Simvastatin-Induced Insulin Resistance May Be Linked to Decreased Lipid Uptake and Lipid Synthesis in Human Skeletal Muscle: the LIFESTAT Study

Research output: Contribution to journalJournal articlepeer-review

Background: A prevalent side-effect of simvastatin is attenuated glucose homeostasis. The underlying mechanism is unknown, but impaired lipid metabolism may provide the link. The aim of this study was to investigate whether simvastatin-treated patients had a lower capacity to oxidize lipids and reduced expression of the major proteins regulating lipid uptake, synthesis, lipolysis, and storage in skeletal muscle than matched controls.

Materials and Methods: Ten men were treated with simvastatin (HbA1c: 5.7 ± 0.1%), and 10 healthy men (HbA1c: 5.2 ± 0.1%) underwent an oral glucose tolerance test and a muscle biopsy was obtained. Fat oxidation rates were measured at rest and during exercise. Western blotting was used to assess protein content.

Results: Patients treated with simvastatin had impaired glucose tolerance compared with control subjects, but fat oxidation at rest and during exercise was compatible. Skeletal muscle protein content of CD36, lipoprotein lipase (LPL), and diacylglycerol acyltransferase (DGAT) 1 were lower, and DGAT 2 tended to be lower in patients treated with simvastatin.

Conclusions: Patients treated with simvastatin had a reduced capacity to synthesize FA and diacylglycerol (DAG) into triacylglycerol in skeletal muscle compared to matched controls. Decreased lipid synthesis capacity may lead to accumulation of lipotoxic intermediates (FA and DAG) and hence impair glucose tolerance.

Original languageEnglish
Article number9257874
JournalJournal of Diabetes Research
Number of pages7
Publication statusPublished - 2018

    Research areas

  • Adiponectin/blood, Adult, Blood Glucose/metabolism, Glucose Tolerance Test, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology, Hypercholesterolemia/drug therapy, Insulin Resistance/physiology, Leptin/blood, Lipid Metabolism/drug effects, Male, Middle Aged, Muscle, Skeletal/drug effects, Simvastatin/pharmacology

ID: 203979371