It is safe to say that we have all heard the term “diabetes.” But when we say that, what we usually mean is “diabetes mellitus.”
This is the full term for the type 1 and types 2 diabetes that is common worldwide. But there is actually another type of diabetes. It is Diabetes Insipidus. And then beneath this type of diabetes are subtypes of Diabetes Insipidus.
We will go through all these in the article below. We will also discuss the symptoms of Diabetes Insipidus. And, we will talk about its relation to Diabetes Mellitus. Then we will go over the diagnosis and treatment of Diabetes Insipidus.
What is diabetes insipidus?
Diabetes Insipidus is characterized by the excretion of large volumes of dilute urine. It involves polyuria and polydipsia. Polyuria is when you urinate higher volumes and at more frequent intervals.
Polydipsia is excessive thirst and often also results in dry mouth. The primary root of the problem in Diabetes Insipidus?
The inability to concentrate urine. This affects both the homeostasis of water as well as the homeostasis of sodium. This happens when not enough ADH (antidiuretic hormone) is produced. It can also occur when ADH can’t produce its actions on the kidneys collecting tubules through aquaporins.
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Symptoms
The symptoms of Diabetes Insipidus include polyuria and polydipsia. Polyuria is a heightened volume and frequency of urine.
In Diabetes Insipidus, the urine output is higher than three liters in 24 hours. It continues to remain high, even when not drinking any water. Polydipsia is excessive thirst and can sometimes include dry mouth.
Types of diabetes insipidus
There are four different types of Diabetes Insipidus. It is crucial to figure out which type you have to get safe and effective treatment.
Pituitary Diabetes Insipidus
Pituitary Diabetes Insipidus happens due to insufficient production and secretion of antidiuretic hormone. This hormone is arginine vasopressin.
This is the result of conditions that affect the hypothalamic neurohypophyseal system. The known causes of pituitary Diabetes Insipidus include:
- Germinoma
- Craniopharyngioma
- Langerhans cell histiocytosis (called LCH for short)
- Local inflammatory diseases
- Autoimmune diseases
- Vascular diseases
- Trauma resulting from surgery or an accident
- Sarcoidosis
- Metastases
- Cerebral malformations
- Cranial Diabetes Insipidus
In rare cases, the underlying cause can be genetic defects in vasopressin synthesis. These are inherited as either autosomal dominant, autosomal recessive, or X-linked recessive traits.
Gestational Diabetes Insipidus
Gestational Diabetes Insipidus happens in pregnancy with the production of an enzyme. The placenta produces this enzyme. The enzyme degrades arginine vasopressin. Not to worry, this is a rare complication.
It is also usually transient, meaning that it goes away once the pregnancy is over. Gestational transient Diabetes Insipidus happens late in pregnancy. It disappears a few days after delivery. A condition called acquired cental Diabetes Insipidus can also occur during pregnancy.
For example, this can happen in someone who has hypophysitis or neuroinfundibulitis. This can occur during late pregnancy or postpartum. If someone already has Diabetes Insipidus, it can come out in pregnancy.
Primary Polydipsia
Primary Polydipsia is an excessive intake of water that occurs in the absence of thirst. This happens due to the suppression of arginine vasopressin secretion by excessive fluid intake. We also call this dipsogenic Diabetes Insipidus.
Nephrogenic Diabetes Insipidus
Nephrogenic Diabetes Insipidus is kidney insensitivity to the antidiuretic effect of arginine vasopressin. There is congenital nephrogenic Diabetes Insipidus, which you are born with.
There is also acquired nephrogenic Diabetes Insipidus, which you develop at some point in your lifetime. Healthy kidneys maintain fluids and prevent electrolyte imbalance. They do this by adjusting the volume and concentration of urine based on what the body needs.
The final urine composition is determined in the collecting duct, which is the last tubular segment in the kidney. Arginine vasopressin regulates water permeability in the collecting duct. There is a complex network of osmosensors, biosensors, and volume sensors.
These measure urine concentration, pressure, and volume. They regulate the secretion of arginine vasopressin from the neurohypophysis. The concentration of the urine happens when arginine vasopressin facilitates water reabsorption through aquaporins. This happens when there is the activation of the vasopressin V2 receptor (called AVPR2 for short) in the collecting duct of the kidneys.
The inability of the kidneys to respond to arginine vasopressin results in AQP deficiency. This leads to constant diuresis, meaning large volumes of dilute urination.
Primary nephrogenic Diabetes Insipidus happens due to mutations in the genes that encode two key proteins: AVPR2 and AQP. Secondary forms of Diabetes Insipidus are caused by biochemical abnormalities, obstructive uropathy, or using certain medications, such as lithium.
Adipsic Diabetes Insipidus
We may have said that there are four types of Diabetes Insipidus, but there is also an extra. This is adipic Diabetes Insipidus.
Luckily, this type is a rare one. In fact, it has only been described in approximately 100 patients. In this condition, there is a deficient or absent thirst response to high plasma osmolality. This is a serious condition, with marked morbidity. This includes association with:
- Severely high sodium in the blood (called hypernatremia)
- A clot in a vein (called venous thromboembolism)
- Mortality (death)
Diabetes insipidus is not related to diabetes mellitus
Diabetes Insipidus is a rare disease of the hypothalamus and neurohypophysis. It manifests itself as polydipsia and polyuria, which can also occur in poorly controlled type 2 diabetes mellitus. Since symptoms of Diabetes Insipidus and Diabetes Mellitus do have some overlap, they can be difficult to distinguish.
Diabetes Mellitus was a known condition affecting blood sugar in ancient Egypt, Greece, and Asia. Diabetes Insipidus, on the other hand, was not described until thousands of years later. In the 1670s,
Thomas Willis noted a different taste of urine from subjects with polyuria than healthy individuals (yes, he tasted urine in the lab!). Willis then began to outline differential diagnosis between Diabetes Mellitus and Diabetes Insipidus. In 1794, Johann Peter Frank described patients with polyuria as excreting nonsaccharine urine. This is when he first introduced the term Diabetes Insipidus.
Although we then knew about Diabetes Insipidus, we knew almost nothing about the function of the pituitary. For the most part, scientists at the time thought that Diabetes Insipidus was kidney disease. In 1912, two clinical observations were suggesting an association between the hypophysis and Diabetes Insipidus.
This was supported by the fact that when the posterior lobe of the pituitary was extracted, this cured Diabetes Insipidus. It had previously been assumed that the antidiuretic hormone was produced in the intermediate lobe of the pituitary.
Around 1950, scientists established that posterior lobe hormones are secreted in the hypothalamus. This was when the antidiuretic hormone was first isolated and synthesized. In recent years, progress with genetics has made it possible to characterize other rare types of Diabetes Insipidus.
Diagnosis
The first step is excluding other potential causes of polyuria (excessive urination). In order to have Diabetes Insipidus, there needs to be low urine osmolality in the presence of high serum osmolality. This will require both a urine test and a blood test to determine if this is what’s happening for you.
A standard water deprivation test is normally done in order to see if you continue to urinate at a high volume, even without any water intake.
The diagnosis of gestational Diabetes Insipidus is difficult. This is because frequent urination is common in pregnancy. The standard water deprivation test above is not recommended during pregnancy. This is due to an increased risk of complications.
Diagnosing the underlying condition is important, but it can be challenging to do. It requires lots of appointments and long term follow-up. Diagnostic precision is crucial because treatment differs substantially from one type to another. False treatment could result in severe consequences.
For example, take low sodium in the blood (called hyponatremia). In a patient with Diabetes Insipidus, this could be interpreted as inadequately controlled diabetes. It could also be interpreted as a syndrome of inappropriate antidiuretic hormone secretion. This can lead to therapeutic errors. All clinical and analytical data should be evaluated together for early and correct diagnosis.
Your health care provider should ask for a thorough medical history. They will ask questions about the onset and duration of your symptoms, any medication use, and any relevant family history. The next step is based on your weight and blood pressure measurements. They will also ask for how many beverages you have consumed in the past 24 hours, as well as how much you have urinated in the last 24 hours.
