Inpatient glycemic management brings significant challenges in the hospital setting.

Hospitalized patients experience fluctuating glucose levels based on various factors, including:

• Critical illness
• Infection
• Sepsis
• Renal failure
• Heart failure
• Dehydration
• Steroid use

Effective management of glucose is crucial for optimal health outcomes. This comprehensive guide to inpatient glycemic management is tailored to healthcare professionals, helping to understand the complexities of inpatient glycemic management and appropriate treatment strategies.

Hyperglycemia in Acute Illness

Hyperglycemia is defined as a blood glucose level ≥ 140 mg/dL, and it often occurs in about 25-50% of non-critically ill hospitalized patients.

Pathophysiology of Hyperglycemia

Acute illness drives hyperglycemia through several mechanisms. Increased hepatic glucose production and impaired glucose use by peripheral tissues leads to elevated blood glucose.

Hyperglycemia then leads to osmotic diuresis, which causes volume depletion, decreased glomerular filtration rate, and progressive hyperglycemia. Hyperglycemia also causes injury at the cellular level, producing proinflammatory cytokines and reactive oxygen species, causing the following:

• Damage to mitochondria from reactive oxygen species
• Endothelial dysfunction as a result of increased nitric oxide, increasing the likelihood of adverse cardiovascular events
• Poor immune function as a result of proinflammatory cytokines like tumor necrosis factor alpha and interleukin-6, leading to these:
  • Impaired wound healing
  • Greater risk of infection
  • Increased multiple organ failure

The breakdown of glycogen from muscles leads to lactic acidosis, which furthers these tissue injuries and predisposes to the pathophysiology of sepsis and sequential organ failure.

Role of Glucoregulatory Hormones

Glucoregulatory hormones include insulin and counter-regulatory hormones: glucagon, catecholamines, cortisol, and growth hormone. Insulin is anabolic, promoting glucose uptake into tissues and preventing the breakdown of proteins and fats.

The counter-regulatory hormones exert different effects. Glucagon regulates hepatic glucose production by breaking down glycogen. However, in a proinflammatory state with elevated insulin, this can lead to insulin resistance, decreased uptake of glucose by peripheral tissues, ongoing hyperglycemia, and progressive inflammation.

Physiologic stress and progressive inflammation leads to increased cortisol and catecholamine release. Epinephrine, the most abundant catecholamine, leads to increased glucagon release and suppressed serum insulin, progressively worsening hyperglycemia and organ dysfunction.

Goals of Inpatient Glycemic Management

Glycemic management in the inpatient setting requires careful regulation of blood glucose levels to achieve the following goals:

• Avoid severe hyperglycemia
• Prevent hypoglycemia
• Avoid volume depletion
• Prevent electrolyte abnormalities
• Improve patient outcomes
• Provide patient education
• Optimize outpatient blood glucose management upon discharge

Importance of Glycemic Control

Maintaining glycemic levels within goal ranges leads to optimal health outcomes.

Uncontrolled hyperglycemia has been linked to increased morbidity and mortality rates among hospitalized patients. On the other hand, hypoglycemia can lead to permanent cognitive impairment, fatal cardiac dysrhythmias, and severe organ dysfunction.

Both hyperglycemia and hypoglycemia can delay wound healing and recovery from illness or surgery. Understanding the steps to maintain appropriate glycemic control is necessary for optimal patient care.

Dangers of Severe Hyperglycemia

Severe hyperglycemia can increase morbidity and mortality in several ways. Elevated blood sugar during hospitalization is associated with the following adverse effects:

• Increased length of hospital stay
• Elevated healthcare costs
• Higher infection risk
• Impaired wound healing
• Greater protein-energy malnutrition
• Increased overall mortality

Effects of Hypoglycemia

In addition to preventing severe hyperglycemia, avoiding hypoglycemia is also a priority, especially when insulin therapy is used.

In many cases, hospitalized patients have decreased oral intake, which reduces their need for glucose-lowering medications.

Hypoglycemia can cause cognitive impairment, leading to falls, aspiration, and organ dysfunction. Hypoglycemia can also affect catecholamine release, potentially leading to fatal cardiac arrhythmias. There are many factors that increase the risk of severe hypoglycemia:

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

Volume Status and Electrolyte Abnormalities

Hyperglycemia raises plasma osmolality, decreases renal function, and affects electrolyte balances of sodium, potassium, chloride, and calcium.

