THE EFFECTIVENESS OF SYNBIOTIC SUPPLEMENTATION ON GLYCEMIC AND LIPID PROFILES IN TYPE 2 DIABETES MELLITUS PATIENTS
Sebuah Tinjauan Sistematis pada Studi Randomisasi Acak
DOI:
https://doi.org/10.53366/jimki.v11i2.771Keywords:
glycemic profile, lipid profile, synbiotic, type 2 diabetes mellitusAbstract
Background: Type 2 diabetes mellitus (T2DM) is a glucose homeostasis disorder characterized by chronic hyperglycemia caused by insulin resistance. It is believed that this condition is associated with intestinal bacteria dysbiosis that potentially worsens T2DM progressivity. A number of experimental studies have recommended synbiotic supplementation, based on the principle of intestinal microbe regulation, as nutrition therapy for T2DM. This systematic review evaluates the effect of synbiotic supplement on T2DM patients’ glycemic and lipid profile.
Methods: Articles published from 2014 to 2021 were searched with a number of search engines: PubMed, ResearchGate, Google Scholar, and Elsevier. This systematic review aims to evaluate the effect of synbiotic supplement on T2DM patients’ glycemic and lipid profile.
Discussion: Eighty randomized control trials (RCTs) met the inclusion criteria to be analyzed qualitatively in this systematic review. The quality of each included study was evaluated with Cochrane’s Risk of Bias (ROB-2). Overall, in comparison to the control (placebo) group, the intervention group that received synbiotic supplementation showed a more significant decrease in fasting glycemic and HbA1c level. T2DM patients also appeared to experience improvement in lipid profile (decrease in cholesterol, triglyceride, and low density lipoprotein cholesterol (LDL-C), along with increase in high density lipoprotein cholesterol (HDL-C)) after receiving synbiotic supplementation. In addition, synbiotic supplementation is evaluated as safe to be consumed by T2DM patients with minimal side effects.
Conclusion: The available evidence demonstrates the potential use of synbiotic supplementation as a nutrition therapy for T2DM treatment.
Keywords: glycemic profile, lipid profile, synbiotic, type 2 diabetes mellitus.
References
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6. Endokrinologi Indonesia. Pedoman Pengelolaan Dan Pencegahan Diabetes Melitus Tipe 2.Pedoman Pengelolaan Dan Pencegahan Diabetes Melitus Tipe 2 Dewasa Di Indonesia. Penerbit PB PERKENI 2021.
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8. Zheng HJ, Guo J, Jia Q, Huang YS, et al.The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res [Internet] 2019;142:303–13. Available from:https://pubmed.ncbi.nlm.nih.gov/30794924/
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11. Ghafouri A, Heshmati J, Heydari I, et al. Effect of synbiotic bread containing lactic acid on blood lipids and apolipoproteins in patients with type 2 diabetes: A randomized controlled trial. Food Sci Nutr 2022;10(12):4419–30.
12. Asemi Z, Khorrami-Rad A, Alizadeh SA, Shakeri H. Effects of synbiotic food consumption on metabolic status of diabetic patients: a double-blind randomized cross-over controlled clinical trial. Clin Nutr [Internet] 2014;33(2):198–203. Available from: https://pubmed.ncbi.nlm.nih.gov/23786900/
13. Shakeri H, Hadaegh H, Abedi F, et al. Consumption of synbiotic bread decreases triacylglycerol and VLDL levels while increasing HDL levels in serum from patients with type-2 diabetes. Lipids [Internet] 2014;49(7):695–701. Available from:https://pubmed.ncbi.nlm.nih.gov/24706266/
14. Mirmiranpour H, Huseini HF, Derakhshanian H. Effects of probiotic, cinnamon, and synbiotic supplementation on glycemic control and antioxidant status in people with type 2 diabetes; a randomized, double-blind, placebo-controlled study. J Diabetes Metab Disord 2020;19(1):53–60.
15. Tajabadi-Ebrahimi M, Sharifi N, Farrokhian A, et al. A Randomized Controlled Clinical Trial Investigating the Effect of Synbiotic Administration on Markers of Insulin Metabolism and Lipid Profiles in Overweight Type 2 Diabetic Patients with Coronary Heart Disease. Exp Clin Endocrinol Diabetes [Internet] 2017;125(1):21–7. Available from: https://pubmed.ncbi.nlm.nih.gov/27219886/
16. Moroti C, Souza Magri L, De Rezende Costa M. Effect of the consumption of a new symbiotic shake on glycemia and cholesterol levels in elderly people with type 2 diabetes mellitus. Lipids Health Dis 2016;11.
