NEW YORK (Reuters Health) - Insulin resistance in normal-weight offspring of patients with type 2 diabetes may be mediated by an inherited defect in mitochondrial oxidative phosphorylation, according to a research team at the Yale University School of Medicine in New Haven, Connecticut.
Little is known about the factors responsible for insulin resistance in persons at risk. Although other research has revealed a strong association between intramuscular lipid content and insulin resistance, Dr. Gerald I. Shulman and associates note in the February 12th issue of The New England Journal of Medicine, the mechanism is unknown.
To investigate, they recruited 14 subjects with a family history of type 2 diabetes and who were insulin-resistant, and 14 insulin-sensitive control subjects with no family history of the disease. All were lean and in excellent health, and the two groups were matched for age, body mass index and activity index.
Insulin-stimulated nonoxidative muscle glucose metabolism was reduced by about 70% in the at-risk group, while intramyocellular lipid content was approximately 80% higher.
Magnetic resonance spectroscopy of the soleus muscle showed that these changes were accompanied by reduced mitochondrial rates of ATP production in muscle and “a reduced ratio of inorganic phosphate to phosphocreatine, which may reflect a lower ratio of type I fibers (mostly oxidative) to type II fibers (mostly glycolytic) in the insulin-resistant subjects.”
In a related commentary, Dr. Roy Taylor notes that the processes observed in muscle are likely to affect beta cells as well. Since altered lipid stores in muscle precede clinical onset of type 2 diabetes by many years, this brings into question the optimal time for initiating glitazone treatment-- which improves insulin sensitivity--for protection of beta cell function.
Dr. Taylor is a physician at the University of Newcastle upon Tyne Medical School in the UK.
Source: N Engl J Med 2004;350:639-641,664-671. [ Google search on this article ]
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