What Is Type 3 Diabetes? Insulin Resistance In The Brain That Could Trigger Alzheimer’s
Most people are aware of type 1 and type 2 diabetes, but did you know there is a type 3 diabetes as well! It is a more obscure term. Although it is not an accepted medical diagnosis, type 3 diabetes has been discussed in the literature as a possible relationship between insulin resistance in the brain and Alzheimer's disease. This link has been described to help explain how metabolic disorders impact brain health, causing cognitive decline and dementia.
Type 3 diabetes is more of a misnomer because it should not be confused with type 3c diabetes, which relates to pancreatic dysfunction. The term "type 3 diabetes," on the other hand, has been loosely used by some scientists to analogously propose that Alzheimer's disease is strongly implicated with insulin resistance in the brain.
This concept was conceptualized by Dr. Suzanne de la Monte and Dr. Jack Wands of Brown University in the year 2008. This hypothesis postulated that Alzheimer's disease may be called type 3 diabetes for it bears many similarities with glucose metabolism disorder type 2 diabetes. Their concept arises from the basic principle that insulin is fundamental to blood sugar regulation, but it is also the case with the brain. When brain cells become insulin-resistant, they lose access to glucose, impairing their function.
Research published in the Journal of Diabetes Science and Technology supports this hypothesis by indicating that insulin resistance can be a significant contributor to the occurrence of dementia, also referred to as Alzheimer's. The symptoms of memory loss and diminished reasoning are associated with impaired glucose metabolism in the body, especially in the cerebral tissue.
Although type 3 diabetes is not a "medical term," its symptoms correlate well with Alzheimer's diseases that are known to reduce the ability to think in an efficient manner and bring down brain health. These signs are:
- Loss of memory, especially short-term.
- Poor judgment and judgment ability
- Failure in recognizing people or places familiar once.
- Failure in the process of reading, writing or processing numbers
- Anxiety, agitation, or mood changes.
- Disorganized thoughts or confusion
- Lack of impulse control
As the disease advances, patients may be afflicted with severe complications including an inability to swallow or control their bodily functions. In the final stages, most patients die from fatal complications such as aspiration pneumonia.
This may not be well understood with regards to type 3 diabetes, or the exact link between insulin resistance and Alzheimer's disease. Some identified contributing factors include the following:
Insulin acts as an important regulatory mechanism of brain functions such as memory and cognition. The reduction in insulin signaling may impair metabolism of brain cells, thus bringing about neurodegeneration.
These diseases show a strong relationship and those individuals diagnosed with type 2 diabetes have double chances of getting Alzheimer's. In the two, the main causes can be chronic inflammation, oxidative stress, and a defect in glucose metabolism.
Insulin resistance associated with obesity, stress, and an unhealthy diet is considered a cause that may increase the chances of Alzheimer's disease.
Researches in Frontiers in Neuroscience and The Lancet Neurology have also highlighted that drugs used for antidiabetic medication may be crucial for the prevention or at least slowing down the course of Alzheimer's.
In 2022, in a study in Pharmaceuticals, researchers studied biomarker uptake in brain regions implicated in the faulty uptake and metabolism of blood sugar in Alzheimer’s patients.
Emerging Therapies
Research into such treatments as intranasal insulin has also been promising. Intranasal delivery of insulin directly to the brain has been reported to enhance glucose uptake by brain cells, improve memory, and boost cognitive performance. While such clinical trials have been shown to be successful, additional research is needed for safety and efficacy.
Medications
For patients being aggressive or agitated, antipsychotic drugs may be prescribed; however, therapies such as cognitive rehabilitation as well as cognitive stimulation therapy serve to preserve memory and executive function.
Lifestyle Interventions
Diet, exercise, and stress management are critical in preventing and managing insulin resistance. A review in the Journal of Alzheimer's Disease also highlighted the benefits of Kirtan Kriya meditation, which can regulate genes involved in insulin and glucose metabolism, improve sleep, and reduce inflammation.
Although type 3 diabetes is not officially recognized, its connection to Alzheimer’s disease underscores the importance of proactive measures for brain health. Some prevention strategies include:
1. Healthy Diet
Consuming a balanced diet rich in antioxidants, whole grains, and healthy fats may support brain health.
2. Regular Exercise
Physical activity improves insulin sensitivity, reduces inflammation, and enhances overall metabolic health.
3. Stress Reduction
Mindfulness practices, including meditation, have been shown to lower stress levels, which can reduce the risk of cognitive decline.
