Effect of Vitamin D Supplementation on Glucose Tolerance in Subjects at Risk for Diabetes With Low Vitamin D.

Type 2 Diabetes Mellitus Clinical Trial

— EVIDENCE  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01726777
• Other study ID #: UTRS-27546
• Status: Completed
• Phase: Phase 2
• First received: November 9, 2012
• Last updated: September 15, 2015
• Start date: October 2012
• Est. completion date: September 2015

Study information

• Verified date: September 2015
• Source: University of Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus
• Vitamin D Deficiency

Intervention

Dietary Supplement:
• Control
Normal cheddar cheese
• Vitamin D
Vitamin D3 supplemented cheddar cheese

Locations

Country	Name	City	State
Canada	University of Guelph	Guelph	Ontario
Canada	Institut de recherches cliniques de Montréal	Montreal	Quebec
Canada	Glycemic Index Laboratories	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
University of Toronto	Dairy Farmers of Canada, Public Health Agency of Canada (PHAC)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fasting serum 25(OH)D	Absolute concentration of serum 25-hydroxy-vitamin D3	24 weeks	No
Other	Change in serum 25(OH)D	Change from baseline in serum 25-hydroxy-vitamin D3	24 weeks	No
Other	Change in serum total cholesterol	Change from baseline in fasting serum total cholesterol	24 weeks	No
Other	Change in serum low-density lipoprotein (LDL) cholesterol	Change from baseline in fasting serum calculated LDL cholesterol	24 weeks	No
Other	Change in serum high-density lipoprotein (HDL) cholesterol	Change from baseline in fasting serum HDL cholesterol	24 weeks	No
Other	Change in serum triglycerides	Change from baseline in fasting serum triglycerides	24 weeks	No
Other	Change in serum apolipoprotein B (apoB)	Change from baseline in fasting serum apolipoprotein B	24 weeks	No
Other	Change in serum c-reactive protein (CRP)	Change from baseline in fasting serum c-reactive protein	24 weeks	No
Other	Change in serum orosomucoid	Change from baseline in fasting serum orosomucoid	24 weeks	No
Other	Change in serum haptoglobin	Change from baseline in fasting serum haptoglobin	24 weeks	No
Other	Change in serum alpha-1-antitrypsin	Change from baseline in fasting serum alpha-1-antitrypsin	24 weeks	No
Other	Change in serum aspartate aminotransferase (AST)	Change from baseline in fasting serum aspartate aminotransferase	24 weeks	Yes
Other	Change in serum alanine aminotransferase (ALT)	Change from baseline in fasting serum alanine aminotransferase	24 weeks	Yes
Other	Serum calcium	Absolute concentration of serum calcium	24 weeks	Yes
Other	Urinary calcium:creatinine ratio	Urinary calcium:creatinine ratio	24 weeks	Yes
Primary	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.	24 Weeks	No
Secondary	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).	24 weeks	No
Secondary	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]).	24 weeks	No
Secondary	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).	24 weeks	No
Secondary	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.	24 weeks	No
Secondary	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.	24 weeks	No
Secondary	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.	24 weeks	No
Secondary	Change in fasting plasma glucose	Change from baseline in fasting plasma glucose	24 weeks	No
Secondary	Change in glucose area under the curve	Change from baseline in incremental area under the glucose response curve after 75g oral glucose	24 weeks	No
Secondary	Change in glycated hemoglobin	Change from baseline in glycated hemoglobin (HbA1c)	24 weeks	No
Secondary	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.	24 weeks	No