Clinical trial NCT01726777: Effect of Vitamin D Supplementation on Glucose Tolerance in Subjects at Risk for Diabetes With Low Vitamin D.
Official title: Effect of Vitamin D Supplementation on Oral Glucose Tolerance in Subjects Exhibiting Marginal Vitamin D Status and an Increased Risk of Developing Diabetes.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Vitamin D Deficiency
Keywords: Randomized controlled clinical trial
Diabetes
Vitamin D
Oral glucose tolerance
Blood glucose
Insulin resistance
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Dairy Farmers of Canada
name: Public Health Agency of Canada (PHAC)
First posted: 2012-11-15
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in plasma glucose concentration 2 hours after consuming 75g oral glucose (2 hour PC glucose, or 2hrPC glucose)
timeFrame: 24 Weeks
Secondary outcomes:
measure: Change in insulin resistance assessed using the homeostasis model assessment of insulin resistance (HOMA-IR)
timeFrame: 24 weeks
measure: Change in Matsuda insulin sensitivity index
timeFrame: 24 weeks
measure: Change in insulin secretion assessed using the homeostasis model assessment of beta-cell function (HOMA-B)
timeFrame: 24 weeks
measure: Change in insulinogenic index
timeFrame: 24 weeks
measure: Change in disposition index derived from HOMA-IR and HOMA-B
timeFrame: 24 weeks
measure: Change in disposition index based on oral glucose tolerance test (OGTT)
timeFrame: 24 weeks
measure: Change in fasting plasma glucose
timeFrame: 24 weeks
measure: Change in glucose area under the curve
timeFrame: 24 weeks
measure: Change in glycated hemoglobin
timeFrame: 24 weeks
measure: Correlation between changes in serum 25-hydroxy-vitamin D concentration (25(OH)D) and changes in 2 hour PC glucose
timeFrame: 24 weeks
Other outcomes:
measure: Fasting serum 25(OH)D
timeFrame: 24 weeks
measure: Change in serum 25(OH)D
timeFrame: 24 weeks
measure: Change in serum total cholesterol
timeFrame: 24 weeks
measure: Change in serum low-density lipoprotein (LDL) cholesterol
timeFrame: 24 weeks
measure: Change in serum high-density lipoprotein (HDL) cholesterol
timeFrame: 24 weeks
measure: Change in serum triglycerides
timeFrame: 24 weeks
measure: Change in serum apolipoprotein B (apoB)
timeFrame: 24 weeks
measure: Change in serum c-reactive protein (CRP)
timeFrame: 24 weeks
measure: Change in serum orosomucoid
timeFrame: 24 weeks
measure: Change in serum haptoglobin
timeFrame: 24 weeks
measure: Change in serum alpha-1-antitrypsin
timeFrame: 24 weeks
measure: Change in serum aspartate aminotransferase (AST)
timeFrame: 24 weeks
measure: Change in serum alanine aminotransferase (ALT)
timeFrame: 24 weeks
measure: Serum calcium
timeFrame: 24 weeks
measure: Urinary calcium:creatinine ratio
timeFrame: 24 weeks
Locations:
city: Guelph
country: Canada
facility: University of Guelph
state: Ontario
city: Toronto
country: Canada
facility: Glycemic Index Laboratories
state: Ontario
city: Montreal
country: Canada
facility: Institut de recherches cliniques de Montréal
state: Quebec
Study officials:
affiliation: University of Toronto
name: Thomas MS Wolever, DM, PhD
role: PRINCIPAL_INVESTIGATOR
References: