hypertonic hyperglycemia syndrome (HTS)

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OVERVIEW

  • This disease is a common emergency of diabetes mellitus, characterized by severe hyperglycemia, high plasma osmolality, and dehydration
  • It may be characterized by thirst, polyuria, polydipsia, fatigue, loss of skin elasticity, drowsiness, and coma.
  • Absolute or relative insufficiency of insulin levels is the underlying cause of the disease
  • Rehydration should be done as soon as possible as prescribed by the physician to reduce high osmolality, lower blood glucose, and correct electrolyte disorders.

    • Definition

  • Hyperosmolar hyperglycemia syndrome (HHS), a clinical type of acute metabolic disorder in diabetes mellitus, is characterized by severe hyperglycemia, high plasma osmolality, and dehydration without significant ketosis, and may have varying degrees of impaired consciousness or coma.
  • HHS most commonly occurs in older patients with type 2 diabetes mellitus who have comorbidities with other diseases, but can also occur in other populations.
  • Not all patients with HHS have a history of diabetes before the onset of the disease, and some patients with diabetes have the disease as their first symptom.

    • Morbidity

  • The disease can develop at any age, and is most common in older patients over 50 years of age, with no significant difference in the number of cases between men and women.
  • The incidence of HHS in the diabetic population ranges from 1% to 5%, with a mortality rate as high as about 15% [2].

    • Causes

    Causes of the disease

    The basic etiology is due to absolute or relative insulin insufficiency, and then under the action of various triggers, the disturbance of glucose metabolism is aggravated, resulting in the manifestation of hyperglycemia, high osmolality, and high blood sodium.

    Triggering factors

  • Various stresses, common stresses include acute infections (such as pneumonia, gastroenteritis, pancreatitis), severe trauma, major surgery, heat stroke, cerebrovascular accident, myocardial infarction and so on.
  • Certain medications, such as glucocorticoids, mannitol, diuretics (furosemide, hydrochlorothiazide), etc.
  • Inadequate water intake or water loss, e.g., fever, extensive burns, elderly patients with reduced thirst or insufficient fluid intake due to inability to obtain water in a timely manner due to mobility problems, etc.
  • Increased glycemic load, e.g., large intake of sugar, etc.
  • Inappropriate interruption of hypoglycemic drug therapy.

    • Symptoms

    Main Symptoms

    The onset of HHS is insidious, usually taking 1~2 weeks from the onset of symptoms to the appearance of impaired consciousness, with occasional acute onset. It often begins with diabetic symptoms, and the condition gradually worsens, and typical dehydration and neurologic symptoms may be present.

    Diabetic symptoms

    There may be thirst, polyuria, polydipsia, and fatigue, but polyphagia is not obvious, and sometimes it even manifests as anorexia.

    Neurological symptoms

  • When the plasma osmolality is >320mOsm/L, apathy and lethargy can be present.
  • When plasma osmolality >350mOsm/L, disorientation, hallucinations, epileptic-like seizures, hemiparesis, hemianopsia, aphasia, visual disturbances, coma, etc. can occur.

    • Symptoms of dehydration

    There may be dry lips and oral mucosa, loss of skin elasticity, sunken eye sockets, cold extremities, oliguria, etc.

    Complications

    HHS can lead to a variety of complications, such as cerebral edema, pulmonary edema, electrolyte metabolic disorders, etc.

    Cerebral edema

    Cerebral edema is the most serious complication, which may be manifested as new or persistently aggravated headache, recurrent vomiting, abnormal respiration and so on.

    Pulmonary edema

    Patients at potential risk for congestive heart failure may develop pulmonary edema, which may be characterized by coughing up sputum and dyspnea.

    Disorders of electrolyte metabolism

    It may be manifested as hypokalemia, hyperkalemia, etc. It is mostly due to the lack of timely potassium supplementation or overly aggressive potassium supplementation during treatment.

    Acute kidney injury

    If the blood supply to kidneys is insufficient for a long period of time, oliguria or anuria will occur, and may even cause kidney failure.

    Consultation

    Department of Medicine

    Endocrinology

    If there is irritable thirst, excessive drinking, excessive urination, fatigue, dizziness, mental depression, etc., it is recommended to consult a doctor promptly.

    Emergency Department

    If drowsiness, blurred consciousness, respiratory distress, low blood pressure or even shock occurs, immediate medical attention is recommended.

    Preparation for medical treatment

    Preparation for medical consultation: registration, preparation of documents, common problems

    Tips for seeking medical treatment

  • If there is excessive drinking or urination, record the changes in water intake and urine output for the doctor’s reference.
  • If there is vomiting, take photos of the vomit for the doctor’s reference.
  • If you have a history of diabetes mellitus, record the blood glucose monitoring value for the doctor’s reference.

    • Preparation Checklist for Doctor’s Visit

    Symptom Checklist

    Especially need to pay attention to the time of symptom onset, special performance, etc.

  • Are there symptoms such as weakness, thirst, excessive drinking, excessive urination, etc.?
  • Are there apathy, drowsiness, hallucinations, seizures, visual disturbances, etc.?
  • Is there any loss of skin elasticity, sunken eye sockets, oliguria, etc.?
  • How long have the above symptoms lasted?
    • List of medical history
  • Is there any history of diabetes? Any self-discontinuation of glucose-lowering medication?
  • Is there any blood relative with diabetes?
  • Are there any acute infections (e.g. pneumonia, gastroenteritis), severe trauma, major surgery, cerebrovascular accident, myocardial infarction, etc.?
  • Are there any extensive burns?
  • Has there been heavy sugar intake, use of glucocorticoids, diuretics (furosemide), etc.?
    • Checklist

    Test results of the last six months, which can be brought to the doctor’s office

  • Laboratory tests: routine blood test, routine urine test, blood biochemistry test, electrolyte test, blood sugar, etc.
  • Imaging tests: Chest CT, etc.
  • Others: electrocardiogram, etc.
    • Medication List

    Medications used in the last 3 months, if available in boxes or packages, can be brought to the doctor

  • Glucose-lowering drugs: Metformin, Glimepiride, Repaglinide, Acarbose, Insulin, etc.
  • Others: dexamethasone, methylprednisolone, mannitol, furosemide, etc.

