Non-diabetic low insulin maybe not so good?

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Brian4
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Non-diabetic low insulin maybe not so good?

Post by Brian4 »

I was at first delighted with my amazingly low insulin, but I did some digging, starting here, and began wondering whether it might not be so great to have really low insulin, even in the complete absence of diabetes.

Has anyone dug into this? I'm inclined to think the finding of low insulin in non-diabetics and later development of amyloid deposition and (a separate matter) dementia, is not causative; specifically, that the people with low insulin are probably malnourished, or perhaps even have already begun to develop dementia.

The key (worrying) paper is:

Differential effects of blood insulin and HbA1c on cerebral amyloid burden and neurodegeneration in nondiabetic cognitively normal older adults.

I have the full paper if anyone wants it. Just message me.

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Re: Non-diabetic low insulin maybe not so good?

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Brian4 wrote:Has anyone dug into this? I'm inclined to think the finding of low insulin in non-diabetics and later development of amyloid deposition and (a separate matter) dementia, is not causative; specifically, that the people with low insulin are probably malnourished, or perhaps even have already begun to develop dementia.
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Brian, thanks for the interesting articles! I will need to re-read, but I believe the issue is not low levels of insulin, but rather low effectiveness of your insulin. I've been a diabetic for twenty years, and in my experience low effectiveness results in higher levels of insulin, not less. That is, until your pancreas can no longer keep up... I would think that having low levels of insulin would mean that you are making very efficient use of your insulin and therefore are probably okay inflammation wise. insulin is a big jagged molecule, and it has long been a theory of mine that it is the insulin itself physically damaging small blood vessels that is causing most bad diabetic outcomes. But I could just be blowing smoke!
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Re: Non-diabetic low insulin maybe not so good?

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Mike, thanks. I hope you're right. The problem is that the "worrying" paper showed that low insulin, even in non-diabetics, was correlated with amyloid deposition and dementia. Hope someone follows up on that research.
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Re: Non-diabetic low insulin maybe not so good?

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from the abstract:
Our results suggest different roles of insulin and HbA1c in AD pathogenesis, in that decreased blood insulin below optimal levels may contribute to increasing cerebral Aβ deposition and neurodegeneration whereas impaired glycemic control may aggravate neurodegeneration through a nonamyloid mechanism in nondiabetic CN older adults
I'm going to bravely wade into the deep water without my inflatable wings:

My understanding is that AD is possible without amyloid, but it occurs in a "small" percentage. (I can't find the article at the moment, maybe 20%?) Any study showing this would have to be a small sample size, involving brain biopsy or possibly CSF evaluation. Then again, perhaps non amyloid isn't "AD", but another subset of dementia. In the US, there is most likely a huge population of "non-diabetics" with insulin resistance, and therefore more likely to have nonamyloid neurodegeneration per the article we are discussing. If this is true, wouldn't we potentially have more nonamyloid neurodegeneration in the US? Pure insulin resistance (without DM) may be less common in South Korea, where the study probably took place.

Just the thoughts that popped to mind.
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Re: Non-diabetic low insulin maybe not so good?

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Has anyone dug into this? I'm inclined to think the finding of low insulin in non-diabetics and later development of amyloid deposition and (a separate matter) dementia, is not causative; specifically, that the people with low insulin are probably malnourished, or perhaps even have already begun to develop dementia.
I think you're spot on to suggest that "malnourishment" is likely the cause of the low insulin and subsequent abeta deposition in this older adult population which wouldn't be the case for you. That said, I've heard Dr. Bredesen say that insulin levels can get "too low" for optimal brain function at which point he recommends sitagliptin (Januvia.) I think <2 mIU/L is his cut-off. Of course, rather than turning to Pharma, you could consider adding a few extra sweet potato wedges to your meals ;).
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Re: Non-diabetic low insulin maybe not so good?

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Julie G wrote: I think you're spot on to suggest that "malnourishment" is likely the cause of the low insulin and subsequent abeta deposition in this older adult population which wouldn't be the case for you. That said, I've heard Dr. Bredesen say that insulin levels can get "too low" for optimal brain function at which point he recommends sitagliptin (Januvia.)
In what population is Dr Bredesen recommending sitagliptin? DM2 only with low insulin? Or?
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Re: Non-diabetic low insulin maybe not so good?

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In what population is Dr Bredesen recommending sitagliptin? DM2 only with low insulin? Or?
I think (could be wrong) anyone with low insulin, but will reach out to clarify. I hope others will jump in with their "take" on this. He mentions this in many lectures and interviews... perhaps even the latest with Rhonda Patrick. Anyone?
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Re: Non-diabetic low insulin maybe not so good?

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Here's Merck's link on sitagliptin MOA. Unlike immediate release injected insulin or an oral sulfonylurea drug which encourage the pancreas to increase insulin output all the time, sitagliptin (one of the dipeptidyl peptidase-4 (DPP-4) inhibitors) works by
enhancing active incretin levels, sitagliptin increases insulin production and lowers glucagon secretion from alpha cells, which decreases hepatic glucose overproduction.


As I type this out, I realize that I have been fixated on low fasting insulin levels only, not necessarily generally low insulin levels. I did not request or read the full article.

Brian4, can you clarify what the study meant by low insulin?
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Re: Non-diabetic low insulin maybe not so good?

Post by Jafa »

I have only tested my fasting insulin 3 times in the last 2 years. First time 8.4, then after giving up bread, my beloved date loaf and porridge it was 5.3. A year ago and after I had unintentially lost weight it was 2. I did wonder at the time if it could get too low. I shall retest. Thankyou Julie, Slacker and Brian. I very much appreciate your collective wisdom. Must away.. I’m moving house today and must get off my phone! Where’s my bucket and mop?
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Re: Non-diabetic low insulin maybe not so good?

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Brian4 wrote:Has anyone dug into this?
Youch this is complicated! Here is a very comprehensive article on the subject. I'm going to need to read many times!

https://www.ncbi.nlm.nih.gov/pmc/articl ... 1587/#B137

Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages

Abstract
Metabolic dysfunction is a well-established feature of Alzheimer’s disease (AD), evidenced by brain glucose hypometabolism that can be observed potentially decades prior to the development of AD symptoms. Furthermore, there is mounting support for an association between metabolic disease and the development of AD and related dementias. Individuals with insulin resistance, type 2 diabetes mellitus (T2D), hyperlipidemia, obesity, or other metabolic disease may have increased risk for the development of AD and similar conditions, such as vascular dementia. This association may in part be due to the systemic mitochondrial dysfunction that is common to these pathologies. Accumulating evidence suggests that mitochondrial dysfunction is a significant feature of AD and may play a fundamental role in its pathogenesis. In fact, aging itself presents a unique challenge due to inherent mitochondrial dysfunction and prevalence of chronic metabolic disease. Despite the progress made in understanding the pathogenesis of AD and in the development of potential therapies, at present we remain without a disease-modifying treatment. In this review, we will discuss insulin resistance as a contributing factor to the pathogenesis of AD, as well as the metabolic and bioenergetic disruptions linking insulin resistance and AD. We will also focus on potential neuroimaging tools for the study of the metabolic dysfunction commonly seen in AD with hopes of developing therapeutic and preventative targets.
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