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

Fudan University

Status: Completed

Conditions: Impaired Glucose Regulation; Type 2 Diabetes; Fatty Liver Disease

Treatments: Behavioral: Intermittent calorie restriction (ICR); Behavioral: Continuous calorie restriction (CCR)

Study type: Interventional

Funder types: Other

Identifiers

NCT04283942

B2019-256R

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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):

  1. Impaired glucose regulation: fasting blood glucose ≥ 100 mg/dL, postprandial blood glucose ≥ 140 mg/dL or HbA1c ≥ 5.7%
  2. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Intermittent Calorie Restriction (ICR)

Experimental group

Description:

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.

Treatment:

Behavioral: Intermittent calorie restriction (ICR)

Control (Continuous calorie restriction, CCR)

Other group

Description:

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.

Treatment:

Behavioral: Continuous calorie restriction (CCR)