17. Kanazawa A, Aida M, Yoshida Y, et al. Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study. Nutrients [Internet] 2021;13(2):1–19. Available from:https://pubmed.ncbi.nlm.nih.gov/33567701/
18. Ebrahimi Z sadat, Nasli-Esfahani E, Nadjarzade A. Effect of symbiotic supplementation on glycemic control, lipid profiles and microalbuminuria in patients with non-obese type 2 diabetes: a randomized, double-blind, clinical trial. J Diabetes Metab Disord [Internet] 2017;16(1). Available from: /pmc/articles/PMC5457616/
19. Giorgino F, Leonardini A, Laviola L, Perrini S, Natalicchio A. Cross-Talk between PPARgamma and Insulin Signaling and Modulation of Insulin Sensitivity. PPAR Res [Internet] 2015;2009. Available from:https://pubmed.ncbi.nlm.nih.gov/20182551/
20. Janani C, Ranjitha Kumari BD. PPAR gamma gene--a review. Diabetes Metab Syndr [Internet] 2015;9(1):46–50. Available from:https://pubmed.ncbi.nlm.nih.gov/25450819/
21. Mahboobi S, Rahimi F, Jafarnejad S. Effects of Prebiotic and Synbiotic Supplementation on Glycaemia and Lipid Profile in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. Adv Pharm Bull [Internet] 2018;8(4):565. Available from: /pmc/articles/PMC6311648/
22. Rose S, Bennuri SC, Davis JE, Wynne R, et al. Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism. Transl Psychiatry [Internet] 2018;8(1). Available from: https://pubmed.ncbi.nlm.nih.gov/29391397/
23. Goswami C, Iwasaki Y, Yada T. Short-chain fatty acids suppress food intake by activating vagal afferent neurons. J Nutr Biochem [Internet] 2018;57:130–5. Available from:https://pubmed.ncbi.nlm.nih.gov/29702431/
24. Si X, Shang W, Zhou Z, Shui G, Lam SM, et al. Gamma-aminobutyric Acid Enriched Rice Bran Diet Attenuates Insulin Resistance and Balances Energy Expenditure via Modification of Gut Microbiota and Short-Chain Fatty Acids. J Agric Food Chem [Internet] 2018;66(4):881–90. Available from:https://pubmed.ncbi.nlm.nih.gov/29327584/
25. Kobyliak N, Falalyeyeva T, Mykhalchyshyn G, Kyriienko D, Komissarenko I. Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial. Diabetes Metab Syndr [Internet] 2018;12(5):617–24. Available from:https://pubmed.ncbi.nlm.nih.gov/29661605/
26. Kassaian N, Feizi A, Aminorroaya A, Amini M. The effects of probiotics and synbiotic supplementation on glucose and insulin metabolism in adults with prediabetes: a double-blind randomized clinical trial. Acta Diabetol 2018;55(10):1019–28.
27. Lee DK, Jang S, Baek EH, Kim MJ, et al. Lactic acid bacteria affect serum cholesterol levels, harmful fecal enzyme activity, and fecal water content. Lipids Health Dis [Internet] 2014;8. Available from:https://pubmed.ncbi.nlm.nih.gov/19515264/
28. Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol [Internet] 2015;33:257–90. Available from:https://pubmed.ncbi.nlm.nih.gov/25581309/
29. Hadi A, Ghaedi E, Khalesi S, Pourmasoumi M, Arab A. Effects of synbiotic consumption on lipid profile: a systematic review and meta-analysis of randomized controlled clinical trials. Eur J Nutr [Internet] 2020;59(7):2857–74. Available from:https://pubmed.ncbi.nlm.nih.gov/32322969/
30. Weitkunat K, Schumann S, Petzke KJ, Blaut M, Loh G, Klaus S. Effects of dietary inulin on bacterial growth, short-chain fatty acid production and hepatic lipid metabolism in gnotobiotic mice. J Nutr Biochem [Internet] 2015;26(9):929–37. Available from:https://pubmed.ncbi.nlm.nih.gov/26033744/
31. Ruan Y, Sun J, He J, Chen F, Chen R, Chen H. Effect of Synbiotics on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials. PLoS One [Internet] 2015;10(7). Available from:https://pubmed.ncbi.nlm.nih.gov/26161741/
32. Kaur N, Gupta AK. Applications of inulin and oligofructose in health and nutrition. J Biosci [Internet] 2017;27(7):703–14. Available from: https://pubmed.ncbi.nlm.nih.gov/12571376/
33. Yadav H, Jain S, Sinha PR. Effect of Dahi containing Lactococcus lactis on the progression of diabetes induced by a high-fructose diet in rats. Biosci Biotechnol Biochem [Internet] 2014;70(5):1255–8. Available from: https://pubmed.ncbi.nlm.nih.gov/16717431/
34. Sewify M, Nair S, Warsame S, Murad M, et al. Prevalence of Neuropathic among Diabetic Patients with Controlled and Uncontrolled Glycemia in Kuwait. J Diabetes Res [Internet] 2016. Available from:https://pubmed.ncbi.nlm.nih.gov/26844231/
35. Mang B, Wolters M, Schmitt B, Kelb K, et al. Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J Clin Invest [Internet] 2016;36(5):340–4. Available from:https://pubmed.ncbi.nlm.nih.gov/16634838/
36. Moroti C, Magri LF, Rensis C, Costa M, Sivieri K. Effect of the consumption of a synbiotic shake on the intestinal microflora of elderly people. Int J Probiotics Prebiotics 2015;5:133–40.
