Rapamycin and Continuous Glucose Monitoring

when i tried one of those things, what i found most interesting was my baseline glucose level. significantly higher than I was hoping. and have -ONE- glass of wine and watch what happens sigh. I think it’s best if no matter how high it goes it comes back down relatively quickly. Like under 90 mins.

but the point is to experiment. I just hate tryna not squish it while I’m sleepin.

It seems to me that the lag before getting the first peak to go down (and then sharply) is consistent with rapamycin-induced mTORC2-mediated insuln resistance: your body releases the normally-effective amount of insulin in response to your breakfast, but your now insulin-resistant tissues don’t’ respond.

Then two things happen to bring your glucose down. First, your pancreas pumps out more insulin. Second, you go for a walk home, which is well known to help dispose postprandial glucose.

Than you stop walking, and your glucose starts to rise again until you eventually burn some up or produce enough insulin to force the GLUT4 doors open.

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The walk home is an arguable caae for day 1 on rapamycin, but i was careful on day 2 not to do any exercise before the second peak had subsided. Hence the two peaks from breakfast/sucrose occur without a walk home.

I will time the walk today

I can see rough timings from fitbit, but i will note the precise times.

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So my breakfast supplement time was 8.50 and i finished it at 8.55

It is now 9.30 BST and glucose is at 7.7. I intend staying in the pub until it is clearly on the way down.

Edit: Interestingly at 9.45 I received an email which caused a burst of Cortisol. This was because I had a response to an appeal I had issued relating to a matter of UK public law, but I could not read the response in the pub. This pushed my glucose level up higher (to somewhere in the 9s). I therefore waited a while longer before going home (until after the new burst of glucose was subsiding).

It makes this day not comparable to other days, but will be an interesting test result of the effect of Rapamycin and Cortisol combined.

I later read the response and had won at least in part (which is obviously good, but I will have to decide whether it is good enough over the next few days).

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So this shows this morning. I think it is clear that it had peaked at 9.44 at 8.2 mmol/L and was nudging off and then the cortisol hit. That took it up to 9.5 peaking at 10.14. I think you can still see an underlying two peak profile, but we will have to see tomorrow now.

I still expect to see two peaks until the Rapamycin is metabolised from my system. I will do a blood test probably on wednesday. I don’t have the results from Thursday last week yet. I expect HbA1c will suffer from this.

I find the low level just before 5pm a bit odd. I had been drinking again and I wonder if Dexcom gets confused. We will see anyway.

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I have just spotted something else that is interesting. Looking at yesterday as a whole

There are patches in the afternoon where the blood glucose drops right down. This is to 3.9 mmol/L which is 70.2 mg/dL (multiply by 18).

What happened was that I finished off my bottle of port around lunch when I was testing some camera equipment, I then walked to my son’s house which is about 10 minutes away. Fixed an immersion heater switch by hitting it with a mole wrench and then went to a pub that has just reopened, had a pint there and went to another pub had a pint there then home.

A little later I went out to a restaurant ate a steak and salad and had some more beer and a small spirit.

I was wondering whether the drop in blood sugar is Dexcom not coping with Alcohol, but in fact it appears to be an interplay between the metabolism of Alcohol (in particular metabolising Acetaldehyde I think) and the production of Glucose from Glycogen.

Hence what you see in the first instance is a drop down to a static level until I start eating and then a slower peak that does not hit the same level as food earlier in the day.

Then after that after the food stops being metabolised and stored away there is a drop until the major effect of alcohol metabolism on the liver wears off (which does not take that long) a minor effect lasts longer than that. After that the blood glucose moves up to about 4.9. (88.2 mg/dL)

Now I can compare this to records from last year:

Looking at my records I had a drink in the afternoon/evening something like a bottle of wine and some whisky.

However, there are two things:

a) You can see my blood glucose was much more varied a year ago. I have seen the reduction in HbA1c, but this is visible from Dexcom.

b) The blood sugar does not drop down to a low level and stay there.

Now I think there are potentially two reasons for this (there may of course be others).

  1. Rapamycin. I was on day 3 of Rapamycin equivalent to taking a dose of 1.7 mg in the morning yesterday. (Today day 4 is 1.3mg equivalent)

  2. Pantethine/Dihydromyrectin. Over the past year I have started taking particularly Pantethine when I drink. Pantethine is a non-rate limited version of vitamin B5 which accelerates the metabolism of Acetaldehyde thereby reducing the negative side effects of ethanol metabolism.

I cannot say at this stage what it is. Whatever it is it clearly overrides the tendency of Rapamycin to increase glucose levels. I do have another G7 session to use and am juggling in my mind whether to continue this 10 day period or to wait a bit to make sure there is no continuing effect of Rapamycin and then get a clean reading.

It is, however, something where I want to get an answer. Any thoughts?

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Another day another breakfast. Same time as yesterday to the minute finishing at 8.55.

Currently (9.41) i am at 7.3 and the cgm says the level is constant ie probably peaking. No extra cortisol so far.

In the end I decided at 10.24 to leave the pub and am home by 10.34. Whether that will cause a peak or not we will see. At the moment Dexcom says its back on the way down. This could be entirely caused by me walking home.

Another day another breakfast.

This one finished earlier at 8.28. I want to wait until the peak before leaving the pub. However, i think rapamycin is wearing off now.

Edit 9.48 glucose has now peaked.

Edit 14.09 Having drunk 35cl red wine, I have decided now is a good time to test the ethanol rapamycin crosstalk so i have gone on a pub crawl.

1 pint Yorkshire blonde

Edit 14.20
1g dhm 3g pantethine blood sugar currently 7.1

Edit 14.34 a pint of cider (Westons) in “The fighting cocks” blood sugar 6.5 is panthine driving blood sugar down to 4 mmol/l or was it rapamycin?

Edit 15.29 another pint of bitter some crisps blood sugar 6.3 “the dark horse” an interesting discussion with the barman about what causes the blood sugar drop

Edit 15.46 this is a pint of “Gollop with zest” in “The Elizabeth of York” where I eat breakfast. Blood sugar 6.3 at the moment i think it is rapamycin that caused the drop in glucose levels with alcohol.

Edit 16.21 this is “old speckled hen” in "the

Edit 16.22 this is “old speckled hen” in “the prince of wales” some more crisps bs 6.7

It’s more likely to be a real metabolic effect: I doubt Dexcom or any CGM would be approved if it was distorted in the presence of alcohol, and if it somehow managed to get approved there would be warnings all over them. Remember, T1Ds are dosing insulin based on the results.

Alcohol inhibits gluconeogenesis, which can acutely lower circulating glucose levels. Diabetics are even warned about alcohol-induced hypoglycemic events.

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I agree with you I think it clearly is a metabolic issue.

Once I have finished this Dexcom session I will look at my notes and try to do some analysis.

Looking at yesterday:

It is clear that the alcohol was keeping down the blood sugar levels. However, interestingly it has not gone as low as on previous days even though I was at a reasonably high blood alcohol level and was taking Pantethine.

I think the difference probably is Rapamycin. We knew that Rapamycin had an effect on glucose messaging, but what I think is new is that not only does it normally put the glucose level up a little bit (on a dose dependent basis), but also when people drink alcohol it increases the reduction in blood glucose. Another possible variation is MK-7 which I took on Sunday, but not Monday.

People have varying metabolism and their glucose handling varies. However, what it says to me is that if people take a high dose of Rapamycin they should be careful with alcohol whilst the serum level of Rapamycin is high because they could be at a risk of a hypoglycemic event.

4mg is not particularly high but reviewing the previous days it was knocking me down to 3.9 on Saturday (day 3) and 4.1 on Sunday (day 4). The low point yesterday was 4.6.

Whereever I get to with this 10 day Dexcom session it has asked some interesting questions that need further investigation.

I will be taking Rapamycin again, but I need to be careful to schedule it at a time which enables me to not have to do the school run. I have some idea how to design a testing routine to look at the issues which appear to be worth looking at. I will be doing another blood test tomorrow and will probably get last Thursday’s results later today. Thursday was just a few hours after taking Rapamycin so I am not sure I will see much of an impact. I would expect tomorrow to see some impact at least in WBC.

Here are a few more days:

The only thing that is really consistent amongst these is that I go for breakfast in a particular pub and the breakfast is the same (apart from Day 2 Rapamycin 4mg which was 100g of sucrose in water).

From a breakfast point of view yesterday and today were both quite interesting as I had breakfast (at different times) and then immediately left the pub. Yesterday I was doing the live streaming for a memorial service so I needed to get in early to test all the equipment. Today actually I wanted to go home really quickly so that any effect of exercise would be soon after eating.

I then don’t tend to eat until about noon 1pm.

So today I was home at 9.32 having been shopping and have finished breakfast at 9.09, but started walking at 9.15. There is, I think, a slight delay as the blood glucose levels get reflected in the interstitial fluid hence I think you can see a false summit of glucose at 9.24, that then dips until 9.34, and then there is a first peak at 9.59 then a second peak at 10.39.

My serum rapamycin levels will be quite low by now.

