Increasing intravenous glucose load in the presence of normoglycemia: effect on outcome and metabolism in critically ill rabbits.
OBJECTIVE
Endocrine disturbances and a feeding-resistant wasting syndrome, characterized by a negative protein balance, promote delayed recovery and poor outcome of critical illness. Parenteral nutrition alone cannot counteract the hypercatabolic state, possibly in part as a result of aggravation of the hyperglycemic response to illness. In critically ill rabbits, we investigated the impact of varying amounts of intravenous glucose while maintaining normoglycemia on mortality, organ damage, and markers of catabolism/anabolism.


METHODS
Prospective, randomized laboratory investigation.


METHODS
University animal and molecular laboratory.


METHODS
Three-month-old male rabbits.


METHODS
Critically ill rabbits were randomized into a fasting group, a standard parenteral nutrition group, and two groups receiving either intermediate or high additional physiological amounts of intravenous glucose while maintained normoglycemic with insulin. These groups were compared with a hyperglycemic group and healthy rabbits. Protein and lipid load was equal for all fed groups.


RESULTS
Varying intravenous glucose load did not affect mortality or organ damage provided hyperglycemia was prevented. Fasted critically ill rabbits lost weight, which was attenuated by increasing intravenous glucose load. As compared with healthy rabbits, mRNA expression and/or activity of several ubiquitin-proteasome pathway components, cathepsin-L and calpain-1, was elevated in skeletal muscle of fasted critically ill rabbits. Intravenous feeding was able to counteract this response. Excessive glucose load and/or hyperglycemia, however, reduced the protective effect of feeding. Genes investigated in the diaphragm and myocardium revealed roughly a similar response. Except in the normoglycemic group with intermediate glucose load, circulating thyroid hormone and insulin-like growth factor-1 levels decreased, most pronounced in hyperglycemic rabbits.


CONCLUSIONS
Increasing intravenous glucose infusion within the physiological range, while maintaining normoglycemia, was safe for organ function and survival of critically ill rabbits. Concomitantly, it reduced the catabolic responses as compared with fasting. Whether this has a beneficial effect on muscle function and mass remains to be investigated.
Derde
Sarah
S
Department of Intensive Care Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
Vanhorebeek
Ilse
I
Ververs
Eric-Jan
EJ
Vanhees
Ine
I
Darras
Veerle M
VM
Van Herck
Erik
E
Larsson
Lars
L
Van den Berghe
Greet
G
D000199:Actins / Q000032:analysis; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D016638:Critical Illness / Q000628:therapy*; D004195:Disease Models, Animal; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000032:analysis; D010447:Peptide Hydrolases / Q000096:biosynthesis; D011817:Rabbits; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D000199:Actins; D001786:Blood Glucose; D007328:Insulin; D014284:Triiodothyronine; D007334:Insulin-Like Growth Factor I; D010447:Peptide Hydrolases; D009218:Myosins; D005947:Glucose; D013974:Thyroxine