Can Vitamin D Supplementation Prevent Type 2 Diabetes?

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Can Vitamin D Supplementation Prevent Type 2 Diabetes by Improving Insulin Sensitivity and Secretion in Overweight Humans?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02112721
• Other study ID #: 1047897
• Status: Completed
• Phase: Phase 4
• First received: April 10, 2014
• Last updated: December 6, 2016
• Start date: May 2014
• Est. completion date: November 2016

Study information

• Verified date: December 2016
• Source: Monash University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Monash University Human Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to determine whether vitamin D supplementation in overweight/obese individuals with vitamin D deficiency can improve insulin secretion and/or insulin resistance by decreasing subclinical inflammation.

Results of the present study may help to identify new strategies to prevent type 2 diabetes in high-risk groups (i.e. overweight and obese individuals, and individuals with a strong family history of diabetes).

Hypothesis: That increasing plasma 25(OH)D concentrations in healthy individuals at risk for type 2 diabetes with low vitamin D levels through vitamin D supplementation, will improve insulin sensitivity and also insulin secretion by reducing the underlying sub-clinical chronic inflammation.

Aims: To establish whether 16-week vitamin D supplementation given to healthy individuals with low vitamin D levels will:

1. improve insulin sensitivity (in vivo and tissue) and/or insulin secretory function

2. determine whether this relationship is mediated by a reduced chronic inflammation

Description:

Numerous studies documented that low vitamin D levels are a serious health risk. Despite the sunny climate in Australia, low vitamin D status is becoming increasingly prevalent and people with vitamin deficiency represent more than 30% of the healthy Australian population. Although sun exposure can maintain good vitamin D levels, often sun exposure is limited as people work long hours indoors, and use sunscreen or protective clothing to reduce skin cancer risk when outdoors. Moreover, it is difficult to obtain sufficient vitamin D from food alone; few foods are naturally rich in vitamin D and in Australia, few foods are fortified.

While the importance of vitamin D for bone mineralization is well known, it is less clear how vitamin D protects against type 2 diabetes and cardiovascular disease. Every day in Australia around 275 adults develop diabetes and its prevalence continues to rise.

We are therefore arguing for a well-designed intervention trial to define the preventive potential and physiological mechanisms of the effects of vitamin D supplementation. In addition, we plan to explore the mechanisms underlying the relationship between vitamin D deficiency and the risk for type 2 diabetes, via its influence on chronic inflammation. Our clinical trial will focus on healthy adults with low vitamin D status and will examine the effects on insulin sensitivity and secretion measured by 'gold standard' methodology when vitamin D is restored to optimum levels. It is in particularly important to determine whether vitamin D affects both or only one of these defects because there is evidence from observational studies that there is a relationship between vitamin D levels and both insulin sensitivity and secretion.

The proposed intervention study will potentially supply important evidence on how restoring vitamin D levels may protect against type 2 diabetes. Such findings could have direct relevance for novel approaches to diabetes prevention.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: November 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Age >18 or <60 years,

• 25(OH)D < 50 nmol/L

• Weight change < 5 kg in last 12 months

• BMI >25kg/m2 but weight <159kg due to DEXA scan restrictions

• Non-diabetic, no allergy, non-smoker, no high alcohol use

• No current intake of medications including vitamin supplements

• No kidney, cardiovascular, haematological, respiratory, gastrointestinal, endocrine or central nervous system disease, as well as no psychiatric disorders, no active cancer within the last five years; no presence of acute inflammation (by history, physical or laboratory examination)

• Not menopausal, pregnanct or lactating

Exclusion Criteria:

• Age <18 or > 60 years

• 25(OH)D > 50 nmol/L

• Weight change > 5 kg in last 12 months

• Diabetes (diagnosed or oral glucose tolerance test (OGTT), hypercalcaemia, allergy

• Current smoking habit, high alcohol use

• Current intake of medications including vitamin supplements

• Kidney, cardiovascular, haematological, respiratory, gastrointestinal, endocrine or central nervous system disease, as well as psychiatric disorder, active cancer within the last five years; presence of acute inflammation (by history, physical or laboratory examination)

• Menopause, pregnancy or lactation

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Dietary Supplement:
• Vitamin D

• Placebo

Locations

Country	Name	City	State
Australia	Monash Centre for Health Research and Implementation	Melbourne	Victoria

Sponsors (3)

Lead Sponsor	Collaborator
Monash University	University of Auckland, New Zealand, University of Victoria

