Uncontrolled Diabetes and Alzheimer’s Disease: Type 3 Diabetes?

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Introduction   

According to the Centers for Disease Control and Prevention, it is estimated that there are 38.4 million people of all ages—or 11.6% of the U.S. population—living with diabetes as of the year 2021 (1). The percentage of adults with diabetes has been found to increase with the aging process, evidenced by the fact that 29.2% of adults aged 65 years and older have been diagnosed with this chronic medical condition. As of 2021, diabetes is currently listed as the 8th leading cause of death globally (2). 22.8 percent of all adults, in the United States, with diabetes were not aware that they had diabetes, and another estimated 97.6 million adults were diagnosed with prediabetes (as of 2021). Left untreated, the condition prediabetes will progress to full blown diabetes in an average of 4-5 years.  This single chronic medical condition is indeed a growing epidemic.  

According to the Alzheimer’s Association, nearly 7 million people are currently living with Alzheimer’s Disease, and this chronic medical condition is, (as of 2021), listed as the 5th leading cause of death in people over the age of 65 years (3). Although age is the greatest risk factor for Alzheimer disease, it is not a normal part of the aging process (4). Between 2000 and 2018 the deaths from heart disease have gone down 7.8%, while the deaths from Alzheimer’s disease have increased by 146% (15). Although there is no known cure for Alzheimer’s Disease at this time, treatments are available to address symptoms (including medications to either slow the progression of the disease or treat isolated symptoms of the condition).  

Diabetes is currently the 8th leading cause of mortality. A common link between the two is the insulin insensitivity that can lead to memory deficit and cognitive decline. (13)  

The purpose of this course is to introduce healthcare professionals to the research findings indicating that the causes and long-term effects of chronic poorly controlled Type 2 diabetes may indeed be directly affecting the cognitive decline associated with Alzheimer’s Disease. In doing so, clinicians will be educated on the importance of early intervention on chronic disease management to lower the incidence of long-term complications. 

Definitions 

Alzheimer’s Disease is a neuroendocrine disease that involves impaired insulin regulation and insulin like growth factor signaling. Both conditions can result in inflammation and oxidative stress. Although there is hesitancy in the medical community to directly relate such independent risk factors as obesity and Type 2 diabetes to Alzheimer’s Disease, there is increasing evidence that suggests that oxidative stress and beta amyloid build-up associated with Alzheimer’s Disease is influenced by the these traditionally “diabetes” related effects and is resulting in altered neurological pathways. Ongoing research is finding in favor of the development of Alzheimer’s Disease actually being more of a metabolic disease in which the brain loses its capacity to effectively utilize the available circulating glucose for energy production. (5, 6) 

Type 3 Diabetes is used to describe the effects of insulin resistance and insulin like growth factor dysfunction on the brain, which leads to increasing levels of cognitive decline and dementia. It is believed that untreated/ uncontrolled/poorly treated diabetes can cause damage to blood vessels, including vessels in the brain. The chronic inflammation that occurs systemically due to hyperglycemia leads to injury of both the brain vessels and surrounding tissues. Studies have shown that persons with poorly controlled Type 2 diabetes may be at very high risk of (45-90%) for the development of certain types of dementia. (7,8). Chronic insulin impairment has been found to compromise neuronal survival, as well as brain matter integrity, further increasing the risk of cell death. 

Research has found that the younger a person is, at the age of onset of Type 2 diabetes, the higher the risk of development of some form of dementia in later life. (9) The thought behind this statement is that living with Type 2 diabetes, especially poorly controlled/ uncontrolled in its management, exposes a person to a higher percentage of glycemic events, both hyperglycemic and hypoglycemic, subjecting the brain (and body) to the untoward effects of glycemic imbalances and insulin resistance. (In comparison, the majority of Type 1 diabetes diagnosis are caught early and treated more aggressively over the person’s lifetime).  

Researchers noted the following connections: 

• a 70-year-old diagnosed with Type 2 diabetes had an 11 percent increased risk for later developing dementia 

• a 65-year-old diagnosed with Type 2 diabetes had a 53 percent increased risk for later developing dementia  

• a 60-year-old diagnosed with Type 2 diabetes had a 77 percent increased risk for later developing dementia  

Furthermore, the brain normally uses large amounts of glucose to function properly. With hyperglycemia and insulin resistance, the hallmarks of Type 2 diabetes, there is ongoing interruption of cellular metabolism which affects a person’s ability to both form and retrieve memories (10).  

Diabetes Categories  

First, a quick review of the categories of diabetes (***both recognized and proposed types) (11): 

• Type 1 diabetes: absolute insulin deficiency due to beta cell destruction 

• Type 2 diabetes: progression of insulin defects in secretion as well as insulin resistance. 

• Gestational diabetes: type of diabetes that occurs due to the hormonal changes that take place during a pregnancy.  

• Mature onset diabetes of the young (MODY): a type of diabetes occurring due to a genetic change, often runs in families. Children with the genetic change will often develop this form of diabetes by the time they are 25. 

• Latent autoimmune diabetes in adults (LADA): This type of diabetes is also referred to as Type 1.5 diabetes; it is an autoimmune disease; persons are often mistaken for T2DM initially, as they may be able to produce insulin for a given time period.  

• Type 3 diabetes is a proposed term for diabetes in which long term insulin resistance, and the resulting accumulation of toxins, inflammation, and neuronal level stress may be causing the cognitive decline seen with Alzheimer’s Disease.  

• Type 4 diabetes is a proposed term for diabetes caused by insulin resistance in older people who are not overweight or do not have obesity. This type of diabetes is not widely recognized or diagnosed as such, because the typical client is not overweight or they do not have obesity, but are simply older in age.   

Symptoms of Type 3 Diabetes 

Symptoms of Type 3 diabetes may include the following (12): 

• Memory loss that affects daily living and social interactions 
• Difficulty completing familiar tasks (routine daily tasks like basic hygiene, cooking, reading comprehension 
• Misplacing/ losing things often; forgetting where something has been placed 
• Decreased ability to make judgments based on information; poor judgement 
• Sudden changes in personality or demeanor, often unrelated to current circumstances 
• Confusion about location or time 
• Increasing withdrawal form previously enjoyed social situation or familiar work setting 

Subtypes of Alzheimer’s Disease 

There are six subtypes of Alzheimer’s Disease (14): 

Pathophysiology 

There are various theories as to how Type 2 diabetes could lead to Alzheimer’s dementia. Poorly controlled diabetes can affect the following (16): 

• Increases the risk of heart disease and stroke, which may affect overall brain health 
• Increases the risk of the development of narrowed arteries due to lipid dysfunction; thus, compromising blood flow to the brain 
• Increases the risk of hypoglycemia, which damages the hippocampus, the part of the brain responsible for cognitive function 
• Increases the risk of hyperglycemia which may impact the development of high levels beta amyloid plaques in the bloodstream 

Symptoms of Poorly Controlled Diabetes 

In order to fully appreciate the effects of both hypoglycemia and hyperglycemia on the functioning of a brain, consider the following diabetic scenarios and pay attention to the symptoms highlighted in bold. You can quickly see how extremes in blood glucose affect the client’s levels of alertness, responsiveness, and orientation. Multiply these effects over several years, as is often the case in a chronic, poorly managed medical condition, and the results add credibility to this proposed neuro-endocrine disconnection. 

Glucose ranges: 

• Hypoglycemia: below 70mg/dl 
• Fasting: Below 99mg/dl is normal 
• Prediabetic: 100-125mg/dl 
• Diabetic: 126mg/dl and above 
• Hyperglycemia: over 180 mg/dl (non-fasting) 
• Diabetic ketoacidosis: over 250 mg/dl with confirmed ketones 

Hypoglycemia 

Researchers found that “4 in 5 people with Type 1 diabetes and nearly half of all people with Type 2 diabetes who take insulin reported a low blood sugar episode at least once over a four-week period” (17,18). Multiple these single statistics over the years that a person may be diabetic and see the emerging connection to chronic brain effects.  

Signs/symptoms of hypoglycemia: 

• Weakness 
• Dizziness 
• Anxiety or irritability 
• Extreme hunger  
• Confusion or trouble concentrating/ speaking 
• Blurred vision 
• Slurred speech and difficulty in coordination  
• Seizures 
• Loss of consciousness 

Hyperglycemia 

Hyperglycemia often goes undetected for years before a person detects physical symptoms that cause them to seek medical attention. In the meantime, chronic elevated levels of glucose continue to cause system wide inflammation and increasing insulin resistance. (19)   

Signs/symptoms of hyperglycemia: 

• Tiredness 
• Listlessness 
• Nausea 
• Frequent urination 
• Dizziness and drowsiness 
• Confusion  
• Loss of consciousness  

Hypoglycemia Unawareness 

Hypoglycemia unawareness refers to a client’s repeated episodes of hypoglycemia (below 70 mg/dl and frequent episodes below 55 mg/dl) so much so that they no longer produce the typical signs and symptoms of a low blood sugar; thus, oftentimes to not seek emergency treatment until the situation is life threatening (20).  

The risk of life-threatening hypoglycemia is elevated. Hypoglycemia unawareness can lead to: 

• Confusion 
• Slurring of speech 
• Unconsciousness, seizures 

Diabetic Ketoacidosis 

Diabetic ketoacidosis (DKA) is a condition in which glucose levels are greater than 250 mg/dl with confirmed ketones (21,22). This usually occurs in the presence of acute illness (heart attack or stroke), or infection (pneumonia or urinary tract infections). In addition, the suboptimal use of insulin therapy (missed doses, partial doses) may trigger this condition.   

Signs/symptoms of DKA: 

• Fast, deep breathing. 
• Dry skin and mouth. 
• Flushed face. 
• Fruity, acetone smell on breath 
• Headache 
• Excessive thirst 
• Frequent urination 
• Muscle stiffness or aches, weakness 
• Nausea and vomiting, abdominal pain 
• Disorientation and decreased alertness 
• Confusion  
• Loss of consciousness 

Hyperosmolar Hyperglycemic NonKetotic Coma 

Hyperosmolar Hyperglycemic NonKetotic coma (HHNK), also known as ‘hyperosmolar, hyperglycemia syndrome’, is a metabolic complication that occurs in the presence of overwhelming physiologic stress (acute infections, and oftentimes, as a side effect of medications that impair glucose tolerance). The result is overwhelming dehydration, due to extreme hyperglycemia.  Glucose levels are greater than 600 mg/dl with no ketones (23,24). 

Signs/symptoms of HHNK: 

• Altered level of consciousness 
• Confusion 
• Disorientation 
• Extreme dehydration 
• Focal or generalized seizure activity 
• Transient hemiplegia (post seizure activity) 
• Coma 

Causes of Type 3 Diabetes 

Causes of Type 3 Diabetes include (25, 26, 27): 

• Uncontrolled/poorly controlled/ undiagnosed diabetes- chronically elevated blood glucose levels increase system wide inflammation; damaged (especially) brain blood vessels are at high risk for dementia, vascular insufficiency, stroke syndromes and more. Ongoing inflammation also created further cellular damage, decreasing the effective of circulating insulin. 
• Development of beta amyloid plaques/proteins, interfering with proper brain communication pathways 
• Tau protein dysfunction (“tangled tau”) chronic inflammation causes disruption of normal pathways within microtubules 
• Amyloid-beta protein dysfunction (build up that has been found to damage brain cells and worsen insulin resistance 
• Insulin resistance in the presence of chronic inflammation, brain cell nutrition is compromised. Chemical imbalances further result in blocking normal nerve pathways and increases in oxidative stress from circulating free radicals (toxins)  
• Genetic predisposition and APOE4 protein gene variant that binds to insulin receptors on neurons 
• Chronic poor diet and nutrition including heavily processed foods, often containing high calorie, sugar, fat percentages, as well as chemical, additives and preservatives. 
• Lack of physical activity 
• Lifestyle behaviors (lack of physical activity, recreational usage of drugs and alcohol, sedentary lifestyles, poor stress management and sleep hygiene practices) 
• Ethnicity higher risk of dementia in certain populations (African American and Hispanic) 
• Environmental exposures to chemical compounds, found in foods, that may cause insulin resistance  

Clinical Signs and Symptoms of Dementia 

When assessing a client for underlying dementia, many subtle signs and symptoms can be attributed to other conditions (medication side effects, underlying depression, and age-related changes). The following eight “A’s of dementia” serve as a guidelines as to what assessment findings are indeed “not age related” but indicative of additional diagnostics to rule out underlying cognition issues (28). 

8 A’s of Dementia: 

• Anosognosia- clients that are not aware of their disability, in this case, being cognitive decline 
• Agnosia-clients are unable to recognize previously familiar stimuli (unable to recognize and identify family members and friends) 
• Aphasia-clients are unable to express language skills (difficulty in reading, writing, and speaking) 
• Apraxia-difficulty in performing skilled motor tasks (unrelated to muscle strength and coordination) 
• Altered perception-the onset of changes in vision, hearing and touch begin to manifest as feelings of paranoia, visual and auditory hallucinations, and possible delusions 
• Amnesia-memory loss that affects the client’s ability to perform once favorable activities, their mood and personality; memory loss may cause client to repeatedly ask the same questions and become easily agitated 
• Apathy-lack of interest and withdrawal from daily activities; increasingly disengaged in daily behaviors 
• Attention deficit-client appears unable to carry out basic daily activities, becoming easily distracted or confused 

