Diabetes Mellitus And Insipidus Can Occur In The Same Person At The Same Time. Here’s When

Diabetes Awareness Month: Diabetes is a chronic health condition that occurs either when the pancreas does not produce enough insulin (a hormone which helps blood sugar enter the cells in the body for use as energy), or when the body cannot effectively utilise the insulin it produces, or when the kidneys cannot properly concentrate urine. The prevalence of diabetes in India is 10.1 crores, according to the Indian Council of Medical Research — India Diabetes (INDIAB) study published in 2023. Diabetes is of two types: diabetes mellitus and diabetes insipidus. 

In diabetes mellitus, the level of glucose in the blood is too high, as a result of which the kidneys try to remove the extra glucose by passing it in the urine. Meanwhile, in diabetes insipidus, the blood glucose levels are normal, but the kidneys cannot properly concentrate urine. 

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Diabetes mellitus is classified into three categories: type 1 diabetes, type 2 diabetes, and gestational diabetes. 

Gestational diabetes occurs when pregnant women without a previous history of diabetes develop high blood sugar levels. 

Type 1 diabetes is a chronic, autoimmune condition in which the pancreas produces little or no insulin. Without insulin, glucose cannot enter the cells and builds up in the bloodstream, as a result of which the person suffers from different symptoms and complications of diabetes. 

The immune system attacks and destroys the cells in the pancreas that make insulin, as a result of which the organ stops making the hormone. 

While type 1 diabetes develops due to genetic or environmental factors, type 2 diabetes is a lifestyle-related condition and develops over time. 

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Type 2 diabetes occurs when the body is not able to make enough insulin, or the insulin produced does not work properly. 

Patients with diabetes insipidus pass too much urine due to problems caused by a hormone called vasopressin (AVP) of antidiuretic hormone (ADH), which plays an important role in regulating the amount of fluid in the body, and is produced by nerve cells in the hypothalamus. 

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When do both diabetes mellitus and diabetes insipidus occur in the same person?

In rare cases, a person can suffer from both diabetes mellitus and diabetes insipidus at the same time. According to a July 1950 study published in the American Journal of Diseases of Children, two researchers reviewed a 1939 study and found a total of 20 cases of occurrence of diabetes mellitus and diabetes insipidus in the same patient. Of all the cases till 1950, only two patients were within the paediatric age group: one was a 13-year-old boy and the other was a 14-year-old boy. 

In several reports, it has been mentioned that a single lesion may cause both diseases. There is also a possibility that the association of diabetes mellitus and diabetes insipidus in the same patient is purely coincidental. 

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A myriad of factors such as trauma, autoimmune conditions, inflammation, pituitary tumours, genetic abnormalities, and drug reactions can cause a person to have both diabetes mellitus and diabetes insipidus. 

“Situations where both diseases coexist are frequently linked to complicated medical disorders. Both types of diabetes can appear simultaneously due to a variety of factors, including trauma, pituitary tumours, autoimmune diseases, certain genetic abnormalities, infections, inflammation, and certain drugs. But it is a very rare and uncommon situation,” Dr M K Singh, HOD, Department of Internal Medicine, Marengo Asia Hospital, Gurugram, told ABP Live.

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Wolfram syndrome can cause a person to have both diabetes mellitus and diabetes insipidus

Another condition in which diabetes mellitus and diabetes insipidus occur in the same person is the Wolfram syndrome, also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). Optic atrophy is a condition in which the optic nerve, which carries images of what the eye sees to the brain, is damaged due to poor blood flow, or shock, toxins, radiation, and trauma. 

Patients with the Wolfram syndrome have diabetes mellitus, followed by optic atrophy in the first decade, cranial diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow early in the third decade, and multiple neurological abnormalities early in the fourth decade, according to US National Institutes of Health (NIH). 

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Diabetes mellitus, the first symptom of Wolfram syndrome, is usually diagnosed around age six. Wolfram syndrome patients need insulin replacement therapy. Around age 11, optic atrophy occurs. Loss of colour and peripheral vision are the first signs. As the vision problems get worse, people with optic atrophy become blind within approximately eight years after signs of optic atrophy first start showing.

About 70 per cent of people with Wolfram syndrome have diabetes insipidus. 

Some patients with Wolfram syndrome can also suffer from primary gonadal atrophy. This is a condition in which the testicle shrinks in size resulting in loss of fertility. This happens due to pituitary gland dysfunction.

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Such patients die prematurely, often due to respiratory failure associated with brainstem atrophy. Brainstem atrophy is the loss of neurons and the connections that help them communicate in the brain.

Eventually, the patient develops all complications associated with this progressive, neurodegenerative disease. 

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Sensorineural deafness that can range in severity from deafness beginning at birth to mild hearing loss beginning in adolescence occurs in 65 per cent of people with Wolfram syndrome. 

