century, in most U.S. community hospitals, hospitalist physicians provide medical care to these patients. In some hospitals, particularly academic and other tertiary care hospitals, hospitalists share this task with endocrinologists. A small number of hospitals have established specialized glycemic (diabetes) management teams led by either a physician or a mid-level provider, such as a nurse practitioner or a physician assistant, to help control blood glucose levels in hospitalized patients. These teams prove to be of great importance not only for successful management of patients with diabetes, but also for diabetes education of patients, nursing staff, and house staff.
The field of inpatient management of diabetes and hyperglycemia has grown substantially in the last several years, accumulating and disseminating important clinical knowledge. This body of knowledge is summarized in this book, so it can reach the audience of hospitalists and endocrinologists, both in practice and in training—the very physicians who take care of hospitalized patients with diabetes and hyperglycemia.
Chapter 1
The Evolution of Glycemic Control in the Hospital Setting
Etie Moghissi, MD, FACE,1 and Silvio Inzucchi, MD2
1Associate Clinical Professor, Department of Medicine, University of California Los Angeles, Los Angeles, CA. 2Professor of Medicine Section of Endocrinology, Yale School of Medicine, New Haven, CT.
DOI: 10.2337/9781580406086.01
Introduction
Patients with diabetes are hospitalized three times more frequently than those without diabetes, and hyperglycemia in the hospital setting is associated with increased mortality, morbidity, longer hospital stays, and cost. Yet at the turn of the twenty-first century, few appreciated the risk of acute hyperglycemia among hospitalized patients. There were no clinical practice guidelines or recommended glycemic targets for inpatients, and every hospital relied on sliding-scale insulin therapy to manage hyperglycemia.
Early observational studies and the seminal 2001 randomized clinical trial of intensive insulin therapy in critically ill patients1 paved the way for diabetes organizations to issue calls for tight glycemic control in the critically ill patients.2–4 Investigations published after these initial recommendations, however, called into question the benefit of maintaining near-normal glycemic control in the critically ill and raised concerns regarding the prevalence of incremental hypoglycemia associated with such an approach.5–8 Notably, the Normoglycemia in Intensive Care Evaluation Using Glucose Algorithm Regulation (NICE-SUGAR) study actually showed that a 14% increased risk of death accompanied dramatically increased rates of severe hypoglycemia in patients whose glucose was controlled to the euglycemic range,9 the latter confirmed by meta-analysis of multiple studies involving the critically ill.8 These findings prompted the American Association of Clinical Endocrinologists (AACE)/American Diabetes Association (ADA) consensus group to evaluate all related published studies and update their recommendations for glycemic targets in hospitalized patients,10 with the goal of recommending reasonable, achievable, and safe glycemic targets. The consensus group chose a target of 140–180 mg/dL for critically ill patients based on the best available evidence. The group’s primary concern was maintaining patient safety, especially the avoidance of hypoglycemia. The panel recommended insulin as the treatment of choice for the majority of hospitalized patients. Continuous intravenous (IV) insulin infusion was recommended for those patients in the intensive care unit (ICU), and scheduled insulin in the form of basal, nutritional, and supplemental injections was preferred for the noncritically ill (Table 1.1). Echoing these recommendations, in 2012 The Endocrine Society issued an updated guidance focused on noncritically ill patients,11 with similar recommendations as the AACE/ADA consensus group. Both groups emphasize that clinical judgment, individualized regimens tailored to each patient, and ongoing assessment of clinical status must be incorporated into day-to-day decisions regarding the management of hyperglycemia.10,11
Table 1.1—Summary of ADA/AACE Recommendations for Management of Hyperglycemia among Hospitalized Patients
| Critically ill | Noncritically ill | |
| Blood glucose target | • 140 to 180 mg/dL(7.8 to 10.0 mmol/L) | • Premeal: <140 mg/dL (<7.8 mmol/L)* • Random: <180 mg/dL (<10.0 mmol/L)* |
| Preferred treatment regimen | • Intravenous insulin infusion of regular insulin • Use validated insulin infusion protocol • Frequently monitor blood glucose to minimize hypoglycemia | • Scheduled subcutaneous administration of insulin, with basal, nutritional, and correction components • Prolonged therapy with sliding-scale insulin as the sole regimen is discouraged • Noninsulin antihyperglycemic agents are not appropriate for most hospitalized patients who require therapy for hyperglycemia |
*Provided these targets can be safely achieved. More stringent targets may be appropriate in stable patients with previous tight glycemic control; less stringent targets may be appropriate in terminally ill patients or those with severe comorbidities.
Stress Hyperglycemia
Approximately one-third of hospital inpatients experience hyperglycemia, with up to a third of these individuals having no previous history of diabetes.12–14 Although a substantial portion of these patients likely have prediabetes or undiagnosed diabetes, acute injury and illness clearly can lead to glucose elevations in those with previously normal glucose tolerance. This stress hyperglycemia results from a complex interplay between inflammatory cytokines, catecholamines, the oxidative stress resulting from gluco- and lipotoxicity, and activation of the hypothalamic-pituitary-adrenal axis, all resulting in insulin resistance and insufficient pancreatic insulin secretion. Treatments commonly used among inpatients, such as glucocorticoids, enteral and parenteral nutrition, and vasopressors also may lead to or exacerbate glucose elevations.15 Regardless of the cause, however, hyperglycemia, particularly when severe, must be treated to reduce adverse outcomes, including dehydration, electrolyte disturbance, infectious complications, and poor wound healing.
Hyperglycemia and Adverse Hospital Outcomes
Epidemiologic studies began to establish a clear link between increasing blood glucose levels and hospital mortality in the late 1990s and early 2000s. In a 1999 publication from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study, the risk of death among 620 patients with diabetes admitted for acute myocardial infarction (MI) rose by 8% with each 18 mg/dL increase in admission blood glucose (relative risk [RR] 1.08, 95% confidence interval [CI] 1.05–1.11; P < 0.001).16 A 2003 retrospective review of data from ICU patients revealed that the mortality rate approximately doubled among patients with a mean glucose value during hospitalization between 160 and 199 mg/dL and roughly tripled among patients with mean glucose between 200 and 299 mg/dL. Above 300 mg/dL, the rate of death was approximately fourfold higher.17 In a large retrospective study of more than 250,000 admissions to 173 hospitals published in 2009, the risk of death nearly doubled for patients with blood glucose 146–199 mg/dL during hospitalization (odds ratio [OR] 1.31; 95% CI 1.26–1.36), independent of severity of illness. The odds of death, adjusted for illness severity, more than doubled at 200–299 mg/dL (OR 1.82; 95% CI 1.74–1.90), and almost tripled for glucose values >300 mg/dL (OR 2.85; 95% CI 2.58–3.14).18 Other observational and controlled studies have unequivocally supported the association between hyperglycemia and inpatient mortality risk.14,19–21 In addition, patients with hyperglycemia are more likely to have prolonged hospital stays, infections, and greater degrees of disability after hospital discharge.14,21–23 Data from outside the ICU further establish the association of hyperglycemia with adverse outcomes.