To the Editor: In his Commentary, Dr Unger1 hypothesized that insulin therapy should be the treatment of last resort in patients with type 2 diabetes because exogenous hyperinsulinemia may increase ectopic lipid deposition in the skeletal muscle and other tissues in insulin-resistant states. The major mechanism proposed for this effect is the demonstration in leptin-deficient animals that insulin receptor substrate 2 is suppressed and the expression of sterol response element binding protein 1c (SREBP-1c) is increased in the liver by hyperinsulinemia. Unger concludes that these effects of insulin may contribute to insulin resistance and increased atherogenesis and potentially explain the higher mortality observed in the intensive arm of the ACCORD study.1
Dandona P, Chaudhuri A, Ghanim H. Insulin Therapy and Lipid Overload in Type 2 Diabetes. JAMA. 2008;300(7):788–790. doi:10.1001/jama.300.7.788-b
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