Vitamin D, Insulin Resistance, and Cardiovascular Disease

Study Overview
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Brief Summary
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In recent years, vitamin D has been shown not only to be important for bone and calcium metabolism but also for homeostasis of critical tissues involved in vascular disease in patients with diabetes. Epidemiological studies indicated the high prevalence of vitamin D deficiency among Type 2 DM patients and suggest an increased risk of cardiovascular disease and hypertension with low vitamin D levels. The objective of this proposal is to evaluate the effects of vitamin D replacement on blood pressure control and vascular disease in vitamin D deficient hypertensive patients with diabetes

Detailed Description
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This is a double blinded, placebo controlled trial. Patients who meet the inclusion criteria will be randomized to placebo or 25(OH)D3, 4,000 IU/d orally for 16 weeks. Enrolled patients will be tested for 24h-blood pressure, brachial arterial blood flow, vascular inflammatory markers and macrophage inflammatory response to modified-lipoproteins at baseline, middle and at the end of the study.

Official Title
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Vitamin D, Insulin Resistance, and Cardiovascular Disease

Conditions
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Vitamin D Deficiency, Insulin Resistance, Type 2 Diabetes Mellitus, Cardiovascular Disease, Hypertension

Intervention / Treatment
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* Drug: Vitamin D3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes 25 (OH) vitamin D levels < 25 ng/ml Age 25 to 80 years Not on insulin for diabetes treatment HbA1c 5.5% -9.5% Mild/moderately increased blood pressure (systolic 120-160, diastolic 80-100) off BP medications Exclusion Criteria: Pregnancy Patients with systolic >160 or diastolic >100 mmHg High urine calcium or history of recurrent kidney stones Cardiovascular disease Stage 3 or worse chronic kidney disease

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Patients in the control group will receive placebo pills (instead of vitamin D) and calcium carbonate 500 mg twice daily. | Drug: Placebo<br>* Placebo pill orally daily Calcium carbonate 500 mg twice daily<br>|
| Active Comparator: Vitamin D<br>Patients in the vitamin D group will receive cholecalciferol 4000 units daily and calcium carbonate 500 mg twice daily. | Drug: Vitamin D3<br>* Cholecalciferol 4000 units orally daily Calcium carbonate 500 mg orally twice daily<br>* Other names: Vitamin D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypertension (24h Blood Pressure, Central Blood Pressure, and Office BP) | 24-hour blood pressure collected by ambulatory automated arm cuff, central mean arterial blood pressure (MAP) collected by non-invasive arterial tonometry and pulse wave analysis/pulse wave velocity, office blood pressure collected by manual aneroid sphygmomanometry. | 0, 2, and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial Artery Reactivity Testing | Brachial artery response to hyperemia assessed by measuring brachial artery diameter every 30 seconds for 180 seconds after a 5-minute occlusion with arm cuff above systolic blood pressure, with response defined as maximal percentage increase above baseline. | 0, 2, and 4 months | 
| Macrophage Cholesterol Metabolism | Macrophage uptake of labeled oxidized low density lipoprotein, assessed by the ratio of post-treatment cholesterol uptake to baseline uptake. | 0 and 4 months | 
| Serum Calcium | Serum calcium assessed by photometric assessment after calcium reaction with NM-BAPTA, then with EDTA | 0, 2, and 4 Month | 
| HbA1C | HbA1c percentage assessed by turbidimetric inhibition immunoassay for hemolyzed whole blood | 0, 2, and 4 month | 
| Vitamin D | 25(OH) Vitamin D assess by liquid chromatography with tandem mass spectrometry | 0, 2, and 4 Month | 
| hsCRP | High sensitivity C-reactive protein assessed by particle-enhanced immunoturbidimetric assay | 0, 2, and 4 Month | 
| Fasting Glucose | Serum fasting glucose assessed by hexokinase method | 0, 2, and 4 Month | 
| Urine Calcium to Creatinine Ratio. | Urine calcium to creatinine ratio assessed by spectrophotometry | 0, 2 and 4 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, Insulin Resistance, Type 2 Diabetes Mellitus, Cardiovascular Disease