Effect of Intermittent Calorie Restriction on MASLD Patients With Abnormal Glucose Metabolism

Study Overview
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Brief Summary
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This study is designed to observe the effect of 5:2 intermittent calorie restriction (fasting 2 days each week) on liver fat content in MASLD patients with abnormal blood glucose.

Detailed Description
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Intermittent caloric restriction (ICR) can effectively reduce weight and facilitate blood glucose control, but whether it can be applied for clinical treatment to metabolic dysfunction-associated steatotic liver disease (MASLD) patients remains unclear. We intend to carry out this study in MASLD patients with abnormal glucose metabolism. It is an open-labeled randomized trial designed to observe the effect of 5:2 intermittent calorie restriction (fasting 2 days each week) on liver fat content in MASLD patients with abnormal blood glucose. 60 patients will be randomly divided into ICR group and control group for 12 weeks of intervention. ICR group: during the 2-day fasting-mimicking period each week, the food based on plant ingredients will be served (4 pieces of nutrition bars / day, 1:2:1 for breakfast, lunch and dinner, 124.4kcal / piece, 497.2kcal / day in total). In the rest 5 days each week, subjects are allowed ad libitum to their usual food. Control group (continuous calorie restriction, CCR): under the guidance of nutritionist, subjects have to learn the method of food calories calculation. The daily calories intake for control group should be: 25 kcal / kg × [height (cm) - 100] kg. Daily food diary is required in both groups. During the experiment, all subjects should maintain their exercise routine. The use of drugs affecting blood glucose and fatty liver should be avoided. After 12 weeks of intervention, the changes of liver fat content were evaluated by magnetic resonance spectroscopy (MRS) and Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF). The effects of ICR on body weight, blood glucose and body fat will also be evaluated. Both groups will be followed up on their changes of weight 4 weeks after intervention.

Official Title
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Effect of Intermittent Calorie Restriction on Metabolic Dysfunction-Associated Steatotic Liver Disease Patients With Abnormal Glucose Metabolism

Conditions
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Fatty Liver Disease, Type 2 Diabetes, Impaired Glucose Regulation

