Effectiveness of a Low-Calorie Diet Combined With Intensive Lifestyle Intervention Using Integrated Personalized Diabetes Management for Achieving Diabetes Remission in Patients With Type 2 Diabetes Mellitus

Official title

Effectiveness of a Low-Calorie Diet Combined With Intensive Lifestyle Intervention Using Integrated Personalized Diabetes Management for Achieving Diabetes Remission in Patients With Type 2 Diabetes Mellitus: A Randomized Controlled Trial

Overview

The goal of this clinical trial is to determine whether a low-calorie diet combined with intensive lifestyle intervention using Integrated Personalized Diabetes Management (iPDM) is more effective than standard care in achieving diabetes remission in adults with overweight and type 2 diabetes mellitus. The study will also evaluate the effects of the intervention on metabolic and clinical outcomes associated with diabetes remission. The main questions it aims to answer are: * Does a low-calorie diet combined with intensive lifestyle intervention using iPDM increase the proportion of participants who achieve diabetes remission compared with standard care? * Does the intervention improve metabolic and patient-centered outcomes, including glycemic control, body weight, body composition, Time in Range (TIR) measured by continuous glucose monitoring (CGM), quality of life, and cost-effectiveness? Researchers will compare participants receiving a low-calorie diet combined with intensive lifestyle intervention using iPDM with participants receiving standard diabetes care to determine whether the intervention is more effective in achieving diabetes remission and improving metabolic health. Participants will: * Be randomly assigned to either the intervention group or the standard care group. * Attend study visits for assessments of diabetes-related clinical and metabolic outcomes throughout the 6-month study. * If assigned to the intervention group, consume two low-calorie meal replacements per day and follow an individualized meal plan providing no more than 1,200 kcal per day during the first 3 months (intensive phase), together with a personalized exercise program, continuous glucose monitoring (CGM), and lifestyle counseling delivered via telemedicine every 2 weeks. During the following 3 months (maintenance phase), continue lifestyle modification with reinforcement sessions delivered via telemedicine every 4 weeks while following a meal plan providing no more than 1,500 kcal per day.

Detailed description

Participants will be randomized into two groups using block of four Group A: Intervention Group B: Standard care

Intervention group Phase 1: Intensive phase (Months 0-3) Month 0: Baseline assessment

* Data collection

* Demographics: sex, age, address, duration of diabetes, diabetes-related complications, comorbidities, current medications, drug/food allergies * Physical examination: body weight, height, waist circumference, blood pressure, pulse rate * Body composition analysis using bioelectrical impedance analysis (BIA) * Fasting plasma glucose (FPG) * Glycated hemoglobin (HbA1c) * Fasting insulin * Lipid profile * Serum creatinine and electrolytes * Liver function tests * Urinalysis and spot urine albumin-to-creatinine ratio (UACR) * Quality of life questionnaires: SF-36 and EQ-5D-5L * Self-management questionnaire: Patient Activation Measure 13 (PAM-13) * Mental health questionnaire: PHQ-2; if PHQ-2 ≥1, proceed with PHQ-9 * Education and support Structured diabetes remission education will be provided by certified diabetes educators, including physicians, nurses, dietitians, and exercise physiologists. * Continuous Glucose Monitoring (CGM) Participants will wear a real-time CGM device (LinX CGM) for 15 days. Physicians will review the data via the LinX application every two weeks through telehealth consultations. * Dietary intervention Participants will be provided with two low-calorie meals per day (400 kcal/meal; carb:protein:fat = 45:30:25) on Monday-Friday * Nutrition education Participants will learn to calculate daily caloric intake (target ≤1,200 kcal/day) and record food intake on Saturdays and Sundays. Dietitians will review logs via telehealth every 2 weeks. * Exercise program Participants will perform a 2-minute walk test and receive a personalized exercise plan. Exercise logs will be reviewed biweekly via telehealth with exercise physiologists.