37. Kavitha K, Gopala Reddy A, Kondal Reddy K, Satish Kumar CSV, Boobalan G, Jayakanth K. Hypoglycemic, hypolipidemic and antioxidant effects of synbiotic in diabetic rats. Vet World [Internet] 2016;9(2):118. Available from: /pmc/articles/PMC4819359/
38. Ekhlasi G, Mohammadi RK, Agah S, Zarrati M, Hosseini AF, Arabshahi SSS, et al. Do symbiotic supplementation have effects in nonalcoholic fatty liver disease?. J Res Med Sci [Internet] 2016;21(7). Available from: https://pubmed.ncbi.nlm.nih.gov/28250783/
39. Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, et al. Helsinki Heart Study: Safety of treatment, changes in incidence of coronary heart disease. N Engl J Med [Internet] 2017;317(20):1237–45. Available from:https://pubmed.ncbi.nlm.nih.gov/3313041/
40. Wan X, Guo H, Liang Y, Zhou C, Liu Z, Li K, et al. The physiological functions and pharmaceutical applications of inulin: A review. Carbohydr Polym [Internet] 2020;246. Available from: https://pubmed.ncbi.nlm.nih.gov/32747248/
2. Sun H, Saeedi P, Karuranga S, Pinkepank M, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract [Internet] 2022;183. Available from:https://pubmed.ncbi.nlm.nih.gov/34879977/
3. Diwan AG, Kuvalekar AA, Dharamsi S, Vora AM, Nikam VA, Ghadge AA. Correlation of Serum Adiponectin and Leptin levels in Obesity and Type 2 Diabetes Mellitus. Indian J Endocrinol Metab [Internet] 2018;22(1):93. Available from: /pmc/articles/PMC5838920/
4. Tanase DM, Gosav EM, Neculae E, Costea CF, et al. Role of Gut Microbiota on Onset and Progression of Microvascular Complications of Type 2 Diabetes (T2DM). Nutrients [Internet] 2020;12(12):1–26. Availablefrom:https://pubmed.ncbi.nlm.nih.gov/33276482/
5. Liu Y, Lou X. Type 2 diabetes mellitus-related environmental factors and the gut microbiota: emerging evidence and challenges. Clinics (Sao Paulo) [Internet] 2020;75. Available from:https://pubmed.ncbi.nlm.nih.gov/31939557/
6. Endokrinologi Indonesia. Pedoman Pengelolaan Dan Pencegahan Diabetes Melitus Tipe 2.Pedoman Pengelolaan Dan Pencegahan Diabetes Melitus Tipe 2 Dewasa Di Indonesia. Penerbit PB PERKENI 2021.
7. Kim YA, Keogh JB, Clifton PM. Probiotics, prebiotics, synbiotics and insulin sensitivity. Nutr Res Rev [Internet] 2018;31(1):35–51. Available from: https://pubmed.ncbi.nlm.nih.gov/29037268/
8. Zheng HJ, Guo J, Jia Q, Huang YS, et al.The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res [Internet] 2019;142:303–13. Available from:https://pubmed.ncbi.nlm.nih.gov/30794924/
9. Naseri K, Saadati S, Ghaemi F, Ashtary-Larky D, et al. The effects of probiotic and synbiotic supplementation on inflammation, oxidative stress, and circulating adiponectin and leptin concentration in subjects with prediabetes and type 2 diabetes mellitus: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials. Eur J Nutr [Internet] 2023;62(2):543. Available from: /pmc/articles/PMC9941248/
10. Li HY, Zhou DD, Gan RY, Huang SY, et al. Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota: A Narrative Review. Nutrients [Internet] 2021;13(9). Available from: https://pubmed.ncbi.nlm.nih.gov/34579087/
11. Ghafouri A, Heshmati J, Heydari I, et al. Effect of synbiotic bread containing lactic acid on blood lipids and apolipoproteins in patients with type 2 diabetes: A randomized controlled trial. Food Sci Nutr 2022;10(12):4419–30.