Intervention / Treatment
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* Behavioral: Intermittent calorie restriction (ICR)
* Behavioral: Continuous calorie restriction (CCR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 18-70 Diagnosed as fatty liver by ultrasound or magnetic resonance imaging BMI ≥ 24 kg/m2 abnormal glucose metabolism: (meeting at least one): Impaired glucose regulation: fasting blood glucose ≥ 100 mg/dL, postprandial blood glucose ≥ 140 mg/dL or HbA1c ≥ 5.7% Diabetes mellitus: diabetic symptoms + plasma glucose concentration ≥ 200 mg/dL at any time or fasting plasma glucose concentration ≥ 100 mg/dL or OGTT 2 h plasma glucose concentration ≥ 200 mg/dL Exclusion Criteria Type 1 diabetes, gestational diabetes and other special types of diabetes Poor blood glucose control, HbA1c > 8.5% within 3 months Taking antidiabetic drugs in the past month Serum ALT > 6 times of normal upper limit Excessive alcohol consumption (alcohol intake: men > 140 g, women > 70 g in the past 6 months) Other liver diseases: such as acute and chronic viral hepatitis, drug-induced hepatitis, immune hepatitis, liver cirrhosis, liver cancer, etc Taking drugs that may affect MASLD in the past three months, such as vitamin E Biliary obstructive diseases Other diseases affecting glucose and lipid metabolism: hyperthyroidism, hypothyroidism, Cushing's syndrome, etc Chronic kidney disease (serum creatinine ≥ 2.0 mg/dL) Life expectancy of no more than 5 years Already pregnant or plan to be pregnant in the near future Mental illness Other conditions affecting follow-up Have participated in other clinical trials in the past 4 weeks Absent of informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients were randomly divided into intermittent calorie restriction group and control group for 12 weeks of intervention. Both groups will be followed up 4 weeks after intervention. ICR group: during the 2-day fasting-mimicking period each week, the food based on plant ingredients will be served (4 pieces of nutrition bars / day, 1:2:1 for breakfast, lunch and dinner, 124.4kcal/piece, 497.2kcal / day in total). In the rest 5 days each week, subjects are allowed ad libitum to their usual food. Control group: continuous calorie restriction (CCR). Under the guidance of nutritionist, subjects have to learn the method of food calories calculation. For each day, the daily calories intake is limited to 25 kcal / kg × standard weight [kg, estimated by height (cm) - 100].
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intermittent Calorie Restriction (ICR)<br>Participants in ICR group were instructed to ensure 2 successive days of fasting-mimicking and 5 days of recovery per week. On fasting-mimicking days, the participants were instructed to consume approximately 500 kcal/day and they were provided with plant-based meal replacement (ZhenBaiNian nutrition bar, Beijing Wanlaikang Nutrition and Health Food Science and Technology Research Institute Co., Ltd, China) to improve adherence and ensured adequate intake of micronutrients. In the rest 5 days of recovery per week, participants were allowed to consume their usual diet. | Behavioral: Intermittent calorie restriction (ICR)<br>* Participants in ICR group were instructed to ensure 2 successive days of fasting-mimicking and 5 days of recovery per week. On fasting-mimicking days, the participants were instructed to consume approximately 500 kcal/day and they were provided with plant-based meal replacement to improve adherence and ensured adequate intake of micronutrients. In the rest 5 days of recovery per week, participants were allowed to consume their usual diet. Participants will receive dietary counseling from experienced nutritionists and eat a balanced diet (macronutrient distribution of approximately 10-15% protein, 55-65% carbohydrate and 20-30% fat).They are required to write daily dietary log. Besides, they are required to maintain their exercise routines and record their daily steps using a unified pedometer (Redmi Smart Band, Xiaomi Corporation, China). The use of drugs affecting blood glucose and LFC will be avoided.<br>* Other names: Intermittent fasting;|
| Other: Control (Continuous calorie restriction, CCR)<br>Participants in control group were instructed to consume the prescribed calories (25 kcal / kg × [height (cm) - 100] kg) every day by eating conventional food without time restriction. | Behavioral: Continuous calorie restriction (CCR)<br>* Participants in CCR group were instructed to consume the prescribed calories (25 kcal / kg × [height (cm) - 100] kg) every day by eating conventional food without time restriction. Participants will receive dietary counseling from experienced nutritionists and eat a balanced diet (macronutrient distribution of approximately 10-15% protein, 55-65% carbohydrate and 20-30% fat).They are required to write daily dietary log. Besides, they are required to maintain their exercise routines and record their daily steps using a unified pedometer (Redmi Smart Band, Xiaomi Corporation, China). The use of drugs affecting blood glucose and LFC will be avoided.<br>* Other names: Daily calorie restriction;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of liver fat content in % | Change of liver fat content in %. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of weight | Change of weight in kilograms. | 12 weeks | 
| Change of blood glucose: fasting blood glucose | Change of fasting blood glucose in mmol/L. | 12 weeks | 
| Change of blood glucose: 2h postload blood glucose | Change of 2h postload blood glucose in mmol/L. | 12 weeks | 
| Change of HbA1c | Change of HbA1c in %. | 12 weeks | 
| Change of liver enzymes: alanine aminotransferase | Change of alanine aminotransferase in U/L. | 12 weeks | 
| Change of liver enzymes: aspartate aminotransferase | Change of aspartate aminotransferase in U/L. | 12 weeks | 
| Change of liver enzymes: γ-glutamyl transpeptidase | Change of γ-glutamyl transpeptidase in U/L. | 12 weeks | 
| Change of lipid profile: total cholesterol | Change of total cholesterol in mmol/L. | 12 weeks | 
| Change of lipid profile: triglyceride | Change of triglyceride in mmol/L. | 12 weeks | 
| Change of lipid profile: high-density lipoprotein-cholesterol | Change of high-density lipoprotein-cholesterol in mmol/L. | 12 weeks | 
| Change of lipid profile: low-density lipoprotein-cholesterol | Change of low-density lipoprotein-cholesterol in mmol/L. | 12 weeks | 
| Change of lipid profile: free fatty acid | Change of free fatty acid in mmol/L. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic dysfunction-associated steatotic liver disease, Type 2 Diabetes