title: Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice.
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.
authors.affiliation: a Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Singamsetty
authors.affiliation: a Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Faraaz Ali
authors.initials: FA
authors.lastname: Shah
authors.affiliation: a Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Lanping
authors.initials: L
authors.lastname: Guo
authors.affiliation: a Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: a Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Sherie
authors.initials: S
authors.lastname: McDonald
authors.affiliation: b Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Sharma
authors.affiliation: a Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Yingze
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: b Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Alonso
authors.affiliation: a Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: O'Donnell
authors.affiliation: a Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: McVerry
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000139:chemically induced; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage* / Q000009:adverse effects*; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D020382:Interleukin-18 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010288:Parenteral Nutrition; D018805:Sepsis / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose
keywords: critical illness; dextrose; hyperglycemia; hyperglycémie; maladie grave; mouse; nutrition; sepsie; sepsis; souris