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

Huazhong University of Science and Technology2,500 enrolled

Overview

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.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 79 Years

Medical Language ↔ Plain English

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.

Locations (5)

Guangxi Medical College

Nanning, Guangxi, China

RECRUITING

Kailuan General Hospital

Tangshan, Hebei, China

RECRUITING

Sinopharm Dongfeng General Hospital

Shiyan, Hubei, China

RECRUITING

Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

Sichuan University

Chengdu, Sichuan, China

RECRUITING

Outcomes

Primary Outcomes

Glycemic control

Change in HbA1c from baseline to the 24-month visit

Time frame: 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

Time frame: 24 months

Secondary Outcomes

Blood 25(OH)D

Change in blood 25(OH)D concentrations from baseline to the 24-month visit

Time frame: 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

Time frame: 60 months

Microvascular disease

Time to the first occurrence of any of the following: nephropathy, retinopathy, or neuropathy

Time frame: 60 months

All-cause mortality

Deaths from any causes

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 24 months

Change in body weight

Change in body weight from baseline to the 24-month visit. The value is reported in kilogram (kg).

Time frame: 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).

Time frame: 24 months

Change in waist circumference

Change in waist circumference from baseline to the 24-month visit. The value is reported in centimeter (cm).

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 24 months

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

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts