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Commentary |

Reinventing Type 2 Diabetes:  Pathogenesis, Treatment, and Prevention

Roger H. Unger, MD
JAMA. 2008;299(10):1185-1187. doi:10.1001/jama.299.10.1185.
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The conventional glucocentric perspective of type 2 diabetes views hyperglycemia as a primary disease caused by an etiologically uncertain combination of obesity-associated insulin resistance and beta cell loss (a disease of glucose metabolism to be treated with antihyperglycemic agents, including high-dose insulin, if necessary). By contrast, the novel lipocentric view depicts the hyperglycemia of type 2 diabetes, and the underlying insulin resistance and beta cell loss, as being secondary to the metabolic trauma caused by ectopic lipid deposition or lipotoxicity.1 If this is in fact the case, hyperglycemia should be corrected by eliminating the lipid overload. The study by Dixon et al2 provides support for this lipocentric hypothesis, by demonstrating that weight loss that follows gastric banding is accompanied by remission of diabetes in 73% of obese patients with type 2 diabetes. This finding supports 45 years of biochemical, physiological, and clinical research pointing to lipid overload as the underlying cause of this disease and of the other coexisting components of the metabolic syndrome.

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