1c 7.66 +/0.81% Setting: Hospital ATR: 0% Inclusion Criteria: DD >= 1 y, IPT > 6 months, knowledge of bolus calculator > 3 months, and invitational only. 30 Major Variables IV1- 15 mins PRP; DWB (30% PRE & 70% over 6h) Measurement Data Analysis/Stats Used t-test S = p < 0.05 Study Findings Evidence/Strengths/Limitations /Confidence to Act Limitations: Small Sample Confidence to Act: Yes, the supporting evidence is strong and is applicable to pediatric population. IV2: START ; DWB (30% PRE & 70% over 6h) IV3: 15 mins PRP IV4: STARTimmediately PRP Exclusion Criteria: Eating disorders, diabetes-related complications, A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Enander (2012) Carbohydrate counting with a bolus calculator improves postprandial blood glucose levels in children and adolescents with type 1 diabetes using insulin pumps. L: Sweden F: Fyrbodal Research Foundation, Skaraborg Research Foundation, Halland research Foundation, and Smith's Medical Conceptual Framework Design/Purpose Sample/Setting PT Design: RCT CD, and FA. n=45 age 13.8+/-3.4y (range 5-19.5) Purpose: To compare glycemic control of PRP vs PP in children and adolescents with T1D using carb counting bolus calculator. ATR: 11% Inclusion Criteria: T1D No previous CC experience EC: NR 31 Major Variables LOS: 12 months DV: PPBG & HbA1c IV1: G A CG IV2: G B manual CC IV3: G CCC on Cozmo pump Measurement Data Analysis/Stats Used A1c ANOVA BG t-test BMI Pearson's correlation coefficient S = p < 0.05 with 80% power Study Findings @ 12 months DV1 increased basal insulin dosage/kg/2 4h - p = 0.015 DV3 < BMI - p = 0.029 BG: DV3 < DV1 - p = 0.014 Evidence/Strengths/Limitations /Confidence to Act LOE: II Strengths: Exclusions discussed Randomized Standardized tools with same calibrations Limitations: Small sample No blinding No discussion of exclusion criteria Funding Confidence to Act: Yes, the study has a low ATR and 80% power. The study is also easy to replicate and applicable to target population. A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author C/B: Yes, from Medtronic, Roche, and Infucare Fullerton (2014) Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus (Review) L: F: Federal Ministry of Education and Research, Germany C/B: No 32 Conceptual Framework Design/Purpose Sample/Setting Major Variables Measurement PT Design: Literature review of RCT’s N Eligible = 154 N Qualitative Studies = 12 = 2230 participants LOS: >= 1 year with 1 year follow up DV: PO, SO, and A1c N Quantitative = 11 IV- IGC: * Testing BG >= 4 times a day * Injecting insulin >= 3 times a day * Adjusting insulin doses according to food intake and exercise plan * Making monthly visits to health care PO: * MC- MI, stroke * MICmanifestation and progression of retinopathy, nephropathy, and ESRD * Severe HE Purpose: To assess effects of intensive vs conventional glycemic targets in T1D in terms of long-term complications. Demographics: MA for 12 studies = 12 years AR = 0-22 y/o MA for 11 studies = 29 y/o AR = 26-43 y/o M A1c = 9.5% and 9.3% Setting: SO: * HRQOL * AE- HE, KA, and weight gain * All-cause mortality * Costs Data Analysis/Stats Used Odds ratios/Risks ratios CI 95% Data analysisReview Manager 5.2 DerSimonian and Laird’s random effects model Study Findings * Supports IGC in young people and at early stages of disease. * S ↓ risk for developing MIC in IGC group. Evidence/Strengths/Limitations /Confidence to Act LOE: I Strengths: R and high level of evidence Limitations: Confidence to Act: Yes, this review is highly reliable with 95% CI. Sensitivity- odds ratios and fixedeffect