Definition

Diabetes mellitus is a metabolic disorder that affects the metabolism of key nutrients like protein, fat, and carbohydrates. In 2019, diabetes affected approximately 9.3% of the global population, or about 463 million people. Due to the high prevalence of diabetes, hyperglycemic crises are commonly encountered in emergency departments.

A hyperglycemic crisis is a serious, potentially life-threatening complication of diabetes mellitus, which can occur in both type 1 and type 2 diabetes patients. There are two primary types of hyperglycemic crises:

1. Diabetic ketoacidosis (DKA) involves elevated blood sugar, increased ketone bodies in the blood, and increased blood acidity.
2. Nonketotic hyperosmolar hyperglycemia (HHS) is characterized by extremely high blood sugar levels (>600 mg/dL), severe dehydration, hyperosmolarity (a high concentration of salts, glucose, and other substances in the blood), without the buildup of acids, and may involve decreased consciousness.

Despite advances in diagnostic criteria and treatment protocols, DKA and HHS continue to cause morbidity and mortality in diabetes patients. The mortality rate for DKA is under 1%, while for HHS, it can be as high as 15%. Early diagnosis, comprehensive laboratory assessment, and effective treatment are crucial for the successful management of hyperglycemic crises.

Causes

Both hyperglycemic crises result from reduced insulin levels, which play a critical role in regulating blood sugar. In DKA, there is a significant drop in insulin production. In HHS, the insulin produced becomes ineffective. Additionally, an increase in glucagon and cortisol hormones, which enhance sugar production in the liver, is observed.

Diabetic Ketoacidosis (DKA)

In DKA, there is a disruption in the metabolism of carbohydrates, proteins, and fats. The rise in blood sugar (hyperglycemia) results from the following mechanisms:

• Increased glucose production (gluconeogenesis).
• Enhanced breakdown of glycogen (the liver’s sugar reserve) into glucose.
• Reduced glucose utilization by the liver, muscle, and fat cells, despite the abundance of glucose in the blood.

With low insulin levels, glucose in the bloodstream cannot enter cells for energy conversion. Consequently, the liver breaks down fats for energy, producing acidic ketone bodies. Excessive accumulation of these ketones leads to blood becoming acidic.

Nonketotic Hyperosmolar Hyperglycemia (HHS)

In HHS, insulin production is only mildly reduced, preventing the breakdown of fat and the formation of ketone bodies. However, insulin resistance prevents the body from using existing insulin to transport glucose into cells. As a result, blood sugar accumulates to extremely high levels and remains unavailable for energy use.

The increase in blood sugar levels and fluid loss in cells is much more significant in HHS compared to DKA.

Risk Factor 

The risk factors for DKA include:

• Female gender.
• Black race.
• Low socioeconomic status.
• Diabetes mellitus patients younger than 45 years.
• Missed insulin doses or incorrect insulin administration.
• Substance abuse (alcohol or drugs).
• Psychiatric disorders.
• Previous history of diabetic ketoacidosis.
• Severe injury or infection.

Similarly, risk factors for HHS include:

• Serious infections and injuries.
• Cardiovascular conditions such as heart attack or stroke.
• Use of certain medications, such as diuretics that increase urine production.
• Missed insulin doses or improper insulin dosing.

Symptoms

DKA typically develops rapidly, within hours after a trigger. In contrast, HHS progresses more slowly, over days to weeks. Common symptoms of both DKA and HHS result from high blood sugar levels, including:

• Increased urination frequency.
• Excessive hunger and thirst.
• Weight loss.
• General body weakness.
• Signs of dehydration or fluid deficiency may also appear:

• • Dry lips or mouth.
  • Sunken eyes.
  • Poor skin elasticity.
  • Rapid heart rate.
  • Low blood pressure.
  • In severe cases, shock.

Diabetic Ketoacidosis (DKA)

In DKA, the accumulation of ketone bodies and acidosis (decreased blood pH) can produce additional symptoms such as:

• Rapid, deep breathing.
• Acetone-like breath odor.
• Nausea or vomiting.
• Severe abdominal pain.
• Rarely, decreased consciousness or coma.

Nonketotic Hyperosmolar Hyperglycemia (HHS)

In HHS, along with weakness and dehydration, symptoms related to the nervous system can develop, such as:

• Visual disturbances.
• Hallucinations.
• Seizures.
• Decreased consciousness or coma.

Diagnosis

For suspected hyperglycemic crises in diabetes mellitus patients, physicians may perform several laboratory tests, including:

• Complete blood count.
• Blood glucose and HbA1c levels.
• Kidney function tests (urea and creatinine).
• Blood ketone levels.
• Electrolyte levels.
• Blood osmolality (concentration of dissolved particles).
• Urine ketone test.
• Blood gas analysis.

Additional tests, such as an EKG, blood cultures, sputum analysis, or a chest X-ray, may be done based on clinical indications.

Management

The main objectives of managing a hyperglycemic crisis are:

• Restoring fluid volume, blood flow, and oxygen delivery to tissues.
• Gradually reducing blood sugar levels and viscosity.
• Correcting electrolyte imbalances.
• Identifying and addressing the underlying causes of the hyperglycemic crisis.
• Providing timely treatment.

Patients will be continuously monitored for response to therapy. Key aspects of hyperglycemic crisis management include:

• Fluid therapy to correct dehydration, using isotonic saline infusion at 15-20 ml/kg of body weight per hour, or 1-1.5 liters for the first hour. The choice of infusion depends on the patient's condition.
• Potassium supplementation if potassium deficiency is present.
• Phosphate supplementation may be considered for patients with complications from low phosphate levels.
• Sodium bicarbonate therapy is controversial in DKA but may be administered.
• Insulin therapy can be initiated once potassium levels exceed 3.3 mmol/L to gradually lower blood sugar.

Complications

Common complications of DKA and HHS include hypoglycemia (low blood sugar) and hypokalemia (low potassium) due to excessive insulin or bicarbonate therapy. Severe hypokalemia and hypoglycemia significantly raise the risk of mortality in hyperglycemic crises.

Cerebral edema, a potentially fatal complication of DKA, affects 0.7-1.0% of children, particularly those newly diagnosed. This complication may also occur in individuals with a longstanding history of diabetes, especially those under 20. Symptoms of brain swelling include reduced consciousness, restlessness, drowsiness, and headache. Headaches typically precede changes in consciousness, followed by nervous system issues such as seizures, urinary and bowel disturbances, slow heart rate, and respiratory arrest. This can occur rapidly due to brainstem compression.

The mortality rate for HHS is higher than for DKA and depends on the severity of comorbid conditions. Severe dehydration, advanced age, and the presence of comorbidities increase the risk of death from HHS.

Prevention

For individuals with diabetes mellitus, there are several steps that can be taken at home to help prevent the onset of DKA and HHS, including:

• Regularly monitor blood sugar levels, especially more frequently when feeling unwell.
• Take medications as prescribed by the doctor and on time.
• Maintain blood sugar levels within the target range set by the healthcare provider.
• Discuss any changes in medications or insulin requirements due to dietary or exercise adjustments with a healthcare professional.

When to See a Doctor?

A hyperglycemic crisis is a medical emergency that requires immediate attention. People with diabetes should seek urgent medical help if they experience a significant deterioration in their condition and discover very high blood sugar levels.

Additionally, individuals with diabetes should check their blood sugar levels if they notice early symptoms of hyperglycemia, such as excessive thirst or an increase in urination frequency.

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