Vitamin D, Insulin Resistance, and Cardiovascular Disease

Washington University School of Medicine125 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

125

Conditions

Vitamin D Deficiency Insulin Resistance Type 2 Diabetes Mellitus

Eligibility

Sex: ALLMin age: 25 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 0, 2, and 4 months

Secondary Outcomes

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.

Time frame: 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.

Time frame: 0 and 4 months

Serum Calcium

Serum calcium assessed by photometric assessment after calcium reaction with NM-BAPTA, then with EDTA

Time frame: 0, 2, and 4 Month

HbA1C

HbA1c percentage assessed by turbidimetric inhibition immunoassay for hemolyzed whole blood

Time frame: 0, 2, and 4 month

Vitamin D

25(OH) Vitamin D assess by liquid chromatography with tandem mass spectrometry

Time frame: 0, 2, and 4 Month

hsCRP

High sensitivity C-reactive protein assessed by particle-enhanced immunoturbidimetric assay

Time frame: 0, 2, and 4 Month

Fasting Glucose

Serum fasting glucose assessed by hexokinase method

Time frame: 0, 2, and 4 Month

Urine Calcium to Creatinine Ratio.

Urine calcium to creatinine ratio assessed by spectrophotometry

Time frame: 0, 2 and 4 Months

Vitamin D, Insulin Resistance, and Cardiovascular Disease

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes