Effects of Vitamin D3 and Yeast Beta-Glucan Supplementation on Glycemic Control and Cardiovascular Disease Risk in Patients With Type 2 Diabetes

Effects of Vitamin D3 and Yeast Beta-Glucan Supplementation on Glycemic Control and Cardiovascular Disease Risk in Patients With Type 2 Diabetes: A Randomized Double-Blind Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Dietary supplement: Vitamin D placebo; Drug: Vitamin D3; Dietary supplement: yeast β-glucan; Dietary supplement: yeast β-glucan placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 2500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gang Liu, PHD; Phone Number: 86-15926238366; Email: liugang026@hust.edu.cn
• Study Contact Backup: Name: Tianyu Guo; Phone Number: 86-18210047875; Email: D202482059@hust.edu.cn

Study Locations

• China
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • Guangxi Medical College
      • Contact: Qiuli Chen
  • Hebei
    • Tangshan, Hebei, China
      • Recruiting
      • Kailuan General Hospital
      • Contact: Shuohua Chen
  • Hubei
    • Shiyan, Hubei, China
      • Recruiting
      • Sinopharm Dongfeng General Hospital
      • Contact: Kun Yang
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Huazhong University of Science and Technology
      • Contact: Gang Liu; Phone Number: 86-15926238366; Email: liugang026@hust.edu.cn
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • Sichuan University
      • Contact: Jiayuan Li

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Type 2 diabetes mellitus diagnosed by a physician based on the diagnostic criteria outlined in the Guideline for the Prevention and Treatment of Diabetes Mellitus in China (2024 Edition);
2. Men or women aged 40-79 years;
3. Convenient access to the study centers and permanent residence in the vicinity for the next five years;
4. Voluntary participation and signed written informed consent.

Exclusion Criteria:

1. History of clinical cardiovascular disease (including myocardial infarction, treatment or hospitalization for heart failure, stroke, and coronary revascularization) within the past 6 months;
2. 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);
3. History of cancer, excluding non-melanoma skin cancer or cancers with a favorable prognosis;
4. History of kidney stones, hypercalcemia, or hyperparathyroidism;
5. 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;

6. Laboratory evaluation:

   • Blood calcium levels greater than or equal to the normal range for the clinical site's laboratory;
   • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels higher than 3 times the normal range for the clinical site's laboratory;
   • eGFR < 30 mL/(min·1.73m²);
7. 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;
8. Participation in other clinical trials within the past 3 months;
9. Planning to become pregnant within the next five years, or currently pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D + yeast β-glucan	Drug: Vitamin D3; Vitamin D3(cholecalciferol),1600 IU per day.; Other Names: cholecalciferol; Dietary supplement: yeast β-glucan; yeast β-glucan, 600mg per day.
Active Comparator: Vitamin D + yeast β-glucan placebo	Drug: Vitamin D3; Vitamin D3(cholecalciferol),1600 IU per day.; Other Names: cholecalciferol; Dietary supplement: yeast β-glucan placebo; yeast β-glucan placebo
Active Comparator: yeast β-glucan +Vitamin D placebo	Dietary supplement: Vitamin D placebo; Vitamin D placebo; Dietary supplement: yeast β-glucan; yeast β-glucan, 600mg per day.
Placebo Comparator: Vitamin D placebo + yeast β-glucan placebo	Dietary supplement: Vitamin D placebo; Vitamin D placebo; Dietary supplement: yeast β-glucan placebo; yeast β-glucan placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	60 months
All-cause mortality	Deaths from any causes	60 months
Microvascular disease	Time to the first occurrence of any of the following: nephropathy, retinopathy, or neuropathy	60 months
Blood 25(OH)D	Change in blood 25(OH)D concentrations from baseline to the 24-month visit	24 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

Other Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology
• Investigators: Principal Investigator: An Pan, PHD, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: February 23, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 6, 2025

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Vitamin D; Cardiovascular Disease; Diabetes Mellitus, Type 2; glycemic control; yeast β-glucan
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Lipids; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Cholecalciferol
• Other Study ID Numbers: VD, Yeast β-Glucan in Diabetes

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No