Last Modified: 2:20pm 16/04/2021

Causes of HHS

Hyperosmolar hyperglycaemic state(HHS) is a serious acute metabolic complication of diabetes mellitus that is characterized by hyperglycaemia (>600 mg/dl), hyperosmolarity (>330 mOsm/L) and, dehydration without ketosis or acidosis.

Hyperosmolar hyperglycaemic state is the most serious complication in patients with type 2 diabetes mellitus and whenever it occurs, it is a medical emergency

It usually occurs in middle aged or elderly individuals with type 2 diabetes mellitus and it may be the presenting feature in around 25% of individuals.

HHS is the type 2 diabetes equivalent of diabetic ketoacidosis (DKA) in type 1 diabetes individuals. Its metabolic differences occur because in individuals with type 2 diabetes mellitus there is a small quantity of insulin remaining enough to suppress lipolysis and the associated acidosis.

This complication is more common is Afro-Caribbean.

HHS occurs less frequently when compared to diabetic ketoacidosis but once it occurs it has a higher mortality rate of about 15%.


The main triggers for hyperglycaemic hyperosmolar state is a relative insulin deficiency and inadequate fluid intake. The state of insulin deficiency impairs glucose utilization in skeletal muscle and increases the production of glucose in the liver through glycogenolysis and gluconeogenesis process.

Failure of glucose entry to cells for utilization causes an increase in the levels of the counter-regulatory hormones(catecholamines) as a result of increased gluconeogenesis, hastened conversion of glycogen to glucose, and inadequate utilization of glucose by peripheral tissues due to insulin resistance.

High blood glucose level (hyperglycaemia) causes osmotic diuresis that leads to intravascular volume depletion. Together with dehydration, the hydration status of the individual is exacerbated.

Since the insulin deficiency in hyperglycaemic hyperosmolar state is relative and not absolute deficiency, there is no development of ketosis because the available insulin is sufficient to prevent production of ketone bodies. There is also a possibility that the liver is less capable of ketone body synthesis or the available insulin/glucagon ratio does not favour ketogenesis.

HHS is associated with lower levels of counterregulatory hormones and free fatty acids have than in DKA in some studies.
Patients who present with severe hyperglycaemia have higher chances of developing osmotic diuresis, severe dehydration and polyuria. This leads to development of severe dehydration and the patient would eventually enter a hyperosmolar state. Due to this reason, patients in hyperosmolar hyperglycaemic state usually have a much higher serum glucose level when compared to those with diabetic ketoacidosis.

Normally, a severe hyperglycaemia draws water from the cells as a result of a created osmolar gradient leading to diuresis; therefore, these patients in hyperosmolar hyperglycaemic state have severe dehydration, a contraction in the extracellular and the intracellular volume.


Ref: Hyperosmolar Hyperglycemic State (HHS) Symptoms and Treatment | Medcrine