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This study is a randomized, double-blind, placebo-controlled trial involving 2,500 individuals aged 40-79 with type 2 diabetes (T2D). The trial includes a 2-year intervention period followed by a 3-year post-intervention follow-up. The primary objective is to investigate (a) the effect of daily supplementation with vitamin D3 (1600 IU) or yeast β-glucan (600 mg) on glycemic control in patients with T2D and (b) whether daily supplementation with vitamin D3 (1600 IU) or yeast β-glucan (600 mg) reduces the predicted 10 year risk of atherosclerotic cardiovascular disease (ASCVD) in patients with T2D. The secondary objectives include evaluating the effects of vitamin D3 or yeast β-glucan supplementation on cardiometabolic risk factors, inflammatory markers, and liver and kidney function indicators, and assessing whether such supplementation reduces the risk of cardiovascular disease, microvascular complications and mortality over the 3-year post-intervention period.
The goal of this randomized, double-blind, placebo-controlled trial, with a 2×2 factorial design in individuals with type 2 diabetes (T2D), is to investigate (a) the effect of daily dietary supplementation with vitamin D3 (1600 IU) or yeast β-glucan (600 mg) on glycemic control in patients with T2D and (b) whether vitamin D3 (1600 IU) or yeast β-glucan (600 mg) supplementation reduces the predicted 10 year risk of atherosclerotic cardiovascular disease (ASCVD) in patients with T2D. Approximately 2,500 subjects aged 40-79 with T2D will be included in this study. Eligible participants will be randomly assigned to one of four groups: (1) daily vitamin D3 (1600 IU) and yeast β-glucan (600 mg); (2) daily vitamin D3 (1600 IU) and placebo for yeast β-glucan; (3) daily placebo for vitamin D3 and yeast β-glucan (600 mg); or (4) daily placebo for vitamin D3 and placebo for yeast β-glucan. At baseline, questionnaires will be administered to collect data on sociodemographic factors, lifestyle habits, health status, cognitive function, and medical conditions, et al. Participants will also undergo physical measurements, and blood, urine, and feces samples will be collected at study centers. The study includes a 2-year intervention period followed by a 3-year post-intervention follow-up. Participants in all groups will take four capsules daily for 2 years: two capsules containing either vitamin D or its placebo and two capsules containing either yeast β-glucan or its placebo. During the 2-year intervention period, questionnaires, physical measurements, and sample collection will be conducted at 6, 12, and 24 months. This trial will also evaluate the effects of supplementation on cardiometabolic risk factors, inflammatory markers, and liver and kidney function indicators, and assess whether it reduces the risk of cardiovascular disease, microvascular complications, and mortality over the 3-year post-intervention period, providing scientific evidence for the health effects of vitamin D or yeast β-glucan in the T2D population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vitamin D + yeast β-glucan | Active Comparator |
| |
| Vitamin D + yeast β-glucan placebo | Active Comparator |
| |
| yeast β-glucan +Vitamin D placebo | Active Comparator |
| |
| Vitamin D placebo + yeast β-glucan placebo | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin D3 | Drug | Vitamin D3(cholecalciferol),1600 IU per day. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glycemic control | Change in HbA1c from baseline to the 24-month visit | 24 months |
| Cardiovascular disease risk | Change in 10-year ASCVD risk score from baseline to the 24-month visit, assessed using China-PAR score, with a score range of 0-100%, where a higher score means a higher ASCVD risk | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Blood 25(OH)D | Change in blood 25(OH)D concentrations from baseline to the 24-month visit | 24 months |
| Major cardiovascular events | Time to the first occurrence of any of the following: myocardial infarction, hospitalized or treated heart failure, stroke, revascularization of coronary arteries, or cardiovascular deaths |
| Measure | Description | Time Frame |
|---|---|---|
| Other events | Incidence of other cardiovascular diseases (not listed above), cancer, infectious diseases and falls | 60 months |
| Change in Health-related quality of life | Change in health-related quality of life from baseline to the 24-month visit, assessed using EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, with a score range of 0-100, where a higher score means higher health-related quality of life |
Inclusion Criteria:
Exclusion Criteria:
History of clinical cardiovascular disease (including myocardial infarction, treatment or hospitalization for heart failure, stroke, and coronary revascularization) within the past 6 months;
History of severe diabetic microvascular complications (diabetic nephropathy with an estimated glomerular filtration rate (eGFR) < 30 mL/(min·1.73m²), proliferative diabetic retinopathy, confirmed diabetic peripheral neuropathy with abnormal nerve conduction studies or small fiber neuropathy testing);
History of cancer, excluding non-melanoma skin cancer or cancers with a favorable prognosis;
History of kidney stones, hypercalcemia, or hyperparathyroidism;
History of severe liver disease, severe kidney disease, severe gastrointestinal disease, severe infectious diseases, severe sarcoidosis or other granulomatous diseases, severe mental illness, or any other condition considered unsuitable for participation judged by the clinic team;
Laboratory evaluation:
Individuals currently taking vitamin D supplements (>400 IU/day), calcium supplements (>600 mg/day), yeast β-glucan supplements (>250 mg/day), or those with a history of allergy or intolerance to vitamin D or prebiotic products;
Participation in other clinical trials within the past 3 months;
Planning to become pregnant within the next five years, or currently pregnant or breastfeeding.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gang Liu, PHD | Contact | 86-15926238366 | liugang026@hust.edu.cn | |
| Tianyu Guo | Contact | 86-18210047875 | D202482059@hust.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| An Pan, PHD | School of Public Health, Tongji Medical College, Huazhong University of Science and Technology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Guangxi Medical College | Recruiting | Nanning | Guangxi | China |
The individual participant data (IPD) sharing will need to be approved by the Institutional Review Board (IRB) and the study investigators with individual specific project request.
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| yeast β-glucan | Dietary Supplement | yeast β-glucan, 600mg per day. |
|
| Vitamin D placebo | Dietary Supplement | Vitamin D placebo |
|
| yeast β-glucan placebo | Dietary Supplement | yeast β-glucan placebo |
|
| 60 months |
| Microvascular disease | Time to the first occurrence of any of the following: nephropathy, retinopathy, or neuropathy | 60 months |
| All-cause mortality | Deaths from any causes | 60 months |
| Change in fasting plasma glucose | Change in fasting plasma glucose from baseline to the 24-month visit. The value is reported in millimole per liter (mmol/L). | 24 months |
| Change in fasting C-peptide | Change in fasting C-peptide from baseline to the 24-month visit. The value is reported in nanogram per milliliter (ng/mL). | 24 months |
| Change in insulin | Change in insulin from baseline to the 24-month visit. The value is reported in microunit per milliliter (μU/mL). | 24 months |
| Change in HOMA-IR | Change in HOMA-IR from baseline to the 24-month visit. HOMA-IR = [Fasting Serum Insulin (μU/mL) × Fasting Plasma Glucose (mmol/L)] / 22.5. Lower values indicate better insulin sensitivity. | 24 months |
| Change in Lipid profile | Change in total cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol from baseline to the 24-month visit. These values are reported in millimole per liter (mmol/L). | 24 months |
| Change in Liver function markers | Change in alanine aminotransferase (ALT), aspartate aminotransferase (AST), a nd gamma-glutamyl transferase (GGT) from baseline to the 24-month visit. These values are reported in units per liter (U/L). | 24 months |
| Change in serum creatinine | Change in serum creatinine from baseline to the 24-month visit. The value is reported in micromole per liter (μmol/L). | 24 months |
| Change in cystatin C | Change in cystatin C from baseline to the 24-month visit. The value is reported in milligram per liter (mg/L). | 24 months |
| Change in eGFR | Change in estimated glomerular filtration rate (eGFR) from baseline to the 24-month visit. The CKD-EPI (2009) method to estimate eGFR value. The value is reported in milliliter per minute per 1.73 square meters (mL/min/1.73 m²). | 24 months |
| Change in blood calcium | Change in blood calcium from baseline to the 24-month visit. The value is reported in millimole per liter (mmol/L). | 24 months |
| Change in body weight | Change in body weight from baseline to the 24-month visit. The value is reported in kilogram (kg). | 24 months |
| Change in BMI | Change in body mass index (BMI) from baseline to the 24-month visit. BMI = Body Weight (kg) / [Height (m)]^2. The value is reported in kilogram per square meter (kg/m^2). | 24 months |
| Change in waist circumference | Change in waist circumference from baseline to the 24-month visit. The value is reported in centimeter (cm). | 24 months |
| Change in waist-to-hip ratio | Change in waist-to-hip ratio from baseline to the 24-month visit. Waist-to-hip ratio = Waist Circumference (cm) / Hip Circumference (cm). Higher values indicate greater central adiposity. | 24 months |
| Change in blood pressure | Change in systolic and diastolic blood pressure from baseline to the 24-month visit. The values are reported in millimeters of mercury (mmHg). | 24 months |
| Change in grip strength | Change in grip strength from baseline to the 24-month visit, assessed using a handgrip dynamometer. The value is reported in kilogram (kg). | 24 months |
| Change in FRAIL scale | FRAIL scale comprises five domains: fatigue, resistance, ambulation, illnesses, and weight loss. Each item is scored as 0 or 1, yielding a total score ranging from 0 to 5, with higher scores indicating greater frailty. Based on the total score, patients were categorized as robust (0 points), pre-frail (1-2 points), or frail (3-5 points). | 24 months |
| Change in C-reactive protein | Change in C-reactive protein (CRP) from baseline to the 24-month visit. The value is reported in milligram per liter (mg/L). | 24 months |
| Change in procalcitonin | Change in procalcitonin from baseline to the 24-month visit. The value is reported in nanogram per milliliter (ng/mL). | 24 months |
| Change in interleukin-6 | Change in interleukin-6 (IL-6) from baseline to the 24-month visit. The value is reported in picogram per milliliter (pg/mL). | 24 months |
| Bone mineral density | Change in bone mineral density from baseline to the 24-month visit, including but not limited to Speed of Sound (SOS), T-score, and Z-score. SOS is reported in meters per second （m/s). T-score and Z-score have no dimensional units. | 24 months |
| Change in baPWV | Change in brachial-Ankle Pulse Wave Velocity (baPWV) from baseline to the 24-month visit. The value is reported in centimeters per second (cm/s). | 24 months |
| Change in ABI | Change in Ankle-Brachial Index (ABI) from baseline to the 24-month visit. ABI=Systolic blood pressure of the ankle (mmHg) / Higher values of bilateral arm systolic pressure (mmHg). | 24 months |
| Change in LSM | Change in stiffness measurement (LSM) from baseline to the 24-month visit, assessed by transient elastography (FibroTouch). The value is reported in kilopascal (kPa). | 24 months |
| Change in UAP | Change in Ultrasound Attenuation Parameter (UAP) from baseline to the 24-month visit, assessed by transient elastography (FibroTouch). The value is reported in Decibel per Megahertz per Centimeter (dB/MHz/cm). | 24 months |
| 24 months |
| Change in Cognitive function (MoCA) | Cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA). The MoCA is a one-page 30-point test. Scores range from 0 to 30, with a score of 26 or above considered normal. The change in score from baseline to 24 months will be calculated. | 24 months |
| Change in Cognitive function (MMSE) | Cognitive function will be assessed using the Mini-Mental State Examination (MMSE). The MMSE is a 30-point questionnaire. Scores range from 0 to 30, with different cut-off points for normal cognition based on education level: >17 for illiterate, >20 for individuals with ≤6 years of education, and >24 for individuals with >6 years of education. The change in score from baseline to 24 months will be calculated. | 24 months |
| Change in depressive mood score | Change in depressive symptom severity from baseline to the 24-month visit, measured by the Patient Health Questionnaire-9 (PHQ-9) score, with a score range of 0-27, where a higher score means more severe depressive symptoms. | 24 months |
| Change in anxiety score | Change in anxiety symptom severity from baseline to the 24-month visit, measured by the Generalized Anxiety Disorder-7 (GAD-7) score, with a score range of 0-21, where a higher score means more severe anxiety symptoms and clinical cut point for anxiety disorder was 10 points. | 24 months |
| Change in Sleep quality | Change in sleep quality from baseline to the 24-month visit, assessed using the Pittsburgh Sleep Quality Index (PSQI), with a score range of 0-21, where a higher score means worse sleep quality. | 24 months |
| Change in BF% | Change in body fat percentage (BF%) from baseline to the 24-month visit. | 24 months |
| Change in fat mass | Change in fat mass from baseline to the 24-month visit. The value is reported in kilogram (kg). | 24 months |
| Change in fat-free mass | Change in fat-free mass from baseline to the 24-month visit. The value is reported in kilogram (kg). | 24 months |
| Concentration of blood metabolites | Blood metabolites, including, but not limited to, fatty acids and lipoprotein particles, quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), are reported in mmol/L. | 24 months |
| Metagenomic analysis of the gut microbiota | The diversity of the gut microbiota will be assessed by high-quality whole-metagenomic sequencing | 24 months |
| DNA methylation level | The relative change in DNA methylation level quantified by pyrosequencing, reported as percentage methylation at specific CpG sites | 24 months |
| Kailuan General Hospital | Recruiting | Tangshan | Hebei | China |
|
| Sinopharm Dongfeng General Hospital | Recruiting | Shiyan | Hubei | China |
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| Huazhong University of Science and Technology | Recruiting | Wuhan | Hubei | 430000 | China |
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| Sichuan University | Recruiting | Chengdu | Sichuan | China |
|
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
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