Vitamin D, Insulin Resistance, and Cardiovascular Disease

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

Study Overview

• Status: Completed
• Conditions: Hypertension; Cardiovascular Disease; Type 2 Diabetes Mellitus; Vitamin D Deficiency; Insulin Resistance
• Intervention / Treatment: Drug: Placebo; Drug: Vitamin D3

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.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Universiy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); American Diabetes Association
• Investigators: Principal Investigator: Carlos Bernal-MIzrachi, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Washington University Endocrinology Department website

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): January 13, 2019
• Study Completion (Actual): January 13, 2019

Study Registration Dates

• First Submitted: August 15, 2008
• First Submitted That Met QC Criteria: August 15, 2008
• First Posted (Estimate): August 18, 2008

Study Record Updates

• Last Update Posted (Actual): February 10, 2020
• Last Update Submitted That Met QC Criteria: January 28, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Vitamin D; Insulin Resistance; Cardiovascular Disease; Type 2 Diabetes Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Nutrition Disorders; Hyperinsulinism; Avitaminosis; Deficiency Diseases; Malnutrition; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Vitamin D Deficiency; Insulin Resistance; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 201103002; R01HL094818 (U.S. NIH Grant/Contract)