Diabetes insipidus is an ancient disease considered under the rubric of diabetes, the Greek descriptive

term for polyuria, which was unrecognized even after the sweetness of urine was reported as a
characteristic of diabetes mellitus in the 17th century. It would be another century before diabetes
insipidus was identified from the insipid rather than saccharine taste of urine in cases of polyuria. After its
increased recognition, pathologic observations and experimental studies connected diabetes insipidus to
the pituitary gland in the opening decades of the 20th century. Simultaneously, posterior pituitary lobe
extracts were shown to be vasoconstrictive (vasopressin) and antidiuretic (antidiuretic hormone). As
vasopressin was purified and synthesized and its assay became available, it was shown to be released in
response to both osmotic and volume stimuli that are integrated in the hypothalamus, and vasopressin
thereby was essential to maintaining internal water balance. The antidiuretic properties of vasopressin to
treat the rare cases of diabetes insipidus were of limited clinical utility until its vasoconstrictive effects
were resuscitated in the 1970s, with the consequent increasing wider use of vasopressin for the treatment
of compromised hemodynamic states. In addition, the discovery of antidiuretic hormone receptor blockers
has led to their increasing use in managing hypo-osmolar states.

What's to know about diabetes insipidus?

Last updated Fri 19 January 2018
By Adam Felman
Diabetes insipidus is a condition where the body loses too much fluid through urination, causing a
significant risk of dangerous dehydration as well as a range of other illnesses and conditions.
It is a rare disorder affecting the regulation of body fluid levels.
People with diabetes insipidus produce excessive amounts of urine, resulting in frequent urination and
thirst. However, the underlying cause of these two symptoms differs from types 1 and 2 diabetes.
The disease takes two main forms: Mephrogenic diabetes insipidus and central or neurogenic diabetes
insipidus.
Central diabetes insipidus occurs when the pituitary gland fails to secrete the hormone vasopressin,
which regulates bodily fluids. In nephrogenic diabetes insipidus, vasopressin secretion is normal, but the
kidneys do not correctly respond to the hormone.
Diabetes insipidus affects roughly 1 in every 25,000 people in the United States.
Fast facts on diabetes insipidus
Here are some key points about diabetes insipidus. More detail and supporting information is in the body
of this article.
 Diabetes insipidus is a condition where the body fails to properly control water balance, resulting in
excessive urination.
 Excessive production of dilute urine in diabetes insipidus is often accompanied by increased thirst
and high water intake.
 Diabetes insipidus can result in dangerous dehydration if a person does not increase their water
intake, such as when a patient cannot communicate their thirst or help themselves.
 As diabetes insipidus is not a common condition, diagnosis involves the exclusion of other common
possible explanations for symptoms.
Symptoms

The need to urinate in large volumes can wake people with diabetes insipidus.
 The main symptom of all cases of diabetes insipidus is frequently needing to pass high volumes of diluted
urine.
The second most common symptom is polydipsia, or excessive thirst.
In this case, results from the loss of water through urine. The thirst prompts the person with diabetes
insipidus to drink large volumes of water.
The need to urinate can disturb sleep. The volume of urine passed each day can be anywhere between 3
liters and 20 liters, and up to 30 liters in cases of central diabetes insipidus.
Another secondary symptom is dehydration due to the loss of water, especially in children who may not
be able to communicate their thirst. Children may become listless and feverish, experience vomiting
and diarrhea, and may show delayed growth.
Other people unable to help themselves to water, such as people with dementia, are also at risk of
dehydration.
Extreme dehydration can lead to hypernatremia, a condition in which the sodium concentration of the
serum in the blood becomes very high due to low water retention. The cells of the body also lose water.
Hypernatremia can lead to neurological symptoms, such as overactivity in the brain and nerve muscles,
confusion, seizures, or even coma.
Without treatment, central diabetes inspidus can lead to permanent kidney damage. In nephrogenic DI,
serious complications are rare, so long as water intake is sufficient.
Treatment
Diabetes insipidus becomes a serious problem only for people who cannot replace the fluid that is lost in
the urine. Access to water and other fluids makes the condition manageable.
If there is a treatable underlying cause of the high urine output, such as diabetes mellitus or drug use,
addressing this should help resolve the diabetes insipidus.
For central and pregnancy-related diabetes insipidus, drug treatment can correct the fluid imbalance by
replacing vasopressin. For nephrogenic diabetes insipidus, the kidneys will require treatment.
Vasopressin hormone replacement uses a synthetic analog of vasopressin called desmopressin.
The drug is available as a nasal spray, injection, or tablet, and is taken when needed.
Care should be taken not to overdose, as this can lead to excessive water retention and, in rare, severe
cases, hyponatremia and fatal water intoxication.
The drug is otherwise generally safe when used at appropriate dosages, with few side effects. It is,
however, not effective if diabetes insipidus occurs as a result of kidney dysfunction.
Mild cases of central diabetes insipidus may not need hormone replacement and can be managed
through increased water intake.
Nephrogenic diabetes insipidus treatments may include:
 anti-inflammatory medicines, such as non-steroidal anti-inflammatory drugs (NSAIDS)
 diuretics, such as amiloride and hydrochlorothiazide
 reducing sodium intake and increasing water intake
A doctor may also advise a low-salt diet, and a person with diabetes insipidus may be referred to a
nutritionist to organize a diet plan.
Reducing caffeine and protein intake and removing processed foods from the diet can be effective steps
to controlling water retention, as well as consuming foods with high water content, such as melons.
Causes
Both types of diabetes insipidus are linked to a hormone called vasopressin but occur in different ways.
 Vasopressin promotes water retention in the kidneys. This also keeps blood pressure at a healthy level.
The main symptom, excessive urine output, can have other causes. These would usually be ruled out
before making a diagnosis of diabetes insipidus.
For example, undiagnosed or poorly managed diabetes mellitus can cause frequent urination.
Central diabetes insipidus
Central diabetes insipidus is caused by reduced or absent levels of vasopressin.
The condition can be present from birth, or primary. Secondary central diabetes insipidus is acquired later
in life.
The cause of primary central diabetes insipidus is often unknown. Some causes result from an
abnormality in the gene responsible for vasopressin secretion.
The secondary type is acquired through diseases and injuries that affect how vasopressin is produced.
These can include brain lesions resulting from head injuries, cancers, or brain surgery. Other body-wide
conditions and infections can also trigger central diabetes insipidus.
Nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus can also be inherited or acquired. This type affects the response of the
kidneys to vasopressin.
Depending on a person's genes, the condition results in the kidneys either completely or partially not
responding to vasopressin. This affects water balance to varying degrees.
The acquired form of nephrogenic diabetes insipidus also reduces the kidneys' ability to concentrate urine
when water needs to be conserved.
Secondary nephrogenic diabetes insipidus can have numerous causes, including:
 kidney cysts that have developed due to a number of conditions, such as autosomal dominant
polycystic kidney disease (ADPKD), nephronophthisis, medullary cystic disease complex, and
medullary sponge kidney
 the release of an outlet tube obstruction from a kidney
 kidney infection
 high blood calcium levels
 some cancers
 certain medications, especially lithium, but also demeclocycline, amphotericin B, dexamethasone,
dopamine, ifosfamide, ofloxacin, and orlistat
 rarer conditions, including amyloidosis, Sjögren's syndrome, and Bardet-Biedl syndrome
 chronic hypokalemic nephropathy, a kidney disease caused by low blood potassium levels
 a cardiopulmonary bypass, which can affect vasopressin levels and may require treatment with
desmopressin
Gestational diabetes insipidus
In rare cases, pregnancy can cause a disturbance of vasopressin, especially during the third trimester.
This occurs due to the placenta releasing an enzyme that degrades vasopressin.
Pregnancy also causes a lower thirst threshold in women, stimulating them to drink more fluids, while
other normal physiological changes during pregnancy can also affect the kidneys' response to
vasopressin.
Gestational diabetes insipidus is treatable during gestation and resolves 2 or 3 weeks following childbirth.
The condition affects only a few women out of every 100,000 women who are pregnant.
 Drugs that affect water balance
Diuretic drugs, commonly referred to as water pills, can also cause increased urine output.
Fluid imbalance can also occur after fluids are administered intravenously (IV). In these cases, the rate of
the drip is stopped or slowed, and the need to urinate resolves. High-protein tube feeds may also
increase urine output.
Diagnosis
The water deprivation test is a reliable test to help diagnose diabetes insipidus. However, the test has to
be performed by a specialist, as it can be dangerous without proper supervision.

