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It appears that hepatic steatosis, which is shared by both lipodystrophy and most if not all obesity patients, may play a key role in the pathogenesis of insulin resistance and type 2 diabetes despite the fact that lipodystrophy is an extreme state and occurs more rarely than obesity. The possible link between lipid and glucose metabolisms via peroxisome activity has been examined and its role in determining hyperglycaemia is suggested. Moreover, new avenues towards a better understanding of insulin resistance at the genomic level have also been proposed. It appears that one of the most fundamental biological phenomena, fuel selection, may underlie the causes of diabetic hyperglycaemia and perplex the role of fat in the aetiology of insulin resistance. 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