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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.

Dandona et al correctly imply that as long as the fatty acids are stored as neutral fat in a fat droplet they are harmless,³ but fatty acids do provide a convenient indicator of lipid overload. Fatty acid–induced metabolic trauma is caused not only by elevations in circulating free fatty acids released from the adipocytes, but also . . . [Full Text of this Article]

Roger H. Unger, MD
roger.unger@utsouthwestern.edu
Touchstone Center for Diabetes Research
University of Texas Southwestern Medical Center
Dallas

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