What type of insulin regimen (basal bolus insulin or other insulin regimens) for hospitalized adult non-critical care patients is more effective in achieving lower overall mean blood glucose and fewer episodes of hypoglycemia?
According to the World Health Organization (WHO), over 347 million people worldwide have diabetes.1 In 2011, an estimated 4.6 million people worldwide died as a result of complications related to hyperglycemia.2 It is projected that diabetes will affect 552 million people and will be the seventh leading cause of death by 2030. Within the US, diabetes caused at least 465 billion dollars in healthcare expenditures in 2011, and 11% of total healthcare expenditure in adults.1-3 Of the direct costs, 43% were related to hospitalized care.4
Glycemic management of hospitalized non-critically ill, adult patients can be challenging. Several factors contribute to hyperglycemia during hospitalization, including known diabetes mellitus (DM) or hospital related hyperglycemia due to hospital administered medications, stress response to acute illness, and mismanagement by practitioners.5 Optimal management of hyperglycemia is essential for improving patient outcomes. Failed recognition and inappropriate treatment of hyperglycemia places patients at risk for multi-organ complications, infection, prolonged hospitalization, and increased mortality. Furthermore, hyperglycemia in the hospital has been associated with poorer prognosis in patients with stroke, COPD exacerbations, community acquired pneumonia, trauma, acute coronary syndrome, stem cell transplantation, and occurrence following surgery.6
Subcutaneous sliding scale insulin (SSI) has historically been the more pervasive therapy utilized for the non-critical hospitalized patient.7 However, SSI does not provide good glycemic control because it is given without regard to carbohydrate intake, previously administered SSI, or the patient's metabolism. Since SSI is typically administered only in response to hyperglycemia and is not individualized based on body size, it is considered to be a reactive therapy. SSI therapy is contrary to normal pancreatic physiology because it provides no basal or long-acting insulin necessary to maintain euglycemia. This in turn promotes labile blood glucose levels instead of producing a steady state of normal glucose levels.6
A randomized control trial (RCT) conducted in 2001 by Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al.8 reported that critically ill patients whose blood glucose was maintained at 70-110 mg/dl (3.9-6.12 mmol/L) had a decrease in morbidity and mortality. The study was restricted to surgical intensive care patients. Despite the study being conducted on a very select patient population, this landmark study is said to have launched a new interest in the development of inpatient glycemic control, which continues today.9 As work continued in glycemic management for critically ill patients, interest grew for better management in the non-critically ill. In 2000, a new type of basal insulin to be administered once daily, in the evening, was approved for use by the US Food and Drug Administration. Use of this insulin grew in the outpatient clinic setting and in 2003 it was approved for administration at any time of the day.10 Slowly, basal insulin started being utilized in hospitals.
In 2006, the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA) partnered on a joint "call to action" for inpatient glycemic control in response to publications favoring tight glycemic control for critical care. In an effort to implement their recommendations for glucose control the AACE and ADA addressed a number of systematic barriers in hospitals. The implementation strategies included the development of institutional glycemic control protocols and standardized basal bolus insulin (BBI) order sets that focused on combination of insulin therapies including basal or long-acting insulin, prandial or mealtime insulin, and correction or supplemental bolus insulin to achieve euglycemia.11 With this manner of insulin administration, the basal insulin is used to suppress hepatic glucose output and decrease the occurrence of fatty acid breakdown, which assists in maintaining normal blood glucose levels. The bolus insulin is rapid-acting insulin that is administered before each meal to manage the glucose spikes that occur with each meal.12
Recent studies have demonstrated that management of hyperglycemia should be modeled after normal pancreatic functions to stabilize a person's metabolism and control blood glucose levels for 24 hours6. The effectiveness and safety of BBI therapy has been demonstrated in several moderate sized clinical trials. Umpierrez13 published the first known randomized control trial (RCT) comparing a BBI protocol with traditional SSI in adult, non-critically ill medical patients. Study subjects were known diabetics that were never started on insulin. This study demonstrated that using a BBI approach resulted in statistically significant lower mean blood glucose levels without significant side effects.13 A follow-up study by the same lead author published in 2011, which targeted non-critical care surgical patients, revealed BBI was also associated with reduced morbidity, improved glycemic control and the same rate of hypoglycemia as SSI.14 Other smaller, single center, retrospective review studies15-17 utilizing pre and post implementation had similar results. The overall mean blood glucose during hospitalization was lower in patients treated with BBI compared to those on SSI with the same or lower incidence of hypoglycemia. Likewise, Murphy D Vercruysse R, Bertucci T, Wall M, Schriever A, Emanuele M, et al.18 reported on a quality improvement project where post-implementation of an evidence-based BBI protocol yielded lower median blood glucose levels with unchanged rate of hypoglycemia.
Despite increased attention to inpatient glycemic management, only 21% of US hospitals had fully implemented noncritical care, adult glycemic control protocols by 2008, and 65% had partially implemented glycemic control protocols or were actively in the planning phase.19 The Society of Hospital Medicine (SHM) published a supplement in 2008 dedicated to addressing inpatient glycemic management that advocated use of BBI to treat inpatients. This publication served as a guide for hospital medicine physicians to focus on the importance of glycemic management.20
The development of a safe and effective method of achieving euglycemia must be a priority for all hospitals. The first step in promoting widespread adoption of BBI in hospitalized non-critical care, adult patients is to break down the barriers to implementation. A primary barrier to the implementation of BBI protocols in hospitals is practitioner's fear of hypoglycemia.6 The literature suggests that implementing BBI protocols might be met with resistance due to the complexity of the orders or misunderstanding of BBI concepts, which could have a negative effect on outcomes.12
When studying the effects of BBI therapy, it is useful to consider the recognized blood glucose goals and definitions. According to the 2012 ADA and AACE guidelines, the pre-meal blood glucose target for non-critically ill adults should generally be <140 mg/dL (7.8 mmol/L) with a random blood glucose level of <180 mg/dL (10.0 mmol/L). Hyperglycemia in the hospital has been defined as any blood glucose >140 mg/dL (7.8 mmol/L), while hypoglycemia is defined as any blood glucose <70 mg/dL (3.9 mmol/L). In addition, severe hypoglycemia in hospitalized patients has been defined as <40 mg/dL (2.2 mmol/L), although this is lower than the approximate level of 50 mg/dL (2.8 mmol/L) at which cognitive impairment begins in normal individuals. As with hyperglycemia, hypoglycemia among inpatients is also associated with adverse short- and long-term outcomes, which explains the need for close monitoring and clear insulin protocol management.21
Despite these endorsements12-17 and ADA and AACE guidelines for BBI, there is relatively little literature or large-scale clinical trials that show significantly improved outcomes, such as morbidity, mortality or length of stay.13 This might be explained in part because of the relatively low rate of adoption of these guidelines in the non-critical care adult population. Due to the complexity of acutely ill adult patients in the non-critical care setting, BBI implementation has been slow to be adopted. A systematic review of the literature is warranted to establish the effectiveness of BBI administration and potentially accelerate its adoption in the hospital setting.
Using keywords of basal-bolus, insulin, diabetes, adults, and non-critical care, an initial search in the databases CINAHL, JBI COnNECT, PubMed, and Cochrane Library indicated that no systematic review on this topic currently exists or is underway.