The term type 3 diabetes brings out the complex relationship between metabolic disorders and brain health. Even though it is not a recognized medical condition, the concept emphasizes the crucial role of insulin in brain function and its possible contribution to Alzheimer's disease. Continued research will hopefully provide hope for therapies such as intranasal insulin and lifestyle modifications.
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GLP-1 receptor agonist drugs such as Ozempic and Wegovy have shown significant benefits for people with diabetes and obesity. However, not everyone experiences the same results.
Now, a study suggests that this variation may be due to genetic resistance, which means that some people are biologically less responsive to these medications, making these drugs less effective.
The new study by scientists at Stanford University in the US showed that about 10 per cent of the general population carry genetic variants that lead to what the researchers called “GLP-1 resistance”.
The GLP-1- receptor agonist drugs typically work by mimicking the hormone GLP-1 (glucagon-like peptide-1), which naturally helps regulate blood sugar by stimulating insulin release. The process slows the emptying of the stomach and reduces appetite.
However, in individuals with certain genetic variants, the team found that higher levels of GLP-1 did not regulate blood sugar better.
The researchers noted that the findings, published in the journal Genome Medicine, may be key to developing new therapies for people with GLP-1 resistance.
“There are a whole class of medications that are insulin sensitizers, so perhaps we can develop medications that will allow people to be sensitized to GLP-1s or find formulations of GLP-1, like the longer-acting versions, that avoid the GLP-1 resistance,” said Anna Gloyn, professor of pediatrics and of genetics at Stanford Medicine.
Also read: Foundayo: US FDA Approves Eli Lilly’s GLP-1 Weight Loss Pill
To zero in on the gene resistant to GLP-1 drugs, the team conducted experiments in humans. They traced this resistance to a PAM variant known as p.S539W.
PAM (peptidyl-glycine alpha-amidating monooxygenase) is an enzyme that is uniquely capable of activating many hormones in the body, including GLP-1.
While the researchers suspected that people with the PAM variant would have lower levels of GLP-1 in their blood, it actually increased levels of GLP-1. Although the exact mechanism is still unclear, experiments in both humans and mice confirmed signs of reduced response to GLP-1.
Analyzing diabetes drug trial data, they found that individuals with these variants were less able to lower their blood sugar levels even after six months of treatment. This suggests that despite having more circulating GLP-1, their bodies are less responsive to it.
“When I treat patients in the diabetes clinic, I see a huge variation in response to these GLP-1-based medications and it is difficult to predict this response clinically,” said Mahesh Umapathysivam, an endocrinologist and clinical researcher at Adelaide University in Australia.
“This is the first step in being able to use someone’s genetic make-up to help us improve that decision-making process,” he added.
Also read: Can Weight Loss Jabs Surge Divorce Rates? What Experts Are Saying
Importantly, participants with the PAM variants did not respond differently to other common diabetes treatments, including sulfonylureas, metformin, and DPP-4i.
The finding may help develop precision medicine, the researchers said. Knowing ahead of time who is likely to respond would help patients get on the right drugs faster, Gloyn said.
Ozempic is primarily indicated for type 2 diabetes management. But some doctors may prescribe it for weight loss in appropriate patients without diabetes.
Previous research has shown that medical conditions such as sleep apnea, along with certain common medications, such as antidepressants, steroids, and contraceptives, can hamper the process of shedding extra pounds.
Another major reason that can hamper weight loss is the side-effects of these drugs that can prompt a person to halt their prescription mid-way.
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Once widely known as non-alcoholic fatty liver disease (NAFLD), the common and dangerous fatty liver condition was rephrased as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) due to its strong link to metabolic health issues like obesity and diabetes.
MASLD now includes patients with fatty liver disease linked to metabolic risk factors such as obesity, diabetes, and hypertension.
Globally, it was observed that all patients who have non-alcoholic fatty liver disease also have some associated form of metabolic dysfunction. The patients reported having either obesity, diabetes, metabolic syndrome, hypertension, or cholesterol problems.
And all these problems eventually lead to significant comorbidities later, like some people developed heart disease, while others developed complications of diabetes.
In view of these, a global consensus process in 2023 involving hundreds of experts from different countries adopted MASLD as it better reflected these underlying causes of the condition.
Also read: Lancet Study Shows Metabolic Liver Disease To Rise Over 38% By 2050: What’s Behind The Surge
MASLD is an umbrella term for liver conditions that develop in the presence of 1 or more cardiometabolic risk factors—including high blood sugar, elevated body mass index (BMI), and hypertension—but in the absence of other causes of liver fat accumulation.
