Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice Academic Article uri icon

Overview

MeSH Major

  • Glucose
  • Hyperglycemia
  • Sepsis

abstract

  • Development of hyperglycemia during sepsis is associated with increased morbidity and mortality. Nutritional support is common practice in the intensive care unit, but the metabolic effects are not well understood. The purpose of this study is to determine the effect of early low-level calorie provision on the development of hyperglycemia in a clinically relevant murine model of sepsis. C57BL/6J mice underwent femoral arterial and venous catheterization followed by cecal ligation and puncture (CLP) or sham surgery and low-dose intravenous dextrose or saline infusion. Blood glucose, plasma insulin, and cytokines were measured after 24 h. Additional septic mice underwent hyperinsulinemic-euglycemic clamps or received intravenous insulin concurrent with dextrose to determine whole-body insulin sensitivity and test the efficacy of insulin to reverse hyperglycemia. Neither dextrose infusion nor CLP alone induced hyperglycemia. Early initiation of low-level dextrose in septic mice produced a variable glycemic response: 49% maintained euglycemia (blood glucose < 200) and 27% developed severe hyperglycemia (blood glucose ≥ 600). Hyperglycemia was associated with increased inflammation and reduced insulin secretion and sensitivity compared with control mice or CLP mice maintaining euglycemia. Insulin prevented the progression to severe hyperglycemia but was ineffective in reestablishing glycemic control once hyperglycemia had developed. In conclusion, early initiation of clinically relevant low-level dextrose (∼ 20% daily caloric requirements) precipitated hyperglycemia akin to an acute diabetic phenotype in septic mice characterized by decreased insulin sensitivity, decreased insulin secretion, and an increased inflammatory response.

publication date

  • October 7, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4756584

Digital Object Identifier (DOI)

  • 10.1139/apnm-2015-0213

PubMed ID

  • 26624964

Additional Document Info

start page

  • 12

end page

  • 9

volume

  • 41

number

  • 1