Patients with diabetes have better survival from septic melioidosis than patients who without diabetes. This difference was seen only in patients taking glyburide prior to presentation and was associated with an anti-inflammatory effect of glyburide

Chaowagul, Wipada

Chierakul, Wirongrong

Day, Nicholas P. J.

Dougan, Gordon

Koh, Gavin C. K. W.

Lee, Sue J.

Limmathurotsakul, Direk

Mahavanakul, Weera

Maude, Rapeephan R.

Peacock, Sharon J.

Schreiber, M. Fernanda

van der Poll, Tom

White, Nicholas J.

Wiersinga, W. Joost

Wuthiekanun, Vanaporn

English

PubMed

BACKGROUND: Patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. Glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. This K(ATP)-channel blocker and broad-spectrum ATP-binding cassette (ABC) transporter inhibitor has broad-ranging effects on the immune system, including inhibition of inflammasome assembly and would be predicted to influence the host response to infection. METHODS: We studied a cohort of 1160 patients with gram-negative sepsis caused by a single pathogen (Burkholderia pseudomallei), 410 (35%) of whom were known to have diabetes. We subsequently studied prospectively diabetics with B. pseudomallei infection (n = 20) to compare the gene expression profile of peripheral whole blood leukocytes in patients who were taking glyburide against those not taking any sulfonylurea. RESULTS: Survival was greater in diabetics than in nondiabetics (38% vs 45%, respectively, P = .04), but the survival benefit was confined to the patient group taking glyburide (adjusted odds ratio .47, 95% confidence interval .28-.74, P = .005). We identified differential expression of 63 immune-related genes (P = .001) in patients taking glyburide, the sum effect of which we predict to be antiinflammatory in the glyburide group. CONCLUSIONS: We present observational evidence for a glyburide-associated benefit during human melioidosis and correlate this with an anti-inflammatory effect of glyburide on the immune system

Koh, GC

Maude, RR

Schreiber, MF

Wiersinga, WJ

Wuthiekanun, V

Lee, Sue

Mahavanakul, W

Chaowagul, W

Chierakul, W

White, Nicholas

van der Poll, T

Day, Nicholas

Dougan, G

Peacock, SJ

Oxford University Research Archive

Glyburide is anti-inflammatory and associated with reduced mortality in melioidosis.

Background. Patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. Glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. This K-ATP-channel blocker and broad-spectrum ATP-binding cassette (ABC) transporter inhibitor has broad-ranging effects on the immune system, including inhibition of inflammasome assembly and would be predicted to influence the host response to infection. Methods. We studied a cohort of 1160 patients with gram-negative sepsis caused by a single pathogen (Burkholderia pseudomallei), 410 (35%) of whom were known to have diabetes. We subsequently studied prospectively diabetics with B. pseudomallei infection (n = 5 20) to compare the gene expression profile of peripheral whole blood leukocytes in patients who were taking glyburide against those not taking any sulfonylurea. Results. Survival was greater in diabetics than in nondiabetics (38% vs 45%, respectively, P = .04), but the survival benefit was confined to the patient group taking glyburide (adjusted odds ratio .47, 95% confidence interval .28-.74, P = .005). We identified differential expression of 63 immune-related genes (P = .001) in patients taking glyburide, the sum effect of which we predict to be antiinflammatory in the glyburide group. Conclusions. We present observational evidence for a glyburide-associated benefit during human melioidosis and correlate this with an anti-inflammatory effect of glyburide on the immune syste

NARCIS 

Glyburide Is Anti-inflammatory and Associated with Reduced Mortality in Melioidosis

Limmathurotsakul, D

Lee, SJ

White, NJ

Day, NP

Oxford University Research Archive (ORA)

Clinical Infectious Diseases

Koh, GCKW

Day, NPJ

University of Melbourne Institutional Repository

Gavin C. K. W. Koh

Rapeephan R. Maude

M. Fernanda Schreiber

Direk Limmathurotsakul

W. Joost Wiersinga

Vanaporn Wuthiekanun

Sue J. Lee

Weera Mahavanakul

Wipada Chaowagul

Wirongrong Chierakul

Nicholas J. White

Tom van der Poll

Nicholas P. J. Day

Gordon Dougan

Sharon J. Peacock

Crossref

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Glyburide Is Anti-inflammatory and Associated with Reduced Mortality in Melioidosis

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Oxford University Research Archive (ORA)

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