Month 1

* Physical examination: body weight, height, waist circumference, blood pressure, pulse rate * CGM for 15 days * Medication review and adjustment * Behavioral education reinforcement Month 2 * Physical examination: body weight, height, waist circumference, blood pressure, pulse rate * CGM for 15 days * Medication review and adjustment * Behavioral education reinforcement Month 3 * Physical examination: body weight, height, waist circumference, blood pressure, pulse rate * Body composition via BIA * Laboratory investigations: FPG, HbA1c, fasting insulin, Lipid profile, creatinine, electrolytes, liver function tests, urinalysis, UACR * Questionnaires: SF-36, EQ-5D-5L, PAM-13, and PHQ-2 (if PHQ-2 ≥1, proceed with PHQ-9) * Satisfaction and experience questionnaire regarding CGM use Phase 2: Maintenance Phase (Months 3-6) During this 3-month phase, health educators will reinforce behavioral strategies aimed at achieving diabetes remission, with a daily caloric intake target not exceeding 1,500 kcal. Participants' body weight will be monitored monthly via telehealth.

Month 6: Final assessment

* Physical examination: body weight, height, waist circumference, blood pressure, pulse rate * Body composition via BIA * Laboratory investigations: FPG, HbA1c, fasting insulin, Lipid profile, creatinine, electrolytes, liver function tests, urinalysis, UACR * Questionnaires: SF-36, EQ-5D-5L, PAM-13, and PHQ-2 (if PHQ-2 ≥1, proceed with PHQ-9)

Standard care group Participants will undergo data collection and follow-up with physicians at months 0, 3, and 6, following standard diabetes care. They will also receive diabetes remission education from certified diabetes educators at month 0, and a behavioral reinforcement session with health educators at month 3, similar to the intervention group.

Interventions

• Behavioral Low-calorie diet
  Participants in the intervention group will receive a Thai food-based low-calorie diet consisting of two meal replacements per day, combined with individualized dietary counseling to achieve a total daily energy intake of ≤1,200 kcal/day during the 3-month intensive phase. During the subsequent 3-month maintenance phase, participants will transition to a Thai food-based energy-controlled diet with reinforcement of behavioral modification strategies and nutritional education delivered via telemed
• Device Continous Glucose Monitor (CGM)
  Real-Time Continuous Glucose Monitoring
• Other Standard Care (in control arm)
  Standard diabetes care with routine clinical visits every 3 months.
• Behavioral Personalized exercise program
  The exercise intervention is individualized according to the FITT (Frequency, Intensity, Time, and Type) principles for adults with type 2 diabetes mellitus. Baseline cardiorespiratory fitness is assessed using the YMCA 3-Minute Step Test. Heart rate recovery following the test is used to classify participants' fitness level and determine their initial exercise prescription. Exercise intensity is subsequently individualized and progressively adjusted using the Rating of Perceived Exertion (RPE)

Primary outcome measures

• Proportion of participants achieving diabetes remission based on HbA1c <6.5% without glucose-lowering medication at 3 months [Time frame: 3 months]

Secondary outcome measures (7)

• Proportion of participants achieving diabetes remission based on HbA1c <6.5% without glucose-lowering medication at ุ6 months [Time frame: 6 months]
• Change in HbA1c from baseline to 3 and 6 months [Time frame: 3 and 6 months]
• Change in body mass index (BMI) from baseline to 3 and 6 months [Time frame: 3 and 6 months]
• Change in waist circumference from baseline to 3 and 6 months [Time frame: 3 and 6 months]
• Change in fat mass from baseline to 3 and 6 months [Time frame: 3 and 6 months]
• Change in skeletal muscle mass from baseline to 3 and 6 months [Time frame: 3 and 6 months]
• Change in Time in Range from baseline to 3 months [Time frame: 3 months]

Eligibility criteria

Inclusion criteria

• Diagnosed with type 2 diabetes mellitus with HbA1c level of 6.0 to 9.0%. Participants with HbA1c of 6.0 to 6.4% were required to be receiving oral glucose lowering medication.
• Diagnosed with type 2 diabetes mellitus for less than 6 years.
• Body mass index of 23 kg/m2 or greater.