models For rare eventsfixed-effect method of Peto A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Conceptual Framework Design/Purpose Sample/Setting Literature review 33 Major Variables Measurement Data Analysis/Stats Used Study Findings Evidence/Strengths/Limitations /Confidence to Act team IV2: CGC ATR: N/A IC: T1D Same treatment regimens in both groups If not same treatment, difference in glycemic target must be clearly identified EC: Unspecified treatment targets Non-RCT Study <1 year No relevant outcomes No separate analysis of patients with T1D Duplicate A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Conceptual Framework Design/Purpose Sample/Setting 34 Major Variables Measurement Data Analysis/Stats Used Study Findings Evidence/Strengths/Limitations /Confidence to Act publication Jovanovic (2004) Efficacy comparison between preprandial and postprandial insulin aspart administration with dose adjustment for unpredictable meal size. L: California, USA F: Novo Nordisk Pharmaceutica ls Inc and Sansum Diabetes Research Institute internship fund PT Design: RCO Purpose: To compare metabolic effects of preprandial vs postprandial injection of bolus insulin lispro. n = 26 LOS: 2 days AUC ANOVA Demographics: AR: 22-82 y/o Mean BMI: 26.2 kg/m2 DV: PP BG Max mean (SD) BGC S = p < 0.05 Setting: OP IV: TIA IV1: PRE 0-5 mins before start of meal ATR: 27% IC: >= 18 y/o with T1D Treated with multiple daily insulin injections Able to calculate insulin-to-carb ratios, dose adjustments IV2: POST Immediately after meal AUC 22% less in DV1 - p < 0.001 Max means (SD): DV2 149.0 (9.9) mg/dL vs. DV1 102.0 (9.2) mg/dL- p < 0.001 both DV1 & DV2 had PP BG < 180 mg/dL - p <0.001 LOE: II Strengths: R, SV, and LR Discussion of search criteria Limitations: No homogeneity of meals and compliance Small sample sized High ATR Funding by Novo Nordisk Confidence to Act: Yes, the study was well designed, low risk, and well measured. EC: Abnormal thyroid, renal A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Conceptual Framework Design/Purpose Major Variables Measurement Data Analysis/Stats Used Study Findings Evidence/Strengths/Limitations /Confidence to Act disease, cardiac ischemia, pregnant, and breastfeeding. C/B: Yes Liberty (2012) Timing of insulin bolus in patients with type 1 diabetes: effect on glucose control and variability using CGMS. Sample/Setting 35 PT Design: BNRPS, OWB to BG Purpose: Effect of insulin bolus timing on overall daily BG control and variability. N = 16 nPRE = 12 nPOST = 12 L: Israel Demographics: >= 18 y/o AR: 23-71 y/o MA: 49.3 +/- 14 M BMI: 27 +/3.7 kg/m2 M A1c: 6.8 +/0.6% DD: 22.1 +/11.6 y F: Not mentioned Setting: OP C/B: No ATR: 25% LOS: 3 days DV: BG 1 & 2 hours PP IV- TIAIV1: PRP CGMMiniMed Medtronic A BG over 72 hours- LBGI, HBGI, BGRI SAS 9 software for M Wilcoxon test for CG Sign test- MO HGBI- DV2 > DV1- p = 0.003 BGRI- DV2 > DV1 - p = 0.003 LOE: II Strengths: R, SV, and LR Discussion of search criteria OWB No C/B indicated by authors MLM for MVA IV2: PP Limitations: No homogeneity of meals Short High ATR Confidence to Act: Yes, the study is reliable and can be easily replicated. IC: T1D Multiple daily injections A1c <= 7.8% A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Conceptual Framework Design/Purpose Sample/Setting 36 Major Variables Measurement Data Analysis/Stats Used Study Findings Evidence/Strengths/Limitations /Confidence to Act CCID EC: Luijf (2010) Premeal injection of rapid-acting insulin reduces postprandial glycemic excursions in type 1 diabetes. L: Netherlands F: Medtronic