Letter by Chaudhuri et al Regarding Article, “Differential Clinical Outcomes Associated With Hypoglycemia and Hyperglycemia in Acute Myocardial Infarction”
To the Editor:
Goyal et al1 have shown that postadmission hypoglycemia was not predictive of mortality, whether subjects were receiving insulin (glucose, insulin, and potassium [GIK]) treatment or not. An equally important observation in their analysis is the effect of postadmission hyperglycemia, which occurred in a substantially greater number of subjects in the GIK group (62.6% versus 44.0%). Although postadmission hyperglycemia increased mortality by 72% in non–insulin-treated subjects, there was only a 20% increase in mortality in GIK-treated subjects (P=0.052).
Glucose is proinflammatory and prothrombotic. Hyperglycemia reduces spontaneous reperfusion, decreases microvascular perfusion, and has detrimental effects on left ventricular remodeling after myocardial infarction.2,3 An insulin infusion of 2.5 U/h in acute myocardial infarction while glycemic control is maintained (glucose <140 mg/dL) is associated with profound anti-inflammatory, profibrinolytic, antioxidant, and cardioprotective effects.4 Insulin also has platelet antiaggregatory and antiapoptotic effects. In a canine model of acute myocardial infarction, low-dose insulin alone reduces myocardial infarct size, whereas glucose and potassium5 lead to hyperglycemia and increase infarct size. Therefore, potential mechanisms exist by which the detrimental cardiovascular effects of hyperglycemia can be neutralized by insulin in subjects with ST-elevation myocardial infarction.
The lower mortality rates in GIK subjects who became hyperglycemic than in those who were not treated with insulin could therefore be due to the insulin component of the GIK infusion. Did the investigators compare the mortality rates in subjects with postadmission hyperglycemia (>140 mg/dL) who received GIK and those who did not?
This analysis and observation will be of great importance in the design of future trials to control hyperglycemia with insulin infusions in subjects with ST-elevation myocardial infarction. If indeed there is a lower mortality in hyperglycemic subjects who were receiving GIK, it would support the hypothesis of a beneficial effect of insulin in ST-elevation myocardial infarction that is not entirely dependent on glucose lowering. This suggests that insulin infusion should be used in hyperglycemic subjects with myocardial infarction to lower glucose and should be maintained even at glucose levels <140 mg/dL, with glucose infusions if necessary, to keep blood glucose levels between 70 and 140 mg/dL.
Dr Dandona has received research support from GlaxoSmithKline, Novo Nordisk, Bristol Meyers Squibb, Takeda Pharmaceuticals, Allergan, Sanofi-Aventis, Conjuchem, Dannipon Pharmaceuticals, Proctor and Gamble Pharma, Mitsubishi, Quigley Pharma Inc, Solvay Pharmaceuticals, Transition Therapeutics, and ToleRx; honorarium from Eli Lilly, Novartis, GlaxoSmithKline, Merck, Novo Nordisk, Takeda, and Sanofi-Aventis; grants from the National Institutes of Health, GlaxoSmithKline, Centers for Disease Control, Bristol Meyers Squibb, Novartis Pharmaceuticals, Abbott Labs, Takeda Pharmaceuticals, Sankyo Pharmaceuticals North America, Oishei Foundation, Citrus Industry of Florida, Solvay Pharmaceuticals, William G. McGowan Charitable Fund, and Millard Fillmore Foundation. Dr Chaudhuri has served as a speaker for Eli Lilly, Sanofi-Aventis, BMS, Novo-Nordisk, and Merck.
Goyal A, Mehta SR, Díaz R, Gerstein HC, Afzal R, Xavier D, Liu L, Pais P, Yusuf S. Differential clinical outcomes associated with hypoglycemia and hyperglycemia in acute myocardial infarction. Circulation. 2009; 120: 2429–2437.
Timmer JR, Ottervanger JP, de Boer MJ, Dambrink JH, Hoorntje JC, Gosselink AT, Suryapranata H, Zijlstra F, van't Hof AW. Hyperglycemia is an important predictor of impaired coronary flow before reperfusion therapy in ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2005; 45: 999–1002.
Chaudhuri A, Janicke D, Wilson MF, Tripathy D, Garg R, Bandyopadhyay A, Calieri J, Hoffmeyer D, Tufail S, Ghanim H, Aljada A, Dandona P. Anti-inflammatory and pro-fibrinolytic effect of insulin in acute ST-elevation myocardial infarction. Circulation. 2004; 109: 849–854.