Intensive Diet and Physical Activity on Diabetes

Study Overview
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Brief Summary
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It is a multicenter, open-label, parallel-group, randomized controlled clinical trial, which is designed to enroll newly diagnosed type 2 diabetes patients with overweight or obesity. The patients are randomized to an intensive diet intervention (intermittent very-low -calorie diet), enhanced physical activity intervention (high-intensity interval training exercise prescription combined with resistance training) or standard education group (diabetes health education only, including lifestyle education and guidance) for 12 weeks. This trial will test the primary hypothesis of whether an intensive lifestyle treatment (diet or physical activity) is more effective than a standard education in glycemic control. The secondary hypotheses are to compare the intensive lifestyle treatment with a standard education on adipose distribution, metabolic parameters, metabolic molecules, Framingham Risk Scores, and quality of life, et al.

Detailed Description
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The trial will recruit 324 patients from 2-3 hospitals within the China Diabetes Clinical Research Network. Eligible criteria include men and women aged 40-70 years; newly-diagnosed type 2 diabetes mellitus; BMI ≥25 kg/m2 and <40 kg/m2. Main exclusion criteria include known type 1 diabetes, usage of insulin; symptomatic cardiovascular diseases, and other serious illness. The proposed trial has 90% statistical power to detect an absolute 0.5% reduction of HbA1c changes between intensive intervention and standard education groups at a 2-sided significance level of 0.05. To achieve the proposed study objectives, we plan to perform the following specific aims: Recruit 324 study participants who meet the eligibility criteria and randomly assign 108 to the intensive diet intervention group, 108 to the enhanced physical activity intervention group and 108 to the standard education group for 12 weeks; Employ a study-wide strategy to encourage standard of care for all participants for the treatment of type 2 diabetes and other metabolic disorders; Obtain clinical data on study outcomes for up to 12 months of follow-up among all trial participants; Perform strict quality control procedures for intervention and data collection; Conduct data analysis according to the intention-to-treat principle; Disseminate the study findings to influence clinical practice and clinical guidelines. The results will be analyzed to examine the pan-omics changes after the interventions and clarify their predictive benefits on the effects of the interventions.

Official Title
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Effect of Intermittent Intensive Diet Intervention and Enhanced Physical Activity on Glycemic Control in Patients With Newly Diagnosed Type 2 diabEtes (IDEATE)

Conditions
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Type2 Diabetes, Life Style

Intervention / Treatment
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* Behavioral: intensive diet intervention
* Behavioral: Enhanced physical activity intervention
* Behavioral: Standard education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 40-70 years; Newly diagnosed type 2 diabetes Duration of type 2 diabetes ≤ 2 years; Antidiabetic treatment maintained for at least 6 weeks before recruitment; 7.0%≤ HbA1c < 9.0%; 25 Kg/m2 ≤ Body mass index (BMI) <40 Kg/m2; Exclusion Criteria: History consistent with type 1 diabetes; Insulin treatment; Severe cardiovascular disease: current angina myocardial infarction within last six months heart failure symptomatic periphery vascular disease Uncontrolled hypertension: systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg; Myocardial ischemia indicated by resting ECG; Foot ulcers, peripheral neuropathy or skeletal disorders; Taking high intensity exercise more than 75 minutes or moderate intensity exercise more than 150 minutes per week during the screening phase Average weekly alcohol intake >140 grams for men and >70 grams for women; ALT or AST levels more than twice the upper limit of the normal range or active liver diseases; eGFR <60 ml/min/1.73 m2, or serum creatinine >1.5 mg/dl for men or 1.3mg/dl for women; or Proteinuria Malignant tumor in active-stage, or in remission stage but less than 5 years from the most recent treatment Hemoglobin concentration <130 g/l for men or <120 g/l for women; Past or present confirmed psychiatric illness or drug dependence; History of food allergies; Surgical history of digestive system; Currently taking medications known to affect weight (e.g. anti thyroid drugs, glucocorticoids); Known to have weight-affecting diseases (e.g. malabsorption, functional bowel disease, uncontrolled low sodium/hyperthyroidism, eating disorders); Known to have metabolism-affecting diseases; Known to have infectious diseases within last month; Possible consumption of food or drugs affecting glucose homeostasis or gut microbiota within the last three months; Other acute diseases supported by clinical evidence which may contradict to the interventions; Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using birth control; Currently participating in another intervention study; Failure to obtain informed consent from participant; Any factors judged by the clinic team to be likely to limit adherence to interventions; Any other medical condition judged by the clinic team not eligible for the trial.

