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Diagnosis and Management of Type 2 Diabetes, 10th Edition, Ch 14, Pt2

Jan 15, 2011
Metabolic: Hyperosmolar Hyperglycemic Nonketotic Syndrome


Steve V. Edelman, MD
Robert R. Henry, MD

This acute metabolic complication is a life-threatening crisis with a high mortality rate that usually is seen in:


  • Elderly patients with Type 2 diabetes (particularly those in nursing homes without access to free water)
  • People with undiagnosed diabetes
  • Those with diabetes that is diagnosed after a long period of uncontrolled hyperglycemia

Pathophysiology of HHNS

Hyperosmolar hyperglycemic nonketotic syndrome has four key clinical features:

  • Severe hyperglycemia — blood glucose usually >600 mg/dL (>33.3 mM) and generally 1000 mg/dL to 2000 mg/dL (55.5 mM to 111.1 mM)
  • Absence of or slight ketosis
  • Plasma or serum hyperosmolality (>340 mOsm)
  • Profound dehydration.

In clinical practice, patients often are seen who have these characteristics but also have mild ketosis and acidosis. Although HHNS and DKA represent opposite ends of a continuum, many patients have some aspects of each syndrome. The two conditions have some similarity in pathophysiology, clinical signs and symptoms, and treatments, with certain important exceptions.

Symptoms and Signs of HHNS

Patients typically develop excessive thirst, confusion, and physical signs of severe dehydration. A comparison of the key features of HHNS and DKA is shown in Table 14.3; several important differences exist in the symptoms and signs:

  • GI symptoms usually are milder in HHNS than in DKA in the absence of ketosis and acidosis.

Because of a lack of severe GI problems (which prompt patients with DKA to seek medical attention within 1 to 2 days), patients with HHNS may tolerate polyuria and polydipsia for weeks and consequently lose significant quantities of fluids and electrolytes before seeking help. Average fluid loss in HHNS is 9 L vs 6.5 L in DKA.

  • Kussmaul’s respiration is rarely observed because of a lack of severe acidosis.
  • Decreased mentation (mild confusion, lethargy) and lack of normal responsiveness are common and correlate best with serum osmolality. These are the usual reasons that patients with HHNS seek medical attention.
  • Focal neurologic signs may be present and may mimic a cerebrovascular event (hemisensory deficits, hemiparesis, aphasia, seizures); these signs decline as biochemical status returns to normal.

A diagnosis of HHNS usually is easily made if one has a high index of suspicion. Patients may be admitted to the neurology or neurosurgical service because only neurologic conditions are considered initially. Routine urine and blood tests can help clarify the diagnosis of HHNS. Health care professionals need to be alert for signs of HHNS in patients at chronic-care facilities because this diagnosis tends to be overlooked in such settings.


Typical laboratory values in HHNS are shown in Table 14.3.


Lifesaving measures may be needed immediately. The primary treatment goal is rehydration to restore circulating plasma volume and correct electrolyte deficits. In addition, the precipitating event should be identified and corrected, and other goals similar to those described for treatment of DKA should be instituted, including providing adequate insulin to restore and maintain normal glucose metabolism. Glucose concentration is the major biochemical end point because patients with HHNS do not have ketosis or acidosis. 

  • CV status should be monitored closely and frequently during fluid replacement to avoid Precipitating CHF, given the fact that most patients with HHNS are older and have preexisting heart disease.
  • Insulin is administered in the same manner as in patients with DKA. At glucose concentrations of 250 mg/dL, the rate of insulin infusion should be decreased to 2 to 3 U/h and dextrose should be added to the IV fluid because oral intake will not be possible for many hours to a few days.
  • Dextrose (50 g) should be given intravenously every 8 hours and insulin dose adjusted accordingly (decreased 1 to 3 U/h) based on plasma glucose measurements every 4 hours.
  • Potassium replacement follows the same guidelines as for DKA, with consideration of the special conditions of patients with HHNS (underlying renal disease is associated with lower urinary potassium losses; preexisting heart disease is associated with greater susceptibility to the effects of potassium).
  • Bicarbonate therapy is contraindicated in absence of acidosis.
  • Phosphate replacement follows the same guidelines as for DKA, with consideration of the effect of phosphate on underlying renal disease.
Metabolic: Hypoglycemia

This metabolic problem occurs in both Type 1 and less commonly in Type 2 diabetes when there is an imbalance between food intake and the appropriate dosage and timing of drug therapy (oral agents, insulin). Other factors that contribute to hypoglycemia are:

  • Exercise
  • Alcohol intake
  • Other drugs
  • Decreased liver or kidney function.
Signs of Hypoglycemia

The incidence of hypoglycemia in patients with Type 2 diabetes is several orders of magnitude lower than in Type 1 diabetes. Nonetheless, patients taking insulin, SFUs, and/or glinides are prone to hypoglycemia.