The water deprivation test challenges the body's hormonal and kidney responses to dehydration.
The water deprivation test involves allowing a patient to become increasingly dehydrated while taking
blood and urine samples.
Vasopressin is also given to test the kidneys' ability to conserve water during dehydration.
In addition to managing the dangers of dehydration, close supervision also allows psychogenic polydipsia
to be definitively ruled out. This condition causes a person to compulsively or habitually drink large
volumes of water.
Someone with psychogenic polydipsia may try to drink some water during this test, despite strict
instructions against drinking.
Samples taken during the water deprivation test are assessed to determine the concentration of urine and
blood, and to measure levels of electrolytes, particularly sodium, in the blood.
Under normal circumstances, dehydration triggers the secretion of vasopressin from the pituitary gland in
the brain, telling the kidneys to conserve water and concentrate the urine.
In diabetes insipidus, either insufficient vasopressin is released, or the kidneys are resistant to the
hormone. Testing these dysfunctions will help define and treat the type of diabetes insipidus.
The two types of the condition are further defined if the urine concentration then responds to injection or
nasal spray of vasopressin.
Improvements in urine concentration demonstrate that the kidneys are responding to the hormone's
message to improve water conservation, suggesting that the diabetes insipidus is central.
If the kidneys do not respond to the synthetic vasopressin, the cause is likely to be nephrogenic.
Before the water deprivation test is carried out by specialists, investigations are done to rule out other
explanations for the high volumes of diluted urine, including:
 Diabetes mellitus: Blood sugar levels in types 1 and 2 diabetes affect urine output and thirst.
 Current courses of medication: The doctor will rule out the role of any current medications, such as
diuretics, in affecting water balance.
 Psychogenic polydipsia: Excessive water intake as a result of this condition can create the high urine
output. It can be associated with psychiatric illnesses, such as schizophrenia.
Insipidus vs. Mellitus
Diabetes insipidus and diabetes mellitus are not related to one another. Their symptoms, however, can
be similar.
The words 'mellitus' and 'insipidus' come from the early days of diagnosing the condition. Doctors would
taste the urine to gauge sugar content. If the urine tasted sweet, it meant that too much sugar was leaving
the body in the urine, and the doctor would reach a diabetes mellitus diagnosis.
However, if the urine tasted bland or neutral, it meant that water concentration was too high, and diabetes
inspidus would be diagnosed. "Insipidus" comes from the word "insipid," meaning weak or tasteless.
In diabetes mellitus, elevated blood sugar prompts the production of large volumes of urine to help
remove the excess sugar from the body. In diabetes insipidus, it is the water balance system that is not
functioning correctly.
Diabetes mellitus is far more common than diabetes insipidus. Diabetes insipidus, however, progresses
far more rapidly.
Of the two conditions, diabetes mellitus is more harmful and harder to manage.