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November 14, 2001

Cytokines and Type 2 Diabetes Mellitus

Author Affiliations

Stephen J.LurieMD, PhD, Senior EditorIndividualAuthorJody W.ZylkeMD, Contributing EditorIndividualAuthor

JAMA. 2001;286(18):2233. doi:10.1001/jama.286.18.2233

To the Editor: Dr Pradhan and colleagues1 found that elevated levels of interleukin 6 (IL-6) were associated with the risk of developing type 2 diabetes mellitus in a large cohort of apparently healthy middle-aged women. Their data are consistent with the results of others.2,3 According to Pradhan et al, type 2 diabetes mellitus may be a manifestation of a long lasting and ongoing cytokine-mediated acute phase response involving IL-6. However, the mechanisms of the diabetogenic action of IL-6 are far from clear. Modulation of insulin secretion by IL-6 does not seem to be a major factor; on the other hand, there is recent evidence that IL-6 may produce insulin resistance.2,3 Cytokines can exert their effects either directly or indirectly, although a direct effect of IL-6 on the insulin–receptor transduction pathway has not been demonstrated. Indirect effects on insulin resistance have been attributed to the stimulatory action of IL-6 on the hypothalamic-pituitary-adrenal axis, hence to induction of a hypercortisolemic state.3 In fact, hypercortisolism leads to insulin resistance in a number of conditions.

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