Diabetes insipidus (DI) is a rare medical condition that disrupts the body's ability to regulate water, resulting in excessive thirst and an unusually high volume of urine. This condition affects the kidneys' ability to concentrate urine and causes individuals to produce between 3 and 20 quarts of dilute, colourless urine daily, compared to an average of 1 to 2 quarts. It is pertinent to note that DI is not related to diabetes mellitus, which disrupts the body's insulin production.

Types Of Diabetes Insipidus

This condition results from damage to the hypothalamus or pituitary gland, which impairs the production or release of vasopressin, a hormone responsible for water retention. When vasopressin levels are inadequate, the kidneys fail to conserve water, leading to excessive urination. It can result from Brain injuries or surgeries, tumours, infections or inflammation and aneurysms.

Nephrogenic Diabetes Insipidus

This type occurs when the kidneys fail to respond to vasopressin, causing excessive fluid loss. Common triggers include chronic kidney disease, and electrolyte imbalances, such as high calcium or low potassium levels. Additionally, medications like lithium

and urinary tract blockages can also cause Nephrogenic DI.

Gestational Diabetes Insipidus

A rare condition seen only during pregnancy, this occurs when the placenta produces an enzyme that breaks down vasopressin or increases prostaglandin levels, reducing kidney sensitivity to the hormone. Symptoms of this are usually mild and often resolve postpartum but can recur in future pregnancies.

Symptoms And Warning Signs

• Severe thirst, often leading to the consumption of over a gallon of water daily
• Frequent urination (polyuria), sometimes exceeding 20 quarts per day
• Nighttime urination and bed-wetting
• Weakness, muscle pain, and preference for cold drinks

In severe cases, dehydration may develop, manifesting as fatigue, dizziness, dry mouth, confusion, nausea, or fainting. Infants and children with DI may exhibit crankiness, poor feeding, slow growth, fever, or vomiting.

Causes And Risk Factors

DI stems from issues with vasopressin production or response. Central DI arises from damage to brain structures, while nephrogenic DI relates to kidney dysfunction. Risk factors include:

- Genetic mutations affecting water regulation

- Certain medications like diuretics or lithium

- Metabolic disorders that alter calcium or potassium levels

- Brain injuries or surgeries

Diagnosis And Testing

Diagnosing DI involves a combination of medical history, physical exams, and specialized tests:

- Urinalysis: Evaluates urine concentration and glucose levels to distinguish DI from diabetes mellitus.

- Blood tests: Check electrolyte, glucose, and vasopressin levels.

- Water deprivation test: Measures changes in weight, blood sodium, and urine concentration during fluid restriction.

- MRI: Detects abnormalities in the hypothalamus or pituitary gland.

- Genetic screening: Identifies inherited risk factors.

Although DI is rare, affecting about 1 in 25,000 people, early diagnosis and targeted treatment can significantly improve quality of life. Researchers continue to explore its causes and treatments to better support those living with this challenging condition.

NBC News producer Susan Kroll, 58, initially attributed her occasional difficulty remembering words to menopause-related brain fog. However, tests revealed an elevated genetic risk of Alzheimer’s disease and abnormal amyloid levels in her brain.

Her journey began when she sought a diagnosis for her mother, who had started experiencing memory problems at 75. While helping her mother, Kroll decided to investigate her own risk after learning that Alzheimer’s risk can be genetic, she wrote on Today.com.

Genetic Testing Revealed An Elevated Alzheimer’s Risk

Testing showed that Kroll’s mother carried two copies of a gene called APOE4. Everyone inherits one APOE gene from each parent. The three common variants are APOE2, which may reduce Alzheimer’s risk; APOE3, the most common variant, which has a neutral effect; and APOE4, which increases the risk.

According to the Mayo Clinic, people with two copies of APOE4 are eight to 12 times more likely to develop Alzheimer’s.

To understand her own risk, Kroll took a cheek-swab genetic test in October 2024.

"I had an APOE4 and APOE3 gene, making me two to three times more likely to develop Alzheimer’s. I was a bit relieved," Kroll wrote.

Also read: Normal Ageing or Alzheimer's? Doctors Explain Six Key Differences to Watch For

Blood Tests And Brain Scans Revealed More

In May 2025, Kroll took a blood test developed to help diagnose Alzheimer’s disease, which had recently been cleared by the US Food and Drug Administration (FDA).

The test measures certain proteins, including a specific form of tau, that can indicate the presence of amyloid plaques in the brain. These protein deposits are considered a hallmark of Alzheimer’s disease.

Kroll said her "results were well outside the normal range". She had also noticed occasional difficulty remembering words, which she had initially attributed to menopause-related brain fog.

She was given personalised recommendations covering diet, exercise, supplements and sleep.

Diet, Exercise And Sleep Changes To Support Brain Health

Kroll made several changes to her daily routine.

"I cut out artificial sweeteners and limited fried and processed foods, red meat, cheese, sweets and alcohol. Every day, I started eating leafy greens, whole grains, veggies and fruit, and every week multiple servings of fish, walnuts, almonds, avocado and berries."

She also intensified her workouts, doing 45–60 minutes of cardio three to four days a week, alongside strength training. She focused on three muscle groups, completing three sets of each exercise with eight to 10 repetitions. She also started going to bed earlier.

Read More: India Gets Its First Alzheimer’s Drug: Know All About Eli Lilly’s Lormalzi

Kisunla Infusions Reduced Amyloid Levels In Her Brain

In December 2025, Kroll began treatment with Kisunla, an anti-amyloid infusion approved by the FDA in 2024.

A previous brain scan had shown elevated amyloid levels in every quadrant of her brain. Clinical trials have shown that Kisunla can slow cognitive and functional decline in eligible patients.

After six infusions, Kroll underwent another brain scan in May 2026 to assess her progress.

Her amyloid score dropped from 86 to four. The radiologist noted, "The amyloid issue has resolved."

Further blood tests showed that her tau levels were normal. Kroll suggested that her dietary changes may have contributed to this result.

Does She Still Have An Elevated Alzheimer’s Risk?

Kroll currently has neither Alzheimer’s disease nor mild cognitive impairment. However, she continues to have positive biomarkers and an elevated genetic risk. She believes the "early interventions helped slow down or potentially stop the progression of changes years before they could worsen".

Her journey is far from over. She continues to receive care at the Alzheimer’s Prevention Clinic, where her blood and biomarkers are monitored monthly.

Obesity drugs such as semaglutide and tirzepatide may offer benefits beyond weight loss and blood sugar control. Researchers say these medicines could also help protect brain function, including memory and other cognitive abilities.

Researchers from the University of Gothenburg and the University of Copenhagen examined evidence on how these drugs affect the brain and their potential to inform treatments aimed at preserving cognitive function. The review was published in the journal Science.

How Do Obesity Drugs Affect The Brain?

Semaglutide and tirzepatide belong to a class of medicines that act on metabolic pathways involved in appetite and blood sugar regulation. They may also influence biological processes important for brain function.

Animal studies suggest that GLP-1 drugs can affect learning and memory. However, findings from human studies have been mixed.

Studies analysing patient records have linked GLP-1 treatment to a lower risk of dementia among people with type 2 diabetes. However, these findings do not establish whether the medicines themselves are responsible for the reduced risk.

Semaglutide Failed To Slow Alzheimer's Progression

The potential benefits of these drugs have also been examined in people with Alzheimer's disease.

In Novo Nordisk's EVOKE and EVOKE+ clinical trials, semaglutide did not slow disease progression in patients with early Alzheimer's disease, despite producing changes in several biological markers associated with the condition.

However, researchers say these findings do not rule out potential benefits in other groups of patients.

People with obesity or type 2 diabetes may experience difficulties with attention, planning and processing speed. These cognitive problems are often associated with metabolic and vascular health, making them potential targets for treatment.

Stina Börchers, first author of the review and a researcher affiliated with the University of Gothenburg and the University of Copenhagen, said it is important to establish whether these treatments can help preserve cognitive abilities, particularly when started before problems become established.

“We need to find out whether these treatments can help people with obesity or diabetes preserve their cognitive abilities, particularly if treatment begins before cognitive problems become established,” Börchers said.

Could Obesity Drugs Lead To New Brain Treatments?

Researchers are trying to understand whether the potential effects of obesity medicines on the brain result from improved metabolism, direct action on the brain, or a combination of both.

Christoffer Clemmensen, senior author of the review and research group leader at the University of Copenhagen, said advances in obesity medicines offer new opportunities to understand how metabolic regulation influences brain function.

“By disentangling the direct and indirect effects of these drugs on the brain, we may ultimately be able to develop treatments specifically aimed at preserving cognitive function,” Clemmensen said.

Why More Clinical Trials Are Needed

The researchers are calling for clinical trials that assess memory and other cognitive abilities from the beginning of treatment.

They also stress the need to monitor older and frail patients. Rapid weight loss and loss of muscle mass could affect physical function and potentially reduce the benefits of treatment in these groups.

For now, whether obesity drugs can help preserve cognitive function remains an important research question. More clinical evidence is needed before they can be considered treatments for protecting brain health.

For 25-year-old Kaela Knight, a nail artist from Colorado, taking tirzepatide, the active ingredient in Eli Lilly's Mounjaro and Zepbound, brought an unusual side effect: skin so sensitive that even a light touch hurt.

Knight started treatment in September 2024 at 210 pounds and eventually reached 125 pounds. But during her second month, as her dose increased from 2.5 mg to 5 mg, she began experiencing burning sensations.

"I always describe it as feeling like a sunburn without any visible redness or irritation," she told the Daily Mail.

The sensation affected her hips, forearms and neck. Episodes lasted 24–48 hours, although some persisted for about a week.

Other patients taking Novo Nordisk's Ozempic and also Mounjaro have reported similar experiences.

Known as allodynia, this nerve-pain condition makes normally harmless sensations, such as clothing brushing against the skin or a light touch, painful. Patients describe it as a sunburn without visible redness or irritation.

Although it is not an established side effect of Ozempic, Wegovy, Mounjaro or Zepbound, medical reports have documented similar symptoms. A direct link remains unproven.

"I have [areas] all over that are burning. It's driving me nuts," one Reddit user wrote. Another said painkillers and lidocaine gels offered little relief.

Some patients report improvement after reducing their dose or stopping treatment.

Also read: Ozempic Hair: GLP-1 Drug Use Linked To 7% Higher Baldness Risk In Men

Why Could Weight-Loss Injections Cause Burning Skin?

Semaglutide, used in Ozempic and Wegovy, mimics the GLP-1 hormone. Tirzepatide, used in Mounjaro and Zepbound, targets GLP-1 and GIP receptors.

Dr Richard Siegel, an endocrinologist at Tufts Medicine, told the Daily Mail that these drugs could potentially affect nerve signalling through the brain and spinal cord.

Another theory involves changes in the fat layer beneath the skin during weight loss, which could affect nerve sensitivity. Neither explanation has been proven.

What Do Medical Reports Reveal?

An October 2025 report documented two cases:

• A 56-year-old woman developed painful skin sensations after switching to semaglutide 2.4 mg. Symptoms resolved without treatment after six weeks.
• A 75-year-old man with type 2 diabetes developed widespread burning after switching to tirzepatide. Symptoms resolved after he discontinued it and returned to oral semaglutide.

Some patients report improvement over time or after reducing their dose.

Dr Siegel said symptoms can last days to weeks, potentially becoming less noticeable as the body adjusts to treatment, much like nausea and constipation.

"It's possible something similar is happening here, where temporary changes in receptor activity alter nerve signaling at first, but become less noticeable as the body adjusts," he said.

Read More: Stopping Ozempic, Wegovy, Mounjaro Linked To 22% Higher Heart Attack, Stroke Risk: Study

Newer Weight-Loss Drugs May Carry A Higher Risk

Clinical trials have also recorded dysesthesia, a broader category of abnormal sensations, including burning and tingling. It is not necessarily the same as allodynia.

In a high-dose oral semaglutide trial, dysesthesia occurred in fewer than 3% of 334 participants, compared with none receiving placebo.

Phase 3 trials of retatrutide, an experimental drug targeting GLP-1, GIP and glucagon receptors, reported:

• 9 mg dose: 8.8%
• 12 mg dose: 20.9%
• Placebo: 0.7%

Who Is More Vulnerable To Allodynia?

Risk factors remain unclear. Dr Siegel believes higher doses could play a role.

"As best as I can tell, it would mostly be people on higher doses of these medications," he said.

He also suggested that people with greater pain sensitivity, including those with fibromyalgia, might be more susceptible.

What Should Patients Do?

Patients experiencing unusual skin burning or sensitivity should consult their doctor. Dose adjustments or alternative treatments may be considered, but medication should not be changed or stopped without medical advice.

Allodynia can also occur with shingles, migraines and nerve damage, so symptoms should not automatically be attributed to weight-loss drugs.

Dr Siegel recommends recording when symptoms occur, where they appear and what makes them better or worse.

Persistent or worsening pain should be medically evaluated.