They will also assess for signs of the following:
- Dehydration
- Bladder distention
- Pituitary hormone hypersecretion
- Pituitary hormone hyposecretion
- Tumor chiasmatic syndrome
- Granulomatosis
- Cancer
The diagnosis will be based on all this information, as well as a biological assessment, pituitary MRI, and results of a desmopressin test.
Your health care provider will follow a series of steps that start with clinical observations. Further along, they will use more sophisticated tools. MRI has proven to be one of the most useful tools when it comes to diagnosing Diabetes Insipidus.
Your imaging specialist will see on MRI pituitary hyperintensity in the posterior part of the sella. This is now considered to be a clear marker of neurohypophyseal functional integrity. Another important MRI finding is a pituitary stalk shape and size. These are considered the most striking findings contributing to the diagnosis.
For early identification of LCH type Diabetes Insipidus, we use a select type of MRI. This is MRI STIR, which stands for Short Inversion Time Inversion Recovery Sequencing.
New data has shown that measuring copeptin in the plasma through a blood test helps to identify patients with underlying kidney defects. This also helps to differentiate between primary polydipsia and pituitary Diabetes Insipidus. This is a crucial differentiation to make.
In severe forms of Diabetes Insipidus, urine osmolality stays below 250 milliosmoles per kilogram. Serum sodium remains greater than 145 millimoles per liter.
In partial forms of Diabetes Insipidus, urine osmolality will be between 250 and 750 milliOsmoles per kilogram. In these types of Diabetes Insipidus, the water deprivation test is important. What if the water deprivation test shows an inability to obtain a maximal urine concentration? This is a good indication that Diabetes Insipidus is occurring. Vasopressin and copeptin measurement are helpful here as well.
At this point, a healthcare provider will perform an MRI on the pituitary gland. What if there is no hyperintensity signal in the posterior pituitary? Then this supports the diagnosis of central Diabetes Insipidus. In this case, primary polydipsia is not present.
Treatment
When treating Diabetes Insipidus, the goal is to decrease urine output and thirst. You also want appropriate fluid balance and normal sodium levels in the blood. It is important to ensure that you can have an acceptable quality of life. Treatment depends upon which type of Diabetes Insipidus you have.
In 1913, extracts from the posterior pituitary gland were used to treat Diabetes Insipidus. In early 1928, scientists observed that some patients with Diabetes Insipidus did not respond to these extracts.
It wasn’t until 1945 that scientists established that the kidney had a critical role in some form of Diabetes Insipidus. In 1955, scientist du Vigneaud received the Nobel Prize in chemistry for the first synthesis of the hormone vasopressin.
This was a massive milestone for the treatment of Diabetes Insipidus.
Typical drug treatment for Diabetes Insipidus includes vasopressin or thiazide diuretics.In the nineties, different forms of extractive vasopressin were available. These included aqueous vasopressin, tannate vasopressin, vasopressin in a suspension of peanut oil, etc. These provided many side effects. That is because of the impurities involved in their preparation. DDAVP is a synthetic analog of natural vasopressin. It is long-lasting and works more specifically on the polyuria itself.
For women with gestational Diabetes Insipidus, treatment with desmopressin is very effective.
Conclusion
Nephrogenic Diabetes Insipidus is its own beast. It is insensitive to desmopressin.
It requires treatment of the underlying disease, as well as supportive measures. There is only really symptomatic treatment available. This includes a low solute diet, diuretics, and prostaglandin inhibitors.
Do you go to the bathroom to urinate often? Do you find you have a large urine volume? And, do you feel thirstier than the average person?
If so, it’s worth asking your health care provider for further testing. You may have Diabetes Insipidus. Testing is important because of the different types of Diabetes Insipidus that exist.
You and your health care provider must determine which type of Diabetes Insipidus you have. This way, your health care provider will be able to provide more specific, guided, informed treatment to your type. You can manage diabetes Insipidus effectively and fairly, simply with a correct diagnosis.
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