Impact of stress-induced diabetes on outcomes in severely burned children

Abstract

Background: Post-burn hyperglycemia leads to graft failure, multiple organ failure, and death. A hyperinsulinemic-euglycemic clamp is used to keep serum glucose between 60 and 110 mg/dL. Because of frequent hypoglycemic episodes, a less-stringent sliding scale insulin protocol is used to maintain serum glucose levels between 80 and 160 mg/dL after elevations >180 mg/dL.

Study design: We randomized pediatric patients with massive burns into 2 groups, patients receiving sliding scale insulin to lower blood glucose levels (n = 145) and those receiving no insulin (n = 98), to determine the differences in morbidity and mortality. Patients 0 to 18 years old with burns covering ≥ 30% of the total body surface area and not randomized to receive anabolic agents were included in this study. End points included glucose levels, infections, resting energy expenditure, lean body mass, bone mineral content, fat mass, muscle strength, and serum inflammatory cytokines, hormones, and liver enzymes.

Results: Maximal glucose levels occurred within 6 days of burn injury. Blood glucose levels were age dependent, with older children requiring more insulin (p < 0.05). Daily maximum and daily minimum, but not 6 am, glucose levels were significantly different based on treatment group (p < 0.05). Insulin significantly increased resting energy expenditure and improved bone mineral content (p < 0.05). Each additional wound infection increased incidence of hyperglycemia (p = 0.004). There was no mortality in patients not receiving insulin, only in patients who received insulin (p < 0.004). Muscle strength was increased in patients receiving insulin (p < 0.05).

Conclusions: Burn-induced hyperglycemia develops in a subset of severely burned children. Length of stay was reduced in the no insulin group, and there were no deaths in this group. Administration of insulin positively impacted bone mineral content and muscle strength, but increased resting energy expenditure, hypoglycemic episodes, and mortality. New glucose-lowering strategies might be needed.

Trial registration: ClinicalTrials.gov NCT00675714.

Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Consort diagram.

Figure 2

Effect of insulin and age on blood glucose levels. Data are represented as the GAM-derived value with the 95% confidence interval denoted as grey bars. A) Patients receiving glucose had lower daily maximum glucose. B) Age influenced blood glucose concentrations. C). Older children require the administration of more insulin when compared to younger children. D) Insulin administration of>200 IU is associated with decreased glucose control.

Figure 2

Effect of insulin and age on blood glucose levels. Data are represented as the GAM-derived value with the 95% confidence interval denoted as grey bars. A) Patients receiving glucose had lower daily maximum glucose. B) Age influenced blood glucose concentrations. C). Older children require the administration of more insulin when compared to younger children. D) Insulin administration of>200 IU is associated with decreased glucose control.

Figure 2

Effect of insulin and age on blood glucose levels. Data are represented as the GAM-derived value with the 95% confidence interval denoted as grey bars. A) Patients receiving glucose had lower daily maximum glucose. B) Age influenced blood glucose concentrations. C). Older children require the administration of more insulin when compared to younger children. D) Insulin administration of>200 IU is associated with decreased glucose control.

Figure 2

Effect of insulin and age on blood glucose levels. Data are represented as the GAM-derived value with the 95% confidence interval denoted as grey bars. A) Patients receiving glucose had lower daily maximum glucose. B) Age influenced blood glucose concentrations. C). Older children require the administration of more insulin when compared to younger children. D) Insulin administration of>200 IU is associated with decreased glucose control.

Figure 3

Change in resting energy expenditure with insulin administration. Data are represented as the GAM-derived values with the 95% confidence interval denoted as grey bars.

Figure 4

Change in lumbar bone mineral content. Data are represented as the GAM-derived values with the 95% confidence interval denoted as grey bars.

Figure 5

Effect of insulin on muscle strength at the time of discharge. Data are expressed as mean ± SEM. *P<0.05 vs. control.

Figure 6

Effect of insulin on serum levels of (A) transferrin, (B) cortisol, (C) α2-macroglobulin, (D) apolipoprotein A1, (E) tumor necrosis factor α (F) macrophage inhibitory protein 1β, (G) interleukin 1β, and (H) interleukin 10. Data are expressed as GAM derived values with the 95% confidence interval denoted as grey bars.

Figure 6

Effect of insulin on serum levels of (A) transferrin, (B) cortisol, (C) α2-macroglobulin, (D) apolipoprotein A1, (E) tumor necrosis factor α (F) macrophage inhibitory protein 1β, (G) interleukin 1β, and (H) interleukin 10. Data are expressed as GAM derived values with the 95% confidence interval denoted as grey bars.

Figure 6

Effect of insulin on serum levels of (A) transferrin, (B) cortisol, (C) α2-macroglobulin, (D) apolipoprotein A1, (E) tumor necrosis factor α (F) macrophage inhibitory protein 1β, (G) interleukin 1β, and (H) interleukin 10. Data are expressed as GAM derived values with the 95% confidence interval denoted as grey bars.

Figure 6

Effect of insulin on serum levels of (A) transferrin, (B) cortisol, (C) α2-macroglobulin, (D) apolipoprotein A1, (E) tumor necrosis factor α (F) macrophage inhibitory protein 1β, (G) interleukin 1β, and (H) interleukin 10. Data are expressed as GAM derived values with the 95% confidence interval denoted as grey bars.

Figure 6

Effect of insulin on serum levels of (A) transferrin, (B) cortisol, (C) α2-macroglobulin, (D) apolipoprotein A1, (E) tumor necrosis factor α (F) macrophage inhibitory protein 1β, (G) interleukin 1β, and (H) interleukin 10. Data are expressed as GAM derived values with the 95% confidence interval denoted as grey bars.

Figure 6

Effect of insulin on serum levels of (A) transferrin, (B) cortisol, (C) α2-macroglobulin, (D) apolipoprotein A1, (E) tumor necrosis factor α (F) macrophage inhibitory protein 1β, (G) interleukin 1β, and (H) interleukin 10. Data are expressed as GAM derived values with the 95% confidence interval denoted as grey bars.

Figure 6

Effect of insulin on serum levels of (A) transferrin, (B) cortisol, (C) α2-macroglobulin, (D) apolipoprotein A1, (E) tumor necrosis factor α (F) macrophage inhibitory protein 1β, (G) interleukin 1β, and (H) interleukin 10. Data are expressed as GAM derived values with the 95% confidence interval denoted as grey bars.

Figure 6

Effect of insulin on serum levels of (A) transferrin, (B) cortisol, (C) α2-macroglobulin, (D) apolipoprotein A1, (E) tumor necrosis factor α (F) macrophage inhibitory protein 1β, (G) interleukin 1β, and (H) interleukin 10. Data are expressed as GAM derived values with the 95% confidence interval denoted as grey bars.