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The Effects of Critical Illness on Intestinal Glucose Sensing, Transporters, and Absorption*

Deane, Adam M. MBBS, PhD, FCICM, FRACP1,2; Rayner, Chris K. MBBS, PhD, FRACP3,4; Keeshan, Alex MBChB, FRCA2; Cvijanovic, Nada BSc(Hon)5; Marino, Zelia BSc(Hon)5; Nguyen, Nam Q. MBBS, PhD, FRACP4; Chia, Bridgette BSc(Hon)5; Summers, Matthew J. BSc2; Sim, Jennifer A. BMSc(Hon)1; van Beek, Theresia MD2; Chapman, Marianne J. BMBS, PhD, FANZCA, FCICM1,2; Horowitz, Michael MBBS, PhD, FRACP3; Young, Richard L. BSc(Hon), PhD5

doi: 10.1097/CCM.0b013e318298a8af
Clinical Investigations

Objectives: Providing effective enteral nutrition is important during critical illness. In health, glucose is absorbed from the small intestine via sodium-dependent glucose transporter-1 and glucose transporter-2, which may both be regulated by intestinal sweet taste receptors. We evaluated the effect of critical illness on glucose absorption and expression of intestinal sodium-dependent glucose transporter-1, glucose transporter-2, and sweet taste receptors in humans and mice.

Design: Prospective observational study in humans and mice.

Setting: ICU and university-affiliated research laboratory.

Subjects: Human subjects were 12 critically ill patients and 12 healthy controls. In the laboratory 16-week-old mice were studied.

Interventions: Human subjects underwent endoscopy. Glucose (30 g) and 3-O-methylglucose (3 g), used to estimate glucose absorption, were infused intraduodenally over 30 minutes. Duodenal mucosa was biopsied before and after infusion. Mice were randomized to cecal ligation and puncture to model critical illness (n = 16) or sham laparotomy (control) (n = 8). At day 5, mice received glucose (100 mg) and 3-O-methylglucose (10 mg) infused intraduodenally prior to mucosal tissue collection.

Measurements and Main Results: Quantitative polymerase chain reaction was performed to measure absolute (human) and relative levels of sodium-dependent glucose transporter-1, glucose transporter-2, and taste receptor type 1 member 2 (T1R2) transcripts. Blood samples were assayed for 3-O-methylglucose to estimate glucose absorption. Glucose absorption was three-fold lower in critically ill humans than in controls (p = 0.002) and reduced by a similar proportion in cecal ligation and puncture mice (p = 0.004). In critically ill patients, duodenal levels of sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcript were reduced 49% (p < 0.001), 50% (p = 0.009), and 85% (p = 0.007), whereas in the jejunum of cecal ligation and puncture mice sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcripts were reduced by 55% (p < 0.001), 50% (p = 0.002), and 69% (p = 0.004).

Conclusions: Critical illness is characterized by markedly diminished glucose absorption, associated with reduced intestinal expression of glucose transporters (sodium-dependent glucose transporter-1 and glucose transporter-2) and sweet taste receptor transcripts. These changes are paralleled in cecal ligation and puncture mice.

1Discipline of Acute Care Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, Australia.

2Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

3Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

4Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

5Discipline of Medicine, Nerve-Gut Research Laboratory, Level-1 Hanson Institute, Adelaide, South Australia, Australia.

* See also p. 202.

This work was performed at the Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia; and Discipline of Medicine, Nerve-Gut Research Laboratory, Level-1 Hanson Institute, Adelaide, South Australia, Australia.

Dr. Deane was jointly responsible for study conception and design, obtaining funding, acquisition of data, interpretation of data in humans and statistical analysis, and drafting and submission of manuscript. Dr. Rayner was responsible for study design, performance of endoscopies, analysis and interpretation of data, obtaining funding, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. Dr. Keeshan was responsible for subject enrollment and safety of endoscopies performed in critically ill patients. Ms. Cvijanovic and Ms. Marino were responsible for studies performed in mice and RNA extraction and quantitative polymerase chain reaction (PCR) measurements in humans and mice. Dr. Nguyen was responsible for performance of endoscopies and critical revision of the manuscript for important intellectual content. Ms. Chia was responsible for studies performed in mice and RNA extraction and quantitative PCR measurements in humans and mice. Mr. Summers, Ms. Sim, and Dr. van Beek were responsible for data collection and storage. Dr. Chapman was responsible for obtaining funding and critical revision of the manuscript for important intellectual content. Dr. Horowitz was responsible for postdoctoral supervision of Dr. Deane and Dr. Young, obtaining funding, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. Dr. Young was jointly responsible for study conception and design, obtaining funding, acquisition of data, supervision of all RNA extraction and quantitative PCR measurements in humans and mice, interpretation of data in mice and statistical analysis, and drafting and submission of manuscript.

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Supported, in part, by Intensive Care Foundation Project Grant, Intensive Care Foundation, Carlton, Victoria, Australia; and Medvet Laboratories Special Research Project Grant (Medvet Laboratories, Underdale, SA, Australia).

Drs. Deane, Keeshan, Cvijanovic, Marino, Nguyen, Summers, Sim, van Beek, Chapman, Horowitz, and Young received grant support from MedVet Labratories and the Intensive Care Foundation, Australia. Dr. Rayner received grant support from MedVet Labratories; Intensive Care Foundation, Australia; Eli Lilly; and Merck. Dr. Chia disclosed that she does not have any potential conflicts of interest.

For information regarding this article, E-mail: adam.deane@adelaide.edu.au

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins