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Nursing Practice Today Nurs Pract Today. 2018; 5(1):222-227. Original Article Insulin injection site and time interval administration for the postprandial control in patient with diabetes type 2: A randomized clinical trial Agus Santosa 1*, Danong Erdiawan 2, Elsye-Maria Rosa 3 1 Departement of Medical Surgical Nursing, School of Nursing and Midwifery, Muhammadiyah University of Purwokerto, Purwokerto, Indonesia 2 Departement of Medical Ward, Dr.Moewardi Hospital, Solo, Indonesia 3 Departent of Management Administration Hospital, Muhammadiyah University of Yogyakarta, Yogyakarta, Indonesia ARTICLE INFO Received 15 June 2017 Revised 4 November 2017 Accepted 20 August 2017 epublished 13 January 2018 Published 7 March 2018 Available online at: http://npt.tums.ac.ir Key words: insulin, postprandial, diabetes type ABSTRACT Background & Aim: insulin injection to the patients suffered from diabetes mellitus need to consider the dose, route, time and injection spot since it will affect to postprandial blood sugar. This study aimed to determine the effectiverness of insulin injection site and interval timing administration to the control of postprandial in diabetes mellitus patients type 2. Methods & Materials: The study was an experimental with Randomized Complete Block Design (RCBD). The population were patients with diabetes mellitus type 2 in dr. Moewardi Hospital Solo, Indonesia, consisted of 60 respondents taken from simple random sampling (allocate by inverse transform random variate generator and with Microsoft Excel), the respondents were divided into 4 blocks or groups (15 respondents/blocks). Injection used was Rapid-acting insulin with the dosage prescribed by the doctor. Injection was done in four (4) locations; abdomen, deltoid, thigh and gluteus. The administration were 0 minutes (along with meals), 10 minutes before meal, 20 minutes before meal and 30 minutes before meal. Two hour postprandial levels were measured using a Glucometer. Data were then analyzed by SPSS 18 with Two-Way ANOVA and Tukey HSD. Result: 55% of the respondents was male and 45% was female. All respondents were 40 years old, most of the respondents were in normal body weight and they have suffered the illness >10 years. There were differences in postprandial levels in people with diabetes who obtained insulin injection at the site of the abdominal, deltoid, thigh and gluteus (P <0.05). There were differences in postprandial levels in people with diabetes who obtained insulin injections at 0, 10, 20 and 30 minutes before meal (P <0.05). The location and the most effective time for insulin injection was in the abdomen at time 0 minute before meal (P <0.05). Conclusion: Injection of insulin made in the abdomen by the time of meals effectively controlled postprandial levels in patients with diabetes mellitus type 2. Introduction 1 Various studies discovered that people with diabetes who manage low plasma levels indicated the incidence of micro vascular complications such as the onset of diabetic retinopathy, nephropathy, and neuropathy were lower compared to patients who did not manage the low plasma levels (1). Therefore, controlling levels in diabetics was very crucial, especially post-prandial levels. * Corresponding Author: Agus Santosa, Postal Address: Departement of Medical Surgical Nursing, Muhammadiyah University of Purwokerto, Purwokerto, Indonesia. Email: agussantosa@ump.ac.id Administering proper insulin injection was one of the ways to manage postprandial levels well controlled (2). Administering insulin injection by a nurse was more often performed in the deltoid area compared to other locations, but there were a few locations that can be done for such insulin injection in the abdomen, thigh and gluteus. The theory stated that insulin worked faster when it was injected into the abdomen. Insulin would come into the body system longer if it was injected in the upper arm, leg or thigh and the slowest was in the buttocks (3). Previous research stated that, insulin should be given immediately before meals, it was done Please cite this article in press as: Santosa A, Erdiawan D, Rosa E.M Insulin injection site and time interval administration for the postprandial control in patient with diabetes type 2: A randomized clinical trial. Nurs Pract Today. 2018; 5(1):222-227

