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Anesthesiology:
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Obesity and Diabetes: Evidence of Increased Perioperative Risk?

Neligan, Patrick J. M.D.*; Fleisher, Lee A. M.D.*

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WE are in the midst of an epidemic of obesity.1 Its prevalence has more than doubled over the past 15 years. A consequence of this is the progressive increase in the number of patients undergoing surgery related to medical complications of obesity—in particular weight loss (bariatric), cardiac, and orthopaedic surgery.2 Although an emerging body of evidence details the practical perioperative management of morbidly obese patients,3 we have little epidemiologic data with which to assess perioperative risk and few available risk-reduction interventions. In the area of cardiac surgery, one large cohort study reported increased perioperative risk in obese patients undergoing coronary artery bypass surgery,4 whereas another study found different conclusions.5 Therefore, the question remains unanswered.
Obese patients are frequently diabetic. Diabetes itself has been associated with increased perioperative risk in cardiac surgery.6,7 Poor glycemic control further worsens risk.8 Importantly, there has been increased attention to the importance of glycemic control in cardiac surgery patients. This may be one means of modifying perioperative risk.9 In this issue of the Journal, Wei Pan and colleagues used a retrospective analysis of nearly 10,000 patients at Texas Heart Institute over a 10-year period to study the interaction between obesity and diabetes.10 Patients were subdivided on the basis of body mass index into overweight-obese and normal weight, and into diabetic and nondiabetic. Obese patients were significantly younger than normal-weight patients at the time of surgery, in line with previous similar studies. The diagnosis of diabetes was based on admission data or therapy. Obesity or diabetes, individually, did not confer additional risk to patients. In contrast, obesity and diabetes (type 1 or type 2) in combination were associated with an elevated risk of postoperative respiratory failure, atrial and ventricular arrhythmias, renal insufficiency, and leg wound infections.
With any retrospective database analysis, it is important to determine if the question being asked (and the association being investigated) has biologic plausibility. Obesity is a heterogeneous disorder characterized by excessive energy intake. There seem to be two separate subsets of obese individuals. One group has been termed the metabolically healthy, but obese.11 Of greater interest are the metabolically obese. These individuals may be of normal weight or obese but are linked by the presence of a constellation of abnormalities that has been termed the metabolic syndrome. This is characterized by hyperglycemia with insulin resistance (including type 2 diabetes), hypertension, central/visceral obesity, and dyslipidemia characterized by high triglycerides and low high-density lipoproteins. This patient population is known to be at elevated risk for long-term cardiovascular events.12–14
Adipose tissue, and in particular visceral fat, is an endocrine, paracrine, and immunologic organ. Obesity is a state of chronic inflammation.15 Insulin is an antiinflammatory hormone. Increased circulating free fatty acids, derived from highly metabolic visceral fat, can cause insulin resistance and promote hepatic steatosis. Tissue macrophages invade adipose tissue and release tumor necrosis factor α. This, in turn, causes the release of interleukin 1, interleukin 6, and other cytokines. There is an alteration in the relative concentrations of adipose-derived hormones, collectively known as adipokines. Leptin, the first adipokine described, is involved in the control of satiety and is markedly proinflammatory. Leptin levels are raised in patients with the metabolic syndrome. Conversely adiponectin, which is thought to be antiinflammatory and enhances insulin sensitivity, is reduced in these patients. Resistin, an adipokine that antagonizes insulin, is elevated in the metabolic syndrome. Hence, the metabolic syndrome produces an inflammatory picture analogous to low-grade sepsis. Interestingly, there are preliminary data that this adipokine picture is associated with an increase in the risk of myocardial ischemia.16 Recent studies have highlighted the contribution of inflammation to myocardial ischemia and infarction.17,18 One would anticipate that the combination of inflammation, the metabolic syndrome, and perioperative stress would have a significant impact on perioperative morbidity and mortality. Long-term therapy for metabolic syndrome includes lifestyle modification, weight loss, tight control of hypertension and diabetes, β blockade, statin, and perhaps fibrate administration, nicotinic acid, and thiazolidinedione (insulin sensitizer) therapy.19,20
What of the perioperative care of patients with metabolic syndrome? There are surprisingly few available data in this setting. One would presume that, as in the general population, patients with this cluster of risk factors would be at increased risk. The absence of such data relates to the low level of recognition of the metabolic syndrome, confusion regarding diagnostic criteria, and ongoing controversy about the validity of the disorder itself.
So how does the current study add to the growing body of literature on the perioperative risk of both diabetes and obesity? Caution must be taken by clinicians in embracing these data. The study is a retrospective analysis of cumulative data over 10 years. During this period, there were considerable changes in the type of patient undergoing cardiac surgery, the nature of the cardiac disease, and the quality and organization of postoperative care. Moreover, the diagnosis of diabetes was based on chart data, not rigorous evaluation. Type 1 and type 2 diabetes were treated as a single disorder. Undoubtedly, the nonobese group contained undiagnosed diabetics and normal-weight, metabolically obese patients. The authors do not inform us of their criteria for diagnosing respiratory failure or renal insufficiency; indeed, there is little consensus on the criteria for these diagnoses in the literature.
We note that data are presented comparing nondiabetic obese patients with normal-weight patients and comparing diabetic obese patients with normal-weight diabetics. No data are presented comparing diabetic obese and diabetic nonobese patients. Without this comparison, it is difficult to draw conclusions regarding the cause of increased risk.
No large prospective study of perioperative risk in obese patients or in those with metabolic syndrome has been performed. Smaller studies of both obesity and cardiac surgery have failed to demonstrate adverse outcomes.5,21–23 In the absence of blinding or standardization of anesthesia techniques, as in studies that have failed to demonstrate increased difficulty with intubation in this patient population, it is impossible to discount Hawthorne effects.
Where does this lead? Proponents of tight glycemic control will suggest rigorous control of blood sugar with insulin in this patient population.24 Insulin has significant antiinflammatory properties.25 Insulin seems to be cardioprotective in the presence of ischemia.9,26 Insulin therapy in perioperative and, in particular, cardiothoracic surgical patients was associated with a significant reduction in the risk of death.27 Enthusiasm for insulin therapy, rather than glycemic control, must be tempered by the knowledge that increased insulin administration is positively associated with death in the intensive care unit regardless of the prevailing blood glucose level.28 In addition, it remains unclear whether these data may be applicable in other clinical situations.
The combination of obesity and diabetes is associated with increased perioperative risk. We would like to see future epidemiologic studies that differentiate patients, obese and nonobese, with the metabolic syndrome from those without. We would like to see studies that differentiate those with type 1 diabetes from those with type 2 diabetes. We would like to see prospective studies of perioperative care of patients with the metabolic syndrome randomized, for example, to receive antiadrenergic therapy, statins, tight glycemic control, or insulin sensitizers. However, if this relationship holds true, then the importance of one nonmodifiable risk factor (obesity) may be mitigated if tighter glycemic control in diabetic patients does modify perioperative risk.
Patrick J. Neligan, M.D.,*
Lee A. Fleisher, M.D.*
*Department of Anesthesiology & Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania. fleishel@uphs.upenn.edu
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