The condition can be defined by excess liver fat accumulation (more than 5 per cent of liver weight) in the presence of metabolic dysfunction, independent of alcohol intake.
It encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma.
“Initially, it was thought that having fatty liver disease without alcohol was a benign condition, but now it is recognized that, since it is associated with lots of metabolic comorbidities, it's no longer benign,” Dr. Ashish Kumar, Professor of gastroenterology and hepatology at Sir Ganga Ram Hospital in New Delhi, told HealthandMe.
He stated that whenever a diagnosis of fatty liver is present, "we should actually include other comorbidities, like obesity, dyslipidemia, which means cholesterol problem, diabetes, sugar problem, pre-diabetes, and hypertension. At least 50–70–80 percent of these patients will have one or more of these comorbidities".
Although alcohol has remained the number one risk for liver disease, MASLD seems to be rising globally, including among people who do not drink. Why?
The reasons include:
a sedentary lifestyle,
increased consumption of fast and processed food,
lack of exercise,
lack of sleep,
stressful life.
Also read: Why Regular Scans Are Crucial for Liver Cancer Patients: Doctors Explain
The experts noted that food, especially the increasingly accessible junk food or processed food, is a major culprit.
“So even if the person is not drinking alcohol, people are developing addiction to processed food, and this is causing an epidemic level of obesity and diabetes. Consequently, MASLD is also increasing, and now it is becoming the number one cause of liver disease,” Dr Kumar said.
According to Dr. Sanjay Goja, Director, Liver Transplant & HPB Surgery, Narayana Hospital, Gurugram, prevention must focus on following a healthy lifestyle like maintaining a healthy BMI, engaging in regular physical activity, and eating a balanced diet.
Controlling diabetes, cholesterol, and blood pressure is also important to prevent the risk of MASLD.
Dr Siddharth Badola, Manipal Hospital, Ghaziabad, suggested sustainable lifestyle changes such as:
Maintaining an adequate body weight: Even slight weight loss (5–10 percent) has been shown to significantly reduce liver fat and inflammation.
Follow a balanced and nutrient-rich diet: People should focus on consuming whole grains, fresh fruits and vegetables, lean proteins, and healthy fats, while limiting refined carbohydrates and processed foods.
Avoid foods with added sugar: Excess consumption of fructose, commonly found in packaged foods and sugary beverages, is a key contributor to fat accumulation in the liver.
Engage in regular physical activity: At least 150 minutes of moderate-intensity exercise per week is recommended to improve insulin sensitivity and liver health.
Manage associated metabolic conditions: Effective control of diabetes, hypertension, and dyslipidemia is essential in reducing the risk of MASLD progression.
Ensure adequate sleep and stress management: Poor sleep quality and chronic stress can negatively impact metabolic balance and liver function.
Keep your body hydrated with ample water intake and follow structured meal timings.
Heart attacks are now affecting younger people. (Photo credit: iStock)
Although a heart attack is generally considered a disease of the elderly, its incidence in young individuals is unfortunately on the rise. The reasons behind this are multifactorial. A heart attack is a condition where one of the arteries (blood vessels) suddenly becomes partially or completely occluded by a thrombus. Although the thrombus generally occurs suddenly, the underlying reason is a chronic process of lipid deposition in the vessel walls called atherosclerosis. Atherosclerosis can begin even in the first decade of life, but events like heart attacks conventionally occurred beyond 45 years in men and 55 years in women. On average, heart attacks occur in Indians about 10 years earlier than in their Western counterparts.
Dr Shyam Sasidharan, Consultant, Department of Cardiology, KIMSHEALTH Thiruvananthapuram, spoke about the early onset of heart attacks. From a population perspective, the rising number of heart diseases due to coronary artery disease (CAD) is significant not only because of its overall negative impact on the healthy population but also due to the potential for preventive interventions.
Acute coronary syndromes, or heart attacks, are on the rise among younger individuals, particularly in our country. Studies of the Asian-Indian migrant population have revealed a probable racial predisposition for premature CAD. However, the majority of the risk can still be attributed to the increased incidence of conventional CAD risk factors in young people, such as obesity, inactivity, diabetes, hypertension, and dyslipidaemia.
Smoking and substance abuse are resulting in more heart disease among the young. Lesser-discussed, unconventional risk factors, such as mental stress, lack of healthy employment practices, environmental pollution, and lack of proper food safety regulations, are in fact contributing significantly to this silent epidemic. COVID-19 infection as well as vaccination were widely attributed as causes of heart attacks in young people, but without adequate scientific evidence.
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