because the insulin worked better when the from food entering the blood (4). The previous research and theories above resulted in postprandial levels that would vary in each injection location and administering time, therefore it was important to know the most effective location of injection and administering of insulin in controlling postprandial levels, so that nurses will provide proper insulin inject and time of administration. Methods The research was experimental with Complete Randomized Block Design (RCBD) (5). RCBD is a randomized design by categorizing the experiment into homogenous blocks called groups and determining randomized treatment design in each group. All group obtained different types of treatments (6,7). Patients suffered from diabetes mellitus type 2 in Dr. Moewardi Hospital Solo, Central Java, Indonesia were selected as the sample of the research. The sample size was determined for a difference in means based on the funding of Dahlan, 2010 (8). The diabetic patients should be 40 years old at least for both male and female to meet in inclusion criteria. Meanwhile, patients with complications (neuropathy diabetic, retinopathy diabetic, nephropathy diabetic); hyper osmolality ketoacidosis were part of exclusion criteria. The selected sample in inclusion criteria were then divided into 4 blocks through single blind by simple random sampling (9). The study finally obtained 60 respondents (15 respondents per group). Insulin was randomly injected in 4 (four) different locations, namely in the subcutaneous abdomen, deltoid, thigh and gluteus, through insulin pens, all injections were conducted by the researcher (10). The time of administration were 0 minutes (along with meals), 10 minutes before meal, 20 minutes before meal and 30 minutes before a meal. Types of insulin administered was Rapid-acting insulin at a dose prescribed by the doctor. The respondents activity was controlled into mild activity. The demographic data were collected through interview and medical records. The research instrument was Glucometer. The blood sugar test was belonged to the hospital which was YSI 2300 STAT Plus Glucose Lactate Analyzer (11). The blood checked was blood level in postprandial. The data 2 h postprandial, were then analyzed by SPSS 18 program package with Two Way ANOVA and Tukey HSD formulas (12,13). The study was registered in Ethics Committee University of Muhammadiyah Yogyakarta with the number of: 441/EP- FKIK UMY/2015. Besides, it was listed in Iranian Registry of Clinical Trials with the number of: IRCT2017062134690N1. Informed consent was given to all of the respondents before the treatment. Results The demography data presented that 55% respondent was male and 45% was female. Furthermore, the respondents were in 40 years old, the body weight of the patients were in normal category at most and they suffered the illness mostly >10 years (Table 1). The study showed different results in postprandial blood levels at each site of injection and time injection administration. Patients obtained abdominal insulin injection showed the lowest postprandial levels compared to injection in the deltoid, thigh and gluteus. Patients who obtained insulin on time with meals or 0 minutes showed the lowest postprandial levels compared to the injection time of 10, 20 and 30 minutes before meal. Injection site in the abdomen affected best postprandial levels with an average score of 156.2 mg / dl, while the injection time at 0 min or concurrently 223

Sample Diabetes Type 2 Simple Random Sampling Block 1 (0 Minute) Block 2 (10 Minute) Block 3 (20 Minute) Block 4 (30 Minute) Randomized Insulin Injection Site Abdomen Deltoid Thigh Gluteus Figure 1. Schematic of the Study Design. Patients with type 2 diabetes were included in the inclusion criteria and then divided into 4 blocks of the timing of injection (block 0 minute, 10 minutes, 20 minutes and 30 minutes before a meal) by simple random sampling, then it was injected at 4 locations (abdominal, deltoid, thigh and gluteus) and measured its postprandial level. Daily insulin dosage obtained by the doctor to the respondent was approximately 8.3UI, while the number of calories obtained by nutritionist was approximately 1876 MPA/ day. There were 71 respondents who participated in the study, however 11 respondents were drop-outs due to various factors. Therefore, 60 respondents (15 respondents per group) were only analyzed. with a meal resulted in proper postprandial levels with a mean score of 160.8 mg / dl. The trend rose in every interval injection of postprandial levels. Trend