Pseudohyponatremia

Hyponatremia is common with severe hyperglycemia, as a result of osmotic fluid shifts from intracellular to extracellular spaces.

True hyponatremia is associated with significant morbidity and mortality in hospitalized patients, but the hyponatremia that occurs with severe hyperglycemia is a pseudohyponatremia, as it corrects to a certain degree with glucose normalization. Studies suggest that corrected sodium levels more accurately predict the morbidity and mortality of hyponatremia associated with hyperglycemia.

Potassium Balance

Hyperkalemia and hypokalemia each occur as a result of fluid shifts between the extracellular and intracellular spaces. Significant volume depletion from osmotic diuresis that often occurs with severe hyperglycemia can cause a reduction in total body potassium yet the serum potassium level may appear normal.  Also a lack of insulin, particularly in diabetic ketoacidosis can prevent potassium from entering cells and raise the serum potassium level.

During treatment of severe hyperglycemia, as volume status is restored and insulin is administered, this forces potassium from the extracellular spaces back into the cells, lowering serum potassium and causing hypokalemia. As hyperglycemia is managed in the inpatient setting, close monitoring of potassium levels is necessary to prevent adverse outcomes.

Setting Glycemic Targets

Individualized glycemic targets should consider various factors like patient age, medical comorbidities, nutritional status, and treatment goals.

The American Diabetes Association (ADA) provides guidelines for glycemic targets in hospitalized patients, emphasizing the importance of tailoring treatment plans to each patient’s unique needs.

Critically Ill Patients

Critically ill patients pose unique challenges in glycemic management due to the physiologic stress response and changes in glucose metabolism that are associated with critical illness.

Several studies have compared intensive insulin therapy to goal ranges of 80-110 mg/dL with glucose values of a more moderate target from 140-180 mg/dL. Critically ill patients maintained in the lower range experienced no significant treatment advantage, yet had a notable increase in mortality and a 10-15 times higher risk of hypoglycemia.

Within critically ill patients in the intensive care unit (ICU), intravenous insulin infusion is the preferred pharmacologic treatment of hyperglycemia, as a result of a more predictable dosing response, less pharmacologic interactions, and appropriateness of use in cases of organ dysfunction. In this ebook, we have outlined the 2024 updated guidelines for glycemic control from the Society of Critical Care Management (SCCM),  with a special focus on the importance of individualized patient care and the use of decision support tools such as EndoTool Inpatient Glucose Management System.

Non-Critically Ill Patients

While a firm glucose target has not been established across all organizations, according to the American Diabetes Association and the Endocrine Society Clinical Practice Guideline, patients in the non-critical care setting should maintain glucose values between 140-180 mg/dL for adequate glucose control. Some recommendations advocate for <140 mg/dL fasting and <180 mg/dL on postprandial glucose checks, while others suggest glucose values between 110-140 mg/dL in select cases to promote wound healing.

Short-Stay Patients

The diabetes management goal for preoperative patients is a glycosylated hemoglobin (HbA1c) level < 8% or blood glucose level 100-180 mg/dL.

Many patients who are hospitalized for short procedures can continue their maintenance medications for diabetes with slight dosage changes. In many patients, they are advised to follow nothing by mouth (NPO) protocol starting at midnight prior to the procedure.

For those patients taking insulin, holding the dose of prandial insulin will continue basal insulin allows for adequate coverage of insulin needs and minimizes the risk of hypoglycemia. In those taking oral hypoglycemic medications, it may be advised to skip the morning dose of medications known to cause hypoglycemia (like sulfonylureas or thiazolidinediones), while those taking SGLT2 inhibitors or dipeptidyl peptidase-4 inhibitors may be able to take their regularly scheduled medications. Metformin is typically held prior to procedures in the event that contrast dye needs to be used.

Special Considerations

Certain clinical cases warrant special recommendations for glycemic control in hospitalized patients:

• Perioperative management of major surgical patients
• Use of enteral nutrition and parenteral nutrition by tube feeding
• Ongoing glucocorticoid therapy
• Use of other medications affecting glucose metabolism such as SGLT-2 inhibitors
• Patients who are post-myocardial infarction
• Type 1 diabetes managed on insulin pump therapy

Approaches to Inpatient Glycemic Management

Inpatient glycemic management requires a number of strategies, including insulin management, oral and injectable hypoglycemic agents, and dietary modifications.

