An overview of hyperglycemia and insulin resistance in the brain
This story does not include health advice. It is for information, inspiration, and awareness purposes.
When we submitted an opinion paper with a compelling hypothesis titled “Can the Brain Be Diabetic” to a peer-reviewed journal in the early 1990s, it was rejected. The collaborators of the paper were not ordinary academicians.
They comprised a neuroscientist, a metabolic health specialist, a distinguished nutritionist (MD/PhD), and a cognitive scientist. When the dean of the faculty asked for further feedback on the rejection, the journal editor informed him that they did not publish pseudoscientific papers or conspiracy theories.
Fast forward to 2024, the CDC says,
“If your blood sugar levels fall outside of your normal range, it can throw your command center off balance. In the same way that diabetes can cause nerve damage to your eyes, feet, and hands, it can also affect your brain by damaging nerves and blood vessels. This can lead to problems with memory and learning, mood shifts, weight gain, hormonal changes, and over time, other serious problems like Alzheimer’s disease.”
Yet, Type 3 Diabetes remains unrecognized as a distinct health condition, awaiting acknowledgment from the medical establishment, a process that may take some time.
However, it is an informal term that brilliant researchers like from Nature have coined. Type III Diabetes, also known as “brain diabetes” or “diabetes of the brain,” refers to a condition where the brain cells become resistant to insulin, leading to impaired insulin signaling and glucose metabolism within the brain.
While not formally recognized as a separate type of diabetes, the term is used to describe hyperglycemia and the insulin resistance observed in the brain, particularly affecting neurological conditions like Alzheimer’s disease.
I don’t want to make this piece a scientific article, as interested readers can publicly access too many on Pubmed. However, I want to make this an informative, educative, and practical piece anyone can easily understand and take necessary precautions to lower the risks of neurodegenerative disorders like dementia.
The Impact of Insulin Resistance on the Brain
At a high level, theories exploring the link between insulin resistance in the brain and neurodegeneration propose that insulin plays a crucial role in neuronal survival, synaptic plasticity, and memory consolidation.
Disruptions in insulin signaling pathways may contribute to neuronal dysfunction and cell death, depicting the importance of understanding and addressing insulin resistance in the brain for optimal cognitive health.
Some studies suggest that insulin resistance in the brain can contribute to the development and progression of Alzheimer's disease, impairing neuronal function and promoting the accumulation of amyloid-beta plaques and tau protein tangles, characteristic of its pathology.
As documented in this 2020 MDPI paper, the connection between Alzheimer’s disease and type 2 diabetes is still debated. Poorly controlled blood sugar may increase the risk of developing Alzheimer’s, leading some to call it “diabetes of the brain” or “type 3 diabetes”.
The paper informs that recent studies suggest a link between type 3 diabetes and Alzheimer’s disease, focusing on impaired insulin signaling in both conditions. Insulin resistance affects the processing of amyloid-β (Aβ) precursor protein toxicity and the clearance of Aβ, contributing to Alzheimer’s disease progression. Insulin-related therapies may slow or halt its complications, suggesting potential treatment avenues.
My understanding from those studies cited in the paper is that diabetes in the brain brings implications like cognitive decline, memory loss, and increased risk of neurodegenerative diseases.
An Overview of Energy Metabolism in the Brain
Understanding the link between diabetes and related conditions hinges on energy homeostasis (balance), crucial for regulating feeding behavior and energy expenditure.
Neurons, lacking regenerative ability, are highly vulnerable to cellular stresses, contributing to neurodegeneration. Neurons, reliant on glucose for energy, require insulin-sensitive glucose transporters for glucose uptake.
Issues with glucose balance, including brain insulin resistance and glucose metabolism impairment, may lead to cerebral glucose hypometabolism in Type 3 diabetes.
Insulin resistance in peripheral tissues and the central nervous system can exacerbate neurodegeneration and cognitive decline. I will cover the mechanism of insulin resistance in the next section.
The desensitization of neuronal insulin receptors, which resembles Type 2 diabetes, is implicated in type 3 diabetes, highlighting the role of glucose balance in neuroendocrine disorders.
So type 3 diabetes, characterized by impaired brain glucose uptake and metabolism, bridges the gap between type 2 diabetes and neurodegenerative diseases, highlighting the intricate relationship between glucose regulation and neurological health.
While it may seem logical to supply the brain with more sugar for energy, the reality is quite different. Frequent episodes of high blood sugar, known as hyperglycemia, can stress the brain.
What’s concerning is that the detrimental effects of high blood sugar accumulate gradually over time, often without immediate notice, leaving many unaware of the impact on their brain health.
Even if we don’t consume any food for days, let alone sugar, the body can still create necessary glucose for the brain, as I explained in a previous story titled Biochemistry of Ketosis Simplified with Nuanced Perspectives and Personal Experiences.
Key Mechanisms of Insulin in the Brain
Insulin, crucial for regulating blood glucose levels, originates from pancreatic beta cells and binds to receptors, initiating actions vital for neuronal survival and CNS function.
These receptors, predominantly found in brain regions like the olfactory bulb, influence synaptic connections, neurotransmitters, and apoptosis. Insulin’s role in modulating GABA, NMDA, and AMPA mechanisms affects long-term potentiation and synaptic plasticity.
