A parallel arm randomised controlled trial to achieve remission in patients with type 2 diabetes mellitus through dietary and behavioural interventions: a study protocol

Background. Type 2 diabetes mellitus (T2DM) poses a significant challenge to healthcare, with its prevalence escalating to epidemic proportions. The aging population, coupled with the increasing burden of T2DM, is exerting immense pressure on healthcare systems worldwide. Therefore, there is a critical need to design and validate innovative interventions to mitigate the effects of this disease. This randomised control trial aims to achieve remission in Indian patients aged 18 years and older diagnosed with T2DM through dietary and behavioural interventions.

Materials and methods. A total of 290 participants with T2DM will be recruited from Indira Colony Urban Enclave, the field practice area of the Department of Community Medicine and School of Public Health at Post Graduate Institute of Medical Education and Research, Chandigarh. Participants will be equally allocated into two arms: intervention (n = 145) and control (n = 145). There will be five measurement timepoints: baseline, 2^nd, 4^th, 6th and 9^th months postrandomisation. The intervention will implement a range of strategies to increase physical activity and promote dietary transitions through behaviour change among patients. The interventions will be designed ensuring a structured approach to behaviour change. Patients from the intervention arm will receive oral hypoglycaemic agents for the first six months of the trial. After this period, medication will be gradually tapered. Patients from the control arm will continue to receive standard care throughout the study. The primary outcome is the number of patients achieving remission of T2DM through behavioural and dietary interventions.

Conclusions. The novelty of this trial lies in its focus on community-based settings, unlike other studies that primarily target clinical or hospital-based environments to achieve clinical outcomes. The intervention integrates dietary and behavioural changes into the community’s cultural, socioeconomic, and dietary habits, making it practical and sustainable for patients to adopt and maintain the lifestyle changes needed for remission.

1. Roth G.A., Abate D., Abate K.H., et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2018 Nov; 392(10159): 1736–1788. https://doi.org/10.1016/s0140-6736(18)32203-7. PMID: 30496103

2. Anjana R.M., Deepa M., Pradeepa R., et al. Prevalence of diabetes and prediabetes in 15 states of India: results from the ICMRINDIAB population-based cross-sectional study. Lancet Diabetes Endocrinol. 2017 Aug; 5(8): 585–596. https://doi.org/10.1016/S2213-8587(17)30174-2. PMID: 28601585

3. Centers of Disease Control and Prevention. Strategies for reducing morbidity and mortality from diabetes through health-care system interventions and diabetes self-management education in community settings. A report on recommendations of the Task Force on Community Preventive Services. MMWR Recomm Rep. 2001 Sep 28; 50(RR-16): 1–15. PMID: 11594724

4. Nugent R. A Chronology of Global Assistance Funding for NCD. Glob Heart. 2016 Dec 1; 11(4): 371–374. https://doi.org/10.1016/j.gheart.2016.10.027. PMID: 27938820

5. Sahoo P.M., Rout H.S., Jakovljevic M. Consequences of India’s population aging to its healthcare financing and provision. J Med Econ. 2023 Feb 23; 26(1): 308–315. https://doi.org/10.1080/13696998.2023.2178164. PMID: 36780290

6. Vellakkal S., Subramanian S.V., Millett C., et al. Socioeconomic Inequalities in Non-Communicable Diseases Prevalence in India: Disparities between Self-Reported Diagnoses and Standardized Measures. PLoS One. 2013 Jul 15; 8(7): e68219. https://doi.org/10.1371/journal.pone.0068219. PMID: 23869213

7. Ke C., Narayan K.M.V., Chan J.C.N., et al. Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations. Nat Rev Endocrinol. 2022 Jul; 18(7): 413–432. https://doi.org/10.1038/s41574-022-00669-4. Epub 2022 May 4. PMID: 35508700