Looking (as I can in Dexcom’s cloud service) at the detailed figures I think when I had peak Rapamycin my blood glucose would be perhaps 0.5 mmol/L (approx) higher than it would be at trough or zero Rapamycin. I intend to download the data in a digital form and calculate some averages.

It is hard with this as obviously we have a number of varying factors, Food and Rapamycin are quite easy to control. Alcohol is controllable up to a point. Cortisol is harder to control although exercise can be planned. Insulin will follow on in interesting ways.

I am not quite sure how Melatonin affects blood sugar (I know it generally reduces it), I think that may be through a reduction in Cortisol.

As a second point I think there is also an issue where the way in which Glucose and Alcohol interact is changed by Rapamycin. However, I think there is a need for more testing controlling more of the different elements and timing.

I have, however, been very pleased with where I have placed the implant. Previously I have used my abdomen and it has been difficult to keep it functioning. On the back of my upper right arm has to some extent enabled me to forget about it and it continues functioning well. In retrospect I should have used the left arm because the vagus nerve is on the right and AIUI if I wish to stimulate the parasympathetic nervous system I should turn to lie on the right. (A good final step to NSDR aka Yoga Nidra) This has not been an issue, but I have been careful to avoid lying on the implant and it woudl be nice not to have to worry about this.

I definitely want to have a CGM when I next take Rapamycin. I have, however, being doing a range of things along with taking Rapamycin such as aiming to increase the ability of RNA Polymerase II to transcribe BECN1 (the gene for Beclin 1). (along with other long genes).

It would be really good if we could track cortisol levels in real time. I have read of research that uses interstitial fluid for that as well.

I have another 72 hours of this G7. I am tempted to power up my remaining G7 session to follow on, but that decision can wait.

Sadly my blood test from last Thursday resulted in the Courier not delivering it until Tuesday this week (Bank Holidays in the UK) which was too late. The courier is supposed to deliver it on the same day. I had another blood test today, but this does mean tracking WBC and HbA1c between the two tests won’t be possible.

I expect WBC to go down and HbA1c to go up. How quickly the Lipids move (if at all) will be interesting, but I have quite a lot of movement in those anyway so there may not be any meaningful result.

The next thing to think about is whether to increase the dose. My concern is that I would then get a longer period of disrupted sleep so I would need to have a useful school holiday within which to do this. I may even drop back down to 2mg from 4, but that is something to think about in the future.

There is, of course, the question as to what impact this is having. My objective is to increase autophagy to ensure that the mitochondrial efficiency of cells is higher so that there is a higher level of cytosolic Acetyl-CoA.

Obviously this is measured by the biomarkers, but I also use a macro camera to look at my bald patch. It does not take static photos that well, but here is one:

What seems to be happening is the developing of quite a few further dark pigmented hair follicles and really fine pigmented hair coming from some of them. I start with the assumption that hair grows quite slowly and the newer follicles have either shorter hair or no hair and just the skin colouring that preceeds producing hair.

It is, of course, the same processes for other cells, but not as visible.

Apologies, but I have just had two testing fails.

Last week the courier failed to take my blood test to the lab in time. Hence they gave me a free test yesterday, but the lab has only done the full blood count and not HbA1c or Cholesterol etc etc. Hence I have neither the result from just after taking Rapamycin or a result now.

Secondly my CGM sensor has just failed. This was probably my fault in that I grabbed my arm with the sensor in with the other arm - not particularly hard. It has lasted almost 9 days without any real problem and I had grabbed that arm previously. I have not implanted my other sensor as I am pretty certain Rapamycin has gone down to levels which are relatively hard to spot. However, I think I will leave any analysis until I have a second sensor run as I don’t think I have enough post Rapamycin to make it worth while.

What I can say, however, is that my WBC doesn’t seem any significantly lower. Again I don’t have a result from last week, the prior week is a different lab, but the week before that is the same lab. Two weeks ago was 3.2 and yesterday 3.1. I don’t think that is significant in isolation. I normally have a low WBC. There did not seem to be anything else that had any particular significance and I only have the FBC anyway.

I have not decided when to take Rapamycin again. I do want to take it more frequently than I have been (which is about every 4 months). Next time I want to put in a CGM in say 4 days before taking Rapamycin. However, I need to expect some disrupted sleep for at least the first night and that means planning for when I don’t have to do the school run.

I think blood glucose is slightly higher with a high blood serum Rapamycin. I don’t, however, have enough data to be sure and although I think one should be careful drinking alcohol after a high dose of Rapamycin because potentially there could be a hypoglycemic event I cannot say that this was necessarily any different because I had Rapamycin. Not enough information.

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I thought I would have a look at Freestyle (which appears to be the main alternative to Dexcom for CGM). They appear to offer a 14 day free trial for self-funding people. I thought people might like to know.