Etiology of Type 2 Diabetes 

Factors that may increase the risk of type 2 diabetes include (29): 

• Obesity or overweight (cells become resistant to insulin in the presence of increased fatty tissue) 
• Physical inactivity 
• Family history (having family members with type 2 diabetes increases a person’s risk, but this risk factor is more influenced by lifestyle than genetics) 
• Race and ethnicity (certain races and ethnicities have higher rates of T2DM) 
• Serum lipid levels 
• Age (over the age of 45 increases risk factor, but is more so dependent on lifestyle and overall health practices than actual age) 
• Preexisting prediabetes or metabolic syndrome 
• Preexisting gestational diabetes 
• Preexisting polycystic ovary syndrome (PCOS) 
• Preexisting medical conditions such as hypertension, high cholesterol, and nonalcoholic fatty liver disease (NAFLD) 

Etiology of Alzheimer’s Disease 

A basic overview of tau tangles and beta amyloid plaques: 

Tangled Tau: Tau protein is a protein found in a neuron. The goal of tau protein is to help stabilize the microtubules, which in turn support healthy neuron functioning by guiding nutrients from cells to the axon and dendrites. In a diagnosis of Alzheimer’s disease, the tau protein forms tangles (abnormal clumping of protein) that actually harm neuronal structures. In doing so, normal synaptic communication is compromised. This type of tau protein dysfunction is referred to a tauopathy, and is a hallmark finding in many neurodegenerative diseases, including frontotemporal dementia.  

Beta Amyloid Plaques Buildup: In comparison, beta amyloid plaques are the unusual clumps of a beta amyloid protein normally found in the tissue between the nerve cells. Along with these unusual plaques, there have been noted bits of neuronal degeneration as well. Normal healthy amyloid proteins are involved in neuroprotection, such as healing after a brain injury, or sealing off leaks in the blood brain barrier. The plaque formations seen in Alzheimer’s Disease are considered to be mutations of the normal protein. 

Additional Risk factors for Alzheimer’s Disease: 

• Age over 65 years old 
• Family history of Alzheimer’s disease 
• Preexisting medical conditions such as cardiovascular disease, hypertension, obesity, and high cholesterol levels 
• Personal history of severe head injury/traumatic brain injury 
• Genetic predisposition and APOE4 protein gene variant that has been found to bind to insulin receptors on neurons 

Treatment 

Reducing the Risk 

Lifestyle behaviors play a big role in reducing a person’s risk of chronic medical conditions such as diabetes and dementia (31): 

• Maintaining optimal body weight. Weight loss of 5-7 percent, for those with excessive body weight, may reduce the risk of diabetes. 
• Daily physical activity of at least 30 minutes a day improves overall health, and well-being, helps in maintaining body weight, lowers stress levels, and improves sleep patterns.  
• Nutrition/dietary patterns that include fresh fruits and vegetables, lean protein, and limited processed and refined foods improve overall health and immunity. 
• Smoking cessation 

Self-Management 

Self-management specific to Type 2 diabetes is centered around healthy lifestyle behaviors, risk reduction, preventive screenings, medication compliance, and ongoing diabetes self-management education (32). A comprehensive plan of care not only reduces the episodes of poorly controlled/uncontrolled hyperglycemia, but also lowers the risk of long-term complications, permanent disability, and poor health outcomes. 

Self-care practices / lifestyle behaviors include the following: 

• Routine daily assessments of blood glucose levels (knowledge is power, as you cannot successfully treat what you don’t know exists) 

• Healthy diet that is nutrient dense, calorie controlled, carbohydrate sufficient, and ???? processed and refined foods and beverages 

• Medication compliance, with ongoing communication between client and provider 

• Risk factor reduction (smoking cessation, proper sleep hygiene, avoidance of illicit drugs, minimal alcohol consumption, daily physical activity (healthcare provider guidance of intake and medication effects)  

• Wellness/ annual/ preventive health screenings, immunizations, biannual dental screenings, daily self-care behaviors 

• Ongoing diabetes self-management education 

The following self-care practices are recommended to lower the risk of Type 3 diabetes and the associated cognitive decline: 

• Activities that focus on mental stimulation (crossword puzzles)  

• Socialization (loneliness heightens risk of social withdrawal, negatively affecting mental health) 

• Learning new activities and hobbies (learning to play a musical instrument, learning a new foreign language, taking dance lessons) 

• Do not say you’re simply “getting old”; avoid negating concerns of cognitive decline by rationalizing its “just part of growing old”.  

