3 Preserving Fertility in Cancer Survivors 4

Before 2001, hospital hyperglycemia was often neglected. This approach changed dramatically when tight glycemic control came to the forefront of hospital medicine after a single-center, randomized controlled trial (RCT) in Leuven, Belgium, of more than 1,500 patients in a surgical intensive care unit (ICU) reported a 42% reduction in mortality rate with use of intensive insulin therapy. Since then, massive efforts have been made worldwide to achieve these goals, with intensive insulin therapy becoming a benchmark in critically ill patients. Gunjan Y. Gandhi, MD, MSc, of the Division of Endocrinology at Mayo Clinic in Jacksonville, Florida, says: “Clinicians realized there are substantial challenges to achieving such ambitious goals in practice: multifold increased risk of hypoglycemia, increased utilization of resources, considerable revamping of infrastructure to implement glycemic management protocols, and additional personnel training and need for intense coordination among varied involved specialties. Although laudable efforts have been undertaken, from the tertiary care academic centers to small community hospitals, for the seamless implementation of insulin protocols, subsequent clinical studies in varied ICU settings did not replicate the amazing benefits reported in the study from Leuven, Belgium.” In addition, some concern started to emerge regarding possible harm. Dr Gandhi explains: “At Mayo Clinic, we conducted what still is the only RCT to assess the role of tight glycemic control (blood glucose between 80 and 100 mg/ dL) intraoperatively in cardiac surgery patients. While we did not see any improvement in patient-important outcomes, we did see an increased risk of deaths and strokes in the group with tightly controlled glucose compared with the group that was treated conventionally.” The much-awaited results of the multicenter, international Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial (of which Mayo Clinic in Rochester, Minnesota, was the only site in the United States) recently reported definitive and not entirely surprising evidence that there is no benefit of tightening glucose control to normal levels compared with a reasonable and achievable goal of 140 to 180 mg/dL in a heterogeneous group of critically ill patients (N>6,000). The results differ from the Leuven trial in that there was an increase in the primary end point (death at 90 days) with intensive glucose control. Severe hypoglycemia occurred in more patients Inpatient Hyperglycemia: What Next?