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Endocrinology - Inpatient Diabetes Management - Fast Facts | NEJM Resident 360

Differentiating between type 1 and type 2 diabetes (see Diabetes in this rotation guide) when a patient presents to the hospital is crucial to ensure safe management. Patients with diabetes are hospitalized for a range of reasons, including:

• Hyperglycemic Emergencies (diabetic ketoacidosis and hyperosmolar hyperglycemic state)

• Intercurrent Illness

• Perioperative Care

Hyperglycemic Emergencies

Diabetic ketoacidosis**(DKA)** and hyperosmolar hyperglycemic state**(HHS)** are the two hyperglycemic emergencies most frequently encountered in diabetes care. Both are conditions of insulin and volume deficiency, but they differ in the following ways:

• DKA is more common in patients with type 1 diabetes but can also occur in patients with type 2 diabetes, particularly in patients on a sodium–glucose cotransporter-2 (SGLT-2) inhibitor.

• HHS typically occurs in patients with type 2 diabetes and is characterized by high effective serum osmolality (>320 mOsm/kg), extreme hyperglycemia (>600 mg/dL), and severe volume depletion.

• DKA and HHS: A mixed picture of both DKA and HHS is more common in patients with long-standing type 2 diabetes who have entered the islet-cell exhaustion phase of disease. Attention to bicarbonate and ketone concentration is useful in this setting.

Precipitating Factors

DKA and HHS can be caused by:

• infection: the most common precipitating factor; always look for a source of infection

• discontinuation of or insufficient insulin therapy: common in young adult patients with type 1 diabetes; can also be iatrogenic if patients cannot eat or drink and are erroneously not given basal insulin

• pancreatitis

• cardiovascular event: myocardial infarction, acute coronary syndrome, stroke

• volume depletion: particularly for HHS

• pregnancy

• drugs that affect glucose metabolism:

• • glucocorticoids

  • sodium–glucose co-transporter 2 (SGLT-2) inhibitors, particularly euglycemic DKA

  • rarely, thiazides, sympathomimetic agents, pentamidine, conventional and atypical antipsychotics

Diagnosis

All patients with diabetes who are unwell should undergo capillary blood-glucose and ketone monitoring. In patients who have been admitted to the hospital or present to an emergency department with suspected glycemic emergency, testing for electrolytes, renal function, and blood gas should be considered.

The following table outlines the diagnostic criteria for DKA and HHS.

Diagnostic Criteria for DKA and HHS

	Mild DKA	Moderate DKA	Severe DKA	HHS
Plasma glucose (mg/dL)	>250	>250	>250	>600
Arterial pH	7.25–7.30	7.00 to <7.24	<7.00	>7.30
Serum bicarbonate (mEq/L)	15–18	10 to <15	<10	15
Urine ketone	Positive	Positive	Positive	Small
Serum ketone	Positive	Positive	Positive	Small
Effective serum osmolality	Variable	Variable	Variable	>320 mOsm/kg
Anion gap*	>10	>12	>12	Variable
Mental status	Alert	Alert/drowsy	Stupor/coma	Stupor/coma

(Reference: Diabetes Care, Hyperglycemic Crises in Adult Patients With Diabetes, American Diabetes Association, 2009. Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association.)

*To calculate the anion gap, use the following formula: [Na − (Cl + HCO3)]. Add 2.5 to the anion gap for every 1 g/dL decrease in serum albumin below the normal value of 4 g/dL.

The measured/uncorrected [Na+] should be used to calculate the anion gap. However, to correct sodium levels for hyperglycemia, add 1.6 mEq/L to the measured sodium level for every 100 mg/dL increase in the glucose level above a level of 100 mg/dL.

Treatment

The goal of treatment for hyperglycemic emergencies is to progressively restore the acid–base balance (in DKA) and ensure adequate volume repletion. The key components of management are:

**1.**Correct volume depletion.

• Isotonic saline is the initial fluid of choice until the patient’s intravascular volume has been restored.

• • Consider using 0.45% saline if the corrected sodium concentration is elevated.

• Add dextrose to intravenous (IV) fluid to prevent hypoglycemia when blood glucose decreases to approximately 300 mg/dL.

• Patients with HHS often have severe volume depletion and require higher volumes of IV fluid volumn repletion than those with DKA.

**2.**Reverse hyperglycemia.

• IV regular insulin is preferred because the clinical effect does not rely on absorption from subcutaneous tissues, which can be impaired in hyperglycemic emergencies due to poor tissue perfusion; it is also easy to titrate and has a short half-life.

• Subcutaneous rapid-acting insulin analogues (lispro and aspart) have been shown to be effective in the treatment of mild-to-moderate DKA in lieu of IV regular insulin.

• Subcutaneous regimens should be started after resolution of DKA/HHS once the patient is able to eat; a long-acting insulin should be overlapped with IV insulin for at least 1 to 2 hours.

**3.**Correct electrolyte imbalances.

• Check electrolytes, blood urea nitrogen (BUN), creatinine, venous pH, and glucose every 2 to 4 hours.

• Start potassium replacement when potassium is 5 mmol/L, renal function is known, and patient is producing urine. Aim to maintain potassium at 4 mmol/L.

• Patients are in a state of total body potassium depletion but may appear hyperkalemic (potassium is shifted out of cells and lost in urine); administer approximately 20 to 30 mEq of potassium with each liter of fluid to maintain normal serum potassium levels.

• Insulin will promote insulin shift intracellularly; initiation of insulin for treatment of DKA may therefore need to be delayed if the potassium is low.

4. Ensure prophylactic anticoagulation.

• Ensure that prophylactic anticoagulation is administered, because patients with DKA and HHS are at higher risk of venous thromboembolic disease due to the proinflammatory state.

Protocol for Management of Adult Patients with DKA or HHS

DKA diagnostic criteria: blood glucose 250 mg/dl, arterial pH 7.3, bicarbonate 15 mEq/l, and moderate ketonuria or ketonemia. HHS diagnostic criteria: serum glucose >600 mg/dl, arterial pH >7.3, serum bicarbonate >15 mEq/l, and minimal ketonuria and ketonemia. †15–20 ml/kg/h; ‡serum Na should be corrected for hyperglycemia (for each 100 mg/dl glucose 100 mg/dl, add 1.6 mEq to sodium value for corrected serum value). (Adapted from ref. 13.) Bwt, body weight; IV, intravenous; SC, subcutaneous.
(Reference: Diabetes Care, Hyperglycemic Crises in Adult Patients with Diabetes, American Diabetes Association, 2009. Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association.) 

When the hyperglycemic emergency has resolved, patients with DKA or HHS should be transitioned from IV to subcutaneous insulin. The following figure explains when and how to make this transition.

(Reprinted courtesy of Dr. Nadine Palermo, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital Diabetes Program 2022.)

Management of Diabetes in Noncritically Ill Hospitalized Patients

Both hypoglycemia and hyperglycemia are associated with adverse outcomes in hospitalized patients. Therefore, the goal of inpatient glycemic management is to prevent complications.

• Aim for blood-glucose concentration between 90–180 mg/dL throughout admission.

• • Patients with life-limiting illness or significant comorbidities can have more-relaxed targets.

  • Tighter glycemic control is not warranted and has been associated with increased morbidity and hypoglycemia.

• Insulin is the preferred method for controlling blood-glucose concentration in hospitalized patients; it can be administered as basal insulin, basal insulin with bolus correction, or via insulin infusion.

• • Hospitalized patients with type 1 diabetes require an insulin regimen with basal and correction components, and additional bolus prandial insulin if they are eating. A patient with type 1 diabetes should always receive basal insulin, even if fasting. Similarly, if the patient is using a continuous subcutaneous insulin infusion pump, it should be continued unless the patient is critically unwell and unable to manage it.

  • Hospitalized patients with type 2 diabetes usually have outpatient antidiabetic agents held due to concerns for glycemic variability, potential need for fasting, or other factors that can affect blood glucose while admitted. In most cases, the outpatient medications are replaced with insulin (basal, prandial, and correctional components) during admission in patients with type 2 diabetes during hospitalization. However, continuing the home medications may be considered in certain circumstances, primarily if a short hospitalization is expected and will not cause major disruptions to usual glycemic determinants.

  • In general, insulin for a patient with diabetes in the inpatient setting can be started at a dose of approximately 0.4 units/kg. Adjustments can be made depending on risk factors as described in the following guide.

Guide to Inpatient Management of Hyperglycemia

(Reprinted courtesy of Dr. Nadine Palermo, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital Diabetes Program.)

The following table outlines potential considerations for the use of noninsulin antihyperglycemic drugs in hospitalized adults with type 2 diabetes:

Considerations for Use of Noninsulin Antihyperglycemic Drugs in Hospitalized Adults

Drug	Consideration
Metformin	Can cause adverse effects in patients with severe kidney impairment
Withhold metformin if:
Patients are unwell and at risk of further deterioration in kidney function
Patients are undergoing surgical or diagnostic procedures with radiocontrast
SGLT-2 inhibitors	Associated with an increased risk of genitourinary infections, volume depletion, and development of DKA
Withhold SGLT-2 inhibitors in unwell patients
Sulfonylureas	Can cause hypoglycemia, especially if the patient is not on a normal diet or is fasting for procedures and tests
GLP-1 receptor agonists	Can exacerbate nausea, vomiting, and anorexia
DPP-4 inhibitors	Can exacerbate heart failure (saxagliptin, alogliptin)
Thiazolidinediones	Can cause fluid retention and exacerbate heart failure
Acarbose	Can cause gastrointestinal adverse effects

Abbreviations: SGLT-2, sodium–glucose co-transporter 2; DKA, diabetic ketoacidosis; GLP-1, glucagon-like peptide 1; DPP-4, dipeptidyl peptidase 4

(Reference: Diabetes: Management of Hyperglycaemia and Diabetes in Hospitalized Patients. Therapeutic Guidelines 2018**.)**

Perioperative Care

No robust studies have evaluated the best method for perioperative management of diabetes and hyperglycemia in the perioperative phase. However, the following approach can be considered:

• Ensure that patients with type 1 diabetes always have basal insulin coverage via insulin infusion or lower-dose (60%–80% of usual) of basal subcutaneous insulin and IV glucose.

• Target glucose range for the perioperative period is 80–180 mg/dL.

• Ensure that a perioperative assessment is performed in patients with high risk of ischemic heart disease, renal complications, or autonomic neuropathy.

• Withhold all oral antihyperglycemic agents the morning of surgery or procedure.

  • Sodium-glucose co-transporter 2 (SGLT2) inhibitors should be held 3 days prior to the procedure.

  • Glucagon-like peptide (GLP-1) agonists dosed weekly should be held the week of surgery.

• Monitor blood-glucose concentration at least every 4 hours in fasting patients and every hour in patients on insulin infusion.

• Insulin pumps can often be continued for short procedures.

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