I find this article fascinating for the shear fact that it confirms what I have been suspecting for quite some time. That diabetes treatment isn’t only a matter of getting enough insulin, it’s even more importantly a matter of reducing glucose toxicity in the body….Why don’t doctors talk more about this? I only know of a few who do address it. Since my daughters both have Mitochondrial disease, I find this to be significantly important and helpful in understanding what too much glucose does to the health of our bodies. I hope you find this as helpful as I did.
Crit Care Med. 2009 Apr;37(4):1355-64.
Tissue-specific glucose toxicity induces
mitochondrial damage in a burn injury
model of critical illness.
Vanhorebeek I, Ellger B, De Vos R, Boussemaere M, Debaveye Y, Perre SV, Rabbani N, Thornalley PJ, Van den Berghe G.
Department of Intensive Care Medicine, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
OBJECTIVE: In critically ill patients, preventing hyperglycemia (HG) with insulin therapy partially prevented organ dysfunction and protected mitochondria. A study in a rabbit model of critical illness indicated that lower blood glucose level, rather than higher insulinemia, is a key factor in such organ protection. In this model, we now investigated the impact of blood glucose lowering vs. hyperinsulinemia (HI) on mitochondria in relation to organ damage. We assessed whether such effects on mitochondria are mediated indirectly via organ perfusion or directly via reducing cellular glucose toxicity. DESIGN: Prospective, randomized laboratory investigation. SETTING: University laboratory. SUBJECTS: Three-month-old male rabbits. INTERVENTIONS: After induction of critical illness by burn injury, followed by fluid-resuscitation and parenteral nutrition, rabbits were allocated to four groups, each a combination of normal or elevated blood glucose levels with normal or elevated insulin levels. This required alloxan administration, immediately followed by intravenous insulin and glucose infusions titrated to the respective targets. MEASUREMENTS AND MAIN RESULTS: In liver, the reduced damage by glucose lowering was not explained by better perfusion/oxygen delivery. Abnormal mitochondrial ultrastructure and function was present in the two hyperglycemic groups, most pronounced with concomitant HI. Affected mitochondrial respiratory chain enzyme activities were reduced to 25% to 62% of values in healthy rabbits, in the presence of up to five-fold increased tissue levels of glucose. This was accompanied by elevated levels of dicarbonyls, which may mediate direct toxicity of cellular glucose overload and accelerated glycolysis. The abnormalities were also present in myocardium, although to a lesser extent, and absent in skeletal muscle. CONCLUSIONS: In a rabbit model of critical illness, HG evokes cellular glucose overload in liver and myocardium inducing mitochondrial dysfunction, which explained the HG-induced organ damage. Maintenance of normoglycemia, but not HI, protects against such mitochondrial and organ damage.
PMID: 19242345 [PubMed - indexed for MEDLINE]
Publication Types, MeSH Terms, Substances, Grant Support
Publication Types:
MeSH Terms:
- Animals
- Blood Glucose*/analysis
- Burns/blood
- Burns/complications
- Burns/metabolism*
- Critical Illness
- Disease Models, Animal
- Glucose/toxicity
- Hyperglycemia/etiology
- Hyperinsulinism/etiology
- Male
- Mitochondria*
- Rabbits
[...] Lower Blood Glucose Level, Rather Than Higher Insulinemia, is a Key Factor in Organ Protection. &laq… [...]