• Open dialogue with healthcare provider to discuss concerns regarding cognitive issues; early detection and intervention of any neurology related conditions lowers long term complications.  

Self-care practices for “better brain health” may not show up on traditional hospital discharge paperwork, nor be part of a traditional hospital stay. Consider the contents in this course and answer the following questions. 

Research Findings 

The researchers continue to study the connection between diabetes and brain health. With both Type 2 diabetes and Alzheimer’s Disease both being confirmed in increasing numbers worldwide, studies are being conducted that continue to show evidence that impaired insulin function and glucose intolerance are major factors in ongoing brain health. As the younger population, including children, continue to test positive for Type 2 diabetes, the focus will be on risk reduction, healthier eating habits, increased activity, and ongoing monitoring. Early intervention and aggressive management can halt and reverse this medical condition and thus, lower the long-term effects on brain health. The focus on both medical conditions needs to occur simultaneously in order to successfully impact the current trajectory of both chronic diseases and their related mortality. (33,34) 

Alzheimer’s Disease does not have a cure at this time. Clients with Alzheimer’s have access to ongoing clinical trials, support groups, and medical therapies. A new focus, though, in the functional medicine arena of healthcare, has expanded research to include other variables that may actually be negatively impacting both chronic medical conditions.  

The long-term effects of chemically refined and processed foods in our diets, the ongoing use of pesticides and herbicides in our food production, and the inclusion of genetically modified organisms (GMO’s) are being studied with interesting outcomes on our overall health. While these foods and products have government level approval, the studies are showing that in certain groups, sensitivities are being developed to these products and affecting people at the cellular level.  

The endocrine disrupting chemicals (EDCs), often found in products such as household cleaners, plastics, detergents, and even personal care products, are considered obesogenic (promoting fat storage, and affecting appetite and satiety), as they interfere with hormone action. In addition, EDCs can cause T2DM as they are known to alter beta cell function and impact, therefore, insulin resistance. Future studies in the area of risk reduction for chronic disease may include unique lifestyle behaviors such as nutrition label reading for GMO ingredients, removal of plasticware from the kitchen, overhauling household cleaning supplies and steering one’s diet to organically grown food products, a shift from the traditional “counting carb intake” to “counting chemical exposure”.  

Case Study 

Your client is a 75-year-old White male, with a dual diagnosis of T2DM and Alzheimer’s Disease. His wife reports the current diabetes diagnosis was confirmed 10 years ago, while the Alzheimer’s diagnosis is relatively new (less than 12 months ago). The client is having frequent episodes of hyperglycemia, and his wife suspects medication noncompliance is an issue (“I’m not sure he is taking his medications as they were prescribed”). The client is alert, oriented x 2, and cooperative with your interview and assessment.  

• What education could you offer the client and his wife on achieving better glycemic control? 
• What questions would you ask about their typical meals at home? 
• What would you say to a client who says they mostly eat fast food due to a lack of interest in cooking at home?  
• What instructions and follow-up care should be given regarding this client’s dual diagnosis of diabetes and Alzheimer’s Disease? 
• What community resources are available for this client and his wife, regarding ongoing Alzheimer’s care? 

During his hospital stay, this client is diagnosed with a significant urinary tract infection. Left untreated (or poorly treated), this client is at high risk for urosepsis.  

• What additional client education do you offer this client and his spouse at time of discharge? 

The wife reports she “thinks her husband isn’t taking his evening medication” anymore. She reports finding some of his medications in the bathroom sink on occasion. She states that she doesn’t want to confront him on the situation, as he “tends to get annoyed with me quite easily sometimes.”  

• What additional family education/ interventions might be offered to improve client compliance?  

• What signs and symptoms do you instruct the spouse to look for, with respect to a worsening urinary tract infection?  

Conclusion

As stated throughout this course, Alzheimer’s Disease does not have a cure at this time. What is important to note is that Alzheimer’s Disease is not a normal part of the aging process. In light of the current research involving glucose levels on brain health, it is imperative to aggressively manage one’s chronic diabetes, along the life spectrum, to lower the risk of diabetic emergencies (both hyperglycemic and hypoglycemic) that can negatively impact brain glucose metabolism.  

Additional Resources/ External Websites:  

• Alzheimer’s Association 
• Alzheimer’s Clinical Trials 
• Alzheimer’s Disease International  
• American Diabetes Association  
• National Institute of Aging

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