8. Uusitupa M. Remission of type 2 diabetes: mission not impossible. The Lancet. 2018 Feb 10; 391(10120): 515–516. https://doi.org/10.1016/s0140-6736(17)33100-8. Epub 2017 Dec 5. PMID: 29221646

9. Lean M.E., Leslie W.S., Barnes A.C., et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet. 2018 Feb 10; 391(10120): 541–551. https://doi.org/10.1016/s0140-6736(17)33102-1. PMID: 29221645

10. Dixit J.V., Giri P.A., Badgujar S.Y. `Daily 2-only meals and exercise’ lifestyle modification for remission of type 2 diabetes mellitus: A therapeutic approach. J Family Med Prim Care. 2022 Sep; 11(9): 5700–5703. https://doi.org/10.4103/jfmpc.jfmpc_129_22. PMID: 36505570

11. Brethauer S.A., Aminian A., Romero-Talamás H., et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg. 2013 Oct; 258(4): 628–637. https://doi.org/10.1097/sla.0b013e3182a5034b. PMID: 24018646

12. Magkos F., Hjorth M.F., Astrup A. Diet and exercise in the prevention and treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020 Oct; 16(10): 545–555. Epub 2020 Jul 20. https://doi.org/10.1038/s41574-020-0381-5. PMID: 32690918

13. Xin Y., Davies A., Briggs A., et al. Type 2 diabetes remission: 2 year within-trial and lifetime-horizon cost-effectiveness of the Diabetes Remission Clinical Trial (DiRECT)/Counterweight-Plus weight management programme. Diabetologia. 2020 Oct; 63(10): 2112–2122. https://doi.org/10.1007/s00125-020-05224-2. Epub 2020 Aug 10. PMID: 32776237

14. Kaur N., Majumdar V., Nagarathna R., et al. Diabetic yoga protocol improves glycemic, anthropometric and lipid levels in high risk individuals for diabetes: a randomized controlled trial from Northern India. Diabetol Metab Syndr. 2021 Dec 23; 13(1): 149. https://doi.org/10.1186/s13098-021-00761-1. PMID: 34949227

15. Mohan V., Radhika G., Sathya R.M., et al. Dietary carbohydrates, glycaemic load, food groups and newly detected type 2 diabetes among urban Asian Indian population in Chennai, India (Chennai Urban Rural Epidemiology Study 59). Br J Nutr. 2009 Nov; 102(10): 1498–1506. https://doi.org/10.1017/S0007114509990468. Epub 2009 Jul 9. Erratum in: Br J Nutr. 2010 Jun;103(12):1851-2. PMID: 19586573

16. Kam J., Puranik S., Yadav R., et al. Dietary interventions for type 2 diabetes: how millet comes to help. Front Plant Sci. 2016 Sep 15 Malleshi N. Finger millet (ragi) – the wonder grain. FoodInfo Online Features. 2004. Accessed January 25, 2024. http://ir.cftri.res.in/id/eprint/1264027; 7: 1454. https://doi.org/10.3389/fpls.2016.01454. PMID: 27729921

17. Anitha S., Kane-Potaka J., Tsusaka T.W., et al. A systematic review and meta-analysis of the potential of millets for managing and reducing the risk of developing diabetes mellitus. Front Nutr. 2021 Jul 28; 8: 687428. https://doi.org/10.3389/fnut.2021.687428. PMID: 34395493

18. Kim J., Hur M.H. The Effects of dietary education interventions on individuals with type 2 diabetes: a systematic review and meta-analysis. Int J Environ Res Public Health. 2021 Aug 10; 18(16): 8439. https://doi.org/10.3390/ijerph18168439. PMID: 34444187

19. Kathirvel S., Jeyashree K., Patro B.K. Social mapping: a potential teaching tool in public health. Med Teach. 2012; 34(7): e529–531. https://doi.org/10.3109/0142159x.2012.670321. Epub 2012 Mar 28. PMID: 22452276