12. Asemi Z, Khorrami-Rad A, Alizadeh SA, Shakeri H. Effects of synbiotic food consumption on metabolic status of diabetic patients: a double-blind randomized cross-over controlled clinical trial. Clin Nutr [Internet] 2014;33(2):198–203. Available from: https://pubmed.ncbi.nlm.nih.gov/23786900/
13. Shakeri H, Hadaegh H, Abedi F, et al. Consumption of synbiotic bread decreases triacylglycerol and VLDL levels while increasing HDL levels in serum from patients with type-2 diabetes. Lipids [Internet] 2014;49(7):695–701. Available from:https://pubmed.ncbi.nlm.nih.gov/24706266/
14. Mirmiranpour H, Huseini HF, Derakhshanian H. Effects of probiotic, cinnamon, and synbiotic supplementation on glycemic control and antioxidant status in people with type 2 diabetes; a randomized, double-blind, placebo-controlled study. J Diabetes Metab Disord 2020;19(1):53–60.
15. Tajabadi-Ebrahimi M, Sharifi N, Farrokhian A, et al. A Randomized Controlled Clinical Trial Investigating the Effect of Synbiotic Administration on Markers of Insulin Metabolism and Lipid Profiles in Overweight Type 2 Diabetic Patients with Coronary Heart Disease. Exp Clin Endocrinol Diabetes [Internet] 2017;125(1):21–7. Available from: https://pubmed.ncbi.nlm.nih.gov/27219886/
16. Moroti C, Souza Magri L, De Rezende Costa M. Effect of the consumption of a new symbiotic shake on glycemia and cholesterol levels in elderly people with type 2 diabetes mellitus. Lipids Health Dis 2016;11.
17. Kanazawa A, Aida M, Yoshida Y, et al. Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study. Nutrients [Internet] 2021;13(2):1–19. Available from:https://pubmed.ncbi.nlm.nih.gov/33567701/
18. Ebrahimi Z sadat, Nasli-Esfahani E, Nadjarzade A. Effect of symbiotic supplementation on glycemic control, lipid profiles and microalbuminuria in patients with non-obese type 2 diabetes: a randomized, double-blind, clinical trial. J Diabetes Metab Disord [Internet] 2017;16(1). Available from: /pmc/articles/PMC5457616/
19. Giorgino F, Leonardini A, Laviola L, Perrini S, Natalicchio A. Cross-Talk between PPARgamma and Insulin Signaling and Modulation of Insulin Sensitivity. PPAR Res [Internet] 2015;2009. Available from:https://pubmed.ncbi.nlm.nih.gov/20182551/
20. Janani C, Ranjitha Kumari BD. PPAR gamma gene--a review. Diabetes Metab Syndr [Internet] 2015;9(1):46–50. Available from:https://pubmed.ncbi.nlm.nih.gov/25450819/
21. Mahboobi S, Rahimi F, Jafarnejad S. Effects of Prebiotic and Synbiotic Supplementation on Glycaemia and Lipid Profile in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. Adv Pharm Bull [Internet] 2018;8(4):565. Available from: /pmc/articles/PMC6311648/
22. Rose S, Bennuri SC, Davis JE, Wynne R, et al. Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism. Transl Psychiatry [Internet] 2018;8(1). Available from: https://pubmed.ncbi.nlm.nih.gov/29391397/
23. Goswami C, Iwasaki Y, Yada T. Short-chain fatty acids suppress food intake by activating vagal afferent neurons. J Nutr Biochem [Internet] 2018;57:130–5. Available from:https://pubmed.ncbi.nlm.nih.gov/29702431/
24. Si X, Shang W, Zhou Z, Shui G, Lam SM, et al. Gamma-aminobutyric Acid Enriched Rice Bran Diet Attenuates Insulin Resistance and Balances Energy Expenditure via Modification of Gut Microbiota and Short-Chain Fatty Acids. J Agric Food Chem [Internet] 2018;66(4):881–90. Available from:https://pubmed.ncbi.nlm.nih.gov/29327584/
25. Kobyliak N, Falalyeyeva T, Mykhalchyshyn G, Kyriienko D, Komissarenko I. Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial. Diabetes Metab Syndr [Internet] 2018;12(5):617–24. Available from:https://pubmed.ncbi.nlm.nih.gov/29661605/
26. Kassaian N, Feizi A, Aminorroaya A, Amini M. The effects of probiotics and synbiotic supplementation on glucose and insulin metabolism in adults with prediabetes: a double-blind randomized clinical trial. Acta Diabetol 2018;55(10):1019–28.
