# Experiment: dropping Metformin



## Eddy Edson (Jul 20, 2019)

I'm experimenting with dropping Metformin. I wanted to keep taking it, for all the possible anti-inflammatory etc etc etc benefits, even though my BG has been "normal" for many months. But then I came across research indicating that it can sometimes interfere with exercise benefits, which led me to also think about whether it might be increasing lactic acid build up when I walk a lot, an issue with my peripheral artery disease. So let's see if I notice anything different when I drop it; I can always go back if my BG spirals out of orbit.

I've really been tracking only my waking BG for the last few months. It's always in the range 4.6 - 5.2. What to expect without the Met?

Met on average seems to deliver an HbA1c reduction of ~10 mmol/mol, which should correspond to an avg BG reduction of ~1.5 mmol/L. But there's a lot of variability and it becomes less effective as baseline BG reduces, though I don't find much research on that. So .... no idea!

I dropped the Met a couple of days ago and it should have mostly cleared out of my system by now. So today is Day 1 of the experiment, and waking BG = 4.8. No difference there. Let's see how that develops & whether I notice any exercise differences.


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## Northerner (Jul 20, 2019)

Good luck Eddy  I think metformin takes a couple of weeks rather than a couple of days to 'clear' the system so the consequences may not be apparent yet.


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## Eddy Edson (Jul 20, 2019)

Northerner said:


> Good luck Eddy  I think metformin takes a couple of weeks rather than a couple of days to 'clear' the system so the consequences may not be apparent yet.



I thought that too, but looking into it, I was surprised to see this:

_Elimination

Renal clearance (see Table 4) is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.

https://www.drugs.com/pro/metformin-extended-release-tablets.html_


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## Docb (Jul 20, 2019)

Keep us posted Eddy.  I've never been convinced that Metformin did anything to my blood glucose levels although I have never been able to do an experiment unconfunded by other factors.

After a week without gliclazide I am convinced that that medication had had a significant effect.


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## Eddy Edson (Jul 20, 2019)

Docb said:


> Keep us posted Eddy.  I've never been convinced that Metformin did anything to my blood glucose levels although I have never been able to do an experiment unconfunded by other factors.
> 
> After a week without gliclazide I am convinced that that medication had had a significant effect.



It does seem to vary a lot between individuals (doesn't everything?). Interesting re gliclazide. Would it be fair to say that the main mode of action is to increase insulin production? While I guess for metformin it's increasing peripheral insulin sensitivity. I would say that my T2 variety has more to do with the latter than the former, so I am expecting to see some impact from cutting metformin.

And one of the possible interactions of metformin with exercise according to the research I referred to is interference with the peripheral insulin sensitivity improvement you get from exercise - the mechanisms cancel each other out to some extent and you might not get the synergies you'd otherwise expect.

So I'm looking for impacts after eating and after exercise, not so much on waking. From my one day's worth of experiment:

- After morning soy coffee+chia seeds, a handful of nuts and a 40 min walk, I scored a 5.3.  That's a smidgen less than I would have expected. So weak support for the interference scenario.

- After berries+pumpernickel+avocado+soy coffee+chia seeds for lunch/brunch, with no exercise, it was 7.0. Maybe half a point higher than I would have expected before cutting the met. So weak support for Met still being useful for post-prandial IS for me, at least in the absence of exercise.

- In the evening after a further ~90 min walking over a couple of sessions and dinner of salmon+beans+a potato+yet more soy coffee+chia it was 6.3.  Ummm ... maybe a bit high? Dunno. But a confounding factor was being obliged to sit through _The Lion King _ (Great CGI work; wish the software used to generate story, script and dialog was as good.)

In terms of non-BG-related exercise impact: at the end of the day, not as zapped from 2 hours walking as I might have been before. But then again it was an extraordinary day for mid-Winter here: 20 degrees, cloudless, gentle breezes; and that probably helped.

The experiment proceeds. _A luta continua_!

PS: And then because I was feeling energetic and the evening is mild, another 30 min walk, followed by a 4.9 reading. Kind of in line with what I would have expected before. But my first 13km+ walking day since around Easter, and not zapped at all & no leg pain to speak of.


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## Docb (Jul 20, 2019)

As far as I am aware gliclazide works by increasing insulin production so this would suggest my problem is related to that rather than insulin resistance.  Give me a couple of weeks to collect some data and I will put the numbers up for criticism.

One of the things that gets me about diabetes is that the only thing that is measured is the outcome - that is bg level - and that treatment is dependent on either the prejudices of, or guesswork by, the HCP.  Not much better than random chance, depending on how good a guesser your HCP is.  In the days when I did production support I would have been fired for taking that approach to a machine that was malfunctioning because it is the most inefficient and expensive way of getting things working better.  If there were two possible broad reasons for a malfunction ( like insulin deficiency or insulin resistance) the first thing I would do is to figure out which it was so that I could get appropriate remedial action in place as quickly as possible.  The last thing you do is to start pulling levers at random hoping that you would hit on the best way forward.


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## DaveB (Jul 20, 2019)

Docb said:


> As far as I am aware gliclazide works by increasing insulin production so this would suggest my problem is related to that rather than insulin resistance.  Give me a couple of weeks to collect some data and I will put the numbers up for criticism.
> 
> One of the things that gets me about diabetes is that the only thing that is measured is the outcome - that is bg level - and that treatment is dependent on either the prejudices of, or guesswork by, the HCP.  Not much better than random chance, depending on how good a guesser your HCP is.  In the days when I did production support I would have been fired for taking that approach to a machine that was malfunctioning because it is the most inefficient and expensive way of getting things working better.  If there were two possible broad reasons for a malfunction ( like insulin deficiency or insulin resistance) the first thing I would do is to figure out which it was so that I could get appropriate remedial action in place as quickly as possible.  The last thing you do is to start pulling levers at random hoping that you would hit on the best way forward.


