Intervention Effects of Optimized Carbohydrate Diet in Patients With Type 2 Diabetes

This study is a multi-center, randomized, crossover investigator-initiated trial conducted at Shanghai Sixth People's Hospital and other centers. Each participant will undergo two 12-week dietary intervention phases, separated by a 6-week washout, for a total study duration of 30 weeks. Participants will be randomly assigned in a 1:1 ratio to one of two intervention order: (1) optimized carbohydrate diet-washout-conventional diabetes diet, or (2) conventional diabetes diet-washout-optimized carbohydrate diet. The optimized carbohydrate diet is a modified diet with adjusted carbohydrate composition and proportions, while the conventional diabetes diet adheres to an energy-matched protocol in accordance with diabetes dietary guidelines. The study aims to explore the effects of the optimized carbohydrate diet on blood glucose control and glucose metabolism in patients with type 2 diabetes, and to systematically assess its impact on cognitive function and a range of physiological and psychological indicators (such as depression, anxiety, appetite, sleep, bowel habits and others).

Study Overview

• Status: Not yet recruiting
• Conditions: Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Other: optimized carbohydrate diet; Other: conventional diabetes diet

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients diagnosed with type 2 diabetes according to the ADA diagnostic criteria
2. HbA1c ≥ 7% and < 9%
3. Antidiabetic medication has been stable for at least 3 months before recruitment
4. Aged 35-70 years
5. Signed the informed consent form

Exclusion Criteria:

