Hyperosmolar Hyperglycemic State (HHS) is a severe, life-threatening metabolic complication of diabetes, primarily affecting individuals with Type 2 diabetes. HHS is characterized by extremely high blood sugar levels and profound dehydration, requiring immediate medical intervention. The mortality rate associated with HHS is significantly higher than that of diabetic ketoacidosis (DKA).
Understanding Hyperosmolar Hyperglycemic State (HHS)
The core mechanism of HHS involves a relative deficiency of insulin paired with increased levels of counterregulatory hormones, such as cortisol and growth hormone. This hormonal imbalance leads to three distinct biological changes: extreme hyperglycemia, hyperosmolarity, and the absence of significant ketosis. The lack of effective insulin prevents glucose from entering the cells, causing a massive accumulation of sugar in the bloodstream.
The blood glucose concentration in HHS often exceeds 600 milligrams per deciliter (mg/dL), which is more than six times the normal range. This extreme level of glucose overwhelms the kidneys’ capacity to reabsorb sugar, leading to a process called osmotic diuresis. The glucose acts as a powerful solute, pulling large amounts of water and electrolytes from the body into the urine, resulting in severe total body water loss, sometimes exceeding 10 liters.
This massive fluid loss concentrates the blood, leading to hyperosmolarity, typically above 320 milliosmoles per kilogram (mOsm/kg). The high osmolality causes water to shift out of the body’s cells, including brain cells, contributing to neurological symptoms. HHS is “nonketotic” because the body produces just enough circulating insulin to prevent the large-scale breakdown of fat (lipolysis).
Since fat breakdown is suppressed, the production of acidic ketone bodies is inhibited, which distinguishes HHS from DKA. The prolonged osmotic diuresis leads to a more gradual onset of symptoms. Consequently, patients often present with a much more profound state of dehydration.
Recognizing the Critical Symptoms
The clinical presentation of HHS is marked by signs of severe dehydration and noticeable neurological changes, often developing slowly over several days or weeks. Patients typically experience excessive thirst, known as polydipsia, and frequent urination, called polyuria, as the kidneys attempt to excrete the excess glucose. As dehydration worsens, the body cannot sustain this output, and urination may actually decrease.
Observable physical signs of profound dehydration include dry mucous membranes, decreased skin turgor, and sunken eyes. The concentrated blood and resulting hyperosmolarity cause fluid to be drawn from brain cells, which directly contributes to the spectrum of neurological symptoms. This can manifest as confusion, lethargy, or altered mental status.
In more severe cases, patients may exhibit focal neurological deficits that mimic a stroke, such as temporary paralysis or weakness, or experience seizures. If the hyperosmolarity is not corrected, the patient’s level of consciousness can deteriorate further into stupor or coma.
Acute Medical Management and Hospital Care
The primary goal of treating HHS is aggressive rehydration to restore circulating volume. This involves the rapid intravenous (IV) administration of isotonic saline solution, such as 0.9% sodium chloride. Fluid replacement must be started immediately because the total body water deficit is substantial, often exceeding 10 liters.
The initial rehydration alone often starts to lower the blood glucose concentration by diluting the blood and improving kidney function. Insulin therapy is intentionally delayed until fluid resuscitation is well underway and serum potassium levels are known and stabilized. Starting insulin too early can cause a rapid shift of water and potassium into the cells, leading to circulatory collapse or dangerously low potassium levels.
Once adequate rehydration has been achieved, low-dose IV insulin is typically administered to safely facilitate glucose uptake by cells and further lower blood sugar. The goal is a gradual reduction in plasma glucose and osmolality to prevent sudden fluid shifts that could lead to cerebral edema. The rate of glucose reduction is closely monitored, with a target plasma glucose level between 250 and 300 mg/dL during the initial acute management phase.
Careful monitoring and correction of electrolyte imbalances, particularly potassium, is also a continuous process during acute care. While initial potassium levels may appear normal or even high due to dehydration, the overall body stores are often depleted. Insulin therapy will drive potassium into the cells, so potassium replacement is administered intravenously as needed to maintain safe levels throughout the course of treatment.
Identifying Triggers and Long-Term Prevention
HHS does not occur without a precipitating event, and an acute illness is the most common trigger, accounting for 50% to 60% of cases. Infections, such as pneumonia or urinary tract infections, are frequent culprits because they cause physiological stress that raises counterregulatory hormone levels, worsening hyperglycemia. Other triggers include new-onset Type 2 diabetes or acute cardiovascular events like a stroke or heart attack.
Certain medications can also contribute, including glucocorticoids (steroids), which impair glucose tolerance, and some diuretics, which increase fluid loss. A lapse in proper diabetes management, such as missing prescribed insulin or oral medication doses, or inadequate water intake, also significantly increases risk.
Preventing this severe complication centers on consistent diabetes management and proactive “sick day” planning. Individuals with diabetes should have a clear plan for monitoring blood sugar and ketone levels when they are ill. It is important to maintain adequate fluid intake, even if appetite is low, and to know when to contact a healthcare provider for medication adjustments during periods of illness.