title: Effect of cilostazol in treating diabetes-associated microvascular complications.
abstract: OBJECTIVE
  Cilostazol (Pletal), a phosphodiesterase-3 inhibitor, was approved in the United States in 1999 to reduce symptoms of intermittent claudication. Cyclic adenosine monophosphate levels increase from inhibition of phosphodiesterase resulting in anti-platelet, anti-inflammatory, and vasodilatory effects. Diabetes mellitus is a chronic disease that causes endothelial and platelet dysfunction leading to both microvascular and macrovascular complications. This mini-review highlights the emerging evidence suggesting benefits of using cilostazol in treating microvascular complications associated with diabetes mellitus.
  
  
  METHODS
  A review of literature was conducted using PubMed and Embase databases focusing on cilostazol use in diabetes mellitus.
  
  
  RESULTS
  Cilostazol demonstrated renoprotective effects in patients with diabetic nephropathy by reducing serum soluble adhesion molecule-1 and monocyte chemoattractant protein-1. Cilostazol's anti-inflammatory actions predictably attenuate glomerular damage from increased leukocyte adherence. Additionally, cilostazol delayed renal dysfunction secondary to type 2 diabetes mellitus as albuminuria was reduced most likely resulting from inhibition of nuclear factor kappa-induced inflammatory and endothelial markers. Cilostazol's anti-inflammatory actions in addition to its vasodilatory actions relieved retinal hypoxia and decreased excessive production of retinal blood vessels suggesting benefit in diabetic retinopathy. Cilostazol did not improve neuropathy symptom scores signifying that it may not be as beneficial in patients with diabetic peripheral neuropathy without diabetic nephropathy or diabetic retinopathy.
  
  
  CONCLUSIONS
  Cilostazol's pleiotropic effects may be beneficial in patients with type 2 diabetes mellitus and diabetic nephropathy. Additional, larger studies need to be conducted to assess the benefits and risks of using cilostazol as an alternative agent in treating patients with diabetic microvascular complications.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA. nicole_asal@uri.edu.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Asal
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.
authors.forename: Karolina A
authors.initials: KA
authors.lastname: Wojciak
mesh_terms: D000077407:Cilostazol; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D006801:Humans; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D013777:Tetrazoles; D014665:Vasodilator Agents; D000077407:Cilostazol
keywords: Cilostazol; Diabetic nephropathy; Diabetic neuropathy; Diabetic retinopathy