Ages Eligible for Study
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Minimum Age: 40 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intensive diet intervention group<br>The participants will be instructed to restrict the total daily calorie intake to 800 kcal by receiving the very-low-calorie meal replacement formula for 2 consecutive days per week. They will be allowed to maintain their normal diet in the remaining 5 days, but need to restrict total intake to 2000 kcal per day. | Behavioral: intensive diet intervention<br>* the participants will be instructed to restrict the total daily calorie intake to 800 kcal by receiving the very-low-calorie meal replacement formula for 2 consecutive days per week. They will be allowed to maintain their normal diet in the remaining 5 days, but need to restrict total intake to 2000 kcal per day.<br>|
| Experimental: Enhanced physical activity group<br>the participants will take high-intensity exercise in accordance with High Intensity Interval Training (HIIT) prescriptions, with maximum heart rate and relative maximal oxygen uptake monitored. They will take both aerobic and resistance training exercise consecutively, and total training time will be expected to reach at least 150 minutes per week. | Behavioral: Enhanced physical activity intervention<br>* the participants will take high-intensity exercise in accordance with High Intensity Interval Training (HIIT) prescriptions, with maximum heart rate and relative maximal oxygen uptake monitored. They will take both aerobic and resistance training exercise consecutively, and total training time will be expected to reach at least 150 minutes per week.<br>|
| Experimental: Standard education group<br>the participants will receive no extra intervention but diabetes health education, which will be carried out in large classrooms, in groups, and over the telephone. The education is mainly consisted of instructions on healthy diet and exercise plans, prevention for acute and chronic complications and self-glycemic monitoring. | Behavioral: Standard education<br>* the participants will receive no extra intervention but diabetes health education, which will be carried out in large classrooms, in groups, and over the telephone. The education is mainly consisted of instructions on healthy diet and exercise plans, prevention for acute and chronic complications and self-glycemic monitoring.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in HbA1C level (%) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in HbA1C level (%) |  | 1 year | 
| proportion of reversal of diabetes |  | 1 year | 
| reduction in the dosage of hypoglycemic drugs |  | 1 year | 
| change in insulin sensitivity | Quantify by HOMA score, which is calculated multiplying fasting plasma insulin (FPI, mIU/L) by fasting plasma glucose (FPG, mmol/L), then dividing by the constant 22.5, i.e. HOMA-IR = (FPI×FPG)/22.5. | 1 year | 
| change in islet β-cell function | Quantify by HOMA score, which is calculated with fasting plasma insulin (FPI, mIU/L) and fasting plasma glucose (FPG, mmol/L), i.e. HOMA-β = 20*FPI/(FPG-3.5). | 1 year | 
| change in liver steatosis quantified by MRI-PDFF (percentage) |  | 1 year | 
| change in body mass index (BMI) | Body weight (kg) and height (m) will be combined to report BMI in kg/m^2 | 1 year | 
| change in visceral fat (cm^2) |  | 1 year | 
| change in serum fetuin-A concentration (μg/mL) |  | 1 year | 
| change in serum GREM2 concentration (pg/ml) |  | 1 year | 
| change in serum Caspase-cleaved Keratin 1 concentration (U/L) |  | 1 year | 
| changes in serum FGF21 concentration (pg/ml) |  | 1 year | 
| changes in overall gut microbiota profile | change in gut microbiota composition and proportion of specific gut flora. | 1 year | 
| depression | Evaluated with PHQ-9 scores. The PHQ is 59-question instrument, referring to the level of interest in doing things, feeling down or depressed, difficulty with sleeping, energy levels, eating habits, self-perception, ability to concentrate, speed of functioning and thoughts of suicide. Responses range from 0 (Not at all) to 3 (nearly every day).The total sum of the responses suggests varying levels of depression. Scores range from 0 to 27. In general, a total of 10 or above is suggestive of the presence of depression. | 1 year | 
| health related quality of life | Evaluated with HQoL scales such as Short Form 12 Health Survey Questionnaire | 1 year | 
| cardiovascular risk | Evaluated with Framingham Risk Scores. Individuals with low risk have 10% or less CHD risk at 10 years, with intermediate risk 10-20%, and with high risk 20% or more. | 1 year |