Citrulline Efficacy to Improve Carbohydrate Metabolism Abnormalities in the Patient Treated With High Doses of Statin
Condition: Atorvastatin
MeSH terms: Congenital Abnormalities
Study type: Interventional

Summary: 
      Hypercholesterolemia is a major cardiovascular risk factor. Statins are the first-line drug
      treatment for hypercholesterolemia and have been shown to be effective in both primary and
      secondary prevention of cardiovascular disease. However, long-term statin therapy is
      associated with impaired carbohydrate metabolism and increased risk of developing type 2
      diabetes (T2D), particularly in patients with metabolic syndrome. The risk of developing T2D
      is higher with high doses of statins.

      Currently the benefits of statins on the reduction of major cardiovascular events and
      mortality are considered superior to the risk of statin-induced diabetes T2D, and no change
      in clinical practice has been recommended to date. However, it now appears necessary to
      develop strategies to reduce the adverse effects of statins on carbohydrate metabolism and
      maintain the carbohydrate tolerance of patients on statins, especially in those at risk of
      developing T2D under statins.

      Statins are able to induce the expression and activity of an enzyme synthesizing nitric oxide
      (NO), the endothelial NO synthase (eNOS), which helps improving insulin sensitivity and
      insulin secretion. However, availability and metabolism of its substrate arginine is impaired
      in obesity and T2D. The investigators thus hypothesized that providing citrulline to statin
      treated patients, the arginine precursor with better gastrointestinal tolerance and
      bioavailability than arginine, would beneficially impact their glucose homeostasis.

      Tested in vivo by Béatrice Morio, a member of the CarMeN laboratory, combining citrulline to
      atorvastatin improved glucose tolerance and insulin sensitivity in mice fed a high fat-high
      sucrose diet. These data therefore suggest that combining citrulline to atorvastatin may
      improve glucose tolerance in statin-treated patients at high risk of developing T2D.

      The objective of the study is therefore to investigate the impact of citrulline
      supplementation (5g/d) vs. placebo for 4 weeks on glucose tolerance assessed during an oral
      glucose tolerance test in patients at risk for developing T2D and treated with atorvastatin
      (40 or 80 mg / day).
    


Intervention name(s): citrulline supplementation; placebo supplementation; glucose tolerance test
Intervention type(s): Dietary Supplement; Dietary Supplement; Procedure
Intervention description(s): 2.5 g per os of citrulline on the morning and the evening (5 g/ jour) during 4 weeks.; 2.5 g of the product in the morning and in the evening during 4 weeks.; 2 exploration mornings distant from 28 days (before and after citrulline) will allow carrying out an oral glucose tolerance test of 2 hours (75 g glucose per os)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Carbohydrate Metabolism; Citrulline; Statine