Non-diabetic low insulin maybe not so good?

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Brian4
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Re: Non-diabetic low insulin maybe not so good?

Post by Brian4 »

slacker wrote: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?
The paper measured fasting insulin.

So there were people without any signs of diabetes, but with insulin, and they had both higher rates of amyloid deposition as well as higher rates of dementia.

But I still think they were likely malnourished.

Let's see what Bredesen says about the rationale of giving sitagliptin to everyone with low insulin levels, if someone can find out from him.
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Re: Non-diabetic low insulin maybe not so good?

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From Brian's first link:
": One SD increase of insulin (4.5 mIU/L) was associated with reduced probability of being Aβ positive (Odds ratio
[OR] 0.553, 95% confidence interval [CI] 0.291-0.952), and 1SD decrease of insulin level was associated
with about 1.8-fold increase in probability of being Aβ positive (OR 1.810, 95% CI 1.050 – 3.441) vice
versa."

"Fasting blood glucose (mg/dL) 97.7 (9.6)
Hyperglycemic status 79 (38.5%)
Fasting blood insulin (mIU/L) 7.9 (4.5)
HbA1c (%) 5.7 (0.4) "

So a 1SD increase would have a fasting insulin of 7.9+4.5 = 12.4 and a 1SD decrease would be 7.9-4.5 = 3.4.

Interesting, because I'd not want a fasting insulin of 7.9, much less 12.4.

These data are from Koreans, average age 68. In this paper, carb % ranged from 63 in the lowest quintile of a "balanced" diet to 73.2 in the highest quintile of an "unbalanced" diet. Wondering what else is going on in those with low insulin levels in the face of these high carb intakes. Personally, my insulin levels drop <1 when I test after fasting for 7 days. I do recall Joe Mercola saying his was <1 while he was wearing a continuous glucose monitor and eating a very low carb diet. Subsequently he decided it was better to periodically spike his carbs around once a week. Also wonder what would show up if insulin was tested two hours after 75 of glucose as Katherine Crofts suggests in her thesis using Dr. Joseph Kraft's data. I think her approach is better as it shows the system's response under load.
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Re: Non-diabetic low insulin maybe not so good?

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This 2014 paper might add to the nuance?

Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

It's full of stuff; they mention this in the conclusion:
The effects of insulin action on brain lipid metabolism, not only cholesterol as described here, but free fatty acids and triglycerides as evidenced by the effects of brain lipoprotein lipase knockout (126), need to be better understood, as does their relationship to the ApoEε4 phenotype.
I thought it was interesting that only ~25% of blood levels of insulin are found in the brain, so even if one's brain is insulin sensitive, if one has very low peripheral levels, is there enough in the brain for its many purposes there? There's mention that the brain may make some of its own insulin, but it seems not much is known about this.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: Non-diabetic low insulin maybe not so good?

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Let's see what Bredesen says about the rationale of giving sitagliptin to everyone with low insulin levels, if someone can find out from him.
Awaiting a response...
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Re: Non-diabetic low insulin maybe not so good?

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From Dr. B:
This [Januvia] is for those who CANNOT generate higher levels—those in whom the low levels are limiting, so that their neurons cannot get the trophic effect of insulin. Of course if they CAN generate (and especially if they can generate and be metabolically flexible, still able to generate ketones, etc.), perfect, and no need to prevent breakdown of their own insulin.
.
Brian, you may want to experiment with occasionally increasing good carbs, like sweet potatoes and broccoli. My guess is that you can easily bump your insulin up to provide enough trophic support. At last measure, mine was 2 mIU/L. I feel very comfortable with that level and wouldn't worry with an occasional lower reading. It's a very dynamic biomarker that we can easily influence with diet.
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Re: Non-diabetic low insulin maybe not so good?

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Julie G wrote:It's a very dynamic biomarker that we can easily influence with diet.
Insulin researcher, Dr.Catherine Crofts, told me that fasting insulin is very pulsatile, it can change dramatically in a few minutes, even without an external input (like food or carby food). She is not a fan of fasting insulin readings and is much more in favor of stress testing the system to see what it does under load. Such as her two hour test after a meal or consuming 75g of glucose after a 12 hour fast.
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Re: Non-diabetic low insulin maybe not so good?

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Julie G wrote:My guess is that you can easily bump your insulin up to provide enough trophic support. At last measure, mine was 2 mIU/L. I feel very comfortable with that level and wouldn't worry with an occasional lower reading. It's a very dynamic biomarker that we can easily influence with diet.
I tend to think Tincup's emphasis on Croft's challenge over time is really important here, and that the fasting insulin results may be as dynamic as how overall insulin levels respond to diet.

Meanwhile, I've always wondered what research supports the notion that 2 mIU/L is safe (Dr. Bredesen's cutoff I think). If the paper I posted above is right, that may mean just .5 mIU/L of insulin in the brain, at least in a fasting state. Maybe the idea is that the postprandial increases raise it enough in the brain. Still, I've wondered a long time whether there is a paper to show what the lowest fasting (or challenge over time) blood level of insulin is that provides enough trophic and other support to the brain. (This is much like my concern about emphasizing very low levels of protein. I'm afraid some of this could come back to bite us, given the paradox-prone nature of biochemistry. Of course, to complicate things further, at the same time it's all going to be individual.)

We often emphasize using a low insulin environment with ketones to offset the hypometabolism in apoe4 brains, but insulin appears to have diverse functions in the brain beyond facilitating glucose metabolism. So by keeping it quite low, are we disrupting other pathways in the brain that may need higher levels for support?
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: Non-diabetic low insulin maybe not so good?

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Julie G wrote:Brian, you may want to experiment with occasionally increasing good carbs, like sweet potatoes and broccoli.
My fasting insulin also puts me in Team Sweet Potato.
circular wrote:We often emphasize using a low insulin environment with ketones to offset the hypometabolism in apoe4 brains, but insulin appears to have diverse functions in the brain beyond facilitating glucose metabolism. So by keeping it quite low, are we disrupting other pathways in the brain that may need higher levels for support?
Would love a detailed answer to this.

Has anyone measured their postprandial insulin? I'm wondering if there's a direct-to-consumer test.
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Re: Non-diabetic low insulin maybe not so good?

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Rainbow wrote: Has anyone measured their postprandial insulin? I'm wondering if there's a direct-to-consumer test.
Stavia measured hers. I believe it was 20. In the US, one could use one of the online lab ordering services (like https://www.walkinlab.com/ https://www.directlabs.com/ ) search online blood tests. In these, you prepay and get a requisition you take to LabCorp or Quest (a few states outlaw this).

Stavia suggested showing up say an hour before the two hours after you eat and tell them what you are trying to accomplish. Or maybe go in the day before and set it up so you can get the lab drawn in a +/- 15 minute window.
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Re: Non-diabetic low insulin maybe not so good?

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Julie G wrote:Brian, you may want to experiment with occasionally increasing good carbs, like sweet potatoes and broccoli. My guess is that you can easily bump your insulin up to provide enough trophic support. At last measure, mine was 2 mIU/L. I feel very comfortable with that level and wouldn't worry with an occasional lower reading. It's a very dynamic biomarker that we can easily influence with diet.
Julie, good ideas. Based on what I know about the biology of aging, I'd like the "area under the curve" for my insulin to be very low, but what Bredesen says about being able to crank out insulin when needed seems important. So I think I'll get a postprandial measurement done after eating more carbs than normal.
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