1. Treatment with insulin
2. Treatment with GLP-1 receptor agonists or DPP-4 inhibitors
3. Occurrence of diabetic ketoacidosis, lactic acidosis, hyperosmolar coma, or recurrent severe hypoglycemia within the past year
4. Having one or more severe chronic diabetic complications, including advanced diabetic retinopathy, macroalbuminuria (urine albumin-to-creatinine ratio ≥300 mg/g), or impaired renal function (eGFR ≤60 ml/min/1.73 m²)
5. Presence of cardiovascular events (e.g., myocardial infarction, stent placement, unstable angina, heart failure, cardiac dysfunction) or cerebrovascular diseases (e.g., intracerebral hemorrhage, ischemic stroke) within the past 6 months
6. Diagnosis of acute or chronic gastrointestinal diseases (e.g., ulcers), hyperthyroidism or hypothyroidism, uncontrolled hypertension, active malignancy not in remission, or other life-threatening diseases
7. Recent use of antibiotics, probiotics, or prebiotics within the past 3 weeks or need for long-term use
8. Unstable medication regimen or use of prescription medications affecting metabolism (e.g., thyroid hormones, glucocorticoids)
9. Pregnancy, breastfeeding, or planning pregnancy
10. Presence of a pacemaker or metal implants, claustrophobia, or other contraindications to fMRI
11. Psychiatric disorders impairing cooperation
12. Expected poor compliance
13. Current or recent (within 4 weeks prior to study initiation) participation in other clinical trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: optimized carbohydrate diet-washout-conventional diabetes diet; Group that starts with the optimized carbohydrate diet	Other: optimized carbohydrate diet; In this dietary pattern, 50-60% of total energy is derived from carbohydrates, 15-20% from protein, and 25-30% from fat. Among the carbohydrates, resistant starch (RS) constitutes 15-20% of daily starch intake (around 40 g/day), slowly digestible starch (SDS) 5%, rapidly digestible starch (RDS) 75-80%, with dietary fiber at 20-40g per 1000 kcal and free sugars contributing less than 5% of total energy.; Other: conventional diabetes diet; In this dietary pattern, 50-60% of total energy is derived from carbohydrates, 15-20% from protein, and 25-30% from fat. Among the carbohydrates, resistant starch (RS) constitutes 5% of daily starch intake, slowly digestible starch (SDS) 5%, rapidly digestible starch (RDS) 90%, with dietary fiber at 14g per 1000 kcal and free sugars contributing less than 5% of total energy.
Experimental: conventional diabetes diet-washout-optimized carbohydrate diet; Group that starts with the conventional diabetes diet	Other: optimized carbohydrate diet; In this dietary pattern, 50-60% of total energy is derived from carbohydrates, 15-20% from protein, and 25-30% from fat. Among the carbohydrates, resistant starch (RS) constitutes 15-20% of daily starch intake (around 40 g/day), slowly digestible starch (SDS) 5%, rapidly digestible starch (RDS) 75-80%, with dietary fiber at 20-40g per 1000 kcal and free sugars contributing less than 5% of total energy.; Other: conventional diabetes diet; In this dietary pattern, 50-60% of total energy is derived from carbohydrates, 15-20% from protein, and 25-30% from fat. Among the carbohydrates, resistant starch (RS) constitutes 5% of daily starch intake, slowly digestible starch (SDS) 5%, rapidly digestible starch (RDS) 90%, with dietary fiber at 14g per 1000 kcal and free sugars contributing less than 5% of total energy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the average incremental area under the curve (iAUC) of postprandial blood glucose over 3 hours	Average incremental area under the curve (iAUC) of postprandial blood glucose over 3 hours will be measured at -2, 0, 10, 16, 18, and 28 weeks using the continuous glucose monitoring system.	-2, 0, 10, 16, 18 and 28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in other parameters of Continuous Glucose Monitoring	Other parameters of Continuous Glucose Monitoring, including Time in Range (TIR), Time Above Range (TAR), Time Below Range (TBR), Mean Glucose, Glucose Variability, Glycemic Excursions, Area Under the Curve (AUC), and other relevant metrics, will be assessed at -2, 0, 10, 16, 18, and 28 weeks.	-2, 0, 10, 16, 18 and 28 weeks
Change in HbA1c	HbA1c will be measured at baseline, 12, 18 and 30 weeks. HbA1c will be expressed in mmol/mol.	Baseline, 12, 18 and 30 weeks
Change in insulin sensitivity	Insulin sensitivity will be assessed at baseline, 12, 18 and 30 weeks.	Baseline, 12, 18 and 30 weeks
Change in other clinical biochemical indicators	Other clinical biochemical indicators will be measured at baseline, 4, 8, 12, 18, 22, 26 and 30 weeks.	Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks
Change in blood glucose	Fasting blood glucose will be measured at baseline, 4, 8, 12, 18, 22, 26 and 30 weeks. During meal tolerance test (MTT) at baseline, 12, 18 and 30 weeks, blood glucose at 0, 30, 60, 90, 120 minutes will be measured. Glucose concentration will be expressed in mmol/L	Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks
Change in insulin and C peptide secretion	Fasting insulin and C peptide concentration will be assessed at baseline, 4, 8, 12, 18, 22, 26 and 30 weeks. During meal tolerance test (MTT) at baseline, 12, 18 and 30 weeks, insulin and C peptide concentration at 0, 30, 60, 90, 120 minutes will be measured. Insulin concentration will be expressed in uU/ml. C peptide concentration will be expressed in ng/ml.	Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks
Change in anthropometry and body composition parameters	Anthropometry and body composition parameters will be measured at baseline, 4, 8, 12, 18, 22, 26 and 30 weeks.	Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks
Change in cognitive function and behavioral performance	Cognitive function changes will be assessed using questionnaires (including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA, Beijing version), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Trail Making Test, Stroop Color and Word Test, and others) at baseline, 12 18, and 30 weeks. Behavioral performance will be assessed using N-back and other paradigms at baseline, 12, 18, and 30 weeks. In addition, subgroups within the two arms will undergo fMRI to assess cognitive function at baseline, 12 18, and 30 weeks.	Baseline, 12, 18 and 30 weeks
Change in appetite	Appetite will be measured by visual analog scales (VAS) and other relevant scales, and will be assessed at baseline, 12, 18, and 30 weeks.	Baseline, 12, 18 and 30 weeks
Change in emotion	Emotion will be measured using the PHQ-9 depression screening scale, the Problem Areas in Diabetes (PAID) questionnaire, and other relevant scales at baseline, 12, 18, and 30 weeks.	Baseline, 12, 18 and 30 weeks
Change in sleep quality	Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire and other methods at baseline, 12, 18, and 30 weeks.	Baseline, 12, 18 and 30 weeks
Change in cardiopulmonary exercise testing performance	Cardiopulmonary exercise testing performance will be conducted at baseline, 12, 18 and 30 weeks.	Baseline, 12, 18 and 30 weeks
Change in blood lipid profiles	Blood lipid profiles will be measured at baseline, 4, 8, 12, 18, 22, 26 and 30 weeks.	Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks
Change in bowel habits	Bowel habits will be assessed using the Bristol Stool Form Scale (BSFS; range: 1-7, with higher scores indicating looser stools) and other relevant scales at baseline, 12, 18, and 30 weeks.	Baseline, 12, 18 and 30 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the iAUC of postprandial blood glucose over 3 hours after each meal	The iAUC of postprandial blood glucose over 3 hours after each meal in patients with type 2 diabetes will be measured at -2, 0, 10, 16, 18, and 28 weeks using the continuous glucose monitoring system.	-2, 0, 10, 16, 18 and 28 weeks
Change in hepatic fat content	Hepatic fat content will be assessed by Fibroscan at baseline, 12, 18 and 30 weeks.	Baseline, 12, 18 and 30 weeks
Change in the levels of cytokines	The levels of cytokines, including FGF21, adiponectin, A-FABP, LCN2, and others, will be assessed using Enzyme-Linked Immunosorbent Assay (ELISA) and other methods at baseline, 12, 18, and 30 weeks.	Baseline, 12, 18 and 30 weeks
Change in immunologic function	The immunologic function will be assessed through isolation and analysis of peripheral blood mononuclear cells at baseline, 12, 18, and 30 weeks.	Baseline, 12, 18 and 30 weeks
Change in multi-omics	Multi-omics research, including metagenomic sequencing, metabolomics analysis, proteomics, lipidomics, genomics, etc., will be assessed at baseline, 4, 8, 12, 18, 22, 26 and 30 weeks.	Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks
Change in appetite-related hormones	Concentration of appetite-related hormones (e.g., ghrelin, PYY, GLP-1 and others) will be measured at baseline, 12, 18, and 30 weeks.	Baseline, 12, 18 and 30 weeks

Collaborators and Investigators

• Sponsor: Shanghai 6th People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 20, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: April 10, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 20, 2025

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 2025-018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No