This is yesterday’s CGM which was 7 days (close to 3 half lifes) after taking 4mg of Rapamycin

As a reminder here is 6th April

I took Rapamycin at 6.15am. It probably took effect mainly about 7.30am onwards.

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Lots of data to dig through here but I have a simple question. All things being equal, is average blood glucose (ABG) higher the day that rapamycin is taken? My A1C data suggests that there is a chronic increase in ABG but doesn’t answer question of acute effects.

It is perhaps a key question. The difficulty is that there are a number of things that affect glucose levels. I am pretty consistent up to an including breakfast, but I walk for about 8-10 minutes to breakfast a and 8-10 minutes back potentially also going to the shops.

On 13th April you can see in fact two post-prandial false summits caused by walking.

My lunch tends to be chia seeds in a smoothie plus a number of apples (1-3).

I think overnight Rapamycin causes blood sugar to be higher by something around 0.5 mmol/L.

What I think I need to do next time is to be very pre-defined on when to walk to and from breakfast and what time to have lunch. I do some calisthenics at some stage, but if I leave that to the afternoon then it won’t impact on the rest.

The problem I have is I do things other than testing Rapamycin’s effects on glucose. (such as running a number of businesses, driving children to and from school etc). Hence it is hard to be that strict on things that affect glucose.

My reading of the glucose effect is that it is dose dependent on blood serum levels of Rapamycin, but I don’t have enough really good data to be sure about that.

Friday 7th (Day 2 Rapamycin) was interesting because I had the 100g sucrose and didn’t walk to the pub, but I haven’t done the same test without Rapamycin.

I raised a concern with the Lab directly about them only doing the FBC and they gave test results on the sample for other biomarkers. I am not sure about these values because of delay, but I can now give at least some comparators.

I had a test with lab A on 15/3, 24/3 (but the FBC failed), 6/4 (all failed), 13/4 (FBC was OK, rest delayed), I had a test with lab B on 30/3. I had 4mg Rapamycin at 6.15am on 6/4 (which is why I had a test later that day. grrr)

These are results which may have some interest (I have ignored a lot).

White Cell Count Lab A 15/3 3.2 Lab B 30/3 2.32 Lab A 13/4 3.1 I include this because it is something to look at. I think Lab A and Lab B have different methodologies which results in figures being systemically different. I don’t see a significant shift here, but 4 weeks is too long to give any useful information.

Total cholesterol Lab A 24/3 5.44 Lab B 13/4 5.51 LDL-C 24/3 2.7 13/4 2.58 I don’t see this as being significant either, but because it is an issue people look at I include it. Triglyceride went down from 2.1 to 2, but I don’t see any value in that data.

Urea 5.4 (24/3) to 5.6 - Still not really a significant shift.

HbA1c 24/3 27.3 (4.6) 13/4 26.8 (4.6) 30/3 Lab B 24.3 (4.4) - This is where we have lost on not having the 6/3 result. However, because of potential methodology differences comparing against Lab B does not mean anything. These figures are on mmol/mol with the percentage in brackets. This particular biomarker can be measured in a number of different ways either including or excluding the labile element to some extent. A lab which I think excludes the labile element came back with 4.18% at one stage. From my point of view it is nice to see this not going haywire, but in a sense I can see that from the CGM readings. My glucose handling in early 2023 is substantially better than that in early 2022 (when I also ran a Dexcom, but a G6)

Iron 24/4 16 30/3 16.2 13/4 22 - maybe something, not out of the ordinary for my data.

Ferritin 24/3 164 30/3 154 13/4 142 - something to investigate further.

Abbott have now sent a trial Freestyle Libre 2. Hence I need to look at a plan of what to do. I am juggling up in my mind whether to increase the dose from 4mg to 6mg (just over root 2 times 4) or 8mg.

Also this time I would be inclined to run the CGM for two solid days before taking rapamycin. Any thoughts?

I think you should get a base line. Track average blood glucose for a month following wash out and then in the week immediately following the dose. Obviously try and keep variables (diet and exercise) as consistent as possible.

So one might have an average blood glucose of 100mg/dL but 110mg/dL on the day of dosing.

Freestyle, however, only provide a 14 day session. Dexcom is 10 days. I do have one more Dexcom to use (and I also have readings from last year and earlier this year). I know my glucose handling is a lot better than it was early in 2022.

I do have a tendency to forget I am wearing a CGM and hence displace it which stops it working. It was, however, a lot better last time as I didn’t need to think much about it, but I really want it in a slightly different location on my left arm so I can turn onto my right side (because of the vagus nerve).