In Reply: Dr Dandona and colleagues are incorrect in stating that I “did not consider that increased free fatty acids and not triglycerides are responsible for insulin resistance.” This has actually been a main focus of mine and of my colleagues since 1994,1 when we first argued for “a role for hyperlipacidemia in the pathogenesis of NIDDM [non–insulin-dependent diabetes mellitus].” Since then, we and many others have published evidence that the toxic consequences of lipid overload are mediated by fatty acids, particularly palmitoyl coenzyme A, and derivatives such as ceramide2 and reactive oxygen species.
Unger RH. Insulin Therapy and Lipid Overload in Type 2 Diabetes—Reply. JAMA. 2008;300(7):788-790. doi:10.1001/jama.300.7.790-a