line of postprandial levels at each site of injection and timing of injections could be seen in (Figure 2). The analysis showed that insulin injection location and timing of the injection affected on postprandial blood levels in patients with type 2 diabetes mellitus (p <0.05) (Table 2). The study discovered that insulin injection site in the abdominal area was the most effective injection site compared to the deltoid area, thigh and gluteus, (Table 3).While the timing of insulin was the most effective at 0 minutes or coincide with meal times (Table 4). Discussion The study discovered that changing of the location of the injection from abdomen to another place, the postprandial concentrations increased by 18.2 mg / dl - 60.6 mg / dl (Table 2). The data indicated that there was a difference in absorbed insulin at each site of injection (3,14). The analysis proved that the injected insulin into the abdomen was 100% absorbed by the body, whereas the deltoid just absorbed 75%. The injected insulin into the thigh was 50% absorbed by the from the abdomen to other locations would reduce the dose of insulin administered (14). The dose of insulin given to patients were varied in this study, depending on the daily dose that the doctor prescribed, however the doses that 224

Figure 2. Trend line postprandial levels at each site of injection and timing of insulin injections in patients with diabetes mellitus type 2. Block 1: Insulin administration with meals or 0 minutes, Block 2: Insulin administration conducted 10 minutes before a meal, Block 3: Insulin administration conducted 20 minutes before meal, and Block 4: Insulin administration conducted 30 minutes before meal. The graph above showed differences in postprandial blood levels at each site of injection and at each time interval injection administration. Table 1. Demographic Characteristic Demographic Characteristic N (%) Sex Male 33 (55%) Female 27 (45%) Age < 40 years old - 40 years old 60 (100%) Long illness < 10 Tahun 17 (10.2%) 10 Tahun 43 (25.8%) Weight Thin 17 (28.3%) Normal 35 (58.3%) Fat 8 (13.3%) Tabel 2. Effect of Insulin Injection Site and Time Interval Administration for the Glucose Control (mg/dl) Time Interval Overall, Site n (SD) F p value 0 10 20 30 mean Abdomen 133.2 141.4 166.5 183.8 156.2 60 Deltoid 151.3 161.5 184.8 200.1 174.4 60 Thigh 172.8 179.2 205.6 244.1 200.1 60 Gluteus 186.0 197.5 228.6 255.3 216.8 60 36.1 2.813 0.004 Overall, mean 160.8 169.9 196.4 220.0 187.0 240 Two-Way ANOVA Test 225

Tabel 3. Multiple Comparison to the effectiveness of controlling postprandial levels to injected location in Abdomen, Deltoid, Thigh and Gluteus (I) Site Injection Abdomen Deltoid Thigh Gluteus Tukey HSD Test Variabel (J) Site Injection Mean Difference (I-J) p value Deltoid -18.22 0.002 Thigh -44.22 0.000 Gluteus -60.62 0.000 Abdomen 18.22 0.002 Thigh -26.00 0.000 Gluteus -42.40 0.000 Abdomen 44.22 0.000 Deltoid 26.00 0.000 Gluteus -16.40 0.008 Abdomen 60.62 0.000 Deltoid 42.40 0.000 Thigh 16.62 0.008 Tabel 4. Multiple Comparison to the effectiveness in controlling postprandial level to injection administration of 0, 10, 20 and 30 minutes before meals. (I) Time Administration 0 Minute 10 Minutes 20 Minutes 30 Minutes Variabel (J) Time Administration Tukey HSD Test patients obtained from the beginning to the end was still the same on a single respondent. The study revealed no significant relationship between the dose of insulin and injection location (p> 0.05).An Injected insulin in abdomen was the most effective in controlling postprandial levels, then the deltoid was on the next, thigh and gluteal had no effect by insulin dose prescribed. The result presented that the small dose of insulin injected to the respondents and the location was on the abdomen, then the postprandial produced would be higher, yet deltoid, thighs and gluteus remained higher than the abdomen. When respondents obtained a large insulin doses and it was injected in abdomen, the produced in would be low, however it would Mean Difference (I-J) p value 10 Minutes -9.1 0.003 20 Minutes -35.58 0.000 30 Minutes -60.03 0.000 0 Minute 9.1 0.003 20 Minutes -26.48 0.000 30 Minutes -50.93 0.000 0 Minute 35. 58 0.000 10 Minutes 26.48 0.000 30 Minutes -24.45 0.000 0 Minute 60.03 0.000 10 Minutes 50.93 0.000 20 Minutes 24.45 0.000 remain high when the injection was in deltoid, thighs and gluteus. Several studies on time variable of injection showed that the addition of injection time from 0 minutes to 10, 20 and 30 minutes before meal would increase postprandial blood concentration 9.1 mg / dl - 60 mg / dl when administered at 10, 20, and 30 minutes (table 3). To a normal person, insulin in the body would increase along with the consumption of food and it would be back to normal within after a meal (15). Insulin would work immediately after injected into the body, if insulin was not administered with a meal, it would not work accordingly with the body's metabolic processes (16), causing levels were higher in after a meal (17,18). The previous studies, discovered that 226

