Science; 3/5/2004; Kiberstis, Paula A. Science 03-05-2004 Type 2 diabetes affects 150 million people worldwide. With new estimates that this number may double by the year 2025, efforts to understand the etiology of the disease have intensified. One of the earliest signs of type 2 diabetes is the development of insulin resistance in muscle, a condition often accompanied by the aberrant accumulation of intracellular fatty acids that are normally broken down by mitochondria. This and other evidence have led researchers to focus increasingly on mitochondrial dysfunction as a possible culprit in the disease. Support for this hypothesis is provided by Petersen et al., who used magnetic resonance spectroscopy to study skeletal muscle function in healthy young offspring of patients with type 2 diabetes. Compared with matched controls, the muscle of these individuals was severely insulin-resistant and showed an 80% increase in the level of intracellular fatty acids as well as a 30% reduction in mitochondrial ATP production. The authors speculate that the insulin resistance is caused by an inherited defect in mitochondrial oxidative phosphorylation. -- PAK N, Engl. J. Med. 350, 664 (2004).