Type 2 Diabetes Mellitus, Vitamin D Deficiency
Conditions
Keywords
Randomized controlled clinical trial, Diabetes, Vitamin D, Oral glucose tolerance, Blood glucose, Insulin resistance
Brief summary
Type 2 diabetes (T2D) is an increasingly common and serious condition. Studies show that low vitamin D levels are associated with increased diabetes risk and that vitamin D may protect against diabetes by reducing chronic inflammation and improving insulin sensitivity and insulin secretion. However, no studies have been able to show that vitamin D actually reduces post-prandial blood glucose levels, the most clinically relevant marker of diabetes. Previously the investigators have shown that cheddar cheese and low-fat cheese can be fortified with high levels of vitamin D and that this cheese is at least as a effective as vitamin D supplements in raising blood vitamin D levels. The main purpose of this study is to see whether vitamin D enriched cheese can improve oral glucose tolerance (reduce blood glucose 2 hours after consuming a drink containing 75g sugar) in people who have low vitamin D levels and are at risk for developing T2D. Other aims are to determine the effect of vitamin D may on insulin sensitivity, insulin secretion, markers of inflammation, blood cholesterol levels, and safety markers such as urinary calcium excretion.
Detailed description
Type 2 diabetes (T2D) is an increasingly prevalent and serious condition whose risk appears to be increased by low serum vitamin D concentrations. Epidemiological studies show an association between increased diabetes risk and low serum vitamin D and studies suggest that vitamin D may protect against diabetes by reducing chronic inflammation and improving insulin sensitivity and insulin secretion. Although clinical studies show some of these effects, no studies have been able to show that vitamin D supplementation reduces post-prandial blood glucose, the most clinically relevant marker of diabetes and dysglycemia. Previously, the investigators showed that cheddar cheese and low-fat cheese can be fortified with high levels of vitamin D3 (28,000IU/ 30g portion) and that, in this form, it is at least as a effective as vitamin D3 supplements in raising serum vitamin D concentrations. Since post-prandial glucose is most sensitive to changes in insulin sensitivity the main purpose of this study is to determine the effect of vitamin D supplementation on oral glucose tolerance (ie. serum glucose 2h after 75g oral glucose) in individuals who are at risk for developing T2D. Secondary objective are to determine the effect of vitamin D supplementation on insulin sensitivity, insulin secretion, inflammatory markers, blood lipids and markers of safety including serum parathyroid hormone levels and urinary calcium excretion.
Interventions
DIETARY_SUPPLEMENTControl
Normal cheddar cheese
DIETARY_SUPPLEMENTVitamin D
Vitamin D3 supplemented cheddar cheese
Sponsors
Dairy Farmers of Canada
Public Health Agency of Canada (PHAC)
University of Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* male or non-pregnant, non-lactating females, aged 18-75 * volunteered to participate by signing the consent form * BMI \<40kg/ m2 * vitamin D insufficient, defined as: serum 25(OH) vitamin D3 (25(OH)D) concentration ≤65nmol/ L * increased risk for diabetes, defined as: FINDRISC score \>10 for Caucasians or \>6 for non-Caucasians OR presence of metabolic syndrome * dysglycemia, defined as:fasting serum glucose 5.6 to 6.9 mmol/L, inclusive OR HbA1c 0.054 to 0.064, inclusive * systolic blood pressure ≤150/95 mmHg if not being treated for hypertension or ≤140/90 mmHg if on treatment for hypertension. * taking no prescription drugs, or stable (for at least 6 weeks) dose of birth control pill, or drug(s) used to treat hypertension, hyperlipidemia, depression or other mental illness or hypothyroid. * taking no supplements, or stable (for at least 6 weeks) dose of supplement(s).
