Eyal Dassau (1,2)
Francis J. Doyle III (1,2)
Howard Zisser (2)
Bruce Buckingham (3)
B. Wayne Bequette (4)
1 Department of Chemical Engineering, UCSB, Santa Barbara, CA 93106
2 Sansum Diabetes Research Institute, Santa Barbara, CA 93105
3 Stanford Medical Center, Stanford, CA 94305
4 Department of Chemical and Biological Engineering, RPI, Troy, NY 12180

Glucose control is desirable not only for type 1 diabetes mellitus (T1DM) patients but also for Intensive Care Unit (ICU) patients. Achieving tight glucose control has been shown to reduce long-term complications of T1DM and decrease morbidity and mortality in the ICU. This can be achieved by combining technological improvements in glucose sensing and insulin delivery with advanced control algorithms. This session will include leading investigators in the field, with a focus on collaboration between physicians and engineers to improve glucose control. The session will be divided into two parts: the first one will be related to glucose regulation in T1DM, the later will be on ICU glucose control.

T1DM patients rely on insulin therapy to control their blood glucose. Traditionally, this involves frequent capillary blood measurements and insulin injections. An innovative solution, in the form of an artificial pancreas, will allow flexibility and improved life style of T1DM patients. This concept is under investigation by a collaboration of physicians and engineers understanding the physiology of glucose management in the context of control. Technological advances include automated insulin pumps and continuous glucose measurement (CGM) systems. The missing link is a controller that will communicate with the pump and sensor and allow continuous glucose regulation and disturbance rejection for meals, physical activity and stress. Automated glycemic control will minimize the undesirable states of high and low glucose levels, thereby minimizing long and short term complications. An overview of model-based (MPC) and run-to-run control strategies, with emphasis on the implications of diabetes control management, based on simulated and real subject data will be given, with emphasis on current hurdles, including time delays in insulin action and glucose sensing, meal detection and modeling of individual insulin/glucose dynamics.

Critically ill individuals may have hyperglycemia and insulin resistance, even if they do not have diabetes. Healthy individuals have a fasting glucose concentration of approximately 80 mg/ dL, but patients suffering from stress hyperglycemia can have blood glucose values greater than 200 mg/dL. A landmark study by Van den Berghe et al. (2001) showed that maintaining blood glucose below 110 mg/dL reduced overall in-hospital mortality by 34%, bloodstream infections by 46%, and acute renal failure by 41% in surgical (predominately cardiac) ICU patients. Results were less dramatic in a medical ICU, where intensive glucose management did not improve mortality but did improve morbidity (Van den Berghe, 2006). In a recent study of ICU patients in septic shock (Brunkhorst, 2008), the rate of severe hypoglycemia (glucose level, ?40 mg per deciliter) was higher in those receiving intensive glucose control than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P = 0.01) and the study was stopped by the data safety monitoring board. In these studies glucose levels have been monitored every 1 to 4 hours, and on average about every 3 hours. The intermittent monitoring of glucose may predispose to a higher rate of hypoglycemia in these intensively treated patients. The ICU is an ideal place to implement closed-loop control, since the patients have 1:1 nursing, central lines for glucose monitoring, and insulin administration. The first step in implementing closed-loop control may be the use of CGM to "supervise" insulin administration. A clinical and engineering overview of protocols to regulate glucose control in the ICU using CGM with or without a closed-loop system will be given.