What is the difference between Hyperosmolar Hyperglycemic State (HHS) and Diabetic Ketoacidosis (DKA)?

From the Guidelines

Hyperosmolar Hyperglycemic State (HHS) and Diabetic Ketoacidosis (DKA) are distinct acute complications of diabetes, with HHS typically characterized by extreme hyperglycemia, hyperosmolarity, and severe dehydration, whereas DKA is marked by significant ketone production, metabolic acidosis, and lower glucose levels. The most recent and highest quality study, 1, highlights the importance of individualized treatment based on careful clinical and laboratory assessment.

Key Differences

• HHS usually occurs in type 2 diabetes, with blood glucose >600 mg/dL, hyperosmolarity >320 mOsm/L, and severe dehydration without significant ketosis or acidosis.
• DKA predominantly affects type 1 diabetics, presenting with lower glucose levels (typically 250-600 mg/dL), significant ketone production, and metabolic acidosis (pH <7.3).

Pathophysiology and Clinical Presentation

• HHS results from relative insulin deficiency, leading to uncontrolled glucose levels but sufficient insulin to prevent ketogenesis.
• DKA stems from absolute insulin deficiency, resulting in uncontrolled fat breakdown and ketone production.
• Clinically, HHS patients often present with more severe dehydration, altered mental status, and a gradual onset, whereas DKA develops rapidly with symptoms like nausea, vomiting, abdominal pain, and Kussmaul breathing.

Treatment and Management

• Treatment for both includes fluid resuscitation and insulin therapy, but HHS requires more aggressive fluid replacement due to severe dehydration.
• DKA management emphasizes correcting acidosis and electrolyte imbalances.
• The most effective approach to managing DKA and HHS involves continuous intravenous insulin in critically ill patients, with a focus on restoring circulatory volume, resolving hyperglycemia, and correcting electrolyte imbalances, as recommended by 1.

Mortality Rates

• HHS carries a higher mortality rate (up to 20%) compared to DKA (1-5%), particularly due to older age and comorbidities of affected patients, as noted in 1.

From the FDA Drug Label

Hyperglycemia, diabetic ketoacidosis, or hyperosmolar coma may develop if the patient takes less Humulin R U-100 than needed to control blood glucose levels Early signs of diabetic ketoacidosis include glycosuria and ketonuria Polydipsia, polyuria, loss of appetite, fatigue, dry skin, abdominal pain, nausea and vomiting and compensatory tachypnea come on gradually, usually over a period of some hours or days, in conjunction with hyperglycemia and ketonemia.

The main difference between Hyperosmolar Hyperglycemic State (HHS) and Diabetic Ketoacidosis (DKA) is not explicitly stated in the provided drug label. However, it can be inferred that:

• DKA is characterized by ketonuria and hyperglycemia.
• The label does not provide a clear distinction between HHS and DKA. Therefore, based on the provided information, no conclusion can be drawn about the difference between HHS and DKA 2.

From the Research

Difference in HHS and DKA

• HHS and DKA are two acute complications of diabetes associated with high mortality rates if not efficiently and effectively treated 3.
• The main difference between HHS and DKA is the presence of significant ketosis in DKA, whereas HHS is characterized by marked hyperglycemia and hyperosmolality with little or no ketosis 4.
• Mortality rates for DKA are generally lower than for HHS, with a mortality rate of less than 1% in the US, compared to 5-16% for HHS 3, 4.
• Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg, marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), and without significant acidosis (pH >7.3) 5.
• DKA is characterized by hyperglycemia, ketone body formation, and metabolic acidosis, with precipitating causes usually being infection or insulin omission 4.
• The treatment of both DKA and HHS involves aggressive rehydration, insulin therapy, electrolyte replacement, and treatment of underlying precipitating events 6, 7.
• The prognosis of both conditions is substantially worsened in patients > 65 years of age and in the presence of coma and hypotension 4.