Insulin is the mainstay of hyperglycemic treatment for most hospitalized patients due to its predictability, titratability, and safety within organ dysfunction. Insulin requirements vary, so it is vital to individualize the treatment approach for hyperglycemia to ensure optimal health outcomes.

The Endocrine Society Clinical Practice Guidelines suggest that scheduled insulin therapy is preferred over oral or injectable diabetes management in the initial hospitalization period for non-critically-ill patients with a recent glycosylated hemoglobin (HbA1c) ≥ 7.5% or who are managed on insulin in the outpatient setting.

Insulin Therapy

Insulin administration may be by subcutaneous injections, insulin infusion pumps, or intravenous insulin infusions, depending on the patient’s clinical status, individual health factors, and level of hyperglycemia. In most patients who are continuing oral intake, the preferred method of insulin treatment includes basal, prandial, and correction scale components.

Insulin Intravenous Infusion

Continuous insulin intravenous infusion is the preferred management of patients in diabetic ketoacidosis, hyperglycemic hyperosmolar state, and other critically ill states. It allows for real-time adjustment of insulin rates based on glycemic variability, volume status, acid-base levels, and oral intake. Insulin infusion protocols give a defined insulin concentration, based on an algorithm with predefined dosage adjustments to achieve optimal glycemic control.

Insulin Pump Infusion

The increasing use of insulin pumps has been shown to improve glycemic control and overall patient outcomes, delivering insulin in a basal-bolus pattern with continuous glucose monitoring, designed to mimic the physiologic release of insulin from the pancreas.

For many patients, the use of the insulin pump has allowed them to achieve excellent glycemic control. In some cases, for patients with type 1 diabetes mellitus who are managed on an insulin pump, these can be continued in the hospital setting. However, this necessitates care by endocrinologists who are trained in the appropriate use of these devices. The American Diabetes Association advocates for the establishment of institutional policies dictating the safe use of insulin pumps during a hospital stay.  There is also the risk of inadvertent discontinuation of the pump during surgical or imaging procedures which may lead to the development of diabetic ketoacidosis.

Basal Insulin

Ongoing insulin management is best achieved through intermediate-acting or long-acting insulin forms.

Intermediate-acting insulin forms include NPH regular insulin, which is typically given every 12 hours based on its half-life. NPH insulin begins to lower glucose within one hour, peaks at 4-6 hours, and lasts for about 12 hours.

Long-acting (basal) forms of insulin include glargine, detemir, or degludec. Long-acting insulin typically takes effect within 1-2 hours, peaks at 5-6 hours, and lasts for 12-24 hours, depending on the formulation.

Bolus Insulin

Short-acting insulin (or rapid-acting insulin), such as aspart, lispro, and glulisine, are typically used as bolus (prandial), sliding scale, and correction scale insulins.

These start working within 15 minutes, peak at 1-2 hours, and last for 4-6 hours. The dosing of bolus insulin should be distributed evenly between meals whenever possible, but it should not be given when meals are skipped.

Basal-Bolus Insulin

Basal-bolus insulin regimens are designed to mimic physiological insulin secretion, providing a continuous level of baseline insulin through long-acting basal forms, plus a bolus of insulin given at mealtimes to aid in metabolizing carbohydrates.

The initial total daily dose of insulin should be estimated as 0.3-0.6 units per kilogram of body weight. The typical divided dosing of basal-bolus regimens includes half of the total daily dose of insulin given as a basal dose once daily, while the other half of the total daily dose is given as short-acting insulin divided over three meals.

Basal-bolus regimens of subcutaneous insulin are preferred for patients in the non-critically ill setting for more optimal glycemic control and is the only dosing modality for patients with Type 1 diabetes.

Correction Insulin

Correction insulin allows for the patient to receive additional short-acting insulin based on the content of their meals, thus reaching tighter glycemic control.

According to a guideline in the J Clin Endocrinol Metab, carbohydrate counting offers appropriate insight into the corrective insulin dosing. It is an important component of a basal-bolus insulin regimen, adding an extra layer of fine-tuning to patients’ glucose management.