insulin injection immediately before a meal was more effective in lowering levels compared with injections immediately after the meal (16,19). Insulin injections were performed at 0 minutes, postprandial levels showed 10 mmol / L (180 mg / dl), while the injection done 30 minutes before meal obtained postprandial levels by 14 mmol / L (255 mg / dl). Insulin injection in the abdomen in the time of meals administration was the most effective in controlling postprandial levels in patients with diabetes mellitus type 2. The study applied Rapid-Acting insulin, if another type of insulin applied, the result would be different. The researcher then required to conduct the follow up study with HbA1c level indicator. Acknowledgement Tanks to Mr. Danong Erdiawan for his contributor in research. Conflict of interest: None References 1. PERKENI. Konsensus Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2. 2011. Jakarta. 2. Syam AF. Pemberian Insulin yang Tepat, Terhindar dari Komplikasi. 2008. Jakarta: Fakultas Kedokteran Universitas Indonesia. 3. Misnadiarly. Diabetes Mellitus, Gangren, Ulcer, Infeksi, Mengenali Gejala Menanggulangi Mencegah Komplikasi. 2006. Jakarta: Pustaka Populer Obor 4. Lindholm A, McEwen J, Riis AP. Improved Glycemic Control With Insulin Aspart. A Randomized Double-blind Cross-Over Trial in Type 1 Diabetes. Diabetes Care. 1999;22(5):801-805. 5. Suwanda. Desain Eksperimen untuk Penelitian Ilmiyah. 2011. Bandung: Alfabeta 6. David IJ and Adehi MU. 2014. Effectiveness of Split-Plot Design over Randomized CompleteBlock Design in Some Experiments. Journal of Biology, Agriculture and Healthcare. 2014:4(19):75-80. 7. Clovis AP. Testing the Effect of blocking in a Randomized Complete Block Design (RCBD). Journal Communications in Statistics - Theory and Methods Volume 10, Issue 23, 2007.p.2447-2459. 8. Dahlan S. Besar sampel dan Cara Pengambilan Sampel dalam Penelitian Kedoteran dan Kesehatan. 2010. Jakarta: Salemba Medika 9. Cochran WJ. Teknik Penarikan Sampel. 2010. Jakarta: UI Press 10. Rahman A. Pengacakan Random Sampling Dengan Pendekatan Inverse-Transform Random Variate Generator Berbasis Distribusi Hipergeometrik. Prosiding Seminar Nasional Teknoin. 2013:4(1): 106-111. 11. Salacinski AJ, Alford M, Drevets K, Hart S, Hunt BE. Validity and Reliability of a Glucometer Against Industry Reference Standards. Journal of Diabetes Science and Technology, 8(1),2014 95 99. 12. Widhiarso W. Analisis Varians Multivarians. 2011. Availabel from: \http://widhiarso.staff.ugm.ac.id/files/analisis%2 0Varians%20Multivariat.pdf 13. Sugiyono. Statistika untuk Penelitian. 2007. Bandung ALFABETA 14. Bantle JP, Neal L, Frankamp LM. Effects of the Anatomical Region Used for Insulin Injections on Glycemia in Type I Diabetes Subjects. Diabetes Case, 1993; 16:12 15. Suckale J, Solimena M. Pancreas Islets in Metabolic Signaling - Focus On The β-cell. Precedings Nature. 2008. 16. Medsafe. Novo Rapid Novo Mix Injection Presentation. New Zaeland Data Sheet. CAS No: 116094-23-6. 2012. Availabel from:http://www.medsafe.govt.nz/profs/datashe et/n/novorapidnovomixinj.pdf 17. Czupryniak L, Ruxer J, Saryusz-Wolska M, Kropiwnicka A, Drzewoski J. Effect of time interval between insulin injection and meal ingestion on metabolic control in type 2 diabetes mellitus. Diabetes Research and Clinical Practice. 2000;50:66. 18. Coscelli C, Iacobellis G, Calderini C, Carleo R, Gobbo M, Di Mario U, et al. Importance of premeal injection time in insulin therapy: Humalog Mix25 is convenient for improved post-prandial glycemic control in type 2 diabetic patients with Italian dietary habits. Acta diabetologica. 2003;40(4):187-92. 19. Jovanovic L, Giammattei J, Acquistapace M, Bornstein K, Sommermann E, Pettitt DJ. Efficacy Comparison Between Preprandial and Insulin Aspart Administration With Dose Adjustment for Unpredictable Meal Size. Clin Ther. 2004;26(9): 1492-1497. 227