Clinical trial NCT02112721: Can Vitamin D Supplementation Prevent Type 2 Diabetes?
Official title: Can Vitamin D Supplementation Prevent Type 2 Diabetes by Improving Insulin Sensitivity and Secretion in Overweight Humans?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Monash University
Sponsor class: OTHER
Collaborators: name: University of Victoria
name: University of Auckland, New Zealand
First posted: 2014-04-14
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Initial Insulin Sensitivity Measure using Euglycaemic glucose clamp
timeFrame: Week 1
measure: Follow up Insulin Sensitivity Measure using Euglycaemic glucose clamp
timeFrame: Week 17
Secondary outcomes:
measure: Initial measurement of inflammatory markers
timeFrame: Week 1
measure: Follow Up Measurement of inflammatory markers
timeFrame: Week 17
measure: Initial Measure of Adiposity (DEXA)
timeFrame: Week 1
measure: Follow Up Measure of Adiposity (DEXA)
timeFrame: Week 17
measure: Initial Oral Glucose Tolerance Test - OGTT
timeFrame: Week 1
measure: Follow Up Oral Glucose Tolerance Test -OGTT
timeFrame: Week 17
measure: Initial Acute Insulin Secretory Response - Intravenous Glucose Tolerance Test
timeFrame: Week 1
measure: Follow up Acute Insulin Secretory Response- Intravenous Glucose Tolerance Test
timeFrame: Week 17
Other outcomes:
measure: Initial - Other Tissue Analyses
timeFrame: Week 1
measure: Follow Up- Other Tissue Analyses
timeFrame: Week 17
measure: Resting systolic and diastolic blood pressure
timeFrame: Week 1
measure: Follow up Resting systolic and diastolic blood pressure
timeFrame: Week 17
measure: Initial Arterial waveform measurement
timeFrame: Week 1
measure: Follow up Arterial waveform measurement
timeFrame: Week 17
measure: Initial Beck Depression Inventory
timeFrame: Week 1
measure: Follow Up Beck Depression Inventory
timeFrame: Week 17
measure: Initial Pain Impact Questionnaire (PIQ-6 questionnaire)
timeFrame: Week 1
measure: Follow Up Pain Impact Questionnaire (PIQ-6 questionnaire)
timeFrame: Week 17
Locations:
city: Melbourne
country: Australia
facility: Monash Centre for Health Research and Implementation
state: Victoria
Study officials:
affiliation: Monash University
name: Barbora de Courten, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mousa A, Naderpoor N, Wilson K, Plebanski M, de Courten MPJ, Scragg R, de Courten B. Vitamin D supplementation increases adipokine concentrations in overweight or obese adults. Eur J Nutr. 2020 Feb;59(1):195-204. doi: 10.1007/s00394-019-01899-5. Epub 2019 Jan 16.
citation: Scott D, Mousa A, Naderpoor N, de Courten MPJ, Scragg R, de Courten B. Vitamin D supplementation improves waist-to-hip ratio and fasting blood glucose in vitamin D deficient, overweight or obese Asians: A pilot secondary analysis of a randomised controlled trial. J Steroid Biochem Mol Biol. 2019 Feb;186:136-141. doi: 10.1016/j.jsbmb.2018.10.006. Epub 2018 Oct 12.
citation: Mousa A, Naderpoor N, de Courten MP, Teede H, Kellow N, Walker K, Scragg R, de Courten B. Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial. Am J Clin Nutr. 2017 Jun;105(6):1372-1381. doi: 10.3945/ajcn.117.152736. Epub 2017 May 10.
citation: de Courten B, Mousa A, Naderpoor N, Teede H, de Courten MP, Scragg R. Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial. Trials. 2015 Aug 7;16:335. doi: 10.1186/s13063-015-0851-6.