Insulin Resistance and Outcomes in Surgery

Insulin resistance is one of the most fundamental reactions to injury and stress (1). In response to an injury, the activation of the neuroendocrine and inflammatory systems very rapidly (within minutes) sets the body in a metabolic state of stress. This includes a halt of anabolic processes, and instead substrates from all bodily stores (fat, carbohydrate, and protein) are released and made available as fuels, as building blocks for acute phase proteins or tissue healing. Central to this potentially massive change in metabolism is the development of insulin resistance. Insulin is the body’s most important anabolic hormone, and to achieve the rapid mobilization of substrates, insulin actions are reduced. In surgical patients, the degree of insulin resistance is related to the magnitude of the operation (1). In major surgical procedures, such as major colorectal operations, up to 90% of the preoperative insulin sensitivity canbe lost after theoperation.This change in metabolism lasts for well over 1 wk, even after moderate surgical stress. What is now becoming more and more evident is that insulin resistance is one of the key mechanisms by which several common surgical complications are triggered. Traditionally, insulin resistance was regarded as the way the body should respond to stress, and for the most part it was believed that it was probably beneficial and purposeful and should not be interfered with. Indeed, in studies of certain situations of severe stress, insulin resistance can be a key for survival. This is true in acute hemorrhage, where insulin resistance is needed to mobilize glucose to achieve fluid movements and plasma refill (2). However, in contrast to this, recent studies in elective surgical patients have suggested that in modern surgical practice, insulin resistance is harmful by prolonging recovery (1), and in this issue of JCEM Sato et al. (3) present a very important study showing a clear relationship between insulin resistance and postoperative complications. In the study by Sato et al. (3), an impressive total of 273 patients undergoing elective cardiac surgery had their insulin sensitivity determined right before and at the conclusion of elective cardiac surgery using the clamp method (although cumbersome, it is the gold standard for these studies). About half the patients had no known diabetes, whereas the rest did, and the diabetic patients were further analyzed on the basis of the preoperative glucose control as determined using glycosylated hemoglobin (HbA1c). The authors report several important findings related to the relationships between clinical outcomes, insulin resistance, andpreoperativeglucose control.Theyconfirmpreviousnotions thatHbA1chas somepredictivevalueandmaydevelop into a marker that should be controlled more carefully to identifypatientsthatneedspecificandmorestringentglucose control. This was evident in the group with the widest spread in HbA1c, the diabetics, but was not confirmed in the nondiabetics. However, in another study in nondiabetic colorectal cancer patients, preoperative HbA1c resulted in higher postoperative glucose levels and also more complications, again mostly infectious (4, 5). Perhaps the most important finding in the study by Sato et al. (3) is the clear relationship between insulin resistance and major complications, in particular infections. In their study, a fall in insulin sensitivity by 50% after surgery increased the risk of major complications by 5to 6-fold and the risk for a severe infection by more than 10-fold. These figures show how important this metabolic parameter is for outcomes. Given that an uncomplicated open upper abdominal operation results in a 50% reduction in insulin sensitivity and that most open colorectal procedures go well beyond this, it is not surprising to find that complications in general and infectious complications in