Exclusion criteria
* subjects not meeting all inclusion criteria * history of renal failure or liver disease * serum creatinine \>1.8 times upper limit of normal (ULN) * serum aspartate or alanine transaminase (AST,ALT) \>3 times ULN * current use of drug or drugs to treat diabetes or use of steroids or pancreatic enzymes * within 6 weeks of randomization, change in dose of supplements or drug(s) used to treat hypertension, hyperlipidemia, depression or other mental illness or hypothyroid. * use of antibiotics within 3 months. * medical or surgical event requiring hospitalization within 3 months of randomization * presence of any condition affecting nutrient absorption * intolerance to cheese * plan to travel outside Canada for more than 14 consecutive days during the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in plasma glucose concentration 2 hours after consuming 75g oral glucose (2 hour PC glucose, or 2hrPC glucose) | 24 Weeks | Change from baseline in plasma glucose concentration 2 hours after consuming 75g oral glucose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Matsuda insulin sensitivity index | 24 weeks | Change from baseline in Matsuda insulin sensitivity index which is (10,000/square root of \[fasting glucose x fasting insulin\] x \[mean glucose x mean insulin during OGTT\]). |
| Change in insulin secretion assessed using the homeostasis model assessment of beta-cell function (HOMA-B) | 24 weeks | Change from baseline in homeostasis model assessment of beta-cell function (HOMA-B) which is 20\*I/(G-3.5) where I is fasting plasma insulin (uU/mL) and G is fasting plasma glucose (mmol/L). |
| Change in insulinogenic index | 24 weeks | Change from baseline in insulinogenic index which is dI0-30/dG0-30, where dI0-30 is the change in plasma insulin between fasting and 30min and dG0-30 is the change in plasma glucose between fasting and 30min after 75g oral glucose. |
| Change in disposition index derived from HOMA-IR and HOMA-B | 24 weeks | Change from baseline in disposition index which is HOMA-B/HOMA-IR, which have been defined above. |
| Change in insulin resistance assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) | 24 weeks | Change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR) which is G\*I/22.5 where G is fasting plasma glucose (mmol/L) and I is fasting plasma insulin (uU/mL). |
| Change in fasting plasma glucose | 24 weeks | Change from baseline in fasting plasma glucose |
| Change in glucose area under the curve | 24 weeks | Change from baseline in incremental area under the glucose response curve after 75g oral glucose |
| Change in glycated hemoglobin | 24 weeks | Change from baseline in glycated hemoglobin (HbA1c) |
| Correlation between changes in serum 25-hydroxy-vitamin D concentration (25(OH)D) and changes in 2 hour PC glucose | 24 weeks | Correlation between change from baseline in serum 25-hydroxy-vitamin D concentration and change from baseline in plasma glucose 2 hours after 75g oral glucose. |
| Change in disposition index based on oral glucose tolerance test (OGTT) | 24 weeks | Change from baseline in ISSI-2 index which is AUCi/AUCg x Matsuda insulin sensitivity index, where AUCi and AUCg, respectively, are the total areas under the plasma insulin and glucose response curves after 75g oral glucose and Matsuda insulin sensitivity index has been defined above. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in serum aspartate aminotransferase (AST) | 24 weeks | Change from baseline in fasting serum aspartate aminotransferase |
| Change in serum alanine aminotransferase (ALT) | 24 weeks | Change from baseline in fasting serum alanine aminotransferase |
| Fasting serum 25(OH)D | 24 weeks | Absolute concentration of serum 25-hydroxy-vitamin D3 |
| Urinary calcium:creatinine ratio | 24 weeks | Urinary calcium:creatinine ratio |
| Serum calcium | 24 weeks | Absolute concentration of serum calcium |
| Change in serum 25(OH)D | 24 weeks | Change from baseline in serum 25-hydroxy-vitamin D3 |
| Change in serum total cholesterol | 24 weeks | Change from baseline in fasting serum total cholesterol |
| Change in serum low-density lipoprotein (LDL) cholesterol | 24 weeks | Change from baseline in fasting serum calculated LDL cholesterol |
| Change in serum high-density lipoprotein (HDL) cholesterol | 24 weeks | Change from baseline in fasting serum HDL cholesterol |
| Change in serum triglycerides | 24 weeks | Change from baseline in fasting serum triglycerides |
| Change in serum apolipoprotein B (apoB) | 24 weeks | Change from baseline in fasting serum apolipoprotein B |
| Change in serum c-reactive protein (CRP) | 24 weeks | Change from baseline in fasting serum c-reactive protein |
| Change in serum orosomucoid | 24 weeks | Change from baseline in fasting serum orosomucoid |
| Change in serum haptoglobin | 24 weeks | Change from baseline in fasting serum haptoglobin |
| Change in serum alpha-1-antitrypsin | 24 weeks | Change from baseline in fasting serum alpha-1-antitrypsin |
Countries
Canada
Outcome results
None listed