Urinary tract problems occur in 60 to 90 per cent of people with Wolfram syndrome. 

Neurological or psychiatric disorders occur in about 60 per cent of people with Wolfram syndrome. 

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Wolfram syndrome is of two types: type 1 and type 2. Wolfram syndrome type 1 is the condition described above. Wolfram syndrome type 2 patients do not develop diabetes insipidus, and have stomach or intestinal ulcers and excessive bleeding after an injury, leading to abnormal bleeding in the gastrointestinal system. 

“Diabetes mellitus and diabetes insipidus can occur together due to a rare genetic syndrome called DIDMOAD. It stands for diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. This is a genetic issue, which occurs very rarely. It occurs in young people, and is characterised by excess urination, increased thirst, weight loss and abnormality in the levels of electrolytes such as sodium and potassium. Normally, this syndrome is treatable and can be treated by conferring treatment techniques of diabetes mellitus as well as diabetes insipidus. The prognosis is good and most of the patients remain well while on this treatment which is lifelong. Genetic analysis needs to be done to see whether some genetic abnormality is responsible for the DIDMOAD syndrome. As an endocrinologist, we often see very, very few cases of this particular condition,” Dr Subhash Kumar Wangnoo, Senior Consultant Endocrinologist and Diabetologist, Apollo Centre for Obesity, Diabetes and Endocrinology, Indraprastha Apollo Hospitals, told ABP Live.

Wolfram syndrome can be managed by giving insulin to the patient to control blood sugar levels, and administering synthetic vasopressin to control diabetic insipidus. 

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What causes Wolfram syndrome? Is it genetic?

Inheritance of Wolfram syndrome is autosomal recessive, which means that two copies of the mutated gene are needed to cause the disorder. 

A 1997 article published by the National Library of Medicine said that a Wolfram gene was found on chromosome 4p16.1, but evidence for locus heterogeneity exists. Locus heterogeneity means that mutations in any number of genes or loci can result in a particular disease. 

There is also a possibility that a minority of patients have a mitochondrial genome deletion.

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More than 90 per cent of Wolfram syndrome type 1 cases are caused due to mutations in the WFS1 gene, which provides instructions for producing a protein called wolframin that is believed to regulate the amount of calcium in cells. 

For cellular functions, including cell-to-cell communication, contraction of muscles, and protein processing to occur, a proper calcium balance is important. The pancreas, heart, muscles, liver, brain, bones, lungs, and kindness have the wolframin protein. 

The cell organelle endoplasmic reticulum, which is responsible for protein production, processing, and transport, contains wolframin. 

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Wolframin plays an important role in the pancreas because the protein helps process a protein called proinsulin into mature insulin.

In people with mutated WFSI genes, wolframin proteins with reduced or absent function are produced. Since the function of the wolframin protein is reduced or absent, calcium levels are not regulated within the cells, and the endoplasmic reticulum does not work correctly. 

When enough functional wolframin is not present in the endoplasmic reticulum, the cell triggers its own death. In other words, apoptosis occurs. 

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When the beta cells, which make insulin in the pancreas, die, diabetes mellitus occurs. Eventually, affected individuals become blind due to the gradual loss of cells along the optic nerve. 

It is due to apoptosis that the different symptoms and complications of Wolfram syndrome type 1 occur. 

When mutated WFS1 genes are responsible for Wolfram syndrome type 1, they are inherited in an autosomal recessive pattern. In other words, both copies of the gene in which each cell are mutated because each parent of the individual carries one copy of the altered gene. Since the parents have one copy each, they do not show the symptoms of Wolfram syndrome type 1. 

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According to some studies, people with one copy of a mutated WFS1 gene are at increased risk of developing individual features of Wolfram syndrome, such as type 2 diabetes, psychiatric illnesses, or hearing loss.

In some people with Wolfram syndrome type 1, the WFS1 gene was not found, which means that the cause of the condition in these individuals is not known. 

Earlier, Wolfram syndrome was fatal by mid-adulthood because of the numerous complications arising due to the disease. But better management has helped increase life expectancy.

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What is the prevalence of Wolfram syndrome?

One in 500,000 people worldwide has Wolfram syndrome type 1, according to NIH. Scientific literature mentions about 200 cases. This means that one in 500,000 people worldwide have both diabetes mellitus and diabetes insipidus.

Wolfram syndrome type 2 has been found in only a few families from Jordan. 

Therefore, patients with Wolfram Syndrome have high blood sugar levels (diabetes mellitus), progressive vision loss due to the degeneration of nerves carrying information from the eyes to the brain (optic atrophy), dysfunction of the pituitary gland that results in excess urine production (diabetes insipidus), hearing loss caused by changes in the inner ear (sensorineural deafness), reduced amounts of testosterone in males (hypogonadism), urinary tract problems, and neurological or psychiatric disorders.

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