Diabetes Mellitus, Type 2
Conditions
Keywords
Vitamin D, yeast β-glucan, Diabetes Mellitus, Type 2, Cardiovascular Disease, glycemic control
Brief summary
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.
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.
Interventions
DRUGVitamin D3
Vitamin D3(cholecalciferol),1600 IU per day.
DIETARY_SUPPLEMENTyeast β-glucan
yeast β-glucan, 600mg per day.
DIETARY_SUPPLEMENTVitamin D placebo
Vitamin D placebo
DIETARY_SUPPLEMENTyeast β-glucan placebo
yeast β-glucan placebo
Sponsors
Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 79 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic control | 24 months | Change in HbA1c from baseline to the 24-month visit |
| Cardiovascular disease risk | 24 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in fasting C-peptide | 24 months | Change in fasting C-peptide from baseline to the 24-month visit. The value is reported in nanogram per milliliter (ng/mL). |
| Blood 25(OH)D | 24 months | Change in blood 25(OH)D concentrations from baseline to the 24-month visit |
| Major cardiovascular events | 60 months | 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 |
| Microvascular disease | 60 months | Time to the first occurrence of any of the following: nephropathy, retinopathy, or neuropathy |
| Change in insulin | 24 months | Change in insulin from baseline to the 24-month visit. The value is reported in microunit per milliliter (μU/mL). |
| Change in HOMA-IR | 24 months | 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. |
| Change in Lipid profile | 24 months | 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). |
| Change in Liver function markers | 24 months | 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). |
| Change in serum creatinine | 24 months | Change in serum creatinine from baseline to the 24-month visit. The value is reported in micromole per liter (μmol/L). |
| Change in cystatin C | 24 months | Change in cystatin C from baseline to the 24-month visit. The value is reported in milligram per liter (mg/L). |
| Change in eGFR | 24 months | 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). |
| Change in blood calcium | 24 months | Change in blood calcium from baseline to the 24-month visit. The value is reported in millimole per liter (mmol/L). |
| Change in body weight | 24 months | Change in body weight from baseline to the 24-month visit. The value is reported in kilogram (kg). |
| Change in BMI | 24 months | 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). |
| Change in waist circumference | 24 months | Change in waist circumference from baseline to the 24-month visit. The value is reported in centimeter (cm). |
| Change in waist-to-hip ratio | 24 months | 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. |
| Change in blood pressure | 24 months | Change in systolic and diastolic blood pressure from baseline to the 24-month visit. The values are reported in millimeters of mercury (mmHg). |
| Change in grip strength | 24 months | Change in grip strength from baseline to the 24-month visit, assessed using a handgrip dynamometer. The value is reported in kilogram (kg). |
| Change in FRAIL scale | 24 months | 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). |
| Change in C-reactive protein | 24 months | Change in C-reactive protein (CRP) from baseline to the 24-month visit. The value is reported in milligram per liter (mg/L). |
| Change in procalcitonin | 24 months | Change in procalcitonin from baseline to the 24-month visit. The value is reported in nanogram per milliliter (ng/mL). |
| Change in interleukin-6 | 24 months | Change in interleukin-6 (IL-6) from baseline to the 24-month visit. The value is reported in picogram per milliliter (pg/mL). |
| Bone mineral density | 24 months | 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. |
| Change in baPWV | 24 months | 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). |
| Change in ABI | 24 months | 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). |
| Change in LSM | 24 months | Change in stiffness measurement (LSM) from baseline to the 24-month visit, assessed by transient elastography (FibroTouch). The value is reported in kilopascal (kPa). |
| All-cause mortality | 60 months | Deaths from any causes |
| Change in UAP | 24 months | 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). |
| Change in fasting plasma glucose | 24 months | Change in fasting plasma glucose from baseline to the 24-month visit. The value is reported in millimole per liter (mmol/L). |
Countries
China
Contacts
CONTACTGang Liu, PHD
CONTACTTianyu Guo
PRINCIPAL_INVESTIGATORAn Pan, PHD
School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed