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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
71
University of Guelph
Guelph, Ontario, Canada
Glycemic Index Laboratories
Toronto, Ontario, Canada
Institut de recherches cliniques de Montréal
Montreal, Quebec, Canada
Change in plasma glucose concentration 2 hours after consuming 75g oral glucose (2 hour PC glucose, or 2hrPC glucose)
Change from baseline in plasma glucose concentration 2 hours after consuming 75g oral glucose.
Time frame: 24 Weeks
Change in insulin resistance assessed using the homeostasis model assessment of insulin resistance (HOMA-IR)
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).
Time frame: 24 weeks
Change in Matsuda insulin sensitivity index
Change from baseline in Matsuda insulin sensitivity index which is (10,000/square root of \[fasting glucose x fasting insulin\] x \[mean glucose x mean insulin during OGTT\]).
Time frame: 24 weeks
Change in insulin secretion assessed using the homeostasis model assessment of beta-cell function (HOMA-B)
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).
Time frame: 24 weeks
Change in insulinogenic index
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.
Time frame: 24 weeks
Change in disposition index derived from HOMA-IR and HOMA-B
Change from baseline in disposition index which is HOMA-B/HOMA-IR, which have been defined above.
Time frame: 24 weeks
Change in disposition index based on oral glucose tolerance test (OGTT)
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.
Time frame: 24 weeks
Change in fasting plasma glucose
Change from baseline in fasting plasma glucose
Time frame: 24 weeks
Change in glucose area under the curve
Change from baseline in incremental area under the glucose response curve after 75g oral glucose
Time frame: 24 weeks
Change in glycated hemoglobin
Change from baseline in glycated hemoglobin (HbA1c)
Time frame: 24 weeks
Correlation between changes in serum 25-hydroxy-vitamin D concentration (25(OH)D) and changes in 2 hour PC glucose
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.
Time frame: 24 weeks
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