Abnormal insulin sensitivity persists up to three years in pediatric patients post-burn

Abstract

Context: The acute hypermetabolic response post-burn is associated with insulin resistance and hyperglycemia, significantly contributing to adverse outcome of these patients.

Objective: The aim of the study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree of insulin resistance in severely burned children for up to 3 yr after the burn injury.

Design, setting and patients: A total of 194 severely burned pediatric patients, admitted to our institute between 2002 and 2007, were enrolled in this prospective study and compared to a cohort of 95 nonburned, noninjured children.

Main outcome measures: Urinary cortisol, epinephrine, and norepinephrine, serum cytokines, and resting energy requirements were determined at admission and 1, 2, 6, 9, 12, 18, 24, and 36 months post-burn. A 75-g oral glucose tolerance test was performed at similar time points; serum glucose, insulin, and C-peptide were measured; and insulin sensitivity indices, such as ISI Matsuda, homeostasis model assessment, quantitative insulin sensitivity check index, and ISI Cederholm, were calculated. Statistical analysis was performed by ANOVA with Bonferroni correction with significance accepted at P < 0.05.

Results: Urinary cortisol and catecholamines, serum IL-7, IL-10, IL-12, macrophage inflammatory protein-1b, monocyte chemoattractant protein-1, and resting energy requirements were significantly increased for up to 36 months post-burn (P < 0.05). Glucose values were significantly augmented for 6 months post-burn (P < 0.05), associated with significant increases in serum C-peptide and insulin that remained significantly increased for 36 months compared to nonburned children (P < 0.05). Insulin sensitivity indices, ISI Matsuda, ISI quantitative insulin sensitivity check index, and homeostasis model assessment were abnormal throughout the whole study period, indicating peripheral and whole body insulin resistance. The insulinogenic index displayed physiological values, indicating normal pancreatic beta-cell function.

Conclusions: A severe burn is associated with stress-induced insulin resistance that persists not only during the acute phase but also for up to 3 yr post-burn.

Trial registration: ClinicalTrials.gov NCT00673309.

Figure 1

Severe burn injury leads to significant alterations of the metabolic response. A and B, Urinary epinephrine and norepinephrine increase initially after burn injury and then decrease to normal levels at around 2 months after injury. C, Twenty-four-hour total urine cortisol levels increase upon burn injury and remain significantly elevated for up to 36 months. D and E, Proinflammatory cytokines are significantly elevated for up to 36 months in response to burn injury. Histograms depict serum concentrations of IL-6 or MCP-1 at steady-state levels. F, REE % predicted increases upon burn injury and decreased over time but remains significantly elevated up to 18 months after injury. Normal range depicted at base of graph (shaded area). Bars represent means; error bars correspond to sem. Asterisks denote statistical difference between burned children vs. nonburned children, P < 0.05.

Figure 2

Burn trauma leads to hyperglycemia and elevated fasting serum insulin concentrations, indicating insulin resistance. Histograms depict fasting serum concentrations of glucose (A), insulin (B), and C-peptide (C). D, HbA1c in burned pediatric patients is not statistically significant from nonburned children. Bars represent means; error bars correspond to sem. Asterisks denote statistical difference between burned children vs. nonburned children, P < 0.05.

Figure 3

OGTT reveals impaired insulin sensitivity for up to 36 months after burn injury. Histograms depict 2-h serum concentrations of glucose (A) and insulin (B), as well as the AUC for glucose (C) and insulin (D) upon glucose challenge during OGTT. Bars represent means; error bars correspond to sem. Asterisks denote statistical difference between burned children vs. nonburned children, P < 0.05.

Figure 4

The metabolic response to burn injury over time. Bars depict significantly elevated values for inflammatory serum cytokines, urinary catecholamines and cortisol, REE, as well as serum glucose, insulin and C-peptide levels during the acute hospital stay and for 36 months after the burn injury when compared with nonburned children.