Myocardial Function and Vitamin D Supplementation in Diabetes.
Condition: Diabetes Complications; Vitamin D Deficiency; Vitamin D Supplementation; Myocardial Dysfunction
MeSH terms: Vitamin D Deficiency; Diabetes Complications
Study type: Interventional

Summary: 
      Vitamin D deficiency is recognized as a cardiovascular risk factor. Diabetic patients are of
      major risk for cardiovascular diseases and typically present with Vitamin D deficiencies.
      Myocardial function is altered in both type I and II diabetic patients but no data is today
      available on the effect of Vitamin D supplementation.

      The aim of the study will be to investigate myocardial function (by deformation imaging
      techniques) at rest and during low-dose dobutamine stress echocardiography in both type I and
      II diabetic patients. Within each diabetic population, myocardial function will be compared
      at baseline between the vitamin D deficient and non-deficient individuals. Furthermore, the
      investigators will study the effect of a 3 month supplementation in those with deficiencies.
    

Detailed description: 
      Rationale:

      Vitamin D exerts a principal role in homeostasis of calcium and phosphorus. However, recent
      studies indicated also its important function in cell differentiation, proliferation and
      growth as well as regulation of the immune system.

      Vitamin Deficiency is today recognized as a risk factor for cardiovascular disease (CVD).
      Diabetic patients are of major risk for CVD. They typically present with Vitamin D
      deficiencies. Experimental studies have established as a result of Vitamin D deficiency
      alterations in intrinsic cardiac contractile and relaxation properties, hypertrophy and
      fibrosis. Regional myocardial function is altered in both type I and II diabetic patients. In
      type II diabetic individuals, myocardial dysfunction is furthermore exacerbated in those with
      Vitamin D deficiency compared to those with normal levels. In patients free from CV risk and
      deficient in Vitamin D, regional myocardial function improved after Vitamin D
      supplementation. To the best of our knowledge, no scientific study is today available on the
      effect of Vitamin D supplementation on regional myocardial function in diabetic patients
      deficient in vitamin D.

      Objectives and Methodology:

        -  To compare regional myocardial linear deformation and torsion, at rest and in response
           to a DB stress in diabetic patients deficient and non-deficient in Vitamin D.

        -  To evaluate the impact of vitamin D supplementation in those with vitamin D deficiency.

      All the diabetic patients will benefit from a clinical (medical history, drug therapy, ECG,
      blood pressure, ...), anthropometric (abdominal obesity indices) and biological (carbohydrate
      and lipid balance, markers of inflammation and heart failure, vitamin D glucose and insulin
      status) evaluation. In addition, conventional echocardiography (remodelling and global
      diastolic and systolic function) complemented by a functional analysis by tissue Doppler
      imaging will be performed. Furthermore, 2D cine loops will be recorded in the apical 4, 3 and
      2- chamber views for the assessment of regional myocardial longitudinal deformations as well
      as in the parasternal short axis (base, mid and apex) for the evaluation of circumferential
      deformations and basal and apical rotation and torsion, at rest and under low dose dobutamine
      (110 and 120 bpm).

      Vitamin D supplementation:

      Patients with vitamin D deficiency will be investigated before and after a 3 month
      cholecalciferol supplementation.

      For this purpose 25-OH-D3 with be evaluated at baseline.

        -  Patients with 29≤ 25-OH-D3 ≥20 ng/mL will receive 200 000 UI orally the first month (100
           000 UI at T0 + 100 000 UI at T0+15 days, UVEDOSE™ Laboratoires Crinex, Montrouge,
           France) followed thereafter for the last 2 months by one daily dose (5 drops orally = 1
           000 UI/day, DÉDROGYL™ , DB Pharma, La Varenne-Saint-Hilaire, France).

        -  Patients with : 19≤ 25-OH-D3 ≥10 ng/mL will receive orally 300 000 UI (100 000 UI at T0
           + 100 000 UI at T0+23days + 100 000 UI at T0+45days; UVEDOSE™ Laboratoires Crinex,
           Montrouge, France) followed thereafter for the last month by one daily dose (5 drops
           orally =1 000 UI/day, DÉDROGYL™ , DB Pharma, La Varenne-Saint-Hilaire, France).

        -  Patients with : 25-OH-D3 <10 ng/mL will receive orally 400 000 UI (100 000 UI at T0 +
           100 000 UI at T0+15days + 100 000 UI at T0+30 days + 100 000 UI at T0+45days, UVEDOSE™
           Laboratoires Crinex, Montrouge, France) followed thereafter for the last month by one
           daily dose (5 drops orally =1 000 UI/day, DÉDROGYL™ , DB Pharma, La
           Varenne-Saint-Hilaire, France).
    

Intervention name(s): Vitamin D3 (cholecalciferol)
Intervention type(s): Dietary Supplement
Intervention description(s): Patients with 29≤ 25-OH-D3 ≥20 ng/mL will receive 200 000 UI orally the first month (100 000 UI at T0 + 100 000 UI at T0+15 days, UVEDOSE™ Laboratoires Crinex, Montrouge, France) followed for the last 2 months by one daily dose (5 drops orally = 1 000 UI/day, DÉDROGYL™ , DB Pharma, La Varenne-Saint-Hilaire, France).
Patients with : 19≤ 25-OH-D3 ≥10 ng/mL will receive orally 300 000 UI (100 000 UI at T0 + 100 000 UI at T0+23days + 100 000 UI at T0+45days; UVEDOSE™) followed for the last month by one daily dose (5 drops orally =1 000 UI/day, DÉDROGYL™ ).
Patients with : 25-OH-D3 <10 ng/mL will receive orally 400 000 UI (100 000 UI at T0 + 100 000 UI at T0+15days + 100 000 UI at T0+30 days + 100 000 UI at T0+45days, UVEDOSE™) followed for the last month by one daily dose (5 drops orally =1 000 UI/day, DÉDROGYL™).
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Type I and II diabetic patients will be investigated. Within each diabetic population, vitamin D deficient and non-deficient individuals will be compared at baseline. Then, within each diabetic population, those with vitamin D deficiency at baseline will be compared before and after a 3 month vitamin D supplementation.
Masking: Single (Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: myocardial function; vitamin D; stress echocardiography; diabetes