Netherlands provided M's only C/B: No PT Design: 3-way RCO Purpose: Effect of rapid acting insulin when given PRP on PP BG in T1D. n = 10 LOS: 3 days Demographics: MA: 45.5 +/12.1 y/o A1c 8.55 +/1.50% DD: 23.8 +/7.8 y Insulin therapy: 8.5 +/- 6.1 y DV: PP BG Setting: Hospital ATR: 0% IV: TIAIV1: PRE: 30 minutes prior to meal IV2: PRE: 15 minutes prior to meal IV3: "0" Immediately before meal CGM- SofSensor Medtronic BS: q15 mins @ 1h PRP, q 10 mins @ 2h PP, and q20 mins @ 3 & 4 hour PP Trapezoid method SPSS 17 for S = p < 0.005 ANOVA Paired sample ttest AUC Fisher exact DV1 had S lower AUC vs. DV2 & DV3 - p <0.029 DV1 had S lower GE vs. DV2 & DV3 - p < 0.009 LOE: II Strengths: Homogeneity of meals and compliance 0% ATR Limitations: Small sample sized Funding by Novo Nordisk Confidence to Act: Yes, strong evidence, easily replicated, and can be generalized to population. IC: Treatment with CSII >= 6M DD: 2 y BMI <= 35 kg/m2 BG 3.5-7.8 mmol/l on day of study A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Conceptual Framework Design/Purpose Sample/Setting 37 Major Variables Measurement Data Analysis/Stats Used Study Findings Evidence/Strengths/Limitations /Confidence to Act EC: BG < or > 3.57.8 mmol/l on day of study Scaramuzza (2010) Timing of bolus in children with type 1 diabetes using continuous subcutaneous insulin infusion HBM Design: NRCT Purpose: To determine optimal timing of bolus injection in children with T1D. n = 30 LOS: 3 days Demographics: Age range (6-20 y/o) Mean age = 15.2 13 females 17 males DV: PP BG L: Italy Setting: Hospital F: NR ATR: 0% C/B: No IC: Diagnosed with T1D for average of 8 years, BMI 22.4, insulin requirement 0.77 +/- 0.21 IV: TIA IV1: PRE: 15 mins PRP IV2: START: immediately PRP IV3: POST: immediately PP M- FreeStyle Lite ANOVA S = p < 0.05 IP- Paradigm 522/722 I- Novorapid AUC BG 60 mins PP: DV1 vs. DV3 - p = 0.044 DV2 vs. DV3- p = 0.024 LOE: III Strengths: Low risk Used same short-acting analog and same meter; glucose meter calibrated daily Standardized meals Same range of preprandial BG (80-140) NCI 0% ATR Limitations: Small sample No blinding and no randomization No discussion of exclusion criteria Confidence to Act: Yes, the study has no ATR, easy to replicate, and low risk. A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Conceptual Framework Design/Purpose Sample/Setting 38 Major Variables Measurement Data Analysis/Stats Used Study Findings High performance liquid chromatography for A1c Model appropriate for crossover design to test for carryover effects if any Mean A1c in from baseline to final - DV1 < DV2 - p = 0.008 Analysis of variance Mean PP BG DV2 > DV1 - p = 0.031 Evidence/Strengths/Limitations /Confidence to Act U/kg/d, and using insulin pump >= 6M Schernthaner (2004) Preprandial vs. postprandial insulin lisproa comparative crossover trial in patients with type 1 diabetes L: Austria F: Eli Lilly & Co C/B: Yes PT Design: RCO Purpose: To compare metabolic effects of preprandial vs postprandial injection of bolus insulin lispro. EC: NR n = 31 nPRE = 16 nPOST = 15 Demographics: Mean age = 31 Mean BMI = 24.3 +/2.3kg/m2 Setting: OP ATR: NR IC: ID, diagnosed before 40 y/ with T1D, II 3+ times/day, HbA1c <= 8%, BMI <35kg/m2, no advanced/rapidl y progressing LOS: 6 months DV: HbA1c & Fructosami ne IV: TIA IV1: PREimmediately PRP IV2: POSTimmediately to 30 minutes PP Colorimetric test by reaction with nitroblue tetrazolium for fructosamine with coefficient of variation of 2% 8-point BG measurements LOE: II Strengths: Randomized Discussion of search criteria Limitations: No homegeneity