Insulin, Rapa and Glucose...anyone else feel like this?

My glucose was always normal. Now, with metformin + Sirolimus it’s low-normal.
It’s my insulin level that seems to be the problem. When I had it checked before I started Sirolimus it was 2. Note that that was not a fasting reading; it was about 2 hours after a large breakfast.
I think some people might be confusing glucose levels and insulin levels. They are obviously completely different (although linked in some ways).

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Unfortunately, I get a weird reaction to Metformin. Itchy skin, headaches, edema, and this very odd thing - veins start bulging (not kidding). My kidney and liver function seem fine according to my bloodwork so I don’t know what it happening, allergic I guess.

So this is interesting. My PCP had an endocrinologist review my test results, he was aware I am on Rapamycin as it is in my file. Here are his comments on my low insulin.

"He is euglycemic with normal A1c. His insulin levels, done I assume because they had been done in the outside study as part of a protocol, are undetectable in the fasting state, which is not surprising given that he is not obese (which would cause insulin resistance, and might result in a higher fasting and especially post prandial insulin level).

At any rate, there is no clinical significance to the insulin level. This would not be part of any testing that we would normally do for a patient like this unless hypoglycemia had been suspected and documented. You can reassure him that there is no significance to this, and I would advise that you not continue to test insulin levels."

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Well, I find that surprising.
My doctor almost fell off his chair when he saw my insulin level…and proceeded to interrogate me to try to find out why it was so low.

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Just because your insulin is very low does not mean you’re getting type I diabetes. Insulin can be low for various reasons. In type I diabetes it is low because the person is unable to produce enough insulin. In people that don’t have type I diabetes it can also be super low and in those cases it’s not because they can’t produce it, they can, it’s low because their body does not need to produce much of it to keep blood glucose levels low. Having very low fasting insulin while having fasting blood glucose that is normal is a sign of having very good insulin sensitivity, particularly that of the liver. That’s a good thing not a bad thing. FYI I have measured my fasting insulin a few times and it was always under 2 and I have no blood glucose problems. I can go to the gym and work out hard after fasting for a full day and don’t have hypoglycemic symptoms. I know a few people who also have extremely low fasting insulin levels. What I have in common with those people is that we all have excellent insulin sensitivity.

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A very entertaining read pointed out by Dr. Mikhail V. Blagosklonny on Twitter today concerning rapamycin combined with other anti-aging drugs/supplements.
It contains a very interesting take on “pseudo diabetes” caused by calorie restriction CR and rapamycin.
It also contains many little tidbits such as: "Also, berberine and statins can be included into the anti-aging formula, especially given that statins prevent rapamycin-induced dyslipidemia."
It was shown almost 50 years ago that phenformin and metformin, anti-diabetic drugs that improve IR, also slow down aging and prevent cancer in rodents

The second article referenced is much newer 09/30/2022

"Rapamycin plus acarbose, starting at 9 months of age (RaAc9). This combination of agents produced a 28% increase in median lifespan in females (p < 0.0001) and a 34% increase in males (p < 0.0001) for data pooled across sites (Figure 1). This was the only treatment that significantly increased survival in both sexes at all three sites tested separately"

I apologize if these articles have been previously referenced on Rapamycin News.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649836/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9741502/

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Could it be that people with higher insulin have more leeway for insulin insensitivity in the sense that:

High fasting insulin = Person doesn’t have to be as insulin sensitive

Low fasting insulin = Person HAS to be insulin sensitive

I also noticed that my average glucose is slightly elevated (with CGM) after taking rapa.
Out of curiosity I tested my ketone before bed and surprisingly it was 0.5mmol/L. This is basically nutritional ketosis and I’m not in a low card diet at all…
Also I took my glucose at the same time and it was 5.9mmol/L or 106mg/dl which in general shouldn’t produce a ketone reading.

Maybe an evidence that rapa is mimicking CR?

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