Intermittent Eating on Glucose Homeostasis in Prediabetes

Study Overview
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Brief Summary
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Prediabetes is a high-risk state for diabetes development, lifestyle modification is the cornerstone of diabetes prevention. Two novel types of intermittent fasting recently have received more attention: the 5:2 diet and time-restricted eating (TRE). TRE requires individuals to eat in a specified number of hours per day (typically 4 to 10 hours) without energy intake restriction. The 5:2 diet involves 5 feast days and 2 fast days per week; participants eat ad libitum without restriction on feast days while 25% of energy needs (approximately 500-800 kcal per day) are consumed on fast day. This randomized controlled trial aimed to evaluate the effect of TRE and the 5:2 diet on glucose homeostasis and cardiometabolic risk factors in prediabetes over 6 months compared to usual health care.

Detailed Description
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Prediabetes is a high-risk state for diabetes development, lifestyle modification is the cornerstone of diabetes prevention. Two novel types of intermittent fasting recently have received more attention: the 5:2 diet and time-restricted eating (TRE). TRE requires individuals to eat in a specified number of hours per day (typically 4 to 10 hours) without energy intake restriction. The 5:2 diet involves 5 feast days and 2 fast days per week; participants eat ad libitum without restriction on feast days while 25% of energy needs (approximately 500-800 kcal per day) are consumed on fast day. Preliminary evidence suggests that both TRE and the 5:2 diet have beneficial effects on glucose control in type 2 diabetes. No much is known about the effects and molecular mechanisms by TRE or the 5:2 diet improves glucose homeostasis in prediabetes. This randomized controlled trial aimed to evaluate the effect of TRE and the 5:2 diet on glucose homeostasis and cardiometabolic risk factors in prediabetes over 6 months compared to usual health care. All eligible participants will participate in an 8-week run-in phase in which they are fed the low-calorie-diet. Participants who pass the run-in phase will be randomly assigned 1:1:1 to one of the three study groups (TRE, the 5:2 diet and control groups). Participants in the TRE group will be instructed to eat during a window of 8 h/d (8 am to 4 pm) over 12 months. Participants in the 5:2 diet group will be instructed to consume 500-600 kcal/d on fast days and eat ad libitum on feast days. Participants in the control group were instructed to receive usual health care.

Official Title
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Effects of Intermittent Eating on Glucose Homeostasis in Prediabetes: A Randomized Clinical Trial

Conditions
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PreDiabetes, Obesity

Intervention / Treatment
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* Behavioral: Time-restricted eating
* Behavioral: The 5:2 diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 18-75 years; Prediabetes; Body mass index (BMI)of 28.0 to 45.0 kg/m2; Exclusion Criteria: History of HIV, hepatitis B or C (self-report) or active pulmonary tuberculosis; Diagnosis of type 1 and type 2 diabetes; History of malignant tumors; Serious liver dysfunction or chronic kidney disease (AST or ALT > 3 times the upper limit of normal, or eGFR<30 ml/min/1.73 m2); History of serious cardiovascular or cerebrovascular disease (angina, myocardial infarction or stroke) in the past 6 months; History of severe gastrointestinal diseases or gastrointestinal surgery in the past 12 months; History of Cushing's syndrome, hypothyroidism, acromegaly, hypothalamic obesity; Being a smoker or having been a smoker in the 3 months prior to their screening visit; Taking medications affecting weight or energy intake/energy expenditure in the last 6 months, including weight loss medications, antipsychotic drugs or other medications as determined by the study physician; Currently participating in weight loss programs; Women who are pregnant or plan to become pregnant; Patients who cannot be followed for 24 months (due to a health situation or migration); Patients who are unwilling or unable to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Time-restricted eating<br>Participants in the TRE group will be instructed to eat during a window of 8 h/d (8 am to 4 pm) | Behavioral: Time-restricted eating<br>* Participants in the TRE group will be instructed to eat during a window of 8 h/d (8 am to 4 pm).<br>|
| Experimental: the 5:2 diet<br>Participants in the 5:2 diet group will be instructed to consume 500-600 kcal/d on fast days and eat ad libitum on feast days. | Behavioral: The 5:2 diet<br>* Participants will be instructed to consume 500-600 kcal/d on fast days and eat ad libitum on feast days.<br>|
| No Intervention: Control<br>Participants in the control group will receive a general lifestyle counseling. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percent of time in range (glucose between 3.9-7.8mmol/L) over 6 months measured with continuous glucose monitoring. |  | Baseline to months 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean glucose levels |  | Baseline and months 6 | 
| Change in glycemic variability |  | Baseline and months 6 | 
| Change in percent of time below range | <3.9 mmol/L | Baseline and months 6 | 
| Change in percent of time above range | >7.8 mmol/L | Baseline and months 6 | 
| Change in resting metabolic rate | Resting metabolic rate will be assessed by indirect calorimetry. | Baseline and months 6 | 
| Change in gut microbiome composition |  | Baseline and months 6 | 
| Change in bile acid level |  | Baseline and months 6 | 
| Change in body weight |  | Baseline and months 6 | 
| Change in body composition | Body composition will be assessed by DEXA. | Baseline and months 6 | 
| Change in waist circumference |  | Baseline and months 6 | 
| Change in body mass index |  | Baseline and months 6 | 
| Change in liver fat | Liver fat will be assessed by liver Fibroscan. | Baseline and months 6 | 
| Change in visceral fat | Visceral fat will be assessed by abdominal CT scan. | Baseline and months 6 | 
| Change in Systolic Blood pressure |  | Baseline and months 6 | 
| Change in Diastolic Blood pressure |  | Baseline and months 6 | 
| Change in blood lipids |  | Baseline and months 6 | 
| Change in HbA1c |  | Baseline and months 6 | 
| Change in insulin sensitivity |  | Baseline and months 6 | 
| Change in β cell function |  | Baseline and months 6 | 
| Change in pulse wave velocity (PWV) |  | Baseline and months 6 | 
| Change in quality of life | Quality of life measured by the 12-item Short-Form Health Survey Questionnaire (SF-12) | Baseline and months 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TRE, The 5:2 diet, Glucose Homeostasis, prediabetes, obesity