Hyperglycemia, nutrition support, and acute illness

The impact of short-term hyperglycemia on morbidity and mortality of hospitalized patients has gained significant attention from clinicians since the landmark prospective, randomized clinical trial by van den Berghe et al, which demonstrated dramatic improvements in morbidity and mortality in critically ill surgical patients with improved glycemic control (80–110 mg/dL) compared to historically accepted glucose targets (180–200 mg/dL). Stress-induced hyperglycemia is a common phenomenon often observed in acutely ill patient populations due to impairments in insulin-mediated glucose uptake in the skeletal muscle, and failure of insulin to suppress hepatic gluconeogenesis. Parenteral nutrition (PN) is frequently a component of care for these patients and, because of its appreciable dextrose load, may further promote elevations in blood glucose. Clinicians responsible for PN administration face daily decisions over how to optimally manage their patients’ glycemic control. Although the overall impact of tight management has been demonstrated in surgical intensive care unit (ICU) patients, the potentially adverse contributions of PN have not been characterized in the setting of appropriate glycemic control and methods for optimal management have yet to be discerned. The purpose of the American Society of Parenteral and Enteral Nutrition 2005 research workshop sponsored by NIDDK (DK06190-04) on Hyperglycemia, Nutrition Support and Acute Illness was to summarize the research that had been conducted on glucose management in hospitalized patients, to describe the pathophysiology that induces the stress-induced hyperglycemia with a focus on the role of the inflammation and the immune system, and to describe protocols that have been endorsed by the American Diabetes Association for glucose monitoring in diabetic patients as well as others that have been utilized by clinicians and researchers providing nutrition support to the critically ill. The ultimate objective of the program was to provide clinical guidelines for optimal glycemic management based upon the current scientific knowledge. The next several issues of JPEN will include papers that were presented at this workshop. In this issue, Dr Jeffrey Mechanick presents the mechanisms of hyperglycemia in acutely ill patients. A comprehensive model of glucose allostasis, immunoneuroendocrine axis activation, and insulin receptor signal transduction is described. The “healthy chaos” that underlies the complex, interactive stress response is introduced, with the caveat that failure to recognize its importance can inject unintentional harm. This article is followed by Dr Anastassios Pittas’ meta-analysis of randomized controlled trials that investigated the impact of insulin therapy on mortality in critically ill patients. Included are trials conducted in cardiac ICU patients that received glucose-insulin and potassium replacement therapies. Also presented are randomized trials in critically ill patients which utilized more aggressive insulin management to achieve improved glycemic control vs those which utilized conventional insulin management and secured less rigid glucose control. The potential benefits of insulin therapy compared to euglycemia were also explored in discussing these trials. It is hoped that readers will find the summaries from the research workshop that are included in the next several JPEN issues useful in highlighting the high priority for improved glycemic control in critically ill patients. We further anticipate that these papers will serve to emphasize the many important research questions that remain, and will help to foster development of a future research agenda. While PN has proven to be life-saving in humans with permanent gastrointestinal failure, it also has well-recognized inherent risks. It is possible that many of the perceived risks of PN will be largely alleviated with more stringent attention to glycemic control.