Possible mechanisms of how statins cause diabetes

This paper was published in Metabolism 2014 Feb 25

Study title and authors:
Statin treatment and new-onset diabetes: A review of proposed mechanisms.

Brault M, Ray J, Gomez YH, Mantzoros CS, Daskalopoulou SS
Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24641882

Brault notes that new-onset diabetes has been observed in clinical trials and meta-analyses involving statin therapy. Brault discusses the mechanisms that may be involved between statins and diabetes.

(a) Statins affect insulin secretion through direct, indirect or combined effects on calcium channels in pancreatic β-cells.
(b) Statins reduce the expression of glucose transporter 4 (GLUT 4). GLUT 4 is a protein that transports glucose from the bloodstream into cells. Reduced GLUT 4 in response to statins results in hyperglycemia (high blood sugar) and hyperinsulinemia (excess levels of insulin in the blood).
(c) Statin therapy decreases other important molecules such as coenzyme Q10, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, and dolichol; their depletion leads to reduced intracellular signaling.
(d) Statins interference with intracellular insulin signaling pathways via inhibition of necessary phosphorylation events (phosphorylation influences protein enzymes) and reduction of small GTPase action (GTPases are key proteins in many critical biological processes such as hormonal and sensory signals, and the protein building ribosomes). 
(e) Statins can decrease levels of peroxisome proliferator activated receptor gamma and CCAAT/enhancer-binding protein which regulate glucose levels.
(f) Statins may also diminish levels of leptin and adiponectin which also play a role in regulating glucose levels.