Brain Insulin Resistance and the Epidemics of Diabetes and Alzheimer's Disease. Clinical trial on Intranasal Insulin Showed Mixed Results
Brain Insulin Resistance and the Epidemics of Diabetes and Alzheimer's Disease. Clinical trial on Intranasal Insulin Showed Mixed Results
Review of the evidence of a common link - and news of results of a clinical trial of intranasal insulin (MemAID).
Having type 2 diabetes mellitus (T2DM) can increase the risk of developing Alzheimer’s disease and related dementias (ADRD). Properly managing T2DM can help reduce the risk of developing ADRD.
Scientists are trying to figure out how brain insulin resistance works in three different situations. The first is when someone has type-2 diabetes, and it affects their thinking. The second is when type-2 diabetes might cause a person to have a neurodegenerative disease, like dementia. The third is when someone has dementia but doesn't have type-2 diabetes. We do not yet fully understand how brain and systemic insulin resistance, thinking, Alzheimer's disease, and related dementias are connected. Here’s an introduction to the problem, more fully explored in this review.
Insulin is a hormone made up of 51 amino acids and is produced by the pancreas. It helps to keep blood sugar levels in the body at a healthy level. It does this by helping the body use glucose from food for energy and by stopping the liver from making too much glucose. Insulin also helps with other processes in the body, like storing energy and helping cells grow. Diabetes mellitus is a condition where there isn't enough insulin or it doesn't work properly. Type 1 diabetes mellitus is usually caused by the body's immune system attacking the cells that make insulin, while type-2 diabetes (T2DM) happens when the pancreas fails to make enough insulin to overcome resistance in the body, which can be caused by things like being overweight, not exercising enough, or getting older.
T2DM is very common and should be taken seriously as a public health issue. Type 2 diabetes mellitus and ADRDs are two of the most common health issues today. Over 8.5 million Americans have T2DM. In the video below, John Campbell breaks down the data; 11.3% of Americans have T2DM, and 96 million are pre-diabetic.
Scientists have found that there are many similarities between T2DM and ADRDs, such as risk factors, comorbidities, and how they affect the body. Most importantly, insulin resistance is a major factor in both T2DM and ADRDs.
Researchers are studying how insulin works in the brain to better understand these conditions and develop treatments for them. In fact, research exists on the effects of intranasal insulin (INI). A small and short-term small, randomized control trial of intranasal insulin in humans (MemAID) published in 2020 found evidence for the positive effects of intranasal insulin on cognition and gait in patients who received the treatment. INI-treated T2DM participants walked faster and had increased cerebral blood flow and decreased plasma insulin. Controls, who received saline, had improved executive functioning and verbal memory.
The control group (saline) had better executive functioning, but this is likely due to the negative effects of the release of aluminum caused by the breakdown of amyloid aggregates. In my view, patients in the MemAID trial should have been given aid in detoxification with a week-long administration of glutathione-enhancing organic chlorella and spirulina and instructed to not take acetaminophen during the trial period for headaches. Citations and videos are below.
Citations:
The Review
Arnold SE, Arvanitakis Z, Macauley-Rambach SL, Koenig AM, Wang HY, Ahima RS, Craft S, Gandy S, Buettner C, Stoeckel LE, Holtzman DM, Nathan DM. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol. 2018 Mar;14(3):168-181. doi: 10.1038/nrneurol.2017.185. Epub 2018 Jan 29. PMID: 29377010; PMCID: PMC6098968. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098968/
MemAID Trial
Novak V, Mantzoros CS, Novak P, McGlinchey R, Dai W, Lioutas V, Buss S, Fortier CB, Khan F, Aponte Becerra L, Ngo LH. MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial. J Neurol. 2022 Sep;269(9):4817-4835. doi: 10.1007/s00415-022-11119-6. Epub 2022 Apr 28. PMID: 35482079; PMCID: PMC9046533. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046533/
I see DISH, also strongly correlated with diabetes, in my patients everyday. These are people who have not been diagnosed with diabetes. A very small percentage may have been told that they were prediabetic years before. No dietary or lifestyle advice from their docs.
I also see a lot of Dupuytren's contracture and trigger finger, aka diabetic hand. None have been diagnosed or realize that they have been insulin resistant for years.
I am also seeing a lot of tremors in over 60's, with no diagnosis. Usually told they are familial.
"In my view, patients in the MemAID trial should have been given aid in detoxification with a week-long administration of glutathione-enhancing organic and spirulina and instructed to not take acetaminophen during the trial period for headaches."
I like that you added this. I concur.