Sliding Scale Insulin

Sliding-scale insulin regimens are commonly used for inpatient hyperglycemic control. However, studies suggest that using sliding-scale insulin as the only method of glucose control should only be used in certain cases and is generally not recommended.

A sliding scale approach is 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 worsened hyperglycemia.

A blood glucose < 140 mg/dL on admission has predicted good success with sliding scale insulin in the hospital setting.

Non-Insulin Therapy

The Endocrine Society Clinical Practice Guidelines suggest that non-critically-ill hospitalized patients who have a recent hemoglobin A1c (HbA1c) < 7.5% and who are not treated with insulin in the outpatient setting may be continued on select non-insulin therapies.

Metformin

Inpatient metformin use has traditionally been avoided, as a result of a theoretical risk of lactic acidosis. However, the incidence of lactic acidosis as a result of metformin use has been estimated at 2-5 cases per 100,000 patients, which is similar to the risk in non-metformin treated patients. Metformin use has a number of demonstrated benefits:

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

However, it is necessary to weigh the risks and benefits of metformin use in the inpatient setting. Its potential for gastrointestinal side effects and contraindication of use in glomerular filtration rate < 30 mL/min must be considered for patient safety.

DPP4 Inhibitors

Dipeptidyl peptidase-4 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.

SGLT2 Inhibitors

While sodium-glucose-cotransporter-2 inhibitors have demonstrated benefit in reducing heart failure mortality and hospitalization and reduced incidence of diabetes-related kidney disease, they are not recommended for use in the management of inpatient hyperglycemic control. They increase the risk of many complications:

• Hypovolemia
• Urinary tract infections
• Diabetic ketoacidosis
• Euglycemic diabetic ketoacidosis

The failure to hold these agents prior to hospitalization when a major surgical procedure is planned may lead to the development of euglycemic DKA if the patient has limited carbohydrate intake.

GLP-1 Receptor Agonists

Glucagon-like peptide-1 receptor agonists are known to be effective in achieving glycemic control and promoting weight management in the outpatient setting. However, little evidence from randomized controlled trials is available to establish their safety and efficacy for inpatient diabetes management.

Inpatient Glucose Monitoring

Point-of-Care Glucose Checks

Point-of-care glucose checks should be performed pre-meal and pre-bedtime in non-critically ill patients who are tolerating a typical diet.

In patients who are NPO, glucose checks should be performed every 4-6 hours. In patients who are critically ill, glucose checks should be at intervals to ensure adequate glycemic monitoring.

Continuous Glucose Monitoring

Continuous glucose monitoring (CGM) is performed by a wearable device that provides continuous, real-time glucose values, and its accuracy is expected to be within 15 mg/dL higher or lower than capillary blood glucose checks. CGM is useful for a number of patient populations:

• Patients at high risk of hypoglycemia (age ≥ 65 years, BMI < 27 kg/m2, total daily insulin dose ≥ 0.6 units/kg, or glomerular filtration rate < 60 mg/dL)
• Patients on insulin infusion pumps
• Patients with other indications for tight glycemic control

Discharge Planning

Effective diabetes education and discharge planning ahead of the day of patient discharge from the hospital are integral components of inpatient glycemic management.

Providing patients with the knowledge and skills necessary to manage their diabetes after discharge helps reduce the risk of readmissions and improves long-term outcomes.

In many cases, as patients’ clinical conditions improve, their non-insulin outpatient diabetes management can be resumed. This includes improvement of kidney function, treatment of infection, resumed good oral intake, and restoration of volume status.

Endocrinology experts suggest resuming non-insulin therapies in stable patients prior to discharge as part of a coordinated care plan.

Diabetes education should include medical nutrition therapy by a licensed diabetes educator and/or registered dietitian for all hospitalized patients with diabetes and hyperglycemia.

Evidence-Based Guidelines

Healthcare providers should follow evidence-based guidelines for inpatient glycemic management. The Endocrine Society Clinical Practice Guidelines provide evidence-based recommendations for the management of inpatient hyperglycemia, emphasizing the importance of a multidisciplinary, individualized treatment approach. The American Diabetes Association provides Standards of Care in Diabetes, outlining general treatment goals and ensuring quality care. The Society of Critical Care Medicine provides treatment recommendations for critically ill patients. Adherence to evidence based guidelines is essential for optimal inpatient glycemic management, promoting patient safety and improved clinical outcomes.

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