Sustained IL-1α, IL-4, and IL-6 elevations following correction of hyperglycemia in children with type 1 diabetes mellitus

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Abstract
Objective: An imbalance of pro-/anti-inflammatory cytokines may accelerate diabetic vascular complications and interfere with proper wound healing. Currently, limited available literature suggests that plasma concentrations of certain pro- and anti-inflammatory cytokines may be altered during hyperglycemia/diabetes mellitus. It is still unclear, however, whether these concepts also apply to children with diabetes, and whether alterations in circulating cytokine levels are a permanent feature of diabetes or an acute effect of fluctuating glucose concentrations. Methods: Twenty-two children with type 1 diabetes mellitus (T1DM) were studied. In 13 children, postprandial morning plasma glucose was > 11.1 mmol/L at least once (hyperglycemic group, or HyG group); in 9 subjects, plasma glucose never exceeded 10.6 mmol/L (non-hyperglycemic group, or non-HyG group). After admission, intensive euglycemia (5.0-6.1 mmol/L) was achieved in all participants via intravenous insulin and dextrose for at least 90 min. Blood samples were drawn every 30 min to determine plasma levels of 14 cytokines and chemokines. Results: Interleukin IL-1 alpha, IL-4, and IL-6 were elevated in HyG group compared with non-HyG not only when plasma glucose was elevated but also during the first 2 h following return to euglycemia. The levels of the other 11 cytokines were not significantly different. Conclusion: Specific cytokines (IL-1 alpha, IL-4, and IL-6) are acutely elevated during hyperglycemia in children with T1DM, and these elevations persist for hours after hyperglycemia has been corrected. Therefore, aside from glycemic control, additional therapeutic measures against elevated proinflammatory signals may be necessary for preventing vascular complications in children with hyperglycemic diabetes.