The association of diabetes with comparable or decreased mortality in the critically ill is well documented in the literature. One explanation is that acute dysglycemia may confer less harm in the diabetic PD 0332991 Inhibitors,Modulators,Libraries patient who has developed a tolerance to the complications of hyperglycemia. The GLUT4 transporter, a signaling molecule that affects myocardial function, is downregulated with chronic hyperglycemia, and is upregulated with administration of insulin. Another possible explanation is selection bias. The high proportion of study patients with diabetes suggests that physicians were more likely to use eProtocol insulin in diabetics than non diabetics. Non diabetic patients had greater severity of illness than diabetics.

We suspect the severely ill non diabetics were more likely Inhibitors,Modulators,Libraries to be selected for blood glucose management with eProtocol insulin, and therefore diabetes was associated with reduced mortality. This studys results are limited, although we studied many patients from a heterogenous population. Generalizability of the results is limited by our use of eProtocol insulin and by the retrospective analysis. Physicians were not required to use eProtocol insulin, and we do not know how many patients were managed without eProtocol insulin. We suspect selection bias because patients supported with eProtocol insulin may be substantially different than those who were not. For example, the proportion of diabetic patients was much higher in this study than expected for a typical ICU. The ICD 9 determination of diabetes did not require hemoglobin A1c values.

Undiagnosed diabetes might then be erroneously categorized as non diabetic. Inhibitors,Modulators,Libraries We do not have the data to pursue further the selection bias issue. We excluded a large number of patients, including those with diabetic ketoacidosis Inhibitors,Modulators,Libraries or who were supported with eProtocol insulin for 1 day. While patients on this study did not receive bolus feeding, we did not quantify enteral or parenteral glucose amount, duration, or frequency. We expect such factors are associated with glucose variability, and should be controlled in future prospective studies. Blood glucose measurements from capillary glucose meters have known analytic inaccuracies, although the meters were calibrated Inhibitors,Modulators,Libraries daily according to industry standards. The clinically relevant question is whether reduction of glycemic variability will improve outcomes.

The answer to that question will require a prospective http://www.selleckchem.com/products/MDV3100.html study aimed at reducing glycemic variability. The large prospective studies looking at glucose management in the critically ill have compared different mean blood glucose targets, with little or less attention paid to other glucose metrics, such as glycemic variability. Furthermore the relationship between glycemic variability, blood glucose target range, and the method of blood glucose control is largely ignored in previously published prospective studies. Multiple studies have reported incongruent results.