Effect of Vitamin D Supplementation on Exercise Adaptations in Patients on Statin Therapy
Condition: Dyslipidemias
MeSH terms: Dyslipidemias
Intervention: Vitamin D; Simvastatin; Placebo
Intervention description: Vitamin D will be given to achieve normal serum levels; Simvastatin in a dose of 40 mg will be provided to the study participants; Placebo will be provided to the study participants
Intervention MeSH terms: Vitamin D; Cholecalciferol; Simvastatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 33.0
Sex: All
Minimum age: 25 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: simvastatin; cardiorespiratory fitness; vitamin D; exercise; mitochondria

Summary:

      Statins along with lifestyle modifications including exercise are commonly prescribed to
      patients with type 2 diabetes. American diabetes association recommends using
      moderate-intensity statin and lifestyle therapy for patients with diabetes aged ≥40 years,
      even without additional cardiovascular disease(CVD) risk factors.. Myopathy is a well known
      adverse effect of statins, which occurs in 1-7% of patients. The spectrum of statin-related
      myopathy ranges from common benign myalgia to rare but life threatening rhabdomyolysis. Being
      lipophilic, simvastatin diffuses nonselectively into extrahepatic tissues such as muscle,
      leading to higher incidence of myopathy among statin users.

      In addition, simvastatin attenuates the exercise-induced increase in cardiorespiratory
      fitness, and reduces the skeletal muscle mitochondrial content and oxidative capacity in
      humans. Impaired cardiorespiratory fitness and mitochondrial function is possibly due to
      reduction in Coenzyme Q10, which is a component of the electron transport chain and is
      indispensable for generation of adenosine triphosphate (ATP) during oxidative phosphorylation
      in mitochondria. Statins or hydroxyl-methylglutaryl coenzyme A (HMA CoA) reductase inhibitors
      interfere with the production of mevalonic acid, which is a precursor in the synthesis of
      coenzyme Q10.

      Mitochondrial dysfunction has also been reported in vitamin D deficient individuals which has
      been attributed to intra-mitochondrial calcium deficiency or deficient enzyme function of the
      oxidative pathway ( by direct effect of vitamin D on enzyme gene or protein expression).
      Thus, vitamin D may improve the statin-mediated changes in cardiorespiratory fitness and
      mitochondrial function by improving the enzymatic machinery involved in oxidative
      phosphorylation which is blocked by statin. This study is being done to look for the effect
      of vitamin D supplementation on simvastatin-mediated change in exercise-mediated
      cardiorespiratory fitness and skeletal muscle mitochondrial content in adults with type 2
      diabetes
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 Diabetes Mellitus

          -  No significant microvascular complication

          -  Age between 25 and 50 yrs

          -  HbA1c<7.5%

          -  LDL-C between 100 to 130mg/dl

          -  Overweight or obese (BMI 25 -39 kg/m2)

          -  Low physical activity(WHO-GPAQ)

          -  Euthyroid , Eugonadal

          -  Vitamin D deficient (<20 ng/ml)

          -  Normal ECG

        Exclusion Criteria:

          -  Use of statins in past 3 months

          -  Use of Thiazolidinediones, Glucagon like peptide -1agonists, Dipeptidyl Peptidase -IV
             inhibitors, steroids, orlistat or other medicines affecting lipid profile or body
             weight

          -  Smoking

          -  On Vitamin D supplementation

          -  Uncontrolled DM with HbA1c>7.5

          -  Uncontrolled hypertension

          -  Significant microvascular complication of DM

          -  Macrovascular disease

          -  Musculoskeletal problems resulting in inability to exercise

          -  Pregnancy