Evidence for Subclinical Myopathy in Asymptomatic Persons with Type 2 Diabetes after Initiation of Simvastatin Therapy
Presentation Number: OR28-5
Date of Presentation: March 7th, 2015
William I Sivitz*1, Manish Suneja2, Daniel K Fox2, Brian D Fink3, Judith A Herlein3 and Christopher M Adams4
1Univ of Iowa and the Iowa City VAMC, Iowa City, IA, 2University of Iowa, Iowa City, IA, 3Iowa City VAMC, Iowa City, IA, 4University of Iowa and the Iowa City VAMC, Iowa City, IA
HMG-CoA reductase inhibitors (statins) prevent vascular events and are widely prescribed, particularly in persons with type 2 diabetes. However, intolerability due to myopathic symptoms often limits their use. We investigated the effects of simvastatin on parameters of mitochondrial function and muscle gene expression in 11 subjects with type 2 diabetes; none of whom had statin intolerance. After withdrawal of statins for two months, we obtained blood samples, performed vastus lateralis muscle biopsies, and assessed whole body resting energy expenditure (REE). We then re-initiated therapy using simvastatin, 20 mg/day, for one month before repeating these studies. As expected, simvastatin lowered LDL, but did not induce myalgias or significant elevations in serum creatine kinase. However, we found subtle but significant reductions in muscle citrate synthase activity and REE. In addition, gene set enrichment analysis of muscle samples significantly repressed gene sets involved in mitochondrial function, and significantly induced gene sets involved in inflammation and remodeling of the extracellular matrix. Further, the effects of simvastatin on muscle gene sets showed some similarities to previously described changes that occur in Duchenne muscular dystrophy, polymyositis, and dermatomyositis. Although statins inhibit an early step in coenzyme Q (CoQ) biosynthesis, we observed no differences in CoQ content within skeletal muscle mitochondria, muscle tissue, or circulating platelets. In summary, we report subtle changes in whole body energetics, mitochondrial citrate synthase activity, and microarray data consistent with subclinical myopathy. Although the benefits of statin therapy are clear, further understanding of muscular perturbations should help guide safety and tolerability.
Nothing to Disclose: WIS, MS, DKF, BDF, JAH, CMA