Maintaining glucose levels within goal ranges in hospitalized adult patients improves health outcomes. During hospital admissions, both uncontrolled hyperglycemia and severe hypoglycemia are associated with increased morbidity and mortality. Consequences may include impaired wound healing, delayed recovery, and organ dysfunction. Understanding how to properly achieve and maintain optimal glycemic control is necessary to provide high-quality patient care.

Achieving Glycemic Control

Glycemic Targets

Setting appropriate glycemic targets is essential for managing blood glucose levels. While individualized glycemic targets should consider many factors, such as patient age, medical comorbidities, nutritional status, and treatment goals, The American Diabetes Association (ADA) recommends a target plasma glucose range of 140-180 mg/dL (7.8-10 mmol/L) for most hospitalized patients. Specific guidelines for various hospital scenarios illustrate the importance of tailoring glycemic goals to each patient’s unique needs.

Blood Glucose Monitoring

Appropriate blood glucose monitoring is crucial to achieve glycemic control.

Point-of-Care Glucose Checks

Point-of-care testing is a primary way of monitoring the appropriateness of glycemic control in many hospitalized patients. Point-of-care capillary glucose checks should be assessed before meals and at bedtime in patients who are not critically ill and are tolerating a normal diet.

In patients who are not taking nutrition by mouth (NPO) or are on tube feedings, point-of-care glucose testing should usually be assessed every 4-6 hours. In critically ill patients, glucose monitoring should occur at intervals that best ensure adequate glycemic monitoring, which may vary on a case-by-case basis.

Continuous Glucose Monitoring

Continuous glucose monitoring (CGM) is accomplished via a wearable device, providing continuous, real-time glucose values. Continuous glucose monitoring (CGM) is often used in the intensive care unit (ICU) and other settings, with the advantages of real-time, on-demand and trending data that allows for more precise insulin titration with less glucose variability. CGM is often employed for specific patient populations:

• Patients using insulin infusion pumps
• Patients at high risk of hypoglycemia (risk factors include age ≥ 65 years, a higher total daily insulin dose ≥ 0.6 units/kg, glomerular filtration rate < 60 mg/dL, or BMI < 27 kg/m2)
• Patients with other indications for more stringent glycemic control
• Hospitalized patients who utilize a CGM device as an outpatient

Managing Acute Hyperglycemia

Insulin therapy is the most common method of glycemic management in hospitalized patients. Choosing the most appropriate insulin regimen requires considering a number of factors:

• Patient’s severity of illness
• Presence of other medical comorbidities
• Patient’s tolerance of oral intake
• Type of diabetes the patient has
• Whether they are insulin naive
• Their current glucose values
• Recent hemoglobin A1c (HbA1c) result prior to hospitalization

Insulin Formulations

Insulin is available in a variety of forms, including differences in onset of action, half-life, potency, and overall utility. Insulin forms are often combined to achieve optimal glycemic metrics. In most patients who are able to maintain oral intake, the preferred method of insulin treatment includes basal, prandial, and correction dosing.

Basal Insulins

Longer-acting insulin is an important component of insulin treatment, as it demonstrates some of the physiologic function of the pancreas. Longer-acting insulin includes both intermediate-acting and basal insulins.

One common form of intermediate-acting insulin is NPH regular insulin. Based on its half-life, it is usually given every 12 hours. NPH insulin starts to lower glucose levels within one hour, it is maximally effective at 4-6 hours, and its effects persist for about 12 hours.

Basal insulins include insulin glargine, detemir, and degludec. Basal insulin is effective within 1-2 hours and remains effective for 12-24 hours, with some variation between different formulations.

Bolus or Prandial Insulins

Short-acting insulin or  rapid-acting insulin is used to provide coverage for carbohydrate intake at meals as well as coverage for elevated glucose values; i.e. correction insulin. Specific forms include aspart, glulisine, and lispro.

