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Inflammation Poses a New Target in Diabetes


 

NEW YORK — The process of inflammation—increasingly seen as a central component in a wide variety of chronic diseases—may prove to be the link between type 2 diabetes and cardiovascular disease, according to Dr. Vivian Fonseca.

This holds potential implications for the treatment of diabetes, with an old therapeutic approach being revisited. “In 1876, a report appeared in the German literature describing improvement in glucosuria in a patient with diabetes using high doses of sodium salicylate,” Dr. Fonseca said at a meeting sponsored by the American Diabetes Association.

It is now known that low-grade inflammation arises from adipose tissue, with adipocytes secreting many cytokines involved in the production of C-reactive protein, fibrinogen, and metalloproteinases, including tumor necrosis factor-α and interleukin-6 (IL-6).

“The master switch for inflammation is the [nuclear transcription factor] NF-B, which is normally present in the cytoplasm with [inhibitory protein] IB kinase,” said Dr. Fonseca, professor of medicine and pharmacology, Tulane University, New Orleans.

“When this NF-B/IB axis receives a signal, whether from a virus or from an adipocyte-derived cytokine, NF-B moves into the nucleus, where it serves as a transcription factor for a wide variety of genes involved in the inflammatory process,” he said.

Whether the use of anti-inflammatory agents to interrupt this NF-B axis may represent a new pharmacologic approach to the treatment of diabetes is now being evaluated in a multicenter study funded by the National Institutes of Health.

The agent being tested is salsalate, which is insoluble at acid pH and therefore does not cause stomach irritation. Salsalate also does not interfere with prostacyclin or cyclooxygenase-2, nor does it raise blood pressure, Dr. Fonseca said.

Preliminary studies with salsalate in a small number of patients have shown that, aside from suppressing inflammation, it also improves glucose utilization, increases insulin secretion, and increases energy expenditure.

Patients are now being recruited for the study; information is available at www.tinsal-t2d.org

Dr. Fonseca disclosed that he receives research support from the American Diabetes Association, the National Institutes of Health, and a number of pharmaceutical companies.

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