Type 3 diabetes describes a form of diabetes that is associated with Alzheimer’s disease. Insulin resistance and insulin deficiency may play a role in the development of Alzheimer’s which leads to cognitive decline. 

The link between insulin resistance and Alzheimer’s disease is still under research, some studies show that there are links between insulin resistance and Alzheimer’s disease. 

What is Alzheimer’s disease?

A common type of dementia is Alzheimer’s disease (AD). Alzheimer’s is a neurodegenerative disease the onset of AD is very subtle and the impairment of behavioural, cognitive function, grasping, language, and attention is very progressive. 

AD can be categorised into preclinical or pre-symptomatic, mild, and dementia stages depending on the degree of cognitive impairment. The death of neuronal cells causes AD. 

Prevalence 

The seventh leading cause of death is dementia and AD is the most common form of dementia. WHO report shows that about 55 million people worldwide have dementia. 10 million new cases are being reported every year. 

Stages and symptoms of Alzheimer 

Preclinical AD

The onset of dementia or changes in brain function is called preclinical AD. 

Mild or early stage of AD  

The person may look healthy but the progression of AD will be seen gradually, this usually lasts 2-4 years. The symptoms of this stage include:  

• Memory loss. 
• Poor judgement.
• Loss of spontaneity and interest.
• Less energy
• Repetition of words or sentences.
• Coordination problems 
• Mood swings
• Language problems
  
  

Moderate AD

This stage lasts for 2 to 10 years, the progression of memory loss gets worse and it will cause problems to daily life activity. The symptoms of this stage include:  

• Difficulty in talking.
• Difficulty in planning.
• Hard time remembering the date, time, and place.
• Getting angry easily. 
• Difficulty falling asleep.
• Wanders off 
  
  

Severe or late stage of AD

Patients with severe AD depend fully on the caretaker. Patients may also be bedridden in this stage. This stage usually lasts 1 to 3 years. 

• Difficulty in remembering the past and present.
• Difficulty in remembering themselves.
• Problems with controlling their bladder and bowel movement. 
• Presence of weight loss, skin infections and seizures. 
• Severe mood swings
• Development of hallucinations. 
• Difficulty in mobility
  
  

Diagnosis of Alzheimer’s disease 

Alzheimer’s disease can be diagnosed by various test methods including:

• Positron emission tomography (PET)
• Magnetic resonance imaging (MRI)
• Biomarkers in cerebrospinal fluid (CSF)
• Volumetric data
• Diffusion tensor imaging (DTI)
• PET scan
• Blood test 

Risk factors of Alzheimer’s:

Modifiable factors

• Type 2 diabetes
• Obesity
• Cardiovascular diseases
• Stroke
• Depression
• Traumatic brain injury 
• Air pollution
• Lifestyle
• Smoking 

Non-modifiable factors

• Age
• Sex
• Race 
• Genetic mutation
• Genetic polymorphisms

What is Type 3 Diabetes?

Type 3 diabetes is a term that describes a link between chronic insulin resistance and deficiency of insulin in the brain and Alzheimer’s disease. According to this theory, a disruption in insulin signalling and glucose metabolism in the brain contributes to the development of Alzheimer’s disease. 

Pathophysiology between AD and T2DM mechanisms 

• Role and production of insulin in the brain

The brain needs a lot of energy to work, more than any other part of the body. It relies on about a quarter of a pound of glucose every day, which is its main fuel, to produce the ATP it requires for functioning. 

The insulin derived from pancreatic neural insulin is the highest percentage used in the brain. Insulin enters the brain mainly by the blood-brain barrier (BBB). This is affected by factors such as diabetes, obesity, inflammation, and triglyceride levels in the blood. 

Many important functions in the brain that are related to the regulation of food intake, body weight, eating habits, and homeostasis of energy are performed by insulin. Insulin also affects neurotransmitters. It also acts as a regulator for long-term memory enhancement and long-term memory suppression.  

• Insulin resistance and β-Amyloid 

The formation of amyloid (a non-crystalline compound, extracellular material gets accumulated in various tissues) is found in Alzheimer’s disease and type 2 diabetes. Accumulation of β-Amyloid forms oligomers. Oligomers are toxic to nerve cells. It is involved in the progression of AD. 

Insulin resistance and decreased levels of IGF-1 will result in decreased levels of brain uptake of insulin and GLP-1, which causes accumulation of β-Amyloid. 

Secretion of inflammatory agents is when the β-Amyloid levels are increased and this results in an on-set of insulin resistance. 

Degradation of β-Amyloid peptidase is mainly by insulin degrading enzymes (IDE). IDE has the ability to degrade insulin, β-Amyloid, and amylin. IDE plays a linking role in insulin resistance and AD. 

• Neuroinflammation 

Activation of the brain’s innate immune system in response to an inflammatory condition is called neuroinflammation. It usually occurs in the early stages of AD. 

Insulin resistance and IGF-1 resistance are caused mainly by neuro-inflammation in the brains of AD patients. 

• Oxidative stress and mitochondrial dysfunction

Oxidative stress which leads to the neuro-degeneration of AD is promoted by insulin resistance in type 2 diabetes. Imbalance of reactive forms of oxygen and nitrogen results in oxidative damage. This results in the oxidation of lipids, protein, and DNA which causes damage to the mitochondria, and genetic mutations in DNA/RNA. 

The presence of oxidative stress compounds in neurofibrillary tangles, neuronal degeneration, and attenuation of ATP production are the most active forms of damage caused by active forms of oxygen produced by oxidative stress in Alzheimer’s disease.
 

• Advanced glycosylation end products (AGEs)

In the AD, advanced glycosylation end products (AGEs) play an important role. Neurotoxic effects are observed in AD because of the formation of amyloid oligomers, which the AGEs promote. AGEs accumulate in cells, in people with diabetes the rate of accumulation is increased.  

• Metabolic syndrome 

In people with diabetes, insulin resistance is connected to a reduced rate of glucose metabolism in the brain. In AD, the brain’s capability of using glucose for function is reduced by 25%. 

• Amylin  

Amylin is a hormone secreted along with insulin by the pancreas. Its function is to induce satiety, inhibit glucagon secretion, and delay gastric emptying. Amylin levels are found in the brains of AD patients using immunofluorescence. 

Amylin acts on the neurons and causes intracellular oxidative stress and inflammatory responses. 

Amylin deposits in the amyloid plaques and mixed amylin-β- plaques. For therapeutic approaches, amylin resistance and hyperamylinemia can be targets. 

Dietary therapy in type 3 diabetes

Studies show that consumption of PUFA and DHA-rich food inhibits the β-Amyloid and tau protein production and helps neurons maintain normal function. An increased risk was linked to low intake of n-3 fatty acids, B vitamins, and antioxidants. 

Consuming phytochemicals has a beneficial effect on diabetes, they help regulate blood glucose concentration, decrease cognitive decline progression, improve insulin resistance, and improve inflammation and/or oxidative damage. 

The risk of AD can be reduced by consuming legumes, nuts, omega-3 fatty acids, vegetables, whole grains, and fruits in higher quantities. Studies show that consumption of plant-based diets showed a higher risk reduction of AD. 

• Omega-3 rich foods: Nuts and seeds like almonds, walnuts, chia seeds, flaxseeds, and pumpkin seeds, salmon, mackerel, tuna, herring, and sardines, flaxseed oil, soybean oil, and canola oil, fortified foods such as yoghurt, milk, eggs and soy.
  
  
• Vitamin B rich foods: Spirulina powder, goat liver, octopus, caviar, mussels, salmon, oyster .
  
  

Conclusion 

AD is caused by many factors and one main factor is insulin resistance. AD caused by insulin resistance is called type 3 diabetes, brain insulin resistance is an important feature of AD. 

Correcting brain insulin resistance can be one of the efficient treatment methods. Studies show that age-related brain insulin resistance can be reduced. People with prediabetes should make lifestyle changes to reduce the risk of peripheral insulin resistance.

 Kripa N
 Senior Clinical Dietitian, Simplyweight