Short-acting forms of insulin usually take effect within 15 minutes, peak at 1-2 hours, and work for 4-6 hours. The dosing of bolus insulin should be distributed evenly between meals. It should not be given when meals are skipped.   According to an endocrinology guideline in the J Clin Endocrinol Metab, carbohydrate counting helps gauge the most appropriate dosage of correction insulin.

Correction Insulin

In addition to a defined basal and bolus regimen, correction insulin provides additional short-acting insulin based on elevated glucose values at mealtimes and other times. This helps patients fine-tune their treatment to achieve tighter glycemic control.

Methods of Insulin Delivery

Insulin administration can be by subcutaneous injections, via insulin infusion pumps, or through intravenous insulin infusions. The recommended route of administration depends on the patient’s severity of illness, the need for intensive insulin therapy, current degree of hyperglycemia, ongoing glucose control, and other organ dysfunction.

Subcutaneous Insulin

For hospitalized patients who are not critically ill, subcutaneous insulin regimens are usually most effective. Whether the regimen used is basal-bolus, basal-correction, or (rarely) correction only, subcutaneous insulin forms offer predictable onsets of action and widely-used dosage regimens. However, regimens of subcutaneous insulin should be individualized to specific patient needs to prevent adverse outcomes.

Intravenous Insulin

Intravenous administration of insulin can be given in defined doses at varying frequencies as a bolus or more commonly as a continuous infusion. Various forms of insulin can be given intravenously, the most common of which is regular insulin. Regular insulin begins to work in about 30-60 minutes, peaks in about 2 to 4 hours, and lasts for about 6 to 8 hours.

Intravenous insulin infusions are commonly used in critically ill patients, especially patients with diabetic ketoacidosis, persistent hyperglycemia, or those undergoing major surgical procedures, as intravenous insulin can be titrated to provide precise glucose control based on frequent glucose measurements.

Subcutaneous Insulin Infusion Pumps

Some patients with type 1 diabetes mellitus are chronically managed on subcutaneous insulin that is delivered by a pump. In some cases, insulin pumps may be continued while patients are hospitalized, depending on the nature and severity of illness. Consultation with an endocrinologist is recommended to continue treatment with insulin infusion pumps during inpatient care.

Selecting an Ideal Insulin Regimen

Basal-Bolus Insulin Regimen

Basal-bolus regimens of subcutaneous insulin are preferred as the main treatment in hospitalized patients who are not critically ill to achieve optimal glycemic control. Basal-bolus insulin regimens are designed to mimic physiological insulin secretion. Basal insulin provides a continuous appropriate level of baseline insulin to meet basic metabolic requirements. In addition, the pancreas releases more insulin upon ingestion of carbohydrates, and bolus insulin imitates this.

The initial total daily dose of insulin is usually given as 0.3-0.6 units per kilogram of body weight. To make a basal-bolus regimen, half of the total daily dose of insulin should be given in the form of long-acting once or twice daily (depending on the form). The other half of the total daily insulin requirement should be administered as short-acting insulin divided over three meals.

Basal-Correction Insulin Regimen

A basal-correction insulin regimen involves the use of basal insulin once or twice daily, plus correction insulin given with meals, usually based on the blood glucose value. While it is less commonly utilized, as compared to a basal-bolus dosing regimen, a basal-correction insulin regimen may offer promising efficacy.

A study in J Diabetes Investig compared the combined use of an incretin (specifically a glucagon-like peptide-1 agonist) with basal insulin, plus correction scale insulin, versus the use of a basal-bolus regimen in non-critically ill medical or surgical patients. Patients who received basal insulin plus dulaglutide, in combination with correction scale insulin, had fewer episodes of hyperglycemia and hyperglycemia.

Correction Insulin and Sliding Scale Insulin Regimens

Sliding scale or correction insulin is a regimen characterized by an algorithm that defines the number of units of insulin to be given based on the blood glucose concentration, usually dosed at mealtimes and bedtime. A sliding scale approach may be useful for hospitalized patients who are normally well-controlled on non-insulin therapies in the outpatient setting, either when those medications are not continued while inpatient or when acute illness temporarily causes more severe hyperglycemia. Recent ADA and SCCM discourage the sole use of sliding scale insulin.  If only sliding scale or correction insulin is utilized, the dosing should be tailored to the specific patient’s weight and diabetes type; not a “one size fits all” protocol.

