Insulin resistance and inflammation are a cause of hyperglycemia after pediatric cardiopulmonary bypass surgery

Alejandro A Floh; Cedric Manlhiot; Andrew N Redington; Brian W McCrindle; Nadia A Clarizia; Christopher A Caldarone; Steven M Schwartz

doi:10.1016/j.jtcvs.2015.06.028

Insulin resistance and inflammation are a cause of hyperglycemia after pediatric cardiopulmonary bypass surgery

J Thorac Cardiovasc Surg. 2015 Sep;150(3):498-504.e1. doi: 10.1016/j.jtcvs.2015.06.028. Epub 2015 Jun 25.

Authors

Alejandro A Floh¹, Cedric Manlhiot², Andrew N Redington², Brian W McCrindle², Nadia A Clarizia², Christopher A Caldarone³, Steven M Schwartz⁴

Affiliations

¹ Department of Critical Care Medicine, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: alejandro.floh@sickkids.ca.
² Department of Pediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
³ Division of Cardiovascular Surgery, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁴ Department of Critical Care Medicine, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.

PMID: 26190660
DOI: 10.1016/j.jtcvs.2015.06.028

Abstract

Objectives: Hyperglycemia is common after pediatric cardiopulmonary bypass (CPB) surgery and is attributed to a state of insulin resistance. We examined the role of CPB-induced inflammation on postoperative plasma glucose, insulin, and the glucose-to-insulin ratio, which was used as a marker of insulin resistance; a decrease in the ratio reflects increased resistance.

Methods: We conducted an ancillary study on a previously published randomized trial of children undergoing CPB surgery. Serial blood glucose, insulin, and cytokines were drawn after CPB and at selected intervals for up to 48 hours after surgery. The primary outcome was plasma insulin levels and glucose-to-insulin ratio. Glucose delivery and feeding status were monitored for potential modifying effects.

Results: The 299 children studied were predominantly male (55%) with a median age of 2.7 (interquartile range [IQR]: 0.5-6.5) years, and weight of 12.6 (IQR: 6.4-10.8) kg. Operations had a median Society of Thoracic Surgery-European Association for Cardio-Thoracic Surgery complexity score of 1 (IQR: 1-2) and CPB time of 82 (IQR: 58-122) minutes. Hyperglycemia occurred in 85% of subjects; odds of hyperglycemia peaked at 6 hours after CPB. Plasma glucose was associated with increased insulin and a lower glucose-to-insulin ratio. Increased interleukin (IL)-6 concentrations were associated with increased glucose (estimate [EST]: 0.55 (±0.13) mmol/L; P < .001) and insulin (EST: 1.14 (±0.12) μmol/L; P < .001) in linear regression adjusted for repeated measures. Paradoxically, increased cytokines were associated with an increased glucose-to-insulin ratio (EST: 0.21 (±0.03) mmol/μmol; P < .001).

Conclusions: Hyperglycemia after pediatric CPB surgery is associated with hyperinsulinemia, which may reflect insulin resistance in some patients. Inflammation induced by CPB may play a causative role in insulin resistance.

Keywords: cardiopulmonary bypass; hyperglycemia; hyperinsulinemia; insulin resistance; pediatrics.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers / blood
Blood Glucose / metabolism*
Cardiopulmonary Bypass / adverse effects*
Child
Child, Preschool
Female
Humans
Hyperglycemia / blood
Hyperglycemia / diagnosis
Hyperglycemia / etiology*
Infant
Inflammation / blood
Inflammation / diagnosis
Inflammation / etiology*
Inflammation Mediators / blood
Insulin / blood
Insulin Resistance*
Interleukin-6 / blood
Linear Models
Male
Nutritional Status
Odds Ratio
Randomized Controlled Trials as Topic
Risk Factors
Time Factors
Treatment Outcome

Substances

Biomarkers
Blood Glucose
IL6 protein, human
Inflammation Mediators
Insulin
Interleukin-6