# Metabolic Effects of Early Nutritional Support in Sepsis: A Translational Investigation

> **NIH NIH K23** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $134,714

## Abstract

PROJECT ABSTRACT
This application is for a Mentored Patient-Oriented Research Career Development Award entitled “Metabolic
Effects of Early Nutritional Support in Sepsis: A Translational Investigation.” I am a pulmonary and critical care
physician at the University of Pittsburgh Medical Center who requires additional training to develop expertise
as a translational researcher using metabolic assessment studies in animal models of sepsis to guide the
development of interventions in patients with critical illness. The central objective of my research project is to
determine how early caloric support impacts metabolism and inflammatory outcomes in the acute phase of
sepsis. Preliminary data from our mouse models suggest that provision of dextrose via an intravenous route,
even at low levels early in the course of sepsis, markedly impairs glucose tolerance and decreases insulin
sensitivity and insulin secretion. We propose that this metabolic dysfunction is mediated through systemic
cytokine release initiated by inflammasome activation of IL1-β. In contrast, provision of low-level dextrose by
the enteral route during early sepsis, is associated with increased levels of circulating incretin hormones,
decreased IL1-β and pro-inflammatory cytokines, and significant improvements in glucose metabolism. The
aims of the study are (1) to determine the effects of early caloric support on inflammasome activation and
metabolism in a mouse model of sepsis, (2) to explore the potentially protective role of enteral activation of the
incretin hormone pathway on inflammation and glucose tolerance in the acute phase of murine sepsis, and (3)
to translate findings on the beneficial role of early enteral dextrose in a pilot interventional trial in critically-ill
patients with sepsis. These studies will provide insight into the optimal timing and route of early caloric support
in the care of septic patients—an area of clinical practice lacking in fundamental biology and clear guidelines
for physicians. The project will provide a unique translational training opportunity that combines exploration of
the metabolic effects of early caloric support in complex animal models with a pilot interventional human study.
The work will be conducted within the Division of Pulmonary, Allergy, and Critical Care Medicine at the
University of Pittsburgh, which has an outstanding record of training physician-scientists and a highly
developed infrastructure for the conduct of translational studies. I am supported by a committed mentoring
partnership of a PhD, with expertise in murine models and metabolism, and an MD, with expertise in critical
illness and patient-orientated research. I will complete my MPH training to gain formal exposure to clinical
research practices and have assembled an Advisory Committee to provide advanced training exposure in the
areas of inflammation, metabolism, and clinical research.

## Key facts

- **NIH application ID:** 10240977
- **Project number:** 3K23GM122069-04S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Faraaz Ali Shah
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $134,714
- **Award type:** 3
- **Project period:** 2016-09-23 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240977

## Citation

> US National Institutes of Health, RePORTER application 10240977, Metabolic Effects of Early Nutritional Support in Sepsis: A Translational Investigation (3K23GM122069-04S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10240977. Licensed CC0.

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