Type 2 Diabetes
Conditions
Keywords
Type 2 diabetes remission, non-surgical intervention, lifestyle modification, epigenetic aging, DunedinPACE
Brief summary
This study is a real-world, prospective clinical cohort study. It will enroll Chinese patients with type 2 diabetes. The aim is to assess the changes in aging biomarkers, primarily DunedinPACE, from baseline to post-remission, and to compare these biomarkers between patients who achieve successful remission and those who do not.
Detailed description
This prospective real-world cohort study will enroll 100 Chinese patients with type 2 diabetes, aged 35-70 years. All participants will receive a 24-week multimodal intervention comprising caloric restriction, dietary counseling, exercise training, and adjustment of glucose-lowering medications. DNA methylation levels will be assessed using the Illumina Epic array to calculate the epigenetic aging clock (DunedinPACE), enabling evaluation of changes in biological aging from baseline to 24 weeks, as well as comparisons between patients with and without successful remission. In addition, changes in inflammatory cytokines, metabolic parameters, body composition, and other aging-related biomarkers will be monitored. The findings are expected to provide novel evidence for the benefits of type 2 diabetes remission.
Interventions
Participants will receive a 24-week comprehensive lifestyle intervention： 1. Individualized calorie-restricted low-carbohydrate diet: 800-1000 kcal/day if body weight \<80 kg, or 1000-1200 kcal/day if ≥80 kg; each meal includes \~200 g vegetables and \~100 g lean protein, with low fat/sugar/salt; avoid high-fat meats and organ foods; daily food weighing and recording required. 2. Aerobic exercise ≥150 min/week at moderate intensity (50-70% of maximal heart rate) plus 2-3 resistance training sessions weekly. 3. Monthly nutrition clinic visits for dietary adjustment. 4. Self-monitoring of weight and fasting glucose ≥2 times/week; monthly in-person follow-ups for the first 6 months. 5. Hypoglycemic agents: baseline doses maintained; if fasting glucose \<7 mmol/L and 2-h postprandial glucose \<10 mmol/L, reduce 1-2 drug types per step; hypoglycemia episodes managed by investigator for dose reduction or discontinuation.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 35 to 70 years. 2. Diagnosis of type 2 diabetes mellitus according to WHO criteria, with disease duration ≤6 years. 3. HbA1c between 7.0% and 9.5%, OR currently on glucose-lowering medications. 4. Fasting C-peptide ≥1.0 ng/mL. 5. Fasting plasma glucose \<13.3 mmol/L. 6. BMI between 25 and 45 kg/m². 7. Willing and able to provide informed consent and comply with study procedures
Exclusion criteria
1. Diabetes mellitus secondary to other causes (e.g., Cushing's syndrome, hypothyroidism, glucagonoma, drug-induced, or genetic factors). 2. BMI \<25 kg/m² or \>45 kg/m²; weight loss \>5% within the last 3 months; actively trying to lose weight within the last 3 months; use of weight-loss agents, contraceptives, glucocorticoids, or any medication other than antidiabetic drugs that may affect study outcome measurements within the last 3 months; history of bariatric surgery. 3. Type 1 diabetes; type 2 diabetes duration \>10 years; gestational diabetes; other specific types of diabetes. 4. Diagnosis of acute metabolic diabetic complications (e.g., diabetic ketoacidosis or hyperosmolar hyperglycemic state) or diabetes insipidus within 30 days, or history thereof. 5. Blood pressure ≥180/110 mmHg or malignant hypertension. 6. History of severe gastrointestinal disease; significant cardiac, hepatic, renal, or other systemic organ dysfunction (NYHA functional class ≥II; ALT and/or AST \>4× upper limit of normal; GFR \<60 mL/min); anemia or other hematological disorders; history of malignancy. 7. History of bariatric surgery or other gastrointestinal surgery causing chronic malabsorption within the past 2 years. 8. Use within 3 months prior to screening of any of the following: i. GLP-1 receptor agonists, GLP-1R/GCGR agonists, GIPR/GLP-1R agonists, or GIPR/GLP-1R/GCGR agonists; ii. Medications affecting body weight, including systemic corticosteroids (intravenous, oral, or intra-articular), tricyclic antidepressants, psychiatric medications, or sedatives (e.g., imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid, valproate derivatives, lithium); iii. Chinese herbal medicines, dietary supplements, or meal replacements that affect body weight; iv. Previous or current use of anti-obesity drugs such as sibutramine, orlistat, phentermine, phenylpropanolamine, mazindol, diethylpropion, lorcaserin, phentermine/topiramate, naltrexone/bupropion; consumption of any alcoholic product within 48 hours prior to screening, or a positive alcohol screening test. 9. Drug abuse or alcohol dependence; severe psychiatric or neurological disorders. 10. Pregnant or breastfeeding women, or women planning to become pregnant within 1 year. 11. Special dietary requirements, or allergy to soy, dairy, or other foods. 12. Current participation in another clinical trial; unwillingness to comply with the lifestyle management and follow-up of this study; or judged by the investigator to be unsuitable for participation. 13. Unwilling or unable to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in DunedinPACE epigenetic clock from baseline to 24 weeks. | Baseline to 24 weeks | DunedinPACE is derived from Illumina Epic DNA methylation data. The change score is compared between participants with and without diabetes remission (remission defined as HbA1c \<6.5% off glucose-lowering drugs for ≥3 months). |
Contacts
CONTACTPengfei Shan
PRINCIPAL_INVESTIGATORPengfei Shan
Second Affiliated Hospital, School of Medicine, Zhejiang University
Outcome results
None listed