It is an open-label, parallel-group, randomized controlled clinical trial, which is designed to enroll people with different glucose metabolism status who are also overweight or obese, including people with normal glucose metabolism, pre-diabetes patients and newly diagnosed type 2 diabetes patients. The patients are randomized to an 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 intends to compare the influence of enhanced physical activity treatment with that of a standard education on liver steatosis, serum glucose and lipids level, insulin sensitivity, cardiovascular metabolic parameters, metabolic molecules, and gut microbiota profile et al.

The trial will recruit 270 patients from 2 hospitals within the China Diabetes Clinical Research Network. Eligible criteria include men and women aged 18-65 years; with normal glucose metabolism or pre-diabetes or newly diagnosed type 2 diabetes; no insulin treatment; BMI ≥23 kg/m2 and <40 kg/m2. Main exclusion criteria include severe cardiovascular diseases, uncontrolled hypertension, and other serious illness. The proposed trial has 90% statistical power to detect an absolute 3.0% reduction of liver triglyceride level changes between intensive physical activity 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:

1. Recruit 270 study participants who meet the eligibility criteria, including 90 people with normal glucose metabolism, 90 pre-diabetes patients and 90 newly diagnosed type 2 diabetes patients, and randomly assign 135 to the enhanced physical activity intervention group and 135 to the standard education group for 12 weeks;
2. Employ a study-wide strategy to encourage standard of care for all participants for the treatment of type 2 diabetes and other metabolic disorders;
3. Obtain clinical data on study outcomes for up to 12 months of follow-up among all trial participants;
4. Perform strict quality control procedures for intervention and data collection;
5. Conduct data analysis according to the intention-to-treat principle;
6. 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.

Inclusion Criteria:

1. Men and women aged 18-65 years;

2. Normal glucose metabolism or pre-diabetes or newly diagnosed type 2 diabetes

   Normal glucose metabolism:

   • FBG<5.6mmol/L and
   • 2h-PG<7.8mmol/L and
   • HbA1c<5.7%;

   Pre-diabetes:

   • 5.6mmol/L ≤ FBG ≤ 6.9mmol/L and/or
   • 7.8mmol/L ≤ 2h-PG ≤ 11.0mmol/L and/or
   • 5.7% ≤ HbA1c ≤ 6.4%;

   Newly diagnosed diabetes:

   o Duration of type 2 diabetes is less than 5 years;

3. No insulin treatment;

4. 23 Kg/m2 ≤ Body mass index (BMI) <40 Kg/m2;

Exclusion Criteria:

Eligibility Minimum Age: 18 Years Maximum Age: 65 Years Sex: All Gender Based: No Accepts Healthy Volunteers: No

Criteria: Inclusion Criteria:

1. Men and women aged 18-65 years;

2. Normal glucose metabolism or pre-diabetes or newly diagnosed type 2 diabetes

   Normal glucose metabolism:

   • FBG<5.6mmol/L and
   • 2h-PG<7.8mmol/L and
   • HbA1c<5.7%;

   Pre-diabetes:

   • 5.6mmol/L ≤ FBG ≤ 6.9mmol/L and/or
   • 7.8mmol/L ≤ 2h-PG ≤ 11.0mmol/L and/or
   • 5.7% ≤ HbA1c ≤ 6.4%;

   Newly diagnosed diabetes:

   o Duration of type 2 diabetes is less than 5 years;

3. No insulin treatment;

4. 23 Kg/m2 ≤ Body mass index (BMI) <40 Kg/m2;

Exclusion Criteria:

1. Severe cardiovascular disease:

   • current angina
   • myocardial infarction or stroke within last six months
   • heart failure (NYHA grading III~IV)
   • symptomatic periphery vascular disease

2. Uncontrolled hypertension: systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg;

3. Myocardial ischemia indicated by resting ECG;

4. Cardiac dysfunction indicated by Echocardiogram;

5. Abnormal HS-TNT or NT-proBNP concentration;

6. Foot ulcers, peripheral neuropathy or skeletal disorders;

7. Taking high intensity exercise more than 75 minutes or moderate intensity exercise more than 150 minutes per week during the screening phase

8. ALT or AST levels more than three times the upper limit of the normal range or active liver diseases;

9. eGFR <60 ml/min/1.73 m2, or serum creatinine >1.5 mg/dl for men or 1.3mg/dl for women; or macro albuminuria (urine albumin/creatinine>300mg/g)

10. Malignant tumor in active-stage, or in remission stage but less than 5 years from the most recent treatment

11. Past or present confirmed psychiatric illness or drug dependence;

12. Currently taking medications known to affect weight (e.g. anti thyroid drugs, glucocorticoids);

13. Known to have weight-affecting diseases (e.g. malabsorption, functional bowel disease, uncontrolled low sodium/hyperthyroidism, eating disorders);

14. Known to have metabolism-affecting diseases;

15. Other acute diseases supported by clinical evidence which may contradict to the interventions;

16. Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using birth control;

17. Currently participating in another intervention study;

18. Failure to obtain informed consent from participant;

19. Any factors judged by the clinic team to be likely to limit adherence to interventions;

20. Any other medical condition judged by the clinic team not eligible for the trial.