Vitamin D, Insulin Resistance, and Cardiovascular Disease

Not Applicable

Completed

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

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients in the control group will receive placebo pills (instead of vitamin D) and calcium carbonate 500 mg twice daily.
Vitamin D	Vitamin D3	Patients in the vitamin D group will receive cholecalciferol 4000 units daily and calcium carbonate 500 mg twice daily.

Primary Outcome Measures

Name	Time	Method
Hypertension (24h Blood Pressure, Central Blood Pressure, and Office BP)	0, 2, and 4 months	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.

Secondary Outcome Measures

Name	Time	Method
Brachial Artery Reactivity Testing	0, 2, and 4 months	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.
Serum Calcium	0, 2, and 4 Month	Serum calcium assessed by photometric assessment after calcium reaction with NM-BAPTA, then with EDTA
Macrophage Cholesterol Metabolism	0 and 4 months	Macrophage uptake of labeled oxidized low density lipoprotein, assessed by the ratio of post-treatment cholesterol uptake to baseline uptake.
Fasting Glucose	0, 2, and 4 Month	Serum fasting glucose assessed by hexokinase method
Urine Calcium to Creatinine Ratio.	0, 2 and 4 Months	Urine calcium to creatinine ratio assessed by spectrophotometry
Vitamin D	0, 2, and 4 Month	25(OH) Vitamin D assess by liquid chromatography with tandem mass spectrometry
hsCRP	0, 2, and 4 Month	High sensitivity C-reactive protein assessed by particle-enhanced immunoturbidimetric assay
HbA1C	0, 2, and 4 month	HbA1c percentage assessed by turbidimetric inhibition immunoassay for hemolyzed whole blood