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

Effect of Vitamin D Supplementation on Oral Glucose Tolerance in Subjects Exhibiting Marginal Vitamin D Status and an Increased Risk of Developing Diabetes.

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Vitamin D Deficiency
• Intervention / Treatment: Dietary supplement: Control; Dietary supplement: Vitamin D

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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1G 2W1
      • University of Guelph
    • Toronto, Ontario, Canada, M5C 2N8
      • Glycemic Index Laboratories
  • Quebec
    • Montreal, Quebec, Canada, H2W 1R7
      • Institut de Recherches Cliniques de Montreal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; 30g normal cheddar cheese once per week	Dietary supplement: Control; Normal cheddar cheese
Experimental: Vitamin D; 30g cheddar cheese containing 28,000IU vitamin D once per week	Dietary supplement: Vitamin D; Vitamin D3 supplemented cheddar cheese; Other Names: Vitamin D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Change in fasting plasma glucose	Change from baseline in fasting plasma glucose	24 weeks
Change in glucose area under the curve	Change from baseline in incremental area under the glucose response curve after 75g oral glucose	24 weeks
Change in glycated hemoglobin	Change from baseline in glycated hemoglobin (HbA1c)	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.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting serum 25(OH)D	Absolute concentration of serum 25-hydroxy-vitamin D3	24 weeks
Change in serum 25(OH)D	Change from baseline in serum 25-hydroxy-vitamin D3	24 weeks
Change in serum total cholesterol	Change from baseline in fasting serum total cholesterol	24 weeks
Change in serum low-density lipoprotein (LDL) cholesterol	Change from baseline in fasting serum calculated LDL cholesterol	24 weeks
Change in serum high-density lipoprotein (HDL) cholesterol	Change from baseline in fasting serum HDL cholesterol	24 weeks
Change in serum triglycerides	Change from baseline in fasting serum triglycerides	24 weeks
Change in serum apolipoprotein B (apoB)	Change from baseline in fasting serum apolipoprotein B	24 weeks
Change in serum c-reactive protein (CRP)	Change from baseline in fasting serum c-reactive protein	24 weeks
Change in serum orosomucoid	Change from baseline in fasting serum orosomucoid	24 weeks
Change in serum haptoglobin	Change from baseline in fasting serum haptoglobin	24 weeks
Change in serum alpha-1-antitrypsin	Change from baseline in fasting serum alpha-1-antitrypsin	24 weeks
Change in serum aspartate aminotransferase (AST)	Change from baseline in fasting serum aspartate aminotransferase	24 weeks
Change in serum alanine aminotransferase (ALT)	Change from baseline in fasting serum alanine aminotransferase	24 weeks
Serum calcium	Absolute concentration of serum calcium	24 weeks
Urinary calcium:creatinine ratio	Urinary calcium:creatinine ratio	24 weeks

Collaborators and Investigators

• Sponsor: University of Toronto
• Collaborators: Dairy Farmers of Canada; Public Health Agency of Canada (PHAC)
• Investigators: Principal Investigator: Thomas MS Wolever, DM, PhD, University of Toronto

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: November 9, 2012
• First Submitted That Met QC Criteria: November 14, 2012
• First Posted (Estimate): November 15, 2012

Study Record Updates

• Last Update Posted (Estimate): September 17, 2015
• Last Update Submitted That Met QC Criteria: September 15, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Diabetes; Vitamin D; Insulin resistance; Blood glucose; Randomized controlled clinical trial; Oral glucose tolerance
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Diabetes Mellitus; Diabetes Mellitus, Type 2; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: UTRS-27546