Non-Insulin Therapies

Other non-insulin diabetes medications play a role in glycemic management of hospitalized patients.

Metformin

Routine advice recommends avoiding inpatient metformin use, based on a theoretical risk of lactic acidosis. However, the incidence of lactic acidosis as a result of metformin use is low, estimated at 2-5 cases per 100,000 patients, which is similar to the risk in non-metformin treated patients. Metformin use during hospitalizations has a number of demonstrated benefits for clinical outcomes:

• Decreased mortality risk in cases of type 2 diabetes mellitus and sepsis
• Improved survival in heart failure
• Reduced length of stay due to various conditions
• Reduced insulin resistance
• Better achievement of goal glucose values

When considering metformin use in hospitalized patients, it is necessary to weigh the risks of patient safety with the potential benefits. Metformin is significantly associated with gastrointestinal side effects, which may be more severe in patients who are acutely ill. A glomerular filtration rate < 30 mL/min is a contraindication to metformin use.  Also, if caloric intake will be minimized during a hospitalization, metformin should be held,

DPP4 Inhibitors

Dipeptidyl peptidase-4 (DPP4) inhibitors are commonly continued in the hospital setting, given their general safety of use and low risk of side effects, such as hypoglycemia and renal dysfunction. One meta-analysis and systematic review demonstrated that the use of DPP4 inhibitors with insulin lead to better glucose control, less hypoglycemia, and lower insulin doses, compared with a basal bolus insulin regimen.

SGLT2 Inhibitors

Evidence is mixed regarding the use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors during hospitalization. SGLT2 inhibitors have demonstrated the benefits of reduced hospitalization related to heart failure, heart failure-associated mortality, all-cause mortality, and incidence of diabetes-related kidney disease. However, they are known to increase the risk of many complications.

• Urinary tract infections
• Genitourinary skin infections
• Hypovolemia
• Euglycemic diabetic ketoacidosis

GLP-1 Receptor Agonists

Glucagon-like peptide-1 (GLP-1) receptor agonists are known to be effective in achieving glycemic control and promoting chronic weight management in the outpatient setting. They pose little risk of hypoglycemia when used as monotherapy, a risk that increases somewhat when they are combined with other medications that may cause hypoglycemia, including insulin.  They can cause notable gastrointestinal side effects, which may complicate illness recovery.

GLP-1 receptor agonists belong to the class of endocrine agents called incretin-based therapy. Incretins are neuroendocrine hormones released in the gut after food intake to regulate nutrient metabolism. In addition to affecting metabolism and glucose regulation, some incretin-based therapies (like GLP-1 receptor agonists) have been shown to have the following benefits to hospitalized patients:

• Improve cerebrovascular circulation
• Stabilize coronary artery endothelium
• Reduce arterial platelet aggregation
• Promote optimal postoperative outcomes

Studies consistently demonstrate the higher efficacy of GLP-1 receptor agonists in glycemic control in non-critically ill hospitalized patients, as compared to insulin therapy. While the available data is promising, more evidence from randomized controlled trials is needed to establish their safety and efficacy for inpatient diabetes management.

Sulfonylureas

Sulfonylureas can provide substantial glucose-lowering effects at relatively lower costs. However, they are not recommended for use in hospitalized patients, as they carry increased risks of hypoglycemia and adverse cardiovascular events.

The Concern of Hypoglycemia

Identifying High-Risk Patients

Certain patients are at higher risk of hypoglycemia, including patients who have renal failure, are of advanced ages, or have fluctuating nutritional intake.

