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How Uncontrolled Diabetes Is Linked to Cognitive Impairment

The relationship is complicated, but the solutions are simpler.

Thoughtful old manThoughtful old man

A team of Spanish researchers has examined how glucose imbalance leads to neurological disorders through the failure of adipocytokines.

What are adipocytokines?

These compounds’ name seems a bit concerning: “adipo-” refers to fat, and a cytokine is a cellular signal most commonly known for being part of the deadly cytokine storm associated with severe immunological problems. However, the two adipocytokines that these researchers studied, adiponectin and leptin, have a beneficial, neuroprotective effect through specific receptors in the brain [1].

The researchers cite a great number of previous studies, some of which are contradictory, in elucidating this relationship. They note another hypothesis that suggests that the ratio between these two compounds (Ad/L) is the most important; however, previous research in this direction has also been contradictory.

However, one thing is clear: metabolic syndrome is dangerous to the brain, as inflammation and hyperglycemia (a characteristic symptom of diabetes) are linked to cognitive impairment through the infliction of oxidative stress [2].

A Bayesian examination

Using Bayesian computer modeling, the researchers set out to examine the precise relationship between metabolic syndrome and brain dysfunction. What they discovered was an extremely complicated relationship between the Ad/L ratio, insulin resistance, and triglycerides or glucose. In the case of elevated triglycerides and high insulin resistance, a higher Ad/L ratio was neuroprotective; however, if glucose was elevated instead, this ratio became associated with reduced cognitive function.

Most critically, and most understandably, the researchers singled out glucose metabolism as playing a key role in the loss of neuroprotection. Even in the presence of insulin resistance, if glucose is controlled, adipocytokines can continue to protect the brain; if it goes out of control, this protective ability is lost.

Furthermore, the researchers single out a particular part of the brain as being particularly vulnerable: the rostral anterior cingulate cortex (rACC). This is responsible for carrying information between key areas of the brain, such as behavior, decision making, learning, and memory.

The authors of this study cite prior research showing that lifestyle interventions, such as diet and exercise, are the best way of preventing this decline [3]. However, they go further by saying that it may be worth investigating treating sufferers of metabolism-related cognitive impairment with the adipocytokines involved, particularly leptin, which has shown beneficial effects in the brains of people with a genetic deficiency.


This study is extremely complicated, merging together several seemingly contradictory explanations for how insulin, glucose, and fats interact within the brain. The researchers actually hold that it may not be detailed enough; they were unable to examine every related hormone, for example, and they state that sex-based differences, preclinical Alzheimer’s disease, and other, undiscovered issues may have played various roles in their results.

While this research clearly warrants further investigation, it may be worth a clinical trial to determine if the administration of adipocytokine-enhancing drugs is beneficial. Furthermore, this research makes it even more clear just how harmful uncontrolled glucose is and how important living a healthy lifestyle is, even for rarely mentioned parts of the brain.

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[1] Harvey, J. (2007). Leptin: a diverse regulator of neuronal function. Journal of neurochemistry, 100(2), 307-313.

[2] Etchegoyen, M., Nobile, M. H., Baez, F., Posesorski, B., GonzΓ‘lez, J., Lago, N., … & Otero-Losada, M. (2018). Metabolic syndrome and neuroprotection. Frontiers in neuroscience, 12, 196.

[3] Atienza, M., Ziontz, J., & Cantero, J. L. (2018). Low-grade inflammation in the relationship between sleep disruption, dysfunctional adiposity, and cognitive decline in aging. Sleep medicine reviews, 42, 171-183.

About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called β€œreal life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.
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