Effect of Low-Calorie Diet and Lifestyle Intervention on Reversal of T2DM

Study Overview
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Brief Summary
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An increase in body fat, even when within the normal BMI range is one of the essential drivers of T2DM in Asian Indians. In this context, the relationship between excess hepatic fat and pancreatic fat appears to be necessary. A low-calorie (high protein and low carb) vegetarian diet with appropriate exercise, in a protocol similar to the DiRECT study, may lead to weight loss, reversal of diabetes, and decrease in ectopic fat.

Detailed Description
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Diabetes is one of the biggest global public health problems. India has 100 million people living with diabetes as per the 2023 data. Reversal of T2DM, the holy grail of diabetes management, was not deemed possible until recently. Primary care-led weight management for remission of type 2 diabetes (DiRECT) trial has been conducted in obese patients with T2DM patients for a period of 2 years in the UK. Research on the effect of dietary intervention would be necessary for Asian Indians since liver fat deposition is more severe than in white Caucasians. Although some nutritionists and physicians are replicating methods of DiRECT study in their patients, it is not clear if similar diets will work effectively in community-dwelling Asian Indians.

Official Title
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Effect of Low-Calorie Diet and Lifestyle Intervention on Reversal of Type 2 Diabetes Mellitus, Hepatic and Pancreatic Fat: A Two-year Randomized Control Trial in New Delhi, India

Conditions
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PreDiabetes, Diet Habit, Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: CURE-DM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with T2DM within the previous 3 years Age 20-65 years BMI >25-45kg/m2 HbA1c> 6.5% at baseline (on current treatment, if any) Exclusion criteria: Recent or screening HbA1c of 9% or higher Weight loss of >5 kg within the previous 6 months Significant cardiopulmonary Hepatic, or another endocrine disease Current participation in any other research drug study in the previous three months Past history of bariatric surgery Malignancy other than minor skin lesions and Possibility of pregnancy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>Phase1 (Partial diet replacement) (850 Kcal/day) (12-20 weeks)): Phase 2 (Gradual increase in calories) (20-28 weeks) (1100 Kcal/day): Phase 3 (Weight loss maintenance) (29-104 weeks) (up to 1200Kcal/day) : | Dietary Supplement: CURE-DM<br>* This randomized controlled prospective trial will be of 2 years duration where 150 patients with T2DM from urban areas of Delhi will be screened. These subjects will be randomized into two groups by computer-generated randomization list using variable block size. Group A (n, 60, test group)will be received a low-calorie diet along with appropriate exercise counseling; and group B (n, 60, Control group) will be received balanced diet along with exercise advice.<br>|
| No Intervention: Control Group<br>Subjects will be given routine care for diabetes and obesity management with no change in medication. The meal plan for the control group will consist of 1400 Kcal/day achieved through small frequently distributed meals constituting around 15% of protein, 60% of carbohydrates and 25% of fat; with a menu resembling standard Indian dietary patterns and meal combinations. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reversal of diabetes | This randomized controlled prospective trial will be of 2 years duration with T2D. These subjects will be randomized into two groups, Group A (intervention group) will receive a professionally supported low-calorie diet along with appropriate exercise counselling; Group B (Control group) will be receiving encouragement to follow standard diet and exercise advice. | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle strength | Handgrip muscle strength by Jamar Dynamometer | 24 Months | 
| Anthropometric assessment | Weight, BMI, circumferences (waist, hip, mid-thigh, mid-arm and neck), skinfold thickness (biceps, triceps, sub scapular, supra-iliac, thigh, lateral thoracic and calf) | 24 Months | 
| Hepatic and Pancreatic Fat | Liver and pancreatic fat fraction (proton-density fat fraction-magnetic resonance imaging (PDFF-MRI) and thigh skeletal muscle area (by MRI). | 24 Months | 
| Body fat | Body fat will be done by Whole body dual-energy X-ray absorptiometry (DEXA scan | 24 Months | 
| Insulin Resistance | Surrogate markers of insulin sensitivity | 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes, Low calorie diet, Asian Indians, hepatic fat, pancreatic fat