Preventing Hypoglycemia

Identifying high-risk patients is imperative to prevent adverse effects related to hypoglycemia. Several measures exist to help prevent hypoglycemia:

• Regular glucose monitoring: Regular plasma glucose monitoring is essential for early detection, prompt correction, and prevention of hypoglycemia.
• Individualized glycemic treatments and insulin dosing: Adjusting insulin doses based on the patient’s severity of illness, glucose levels, blood glucose variability, other medications, and nutritional intake helps minimize the risk of hypoglycemia.
• Healthcare professional education and training: Educating healthcare providers on how to identify risk factors for hypoglycemia can prevent it from occurring.
• Established hypoglycemia protocols: Adopting hospital-wide protocols for hypoglycemia treatment allows for prompt glucose correction.

Personalized intravenous insulin dosing softwares such as EndoTool Insulin Dosing Software have demonstrated a higher level of patient safety with a proven reduction in hypoglycemia rates in hospital settings.

Treatment of Hypoglycemia

In addition to preventing severe hyperglycemia, avoiding hypoglycemia is also a priority, especially when insulin therapy is used. Oftentimes, hospitalized patients have decreased nutritional intake, which lessens their need for glucose-lowering medications.

Hypoglycemia can cause cognitive impairment, which may lead to falls, aspiration, and subsequent organ dysfunction. Hypoglycemia can also affect the release of catecholamines, potentially leading to fatal cardiac dysrhythmias. Many factors can increase the risk of severe hypoglycemia:

• Advanced age
• Impaired kidney function
• Insulin-dependent diabetes
• History of hypoglycemia
• Poor nutrition status
• Lower body mass index
• Other medical problems

Immediate treatment of hypoglycemic events involves administering 15-20 grams of fast-acting carbohydrates, such as glucose tablets, glucose gel, or fruit juice. In severe hypoglycemia cases, especially if the patient has altered mental status, intravenous dextrose or intramuscular glucagon may be necessary.

Special Considerations

Perioperative Glucose Management

Managing blood glucose levels in surgical patients is critical to reduce the risk of postoperative complications. Preoperative clinical assessments, intraoperative glucose monitoring, and postoperative treatment adjustments are imperative components of perioperative glucose management.

Cardiac Surgery

Perioperative hyperglycemia and hypoglycemia amid cardiac surgery are associated with increased morbidity and mortality. Dysglycemia, which refers to abnormal fluctuations in glucose levels, commonly occurs in the perioperative period. While there are currently no widely accepted precise glucose target ranges in the perioperative period for cardiac surgery patients, severe hyperglycemia or critical hypoglycemia pose significant risks.

GLP-1 receptor agonists have been shown to improve outcomes after acute myocardial infarction and other cardiovascular surgeries in diabetic patients.

Hyperglycemia from Glucocorticoid Treatment

Glucocorticoids can induce hyperglycemia, often necessitating higher insulin doses. Patients taking glucocorticoids may require more frequent blood glucose monitoring for adequate insulin titration.

Nutritional Support-Induced Hyperglycemia

Patients receiving nutrition support, as either enteral or parenteral nutrition, often need adjustments in their insulin regimen to account for the carbohydrate content of their nutritional support. Regular monitoring and titration of insulin doses are essential in these patients.

Conclusion

It is necessary to follow evidence-based guidelines for inpatient glycemic management to promote optimal clinical outcomes. Professional recommendations such as the Endocrine Society Clinical Practice Guidelines, the Standards of Care in Diabetes from the American Diabetes Association, and treatment recommendations from the Society of Critical Care Medicine are valuable resources for inpatient diabetes management. Diabetes treatment is a rapidly developing landscape, with new drugs and glucose monitoring tools continually being developed and studied. As additional high-quality research and randomized clinical trials become available, it is crucial to remain current on best practices for diabetes treatment.

About EndoTool

EndoTool insulin dosing software recommends individual insulin dosing for patients on IV or subcutaneous insulin. The recommended dosing is specific and different for each patient based on multiple clinical characteristics. The FDA-cleared platform is utilized in hundreds of hospitals across the United States and is fully integrated with all major electronic medical records. To see how EndoTool can support your institution, get in touch today.