European Heart Journal Advance Access originally published online on August 14, 2006
European Heart Journal 2006 27(17):2141-2142; doi:10.1093/eurheartj/ehl188
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Glucose, insulin, and acute myocardial infarction
UND Life Sciences
13800 Fairhill Road
321 Shaker Heights
OH 44120
USA
Tel: +1 216 231 5548
Fax: +1 928 833 0316
E-mail address:
undurti{at}hotmail.com
Goyal et al.1 reported that higher plasma glucose levels after acute myocardial infarction (AMI) predicts higher mortality in non-diabetic patients, which is not surprising as glucose is pro-inflammatory and insulin has anti-inflammatory actions.
Glucose–insulin–potassium (GIK) regimen improves myocardial function during endotoxic shock2,3 and this beneficial action has been attributed to insulin2–4 because of its inhibitory action on tumour necrosis factor-
(TNF-), macrophage migration inhibitory factor (MIF), superoxide anion production, and increase in the synthesis of eNO4,5 and anti-inflammatory cytokines.2 CREATE-ECLA Trial failed to reproduce the beneficial effects of GIK regimen in AMI,6 as the mean serum glucose levels were 162, 187, and 155 mg% in the GIK infusion group at baseline, 6 h, and 24 h after randomization when compared with 162, 148, and 135 mg% in the control, respectively. The higher serum glucose levels in the GIK group could be responsible for the negative results observed in the CREATE-ECLA trial, as glucose has pro-inflammatory actions, whereas insulin is anti-inflammatory in nature.2,4,5 In fact, lack of increase in mortality in the GIK group, despite the higher serum glucose levels could be due to the anti-inflammatory actions of insulin. Based on the results from the CARDINAL study, I propose that GIK regimen should be given in such a manner that not only plasma glucose levels are maintained 
80–100 mg%, but also production of pro-inflammatory cytokines is suppressed and synthesis and release of anti-inflammatory cytokines is enhanced, and failure to do so would give negative results. Since, there could be individual variations in response to the anti-inflammatory actions of insulin in response to GIK regimen this has to be given due weightage. I suggest that the CREATE-ECLA trial results would have been positive, provided the investigators infused adequate amounts of insulin to keep plasma glucose levels 
110 mg%. This is supported by the observation that intensive insulin treatment improved survival of the critically ill surgical patients and those without diabetes mellitus who had blood glucose concentrations 110–144 mg% (6.1–8.0 mmol/L) had a 3.9-fold higher risk of death than patients without diabetes who had lower glucose concentrations.7
Pyruvate, the intermediate product of glucose metabolism, protects myocardium, intestines, hepatic, and renal tissues from reactive oxygen species and cytokines, and ischemia/reperfusion-induced injury. Pyruvate-inhibited TNF- production, reduced circulating HMGB1 (high-mobility group B1) levels and NF-
B signalling pathways, decreased COX-2 (cyclo-oxygenase-2), iNOS (inducible nitric oxide synthase), and IL-6 (interleukin-6) mRNA expression in animal models with shock, and quenched free radicals.7 Hence, I suggest that plasma levels of TNF-, MIF, HMGB1, IL-6, IL-4, IL-10, pyruvate, and various free radicals need to be measured in addition to plasma glucose concentrations to ensure that GIK regimen adopted is adequate to ensure its beneficial actions. In the absence of such a comprehensive assessment, it is not prudent to discard GIK regimen in the treatment of AMI as being not beneficial.
References
- Goyal A, Mahaffey KW, Garg J, Nicolau JC, Hochman JS, Weaver WD, Theroux P, Oliveira GB, Todaro TG, Mojcik CF, Armstrong PW, Granger CB. (2006) Prognostic significance of the change in glucose level in the first 24 h after acute myocardial infarction: results from the CARDINAL study. Eur Heart J 27:1289–1297.
[Abstract/Free Full Text] - Jeschke MG, Klein D, Bolder U, Einspanier R. (2004) Insulin attenuates the systemic inflammatory response in endotoxemic rats. Endocrinology 145:4084–4093.
[Abstract/Free Full Text] - Hinshaw LB, Archer LT, Benjamin B, Bridges C. (1976) Effects of glucose or insulin on myocardial performance in endotoxin shock. Proc Soc Exp Biol Med 152:529–534.[CrossRef][Medline]
- Das UN. (2001) Is insulin an anti-inflammatory molecule? Nutrition 17:409–413.[CrossRef][Web of Science][Medline]
- Das UN. (2002) Is insulin an endogenous cardioprotector? Crit Care 6:389–393.[CrossRef][Web of Science][Medline]
- Mehta SR, Yusuf S, Diaz R, Zhu J, Pais P, Xavier D, Paolasso E, Ahmed R, Xie C, Kazmi K, Tai J, Orlandini A, Pogue J, Liu L. CREATE-ECLA Trial Group Investigators. (2005) Effect of glucose–insulin–potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial. JAMA 293:437–446.
[Abstract/Free Full Text] - Das UN. (2006) Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. Med Sci Monit 12:RA79–RA84.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||