of meals and compliance Small sample sized Funding by Eli Lilly & Co Confidence to Act: Yes, the study was well designed with reliable results. A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old PRE-PRANDIAL INSULIN ADMINISTRATION Author Conceptual Framework Design/Purpose Sample/Setting 39 Major Variables Measurement Data Analysis/Stats Used Study Findings Evidence/Strengths/Limitations /Confidence to Act complications. EC: History of severe hypoglycemia, proliferative retinopathy, nephropathy, liver disease, or insulin allergy/resistanc e A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/B-conflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, II-insulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MIC- microvascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCTnon-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old Running head: PRE-PRANDIAL INSULIN ADMINISTRATION FINAL REPORT 40 Appendix F Table 2 Synthesis Table Cobry Danne Danne De Palma Enander Fullerton Jovanovic Liberty Luijf Scaramuzza Schernthaner 2003 2007 2011 2012 2014 2004 2012 2010 2010 2004 III II II III II I II II II III II CO RCO RCO PS RCT Literature review RCO NRPB RCO NRCT RCO 23 76 26 38 45 23 studies 26 16 10 30 31 1230 6-17 2.4-6.9 6-18 5-19.5 0-43 22-82 23-71 45.5 +/_ 12.1 6-20 23.3-53 OP Hospital OP Hospital OP Literature review OP OP Hospita l Hospital OP Setting Age range N Demographics Design LOE Year 2010 A-average, AA-average age, A1c-HbA1c, AE- adverse events, AR-age range, ATR-attrition rate, AUC-area under the curve, BG-blood glucose, BGC-blood glucose concentration, BGRI-blood glucose risk index, BNRPS-blinded non-randomized pilot study, BS- blood sample, C/Bconflict/bias, CC-carb counting, CCID-carbohydrate counting for insulin dose, CD-celiac disease, CFB-change from baseline, CG-comparison group, CGC- conventional glucose control, CGM-continuous glucose monitoring, CO-crossover, CSII-continuous subcutaneous insulin infusion, DD-diabetes duration, DV-dependent variable, DWB-dual wave bolus, E-efficacy, EC-exclusion criteria, F-funding agency, FA-food allergy, G-group, G A-group A, G B-group B, GE-glucose excursion, HBGI-high BG indices, HBM-health belief model, HE- hypoglycemic episodes, HRQOL- health related quality of life, I-insulin, IC-inclusion criteria, ID-insulin dependent, IGC- intensive glucose control, IIinsulin injection, IPT-insulin pump therapy, IV-independent variable, KA- ketoacidosis, L-location, LBGI-low BG indices, LOE-level of evidence, LOS-length of study, LR-low risk, M-meter, MA-mean age, MC- macrovascular complications, MI- myocardial infarction, MICmicrovascular complications, MLM-mixed linear model, MO-matched observations, MVA-multivariable analysis, NRCT-non-randomized control trials, NS-non-significant, NR-not reported, OSNIT-one sided non-inferiority test, OP-outpatient, OWB-one way blinding, P-potential, PBGP-point BG profile, PG-parallel group, PM-post meal, PO- primary outcome, PP-postprandrial, PRP-preprandial, PRP II- preprandial insulin satisfaction, PS-pilot study, PT-physiologic theory, R-randomized, RCO-randomized cross over, RCT-randomized controlled trials, ROLT-randomized open-label trials, S-significant, SO- secondary outcome, SV-supervised, TIA-insulin administration, T1D-type 1 diabetes, T2D-type 2 diabetes, TDID-total daily insulin dose, STSQM-Diabetes treatment satisfaction questionnaire, Y/O-years old 41 USA German y Germa ny Italy Swede n N/A USA Israel Netherl ands Italy Austria 0 7 15 0 11 N/A 27 25 0 0 NR T1D T1D T1D T1D T1D T1D T1D T1D T1D T1D T1D PP BG PP BG PP BG PP BG & A1c PP BG PP BG PP BG PP BG A1c & Fructosami ne TIA TIA Avg.PP BG, A1 , Fructo samin e, & satisfa ction TIA and combo of I TIA CC mecha nism IGC or CGC TIA TIA TIA TIA TIA and PRE Adjust ed premeal insulin dosag es based on carb conte nt had 0.5% lower ↓ with IGC A1C S Findings IV DV Diagnosis ATR % Location PRE-PRANDIAL INSULIN ADMINISTRATION ↓ mean from baseline in PRP II v. POST ↓PR P II v. STAR T& POST ↓ PRP II v. STAR T& POST ↓PRP II v. POST ↓ CC with pump v. CG 42 PRP & PP II had PP BG < 180 mg/dL ↑ when II PP v. PRP ↓ PRP II v. POST ↓ START v. POST ↓in CC with pump BMI BG max BG PRE-PRANDIAL INSULIN ADMINISTRATION ↓when II 15-30 mins PRP ↓ PRP II v. STAR T& POST ↓when II 15-30 mins PRP GE ↓ PRP II v. STAR T Basal Insulin Dose Satisfaction Fructosamine AUC ↓ 22% in PRP II ↑ PRP II ↑ in CG ↓ 30 mins PRP v. 15 mins PRP & immedi ately PRP ↓ 30 mins PRP v. 15 mins PRP & immedi ately PRP ↑ in mean BG in POST v. PRP II PRE-PRANDIAL INSULIN ADMINISTRATION 43 MIC ↓ in IGC Recommendations II 20 mins PRP PRP II PP II is prefer red for parent s of preschool aged childre n II 15 mins PRP CC with bolus calcul ator can help ↓ PP BG PRP Appendix G PRP II PRP II II 15 mins PRP II 15 mins PRP PRP II preferred but PP II is acceptable PRE-PRANDIAL INSULIN ADMINISTRATION 44 PRE-PRANDIAL INSULIN ADMINISTRATION Appendix H 45 PRE-PRANDIAL INSULIN ADMINISTRATION 46 Appendix I Demographic Table Gender Ethnicity Age Age of Diagnosis Male 3 African American 3 8-12 2 7-10 5 Female 4 Hispanic 3 13-17 5 11-14 2 Hispanic & Caucasian 1 15-18 Cost Analysis Materials Printing costs Pens (available in each exam room) Travel time & cost (gasoline) Total Cost 5-10 0 6 hours ; $30 35 PRE-PRANDIAL INSULIN ADMINISTRATION 47 Appendix J 6850 North Durango Drive, Suite #301, Las Vegas, Nevada 89149 Phone: 702-641-8500 • Fax: 702-641-8502 • pedsendo@horizonviewmc.com Dear Parents of Horizon View Medical Center, My name is Ngoc Quyen Bui RN, and I am a Doctor of Nursing Practice at Arizona State University. I have been granted permission from Dr. Rola Saad and Nurse Practitioner Trisha Briones APRN, CPNP to complete a practice change project for Horizon View Medical Center. I am working under the direction of Diana Jacobson PhD, RN, PPCNP-BC, FAANP at Arizona State University College of Nursing and Health Innovation. The purpose of this Doctor of Nursing Practice (DNP) project is to educate you and your child about giving your child’s insulin prior to the planned meal instead of giving the insulin after your child completes his or her meal. As a part of this DNP project, we would like to have you and your child fill out two short surveys, once at the beginning of the project and once again three months later, that ask questions about you, your child’s health, your child’s diabetes management and your knowledge about diabetes. Your child’s blood glucose, hemoglobin A1c, and weekly blood glucose reports will be obtained from the electronic medical records at Horizon View Medical Center as part of this project. Your part in the DNP project will take the length of a routine office clinic visit (15-30 minutes) on two different days and this includes the time for diabetes management education and the completion of the surveys. The inclusion criteria for parents and children in this project include a diagnosis of type 1 diabetes for at least 3 years for the child, stability of your child’s health on his or her current health plan, the child’s age between 6-18 years old, English speaking for both the child and parent, and the child with a HbA1c greater than 8% since last office visit. A four digit identification (ID) number using the last four digits of your telephone number will be created at the initial visit. The purpose of this ID number is to protect you and your child’s privacy. Please let the front office staff or one of the providers know if you are interested in participating and Ms. Bui will give you more information. Sincerely, Ngoc Quyen Bui RN ASU IRB IRB # STUDY00003484 | Approval Period 1/3/2016 – 1/2/2017 PRE-PRANDIAL INSULIN ADMINISTRATION Appendix K How to create an identification (ID) number • • Choose a home, work, or cell phone that you and your child can easily remember. Use the last 4 digits of this phone number to create your personal ID for this research study. 48 PRE-PRANDIAL INSULIN ADMINISTRATION 49 Appendix L Teaching Handout Glycemic goals: 6-12 years HgA1c Before Meals BG Bedtime/Overnight BG ≤ 7.5% 90-180 mg/dL 100-180 mg/dL 90-130 mg/dL 90-150 mg/dL 13-19 years ≤ 7% Recommended carbohydrates per meal: Male 5-12 years 13-19 years 45-60g 60-75g Female 45-60g 45-75g For hypoglycemic episodes, fast acting snacks need to provide 15-30g of carbohydrate • • • • 3-5 pieces of hard candy 4-6 ounces of regular soda or orange juice 2 tablespoons of raisins 8 ounces of nonfat or low fat milk Schedule for Insulin Administration: If blood glucose level is: Give the insulin at this time before eating: < 200 mg/dL 10 minutes prior to meal 200-300 mg/dL 20 minutes prior to meal > 300 mg/dL 30 minutes prior to meal If unable to predict carb intake Correct the blood sugar prior to eating using the chart above Contact information: • • In case of emergency: call 9-1-1 For questions or concerns: call 702-641-8500 or email diabetes@horizonviewmc.com References: 1. 2. 3. Centers for Disease Control and Prevention http://www.cdc.gov/features/diabetesinschool/ International Diabetes Federation https://www.idf.org/sites/default/files/attachments/HI62553-Carbohydrate-Counting-forChildren.pdf American Diabetes Association http://www.diabetes.org/food-and-fitness/food/what-can-i-eat/understandingcarbohydrates/carbohydrate-counting.html PRE-PRANDIAL INSULIN ADMINISTRATION 50 Appendix M First visit Child Survey ID number Age: Gender: Boy or Girl Ethnicity: Hispanic/Latino Asian Caucasian Black Other 1. When do you give yourself insulin shots? Before meals 2. During meals Date: What was your last HbA1c: ______ Pacific Islander Native American After meals Are you comfortable giving yourself insulin shots? 0 No 1 Maybe 2 Yes 3. Do you know your current insulin to carbohydrate ratio (I:C)? If yes, what is it? Yes No I don’t know 4. Put a check next to all the snacks that give you at least 15g of carbohydrates in case your blood sugar is less than 70 mg/dL? ⃝ 3-5 pieces of hard candy 4-6 ounces of regular soda or orange juice 2 tablespoons of raisins 8 ounces of nonfat or low fat milk Where on your body can you give insulin? Put a check mark next to all that are true. ⃝ ⃝ ⃝ 5. ⃝ ⃝ ⃝ 6. ⃝ ⃝ ⃝ ⃝ ⃝ ⃝ Stomach Back of your arms Thighs How many days go by before you change where you give insulin? I never change where I inject insulin. 1 day 2 days 3 days 4 days 5 days Pre-assessment survey for Parents ID number Child’s current age: Child’s Age at diagnosis: Please circle Parent Ethnicity: Hispanic/Latino Asian Native American Other 1. Date: Current HbA1c: Caucasian Black Pacific Islander When do you or your child currently administer short-acting insulin? PRE-PRANDIAL INSULIN ADMINISTRATION Before meals 2. During meals 51 After meals Do you think administering insulin before meals would improve your child’s blood glucose control? No I don’t know How comfortable are you with insulin administration? 1 2 3 4 Uncomfortable at A little Somewhat Most of the time I all times uncomfortable comfortable am comfortable most of the time Yes 3. 4. What is your child’s current Insulin to carbohydrate ratio (I:C)? 5. Fill in the blank: If your child’s blood glucose level is: < 200 mg/dL 200-300 mg/dL > 300 mg/dL If unable to predict carbohydrate intake 5 Very comfortable all the time Give the insulin at this time before eating: ____ minutes prior to meal ____ minutes prior to meal ____ minutes prior to meal Correct the blood sugar prior / after (circle one) to eating using the chart above 6. What area does your child use for insulin administration? 7. 8. How often does your child rotate injection sites? 9. What do you do if your child is sick and does not want to eat? Appendix N PRE-PRANDIAL INSULIN ADMINISTRATION 52 Second Visit Child Survey ID number Age: Gender: Boy or Girl 1. When do you give yourself insulin shots? Before meals 2. During meals Yes 4. ⃝ After meals Are you comfortable giving yourself insulin shots? 0 No 3. Date: What was your last HbA1c: ______ 1 Maybe 2 Yes Do you know your current insulin to carbohydrate ratio (I:C)? If yes, what is it? No I don’t know Put a check mark next to all the snacks that give you at least 15g of carbohydrates in case your blood sugar is less than70 mg/dL? 3-5 pieces of hard candy 4-6 ounces of regular soda or orange juice 2 tablespoons of raisins 8 ounces of nonfat or low fat milk 5. Where on your body can you give insulin? Put a check mark next to all answers that are true. ⃝ ⃝ ⃝ ⃝ Stomach Back of your arms Thighs 5. How many days go by before you change where you give insulin? ⃝ I never change where I inject insulin. ⃝ 1 day ⃝ 2 days ⃝ 3 days ⃝ 4 days ⃝ 5 day ⃝ ⃝ Post-assessment survey for Parent ID number: 1. Date: Did you notice a change in blood glucose control with pre-meal administration? If yes or sometimes, what did changes did you notice? Yes No Sometimes ________________________________________________________________________________ 2. In the last week, how many times did your child have symptoms of hypoglycemia (IE. dizziness, clamminess, confusion, seizures)? PRE-PRANDIAL INSULIN ADMINISTRATION 0 days per week 3. 1-3 days per week 2 A little uncomfortable most of the time 3 Somewhat comfortable 4 Most of the time I am comfortable 5 Very comfortable all the time Are you satisfied with pre-meal administration of insulin for your child? 1 Extremely dissatisfied 5. 6-7 days per week How comfortable are you with administering insulin for your child? 1 Uncomfortable at all times 4. 4-5 days per week 53 2 Somewhat dissatisfied 3 Neither satisfied or dissatisfied 4 Satisfied 5 Extremely Satisfied Was your child hospitalized, injured, or ill in the last 3 months? Describe the changes, if any, that occurred with your child’s blood sugar control during these times. Please explain below. 6. What do you do if your child is sick and does not want to eat? 7. What area does your child use for insulin administration? 8. How often does your child rotate injection sites? 9. Fill in the blank: If your child’s blood glucose level is: < 200 mg/dL 200-300 mg/dL > 300 mg/dL If unable to predict carb intake Give the insulin at this time before eating: ____ minutes prior to meal ____ minutes prior to meal ____ minutes prior to meal Correct the blood sugar prior / after (circle one) to eating using the chart above 10. Please write any other comments or concerns about pre-meal insulin administration here: