What are the complications of hyperglycemia (high blood sugar) in the acute setting?

From the Guidelines

Acute hyperglycemia can lead to several serious complications that require prompt intervention, and the most recent guidelines recommend initiating insulin infusion therapy for critically ill adults with persistent severe hyperglycemia (≥ 10 mmol/L on two occasions [> 180 mg/dL]) 1. The most severe complications of hyperglycemia include diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), both of which can be life-threatening.

• DKA typically presents with blood glucose >250 mg/dL, arterial pH <7.3, bicarbonate <18 mEq/L, and positive ketones,
• while HHS features extreme hyperglycemia (>600 mg/dL), hyperosmolality (>320 mOsm/kg), and minimal ketosis. Other acute complications include:
• dehydration due to osmotic diuresis,
• electrolyte abnormalities (particularly potassium, sodium, and phosphate imbalances),
• increased risk of infection,
• impaired wound healing, and
• acute kidney injury. Neurological complications can manifest as altered mental status, confusion, or in severe cases, cerebral edema. Cardiovascular effects include increased risk of thrombosis, myocardial infarction, and stroke. Treatment involves insulin administration (typically starting with an IV insulin bolus of 0.1 units/kg followed by continuous infusion at 0.1 units/kg/hour),
• aggressive fluid resuscitation (1-2 L of normal saline in the first hour for adults),
• electrolyte replacement (particularly potassium when levels fall below 5.2 mEq/L), and
• addressing the underlying cause of hyperglycemia. Regular monitoring of glucose, electrolytes, and acid-base status is essential during treatment to prevent complications like hypoglycemia and hypokalemia, as recommended by the Society of Critical Care Medicine guidelines on glycemic control for critically ill children and adults 2024 1. The American Diabetes Association (ADA) and American Association of Clinical Endocrinology (AACE) similarly recommend initiation of insulin infusion therapy for critically ill adults with persistent severe hyperglycemia (≥ 10 mmol/L on two occasions [> 180 mg/dL]) 1. In addition, the U.S. Centers for Medicare and Medicaid Services has quality measures for hospital-acquired events to measure and report the rate of adults with one BG greater than or equal to 16.7 mmol/L (300 mg/dL) or multiple BG greater than or equal to 11.1 mmol/L (200 mg/dL) also for severe hypoglycemia (< 2.2 mmol/L [40 mg/dL]) plus criteria for failure to monitor adequately 1. It is also important to note that hyperglycemia is associated with poor immune response, increased cardiovascular events, thrombosis, inflammatory changes, delayed healing, and other problems, as stated in the American College of Physicians guideline 1. Furthermore, the American Heart Association/American Stroke Association guideline recommends maintaining the blood glucose in a range of 140 to 180 mg/dL in all hospitalized patients 1. However, the most recent guideline from the Society of Critical Care Medicine takes precedence, and initiating insulin infusion therapy for critically ill adults with persistent severe hyperglycemia (≥ 10 mmol/L on two occasions [> 180 mg/dL]) is the recommended approach 1.

From the FDA Drug Label

Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin Hyperglycemia can be brought about by any of the following: Omitting your insulin or taking less than your doctor has prescribed. Eating significantly more than your meal plan suggests. Developing a fever, infection, or other significant stressful situation. In patients with type 1 or insulin-dependent diabetes, prolonged hyperglycemia can result in DKA (a life-threatening emergency) The first symptoms of DKA usually come on gradually, over a period of hours or days, and include a drowsy feeling, flushed face, thirst, loss of appetite, and fruity odor on the breath. With DKA, blood and urine tests show large amounts of glucose and ketones. Heavy breathing and a rapid pulse are more severe symptoms If uncorrected, prolonged hyperglycemia or DKA can lead to nausea, vomiting, stomach pain, dehydration, loss of consciousness, or death.

The complications of hyperglycemia in the acute setting include:

• Diabetic Ketoacidosis (DKA): a life-threatening emergency that can occur in patients with type 1 or insulin-dependent diabetes
• Nausea and vomiting
• Stomach pain
• Dehydration
• Loss of consciousness
• Death These complications can arise if hyperglycemia is left uncorrected, and it is essential to obtain medical assistance immediately if symptoms persist or worsen 2.

From the Research

Complications of Hyperglycemia

• Hyperglycemia can lead to life-threatening complications such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) 3, 4, 5, 6, 7
• DKA is characterized by hyperglycemia, ketone body formation, and metabolic acidosis, while HHS is manifested by marked elevation of blood glucose, hyperosmolality, and little or no ketosis 7

Clinical Presentation and Management

• The clinical management of DKA and HHS involves careful evaluation and correction of the metabolic and volume status of the patient, identification and treatment of precipitating and comorbid conditions, a smooth transition to a long-term treatment regimen, and a plan to prevent recurrence 4
• Aggressive administration of intravenous fluids with appropriate replacement of electrolytes, primarily potassium, is the first step in acute management of these disorders, followed by administration of insulin in patients with DKA 3
• Common pitfalls in management include premature termination of intravenous insulin therapy and insufficient timing or dosing of subcutaneous insulin before discontinuation of intravenous insulin 3

Prevention and Mortality

• Hyperglycemic emergencies are usually preventable but depend on patient compliance and adherence as well as medical infrastructure 6
• The mortality rates of DKA and HHS remain high, with DKA mortality rates between 3.4% and 4.6% and HHS mortality rates approximately 15% 7
• Improved patient education and implementation of measures such as home glucose and ketone monitoring might decrease the number of hospital admissions due to DKA and HHS 7