Hypoglycemia should be suspected in patients who demonstrate the following clinical signs; a diagnosis of hypoglycemia is confirmed in a symptomatic patient if a plasma glucose level <60 mg/dL (<3.3 mM) is found:

  • Mild hypoglycemia is associated with adrenergic or cholinergic symptoms such as:
    • Pallor
    • Diaphoresis
    • Tachycardia
    • Palpitations
    • Hunger
    • Paresthesias
    • Shakiness
  • Moderate hypoglycemia (<40 mg/dL) is associated with neuroglycopenic symptoms of altered mental and/or neurologic functioning such as:
    • Inability to concentrate
    • Confusion
    • Slurred speech
    • Irrational or uncontrolled behavior
    • Slowed reaction time
    • Blurred vision
    • Somnolence
    • Extreme fatigue
  • Severe hypoglycemia (<20 mg/dL) is associated with extreme impairment of neurologic function to the extent that the assistance of another person is needed to obtain treatment; symptoms include:
    • Completely automatic/disoriented behavior
    • Loss of consciousness
    • Inability to arouse from sleep
    • Seizures
  • Nocturnal hypoglycemia is associated with over 50% of cases of severe hypoglycemia; early symptoms do not awaken patients and the predinner intermediate-acting insulins may cause hyperinsulinemia and hypoglycemia in the early morning hours.

It is important to understand that hypoglycemia does not necessarily progress in a linear fashion from mild to severe. For example, some patients might develop neuroglycopenic symptoms before adrenergic or cholinergic symptoms, and other patients may overlook or ignore adrenergic or cholinergic symptoms and progress to neuroglycopenia.


The goal of treatment is to normalize the plasma glucose level as quickly as possible:

  • Mild hypoglycemia is treated most effectively by having the patient ingest approximately 15 g of readily available carbohydrate by mouth. Sources of carbohydrate (15 g) include:
    • Three glucose tablets (5 g each)
    • ½ cup fruit juice
    • 2 tablespoons raisins
    • Five Lifesavers candy
    • ½ to ¾ cup regular soda (not diet)
    • 1 cup milk
 If symptoms continue, treatment may need to be repeated in 15 minutes. Most patients can resume normal activity following treatment.
  • For moderate hypoglycemia, larger amounts of carbohydrate (15 to 30 g) that are rapidly absorbed may be needed. Patients usually are instructed to consume additional food after the initial treatment and wait approximately 30 minutes before resuming activity. Measuring blood glucose levels during treatment and the recovery periods can help determine the effectiveness of treatment. Some patients, however, may continue to have neuroglycopenic symptoms for an hour or longer after blood glucose levels have increased to above 100 mg/dL.
  • Severe hypoglycemia requires rapid treatment. IV glucose (50 cc 50% dextrose or glucose followed by 10% dextrose drip) is the most effective route; however, glucagon (1 mg for adults) can be administered intramuscularly at home with positive results. Several emergency kits for intramuscular administration of glucagon by a family member or friend are available from Lilly (glucagon for injection vials and emergency kit) and Novo Nordisk (BlucaGen HypoKit). Individuals who are unable to swallow should be given glucose gel, honey, syrup, or jelly on the inside of the cheek. After the initial response, a rapid-acting, carbohydrate-containing liquid should be given until nausea subsides; then a small snack or meal can be consumed. Blood glucose levels should be monitored frequently for several hours to assure that the levels remain normal and to avoid over treatment. The individual’s health care team should be informed of any severe hypoglycemic episodes.         
Prevention of Hypoglycemia

Patients can take certain measures to avoid hypoglycemia:

  • Know the signs and symptoms of hypoglycemia.
  • Try to eat meals on a regular schedule.
  • Carry a source of carbohydrate (at least 10 to 15 g).
  • Perform SMBG regularly for early detection of low blood glucose levels; initiate treatment at the first signs of hypoglycemia.
  • Take regular insulin at least 30 minutes before eating. (Patients who take their regular insulin immediately before or after a meal will be prone to delayed hypoglycemia.) A fast-acting insulin analogue should be taken 5 minutes before consumption of meal.
  • Schedule exercise appropriately; adjust meal times, caloric intake, or insulin dosing to accommodate physical activity; use SMBG (before, during, after strenuous activity) to determine the effect of exercise on blood glucose levels and to detect low blood glucose levels.
  • Check blood glucose level before going to sleep to avoid nocturnal hypoglycemia; perform nocturnal (3 AM) monitoring:
    • If hypoglycemia has occurred during the night
    • When evening insulin has been adjusted
    • When strenuous activity has occurred the previous day
    • During times of irregular eating schedules or erratic glucose control
  • Several nutrition bars that are low in fat have been developed to help prevent hypoglycemia (e.g., Extend Bar).

Infection is the primary cause of metabolic abnormalities leading to diabetic coma in patients with diabetes. Because of the potentially severe consequences of untreated infections, prompt diagnosis and treatment are essential. Infections are often occult in diabetic patients and require a high index of suspicion. Common infections in patients with diabetes are shown in Table 14.4.

Edelman _Tab14-4a
Edelman _Tab14-4b
Quality of Life

Patients with blood glucose values consistently >200 mg/dL will have a reduced quality of life. Poorly controlled blood glucose values will lead to excessive thirst and urination, causing nocturia and poor sleep. Poor sleep will lead to daytime tiredness and poor work performance in adults. Patients will have frequent urinary tract infections, tooth and gum disease, and blurry vision. It has also been shown that the elderly experience cognitive impairment and a higher incidence of falls.


Peragallo-Dittko V, ed. A Core Curriculum for Diabetes Education. 2nd ed. Chicago, IL: American Association of Diabetes Educators; 1993.

Porte D, Sherwin RS. Ellenburg and Rifkin’s Diabetes Mellitus. 5th ed.

Stamford, CT: Appleton and Lange; 1997.


© Copyright 2010. Steven V. Edelman, MD, Robert R. Henry, MD, Professional Communications, Inc. All rights reserved.

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