Exclusion criteria

• Receiving more than two oral glucose-lowering medications.
• Receiving insulin therapy.
• Use of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) within 3 months before study enrollment.
• Use of medications known to affect HbA1c within 3 months before study enrollment, including corticosteroids, vitamin C (excluding vitamin C obtained from natural dietary sources or fruits), vitamin E, trimethoprim-sulfamethoxazole, or hydroxyurea.
• History of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the previous 6 months.
• Unstable psychiatric disorders within the previous 2 years, including major depressive disorder, bipolar disorder, or schizophrenia.
• Pregnant or breastfeeding women, or women planning to become pregnant within 12 months.
• Presence of any of the following medical conditions based on medical history and clinical records, including chronic kidney disease with an estimated glomerular filtration rate less than 45 mL/min/1.73 m2, liver cirrhosis or hepatitis with alanine aminotransferase or aspartate aminotransferase more than 3 times the upper limit of normal, chronic alcohol abuse, hypothyroidism with thyroid-stimulating hormone more than 10 uIU/mL, HIV infection, anemia (hemoglobin less than 10 g/dL), iron deficiency, vitamin B12 deficiency, folate deficiency, thalassemia, glucose-6-phosphate dehydrogenase deficiency, hemolytic anemia, or hemoglobin more than 16 g/dL, heart failure or ischemic heart disease within the previous 6 months.
• History of blood donation or blood transfusion within the previous 3 months.
• Uncontrolled diabetic retinopathy or other uncontrolled retinal disease, including maculopathy, based on medical records.
• Signs, symptoms, or a history of malignancy within 5 years before screening, except for basal cell carcinoma, squamous cell carcinoma of the skin, or other carcinoma in situ.
• Major surgery within 90 days before enrollment or planned major surgery within 6 months after enrollment.
• No access to a smartphone capable of supporting the study application and internet-based data transmission.
• Unable to maintain communication with the study investigators according to the study protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Thailand · 1 center

• King Chulalongkorn Memorial Hospital — Bangkok

Publications

• Ehrhardt N, Al Zaghal E. Continuous Glucose Monitoring As a Behavior Modification Tool. Clin Diabetes. 2020 Apr;38(2):126-131. doi: 10.2337/cd19-0037. PMID 32327884
• Look AHEAD Research Group; Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM, Espeland MA, Evans M, Foreyt JP, Ghazarian S, Gregg EW, Harrison B, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall PMID 23796131
• Gregg EW, Chen H, Bancks MP, Manalac R, Maruthur N, Munshi M, Wing R; Look AHEAD Research Group. Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study. Diabetologia. 2024 Mar;67(3):459-469. doi: 10.1007/s00125-023-06048-6. Epub 2024 Jan 18. PMID 38233592
• Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia. 2011 Oct;54(10):2506-14. doi: 10.1007/s00125-011-2204-7. Epub 2011 Jun 9. PMID 21656330
• Umphonsathien M, Prutanopajai P, Aiam-O-Ran J, Thararoop T, Karin A, Kanjanapha C, Jiamjarasrangsi W, Khovidhunkit W. Immediate and long-term effects of a very-low-calorie diet on diabetes remission and glycemic control in obese Thai patients with type 2 diabetes mellitus. Food Sci Nutr. 2019 Feb 11;7(3):1113-1122. doi: 10.1002/fsn3.956. eCollection 2019 Mar. PMID 30918654
• Guldemond N. What is meant by 'integrated personalized diabetes management': A view into the future and what success should look like. Diabetes Obes Metab. 2024 Mar;26 Suppl 1:14-29. doi: 10.1111/dom.15476. Epub 2024 Feb 8. PMID 38328815
• Sattar N, Welsh P, Leslie WS, Thom G, McCombie L, Brosnahan N, Richardson J, Gill JMR, Crawford L, Lean MEJ. Dietary weight-management for type 2 diabetes remissions in South Asians: the South Asian diabetes remission randomised trial for proof-of-concept and feasibility (STANDby). Lancet Reg Health Southeast Asia. 2023 Feb;9:100111. doi: 10.1016/j.lansea.2022.100111. PMID 36777452
• Taheri S, Zaghloul H, Chagoury O, Elhadad S, Ahmed SH, El Khatib N, Amona RA, El Nahas K, Suleiman N, Alnaama A, Al-Hamaq A, Charlson M, Wells MT, Al-Abdulla S, Abou-Samra AB. Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial. Lancet Diabetes Endocrinol. 2020 Jun;8(6):477-489. doi: PMID 32445735

Identifiers

NCT: NCT07748949 · 0890/68 · Ratchadapiseksompotch Fund · RCPT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