27. Lee DK, Jang S, Baek EH, Kim MJ, et al. Lactic acid bacteria affect serum cholesterol levels, harmful fecal enzyme activity, and fecal water content. Lipids Health Dis [Internet] 2014;8. Available from:https://pubmed.ncbi.nlm.nih.gov/19515264/
28. Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol [Internet] 2015;33:257–90. Available from:https://pubmed.ncbi.nlm.nih.gov/25581309/
29. Hadi A, Ghaedi E, Khalesi S, Pourmasoumi M, Arab A. Effects of synbiotic consumption on lipid profile: a systematic review and meta-analysis of randomized controlled clinical trials. Eur J Nutr [Internet] 2020;59(7):2857–74. Available from:https://pubmed.ncbi.nlm.nih.gov/32322969/
30. Weitkunat K, Schumann S, Petzke KJ, Blaut M, Loh G, Klaus S. Effects of dietary inulin on bacterial growth, short-chain fatty acid production and hepatic lipid metabolism in gnotobiotic mice. J Nutr Biochem [Internet] 2015;26(9):929–37. Available from:https://pubmed.ncbi.nlm.nih.gov/26033744/
31. Ruan Y, Sun J, He J, Chen F, Chen R, Chen H. Effect of Synbiotics on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials. PLoS One [Internet] 2015;10(7). Available from:https://pubmed.ncbi.nlm.nih.gov/26161741/
32. Kaur N, Gupta AK. Applications of inulin and oligofructose in health and nutrition. J Biosci [Internet] 2017;27(7):703–14. Available from: https://pubmed.ncbi.nlm.nih.gov/12571376/
33. Yadav H, Jain S, Sinha PR. Effect of Dahi containing Lactococcus lactis on the progression of diabetes induced by a high-fructose diet in rats. Biosci Biotechnol Biochem [Internet] 2014;70(5):1255–8. Available from: https://pubmed.ncbi.nlm.nih.gov/16717431/
34. Sewify M, Nair S, Warsame S, Murad M, et al. Prevalence of Neuropathic among Diabetic Patients with Controlled and Uncontrolled Glycemia in Kuwait. J Diabetes Res [Internet] 2016. Available from:https://pubmed.ncbi.nlm.nih.gov/26844231/
35. Mang B, Wolters M, Schmitt B, Kelb K, et al. Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J Clin Invest [Internet] 2016;36(5):340–4. Available from:https://pubmed.ncbi.nlm.nih.gov/16634838/
36. Moroti C, Magri LF, Rensis C, Costa M, Sivieri K. Effect of the consumption of a synbiotic shake on the intestinal microflora of elderly people. Int J Probiotics Prebiotics 2015;5:133–40.
37. Kavitha K, Gopala Reddy A, Kondal Reddy K, Satish Kumar CSV, Boobalan G, Jayakanth K. Hypoglycemic, hypolipidemic and antioxidant effects of synbiotic in diabetic rats. Vet World [Internet] 2016;9(2):118. Available from: /pmc/articles/PMC4819359/
38. Ekhlasi G, Mohammadi RK, Agah S, Zarrati M, Hosseini AF, Arabshahi SSS, et al. Do symbiotic supplementation have effects in nonalcoholic fatty liver disease?. J Res Med Sci [Internet] 2016;21(7). Available from: https://pubmed.ncbi.nlm.nih.gov/28250783/
39. Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, et al. Helsinki Heart Study: Safety of treatment, changes in incidence of coronary heart disease. N Engl J Med [Internet] 2017;317(20):1237–45. Available from:https://pubmed.ncbi.nlm.nih.gov/3313041/
40. Wan X, Guo H, Liang Y, Zhou C, Liu Z, Li K, et al. The physiological functions and pharmaceutical applications of inulin: A review. Carbohydr Polym [Internet] 2020;246. Available from: https://pubmed.ncbi.nlm.nih.gov/32747248/
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THE EFFECTIVENESS OF SYNBIOTIC SUPPLEMENTATION ON GLYCEMIC AND LIPID PROFILES IN TYPE 2 DIABETES MELLITUS PATIENTS: Sebuah Tinjauan Sistematis pada Studi Randomisasi Acak. (2025). JIMKI: Jurnal Ilmiah Mahasiswa Kedokteran Indonesia, 11(2), 1-15. https://doi.org/10.53366/jimki.v11i2.771
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