While insulin crosses the blood-brain barrier through receptor-mediated transport, its actual synthesis within the brain remains debatable.
Dysfunctions in insulin receptors may lead to brain disorders. Recent studies suggest that insulin’s transcriptional regulation influences physiological functions and disease pathways.
Reduced brain insulin levels, potentially age-related, may contribute to Alzheimer’s disease by affecting amyloid metabolism. Understanding insulin’s role in healthy and diseased brains is essential for solving its therapeutic potential in neurodegenerative conditions.
Insulin degrading enzyme (IDE) dysregulation in type 2 and type 3 models suggests a link between hyperinsulinemia, glucose intolerance, and Aβ accumulation, implicating IDE dysfunction in neurodegeneration.
IDE typically regulates insulin, Aβ, and amyloid precursor protein (APP) levels, maintaining a balance crucial for neuronal health. In type 3 diabetes, impaired insulin signaling disrupts Aβ clearance, promoting its intraneuronal buildup and subsequent neurotoxic effects.
The relationship between type 3 diabetes and brain insulin resistance remains contentious, with theories proposing Aβ toxicity-induced insulin resistance or insulin resistance-driven Aβ accumulation.
Insulin’s role in promoting Aβ trafficking and extracellular excretion while inhibiting intracellular accumulation through IDE activation emphasizes its pivotal role in Aβ metabolism.
Insulin resistance facilitates the entry of pro-inflammatory agents, leading to widespread inflammation beyond the brain and causing systemic disruption. The phenomenon of “inflamm-aging” occurs due to this inflammation, spreading throughout the body and disrupting normal physiological processes.
Thus, the convergence of type 2 diabetes and Alzheimer's disease suggests a unified approach to addressing this emerging disease entity, coined type 3 diabetes, highlighting shared molecular pathways and therapeutic targets in both conditions.
Conclusions
The concept of Type 3 Diabetes, also known as “brain diabetes,” depicts the intricate relationship between insulin resistance and neurodegenerative disorders like Alzheimer’s disease.
While not formally recognized as a separate type of diabetes, the term elucidates the insulin resistance observed in the brain, particularly in conditions associated with cognitive decline.
The emerging evidence suggests that insulin plays a crucial role in neuronal survival, synaptic plasticity, and memory consolidation, emphasizing the importance of addressing insulin resistance in the brain for optimal cognitive health.
Further research is warranted to untangle the mechanisms underlying Type 3 Diabetes and explore potential therapeutic interventions aimed at mitigating its debilitating effects on brain function.
So far, we know that insulin resistance precipitates heightened oxidative stress within the brain, resulting in harmful consequences. Oxidative stress, like the corrosion on a bicycle chain, gradually undermines cellular integrity. In this context, it impairs the functionality of brain cells and compromises the synaptic connections, facilitating inter-neuronal communication.
When oxidative stress escalates unchecked, it engenders a state of disarray akin to an unruly gathering within the brain. Consequently, cellular processes become disrupted, contributing to an unfavorable environment.
The mechanism through which insulin resistance instigates this upheaval primarily targets the mitochondria, the cellular powerhouses responsible for energy production. These mitochondria fail to function effectively when impaired, disrupting vital cellular processes. Nothing can be worse than this in our delicate brains.
Takeaways
I want to offer practical takeaways from the insights I provided in this story based on my experience as I suffered from prediabetes and abdominal obesity in my younger years.
Monitor blood sugar levels regularly to maintain optimal glucose balance and mitigate the risk of hyperglycemia, which can adversely affect brain health.
Consume a balanced diet rich in nutrient-dense foods to support overall metabolic health and promote proper glucose metabolism in the brain. Limit the consumption of processed sugars and refined carbohydrates, which can lead to fluctuations in blood sugar levels and exacerbate insulin resistance in the brain.
Move the body regularly and engage in regular physical activity (at least 150 minutes weekly) to improve insulin sensitivity and enhance glucose uptake in peripheral tissues and the central nervous system.
Get adequate sleep and manage stress to optimize brain function and mitigate the adverse effects of chronic stress on insulin signaling.
Consider mindfulness practices like meditation and diaphragmatic breathing exercises in your daily routine to reduce oxidative stress and neuroinflammation, which can impair insulin signaling in the brain.
Stay mentally active by engaging in activities that stimulate cognitive function, like reading, puzzles, and social interactions, to promote synaptic plasticity and memory consolidation.
Maintain a healthy weight through portion control and mindful eating habits to reduce the risk of obesity-related insulin resistance and metabolic dysfunction.
Stay informed about the latest research developments in neuroendocrinology and diabetes to understand better the underlying mechanisms of Type 3 Diabetes and its implications for brain health.
Advocate for increased awareness and recognition of Type 3 Diabetes as a distinct health condition to facilitate early detection, intervention, and management strategies tailored to mitigate its impact on cognitive function and overall well-being.
By implementing these practical strategies and staying informed about the evolving understanding of Type 3 Diabetes, you can take proactive steps to safeguard brain health and reduce the risk of neurodegenerative diseases associated with insulin resistance in the brain.
Thank you for reading my perspectives. I wish you a healthy and happy life.
If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.