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Patients who have HHS are usually older type 2 diabetics with the gradual onset of polydipsia, polyuria, and lethargy. They become extremely dehydrated, with reduction in urinary output, and have very high serum glucose levels, accompanied by alterations in mental status.


  1. Epidemiology

    1. Risk factors include older age, nursing home residence, inability to recognize thirst, and lack of access to fluids.

    2. Mortality rate is 5–6%, compared to < 2% in patients with DKA.

  2. Pathogenesis

    1. Reduced effective insulin concentrations and a concomitant increase in counterregulatory hormones lead to increased hepatic and renal glucose production and impaired glucose utilization in peripheral tissues.

    2. Glycosuria leads to an osmotic diuresis with loss of free water in excess of electrolytes, leading to hyperosmolality.

    3. As volume depletion occurs, urinary output drops, and hyperglycemia worsens.

    4. Insulin levels are higher than in DKA and are adequate to prevent lipolysis and ketogenesis.

  3. Precipitating factors

    1. The 3 most common precipitants are infection, lack of compliance with insulin, and first presentation of diabetes.

    2. Other precipitants include postoperative state, cerebrovascular accident, MI, pancreatitis, alcohol abuse, trauma, thyrotoxicosis, and medications (eg, corticosteroids, atypical antipsychotic drugs [especially olanzapine and risperidone], total parenteral nutrition).

  4. Clinical manifestations

    1. History

      1. Symptoms and signs usually evolve over several days or even weeks.

      2. Common findings include polyuria followed by decreased urinary output, polydipsia, fatigue, and weight loss.

      3. Abdominal pain generally does not occur in HHS, as it does in DKA.

      4. Neurologic manifestations

        1. Lethargy and disorientation common

        2. Focal neurologic findings, including seizures, can occur with hyperglycemia and resolve with normalization of serum glucose.

        3. Changes in mental status correlate with the degree of hyperosmolarity.

          1. 20–25% present with coma.

          2. Coma is present in half of the patients with effective serum osmolality of ≥ 320 mOsm/L.

          3. Must search for another cause of altered mental status if osmolality < 320 mOsm/L

    2. Physical exam

      1. Hypothermia often seen resulting from peripheral vasodilation

      2. Signs of dehydration often seen (seeChapter 28, Acute Kidney Injury)

      3. Tachycardia and hypotension suggest severe dehydration or underlying sepsis.


  1. Typical total body water deficit is 20–25% (about 9 L).

  2. See Table 12-12 for laboratory findings in HHS compared with DKA.

Table 12-12.Laboratory findings in HHS and DKA.


  1. Patients with HHS generally need more fluid and less insulin than those with DKA.

  2. Figure 12-2 outlines ...

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