20. Buse J.B., Caprio S., Cefalu W.T., et al. How do we define cure of diabetes? Diabetes Care. 2009 Nov; 32(11): 2133–2135. https://doi.org/10.2337/dc09-9036. PMID: 19875608

21. Nagi D., Hambling C., Taylor R. Remission of type 2 diabetes: a position statement from the Association of British Clinical Diabetologists (ABCD) and the Primary Care Diabetes Society (PCDS). British Journal of Diabetes. 2019 Jun 27; 19(1): 73–76. https://doi.org/10.15277/bjd.2019.221

22. Kelly J., Karlsen M., Steinke G. Type 2 diabetes remission and lifestyle medicine: a position statement from the American College of lifestyle medicine. Am J Lifestyle Med. 2020 Jun 8; 14(4): 406–419. https://doi.org/10.1177/1559827620930962. PMID: 33281521

23. Viswanathan V., Krishnan D., Kalra S., et al. Insights on medical nutrition therapy for type 2 diabetes mellitus: an indian perspective. Adv Ther. 2019 Mar; 36(3): 520–547. https://doi.org/10.1007/s12325-019-0872-8. Epub 2019 Feb 7. PMID: 30729455

24. Hennink M.M., Leavy P. Understanding focus group discussions. New York: Oxford University Press; 2014. https://doi.org/10.1093/acprof:osobl/9780199856169.001.0001. ISBN: 9780199856169

25. Thangaratinam S., Redman C.W. The Delphi technique. The Obstetrician & Gynaecologist. 2005 Apr; 7(2): 120–125. https://doi.org/10.1576/toag.7.2.120.27071

26. Jyani G., Sharma A., Prinja S., et al. Development of an EQ5D Value Set for India Using an Extended Design (DEVINE) Study: The Indian 5-Level Version EQ-5D Value Set. Value Health. 2022 Jul; 25(7): 1218–1226. https://doi.org/10.1016/j.jval.2021.11.1370. Epub 2022 Jan 5. PMID: 35779943

27. Goldenberg J.Z., Day A., Brinkworth G.D., et al. Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data. BMJ. 2021 Jan 13; 372: m4743. https://doi.org/10.1136/bmj.m4743. PMID: 33441384

28. Hemming K., Taljaard M., Moerbeek M., et al. Contamination: How much can an individually randomized trial tolerate? Stat Med. 2021 Jun7; 40(14): 3329–3351. https://doi.org/10.1002/sim.8958. Epub 2021 May 7. PMID: 33960514

29. Jin S., Bajaj H.S., Brazeau A.S., et al. Remission of type 2 diabetes: user’s guide. Can J Diabetes. 2022 Dec; 46(8): 762–774. https://doi.org/10.1016/j.jcjd.2022.10.005. Epub 2022 Nov 11. PMID: 36567080

30. Pandey A., Bolia N.B. Millet value chain revolution for sustainability: A proposal for India. Socio-Economic Planning Sciences. 2023 Jun; 87: 101592. https://doi.org/10.1016/j.seps.2023.101592

31. Erler M., Keck M., Dittrich C. The changing meaning of millets: Organic shops and distinctive consumption practices in Bengaluru, India. Journal of Consumer Culture. 2020 Jan 27; 22(1): 124–142. https://doi.org/10.1177/1469540520902508

32. Lichtenstein G.R., Yan S., Bala M., Hanauer S. Remission in patients with Crohn’s disease is associated with improvement in employment and quality of life and a decrease in hospitalizations and surgeries. Am J Gastroenterol. 2004 Jan; 99(1): 91–96. https://doi.org/10.1046/j.1572-0241.2003.04010.x. PMID: 14687148

33. Banerji M.A., Chaiken R.L., Lebovitz H.E. Long-term normoglycemic remission in black newly diagnosed NIDDM subjects. Diabetes. 1996 Mar; 45(3): 337–341. https://doi.org/10.2337/diab.45.3.337. PMID: 8593939