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Incretion hormones as a therapeutic target in sepsis: a review

Shah, Faraaz (2018) Incretion hormones as a therapeutic target in sepsis: a review. Master Essay, University of Pittsburgh.

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Abstract

Sepsis is a complex medical illness characterized by a deleterious pro-inflammatory response to an inciting infection leading to multi-system organ dysfunction. From a public health perspective, sepsis affects over one million Americans annually with considerable in-hospital mortality, substantial associated healthcare costs, and increased physical and neurocognitive deficits in survivors of sepsis hospitalizations. Dysglycemia during sepsis hospitalization – manifesting through either hypoglycemia, hyperglycemia, or increased glycemic variability –confers increased risk of organ dysfunction and death. Novel targets for the treatment of sepsis and maintenance of glucose homeostasis are needed.

The incretin hormone axis has emerged recently as a therapeutic target in the management of diabetes mellitus. The intestine-derived incretin hormones glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted by enteroendocrine cells in response to enteral nutrients and potentiate insulin release from pancreatic beta cells in a glucose-dependent manner. Incretin hormones have additional pleiotropic effects on improving insulin sensitivity and reducing systemic inflammation. Medications targeting increased incretin activity are effective in improving glycemic control in diabetic patients and reducing cardiovascular risk.

Manipulation of incretin hormones may provide a means of attenuating the pro-inflammatory response and promoting euglycemia in sepsis. Incretin-based therapies demonstrate the potential to decrease immune cell activation and inhibit pro-inflammatory cytokine release in response to inflammatory stimuli. Targeting increased incretin activity reduces organ dysfunction and improves survival in preclinical septic models. However, clinical trials of increased incretin activity during acute hospitalizations are limited. Several small clinical trials suggest benefits in glycemic control with the use of exogenous GLP-1 infusion, but these studies were performed in mixed-populations of critically-ill patients and studies specifically in septic patients are lacking. Further clinical studies of the effects of incretin hormones specifically in septic populations are needed.


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Details

Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Shah, Faraazfas29@pitt.edufas29
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
Committee ChairFinegold, Daviddnf@pitt.edudnfUNSPECIFIED
Committee MemberPitt, Brucebrucep@pitt.edubrucepUNSPECIFIED
Date: 2018
Date Type: Submission
Number of Pages: 45
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Multidisciplinary MPH
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Uncontrolled Keywords: incretin, sepsis, hyperglycemia, glucagon-like peptide-1, glucose-dependent insulinotropic peptide
Date Deposited: 20 Sep 2018 20:12
Last Modified: 20 Sep 2018 20:12
URI: http://d-scholarship.pitt.edu/id/eprint/34991

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