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Initial - Other Tissue Analyses	We will measure changes in the expression and activation of important insulin signalling proteins, including the insulin receptor,and we will measure inflammation markers in skeletal, muscle and adipose tissue.	Week 1	No
Other	Follow Up- Other Tissue Analyses	We will measure changes in the expression and activation of important insulin signalling proteins, including the insulin receptor,and we will measure inflammation markers in skeletal, muscle and adipose tissue.	Week 17	No
Other	Resting systolic and diastolic blood pressure	Resting systolic and diastolic blood pressure and pulse rate will be measured using an automated oscillometric measurement system (Dinamap, USA) after a 30 minute rest.	Week 1	No
Other	Follow up Resting systolic and diastolic blood pressure	Resting systolic and diastolic blood pressure and pulse rate will be measured using an automated oscillometric measurement system (Dinamap, USA) after a 30 minute rest.	Week 17	No
Other	Initial Arterial waveform measurement	This is done with the BP+ device (Uscom, Australia). This is a device for non-invasive measurement of central blood pressure and augmentation index using an oscillometric method.	Week 1	No
Other	Follow up Arterial waveform measurement	This is done with the BP+ device (Uscom, Australia). This is a device for non-invasive measurement of central blood pressure and augmentation index using an oscillometric method.	Week 17	No
Other	Initial Beck Depression Inventory	The Beck Depression Inventory (BDI), created by Dr. Aaron T. Beck, is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. It is designed for individuals aged 13 and over, and is composed of items relating to symptoms of depression such as hopelessness and irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex.	Week 1	No
Other	Follow Up Beck Depression Inventory	The Beck Depression Inventory (BDI), created by Dr. Aaron T. Beck, is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. It is designed for individuals aged 13 and over, and is composed of items relating to symptoms of depression such as hopelessness and irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex.	Week 17	No
Other	Initial Pain Impact Questionnaire (PIQ-6 questionnaire)	PIQ-6 measures the severity of pain and its impact on work and leisure activities, as well as on emotional well-being within a variety of diseases and general populations. This survey is intended for adults 18 years of age and older.	Week 1	No
Other	Follow Up Pain Impact Questionnaire (PIQ-6 questionnaire)	PIQ-6 measures the severity of pain and its impact on work and leisure activities, as well as on emotional well-being within a variety of diseases and general populations. This survey is intended for adults 18 years of age and older.	Week 17	No
Primary	Initial Insulin Sensitivity Measure using Euglycaemic glucose clamp	The clamp will be used to measure insulin sensitivity. The clamp is initiated by an intravenous bolus injection of insulin (9milliUnit/kg). Insulin is then constantly infused at a rate of 40 milliUnit.m-2.min-1 for 120 min into an arm vein, whilst glucose is variably infused to maintain euglycaemia. Plasma glucose values will be monitored every 5 minutes during the clamp and the variable infusion rate of glucose is adjusted to maintain blood glucose at a constant value of 5mmol/L.	Week 1	No
Primary	Follow up Insulin Sensitivity Measure using Euglycaemic glucose clamp	The clamp will be used to measure insulin sensitivity. The clamp is initiated by an intravenous bolus injection of insulin (9milliUnit/kg). Insulin is then constantly infused at a rate of 40 milliUnit.m-2.min-1 for 120 min into an arm vein, whilst glucose is variably infused to maintain euglycaemia. Plasma glucose values will be monitored every 5 minutes during the clamp and the variable infusion rate of glucose is adjusted to maintain blood glucose at a constant value of 5mmol/L.	Week 17	No
Secondary	Initial measurement of inflammatory markers	Plasma inflammatory markers (interleukin 1ß, 6, 8 and 10, TNFa, macrophage migration inhibitory factor, monocyte chemotactic protein-1) will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA) (interassay Coefficients of Variation: 7.2%, 10.2%, 5.8%, respectively). Plasma C- reactive protein (hsCRP) via a high sensitivity assay (BN-II nephelometer; Dade Behring Diagnostics, NSW).	Week 1	No
Secondary	Follow Up Measurement of inflammatory markers	Plasma inflammatory markers (interleukin 1ß, 6, 8 and 10, TNFa, macrophage migration inhibitory factor, monocyte chemotactic protein-1) will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA) (interassay Coefficients of Variation: 7.2%, 10.2%, 5.8%, respectively). Plasma C- reactive protein (hsCRP) via a high sensitivity assay (BN-II nephelometer; Dade Behring Diagnostics, NSW).	Week 17	No
Secondary	Initial Measure of Adiposity (DEXA)	body composition by dual energy x-ray absorptiometry (DEXA), which is a non-invasive assessment of soft tissue composition by region with a precision of 4-5%; central adiposity assessed in duplicate using a constant-tension tape for taking waist, and hip circumference. Bioimpedance measurement will be also collected for validation purposes.	Week 1	No
Secondary	Follow Up Measure of Adiposity (DEXA)	body composition by dual energy x-ray absorptiometry (DEXA), which is a non-invasive assessment of soft tissue composition by region with a precision of 4-5%; central adiposity assessed in duplicate using a constant-tension tape for taking waist, and hip circumference. Bioimpedance measurement will be also collected for validation purposes.	Week 17	No
Secondary	Initial Oral Glucose Tolerance Test - OGTT	After a 10-12 h overnight fast, participants will ingest 75g of glucose over 2 mins. Blood samples will be drawn at 0, 30, 60, 90 and 120 min for plasma glucose and insulin concentrations. We will evaluate the area under the curve.	Week 1	No
Secondary	Follow Up Oral Glucose Tolerance Test -OGTT	After a 10-12 h overnight fast, participants will ingest 75g of glucose over 2 mins. Blood samples will be drawn at 0, 30, 60, 90 and 120 min for plasma glucose and insulin concentrations. We will evaluate the area under the curve.	Week 17	No
Secondary	Initial Acute Insulin Secretory Response - Intravenous Glucose Tolerance Test	This will be measured in response to 25g intravenous glucose and calculated as the average incremental plasma insulin level from the third to the fifth minute after the glucose bolus.	Week 1	No
Secondary	Follow up Acute Insulin Secretory Response- Intravenous Glucose Tolerance Test	This will be measured in response to 25g intravenous glucose and calculated as the average incremental plasma insulin level from the third to the fifth minute after the glucose bolus.	Week 17	No