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

Overview

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).

Interventions

• 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.

Primary outcome measures

• Change in the average incremental area under the curve (iAUC) of postprandial blood glucose over 3 hours [Time frame: -2, 0, 10, 16, 18 and 28 weeks]

Secondary outcome measures (12)

• Change in other parameters of Continuous Glucose Monitoring [Time frame: -2, 0, 10, 16, 18 and 28 weeks]
• Change in HbA1c [Time frame: Baseline, 12, 18 and 30 weeks]
• Change in insulin sensitivity [Time frame: Baseline, 12, 18 and 30 weeks]
• Change in other clinical biochemical indicators [Time frame: Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks]
• Change in blood glucose [Time frame: Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks]
• Change in insulin and C peptide secretion [Time frame: Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks]
• Change in anthropometry and body composition parameters [Time frame: Baseline, 4, 8, 12, 18, 22, 26 and 30 weeks]
• Change in cognitive function and behavioral performance [Time frame: Baseline, 12, 18 and 30 weeks]
• Change in appetite [Time frame: Baseline, 12, 18 and 30 weeks]
• Change in emotion [Time frame: Baseline, 12, 18 and 30 weeks]
• Change in sleep quality [Time frame: Baseline, 12, 18 and 30 weeks]
• Change in bowel habits [Time frame: Baseline, 12, 18 and 30 weeks]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Treatment with insulin
• Treatment with GLP-1 receptor agonists or DPP-4 inhibitors
• Occurrence of diabetic ketoacidosis, lactic acidosis, hyperosmolar coma, or recurrent severe hypoglycemia within the past year
• 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)
• 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
• 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
• Recent use of antibiotics, probiotics, or prebiotics within the past 3 weeks or need for long-term use
• Unstable medication regimen or use of prescription medications affecting metabolism (e.g., thyroid hormones, glucocorticoids)
• Pregnancy, breastfeeding, or planning pregnancy
• Presence of a pacemaker or metal implants, claustrophobia, or other contraindications to fMRI
• Psychiatric disorders impairing cooperation
• Expected poor compliance
• Current or recent (within 4 weeks prior to study initiation) participation in other clinical trials

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Lu Y, Zhang R, Yang J, Liu D, Wu Q, Long X, Cheng D, Guo J, Li Q, Zhang Y, Kang P, Wang Q, Gao X, Zeng R, Zhang M, Fang Q, Jia W, Ni Y, Li H. Intervention effects of optimised carbohydrate diet in patients with type 2 diabetes: study protocol for a randomised controlled crossover trial. BMJ Open. 2025 Oct 7;15(10):e106756. doi: 10.1136/bmjopen-2025-106756. PMID 41062131

Identifiers

NCT: NCT06936657 · 2025-018

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