    • Diagnosis

    Diagnosis is based on

    Medical history

    Patients with this disease may have the following medical history.

  • Past history of diabetes mellitus.
  • History of discontinuing treatment with glucose-lowering medications on their own.
  • Recent history of high sugar intake, use of medications such as glucocorticoids, mannitol, and diuretics.
  • Presence of stressful conditions such as acute infections (pneumonia, gastroenteritis, pancreatitis, etc.), severe trauma, major surgery, heat stroke, cerebrovascular accident, myocardial infarction, etc.
  • Presence of inadequate water intake or water loss, such as extensive burns.

    • Clinical manifestations

    Often first manifested as diabetic symptoms (such as excessive drinking, polyuria, irritable thirst, etc.), the condition gradually aggravated, may appear typical dehydration and neurological symptoms (such as sunken eye sockets, poor skin elasticity, lethargy, etc.).

    Laboratory Tests

    Blood glucose

    A blood glucose test is performed to clarify the patient’s blood glucose, which may be at or above 33.3 mmol/L.

    Electrolytes
  • Blood levels of potassium and sodium are measured to help determine the presence of electrolyte disorders.
  • There may be an increase or decrease in blood potassium and an increase in blood sodium.
    • Blood Gas Analysis

    There may be serum HCO3- ≥18mmol/L, arterial blood pH ≥7.30, anion gap <12mmol/L, etc.

    Blood osmolality

    Plasma osmolality ≥320 mOsm/L may be present.

    Urine Routine

    There may be strong positive urine glucose, negative urine ketones, and proteinuria and tubular urine in renal injury.

    Imaging

    X-rays, CT, and other tests are helpful in understanding the presence of pathogenic triggers, as well as other complications and concomitant illnesses.

    Electrocardiography

    It is useful to know whether there is any cardiac function abnormality.

    Differential Diagnosis

    Other causes of diabetic coma

    Hyperosmolar hyperglycemic syndrome needs to be differentiated from diabetic ketoacidosis, hypoglycemic coma, and lactic acidosis, among other emergencies, as shown in the table below.

    Diabetic ketoacidosis Hyperosmolar hyperglycemic state Hypoglycemic coma Lactic acidosisHistory diabetes mellitus and infection, insulin withdrawal or interruption in older diabetic patients, often with history of infection, vomiting, diarrhea history of diabetes mellitus, history of eating few meals, hyperactivity, or failure to eat after injecting insulin or taking glucose-lowering medications liver or kidney insufficiency, shock, history of taking bisacodyl drugsmedical historyDiabetes and infection, insulin withdrawal or interruption, etc.Older diabetic patients, often with a history of infection, vomiting, diarrheaHistory of diabetes mellitus, poor meal intake, excessive activity, or failure to eat after insulin injection or glucose-lowering medicationsHistory of hepatic or renal insufficiency, shock, metformin useOnset symptoms slow onset, 1 to 4 days, nausea, vomiting, thirst, polyuria, etc. slow onset, 1 to 2 weeks, marked thirst, drowsiness, coma more acute onset, hours, hunger, excessive sweating, palpitations, hand tremors, etc. acute onset, 1 to 24 hours, anorexia, nausea, lethargy, and accompanying morbidity symptomsOnset of symptomsSlow onset, 1～4 days, nausea, vomiting, thirst, polyuria, etc.Slow onset, 1~2 weeks, obvious thirst, drowsiness, comaRapid onset, a few hours, hunger, excessive sweating, palpitations, hand tremors, etc.Sharp onset, 1～24 hours, anorexia, nausea, lethargy and accompanying morbid symptoms

    Skin water loss, dryness, severe dehydration dampness, excessive sweating, pale water loss, flushing

    Skin

    Water loss, dryness

    Severe dehydration

    Dampness, excessive sweating, pallor

  • Loss of water, flushing
  • Breathing deep, fast fast deep, fast deep, fast

    • Breathing

  • Deep, fast
  • Fast
  • Deep, fast

    • Deep. Fast.

  • Pulse fine, fine, fine, fine and full, fine.
  • Pulse

    • Fine

    Fast.

    Fast and full

    Fine Tachycardia

  • Blood Pressure Decreasing or Normal Decreasing Normal or Slightly Higher Decreasing
  • Blood Pressure

    • Decreasing or normal

    Decreasing

    Normal or slightly higher

  • Decreasing
  • Urine sugar ＋＋＋＋＋＋＋＋ negative negative or ++++
  • Urine Sugar
  • ＋＋＋＋

    • ＋＋＋＋

  • Negative
  • Negative or ++++
  • Urine ketones + to + + + + Negative or + Negative Negative
  • Urinary ketones

    • ＋～＋＋＋

    Negative or +

  • Negative
  • Negative
  • Blood glucose is elevated, mostly 16.7～33.3mmol/L significantly elevated, mostly >33.3mmol/L significantly reduced, <2.5mmol/L normal or elevated
  • Blood glucose
  • Elevated, mostly 16.7～33.3mmol/L
  • Significantly elevated, mostly >33.3mmol/L