Yes, there is a lot of guesswork by HCPs with regard to diabetes medication e.g. start with Metformin. If that doesn't work add Gliclazide and so on. These two meds have completely different functions with the former more relevant to T2 and the latter really only T1 (or those T1s mis-diagnosed as T2). HCPs hold Metformin in high regard but it only ever has a small effect on BS. Gliclazide can have a big effect unless all your beta cells are dead. The eternal problem is that there are no good tests to distinguish between the different diabetes types hence the guesswork. GAD 'proves' T1 (but not exclusively) and that's about it. Body weight can be a good differentiator.


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## leonS (Jul 20, 2019)

Doctors are not Engineers!


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## Docb (Jul 20, 2019)

leonS said:


> Doctors are not Engineers!





I rather like DaveB's idea about the difference between T1 and T2; T2 being insulin resistance and treatable by drugs that reduce resistance and T1 being impaired production of insulin.  Sort of makes sense in that those we currently call T1 are those with near 100% impairment and blatantly need insulin treatment whereas those who still have a degree of home made insulin production can get things under control by a combination of drugs to boost insulin production and reducing carb intake so as not to overload whatever insulin production they have.  Must be some complications with that simple idea which I am ignorant about but wouldn't it be good if there was some way of getting a handle on pancreatic function.  I'm sure those well versed in the medical black arts will tell me it can't be done, but that's what my technical brain is telling me anyway.


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## Eddy Edson (Jul 21, 2019)

The more I dig into T2, the less I seem to understand it. And what the mechanism of Metformin is supposed to be. Maybe more on that later ...

Day 2 of experiment:

I had a rough night, waking at 3am with a stomach upset (I blame the salmon), dozing, waking again at 5am ravenous. Scoffed nuts and snowpeas, slept again at about 6am, woke at 10am.  So not a good day for data but FWIW consistent with yesterday. So far since waking thru mid-afternoon I've tried to do the same as yesterday, food and exercise wise - boring but anything for science.

Final waking BG: 5.0.
After coffee+chia+40 min walk:  5.6  (noting that the extra-large flat white has Bonsoy milk, which is sweetened with tapioca syrup for 20+ grams of carbs, so I'd expect it to have an impact, plus I'm generally in a bit of pain from the PAD after a 40 min walk early on, which maybe does also. But the last couple of days it seems to be a bit better).
After berries etc lunch/brunch, no exercise: 7.3

Each of those data points is 2-3 ticks higher than yesterday's equivalents, maybe down to disturbed sleep, stomach probs, nuts/snowpeas scoffing early on. Or measurement error, or squidginess, or whatever.

So far the data seems to support:

- Maybe minor short-term improvement in insulin sensitivity from exercise in the absence of much food.
- But maybe minor reduction in post-prandial IS.
- Maybe slightly better walking, maybe from reduction in lactic acid build up.
- No change to waking BG.

But obviously way too early to really say anything.

Update pre-bed: Blah - my stomach probs came back - almost like Metformin side effects! I guess I've got a bug or I've eaten something. 

Anyway, I'm provisionally blaming that for a high pre-bed reading, 5.7. Haven't eaten anything for hours apart from a few nuts & would have been in the 4's previously. If I'm wrong about the bug etc then it looks like cutting the Met may indeed have a significant impact on my underlying BG, which I'd expect to see reflected in tomorrow's waking read, I suppose.

More importantly, really, walking does seem to be better at least for now, despite the gammy tummy.


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## Docb (Jul 21, 2019)

Eddy Edson said:


> The more I dig into T2, the less I seem to understand it. And what the mechanism of Metformin is supposed to be. Maybe more on that later ...



Amen to that Eddy.


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## Northerner (Jul 21, 2019)

Docb said:


> The last thing you do is to start pulling levers at random hoping that you would hit on the best way forward.


Surely you'd only start doing that after you'd switched it off, then switched it back on again?  

I think there are a lot more variables at play with human beings, as diabetes has so many factors and influences it can't be boiled down to a 'this' or 'that', so HCPs follow treatment paths that suggest courses of action and medication. You can have insulin insufficiency or impairment, or both, plus there may be many more individual influencing factors. I don't think we're quite at the stage yet where Bones McCoy can just sweep a red light over us and pinpoint a solution, although things are progressing  Probably just too expensive at the moment to perform the suite of tests that could narrow things down, far cheaper to just use relatively informed guesswork.


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## Sharron1 (Jul 21, 2019)

Eddy Edson said:


> I'm experimenting with dropping Metformin. I wanted to keep taking it, for all the possible anti-inflammatory etc etc etc benefits, even though my BG has been "normal" for many months. But then I came across research indicating that it can sometimes interfere with exercise benefits, which led me to also think about whether it might be increasing lactic acid build up when I walk a lot, an issue with my peripheral artery disease. So let's see if I notice anything different when I drop it; I can always go back if my BG spirals out of orbit.
> 
> I've really been tracking only my waking BG for the last few months. It's always in the range 4.6 - 5.2. What to expect without the Met?
> 
> ...


Really interesting. It is an experiment that I have often thought about.  I have also wondered about the effectiveness of metformin. From my understanding I thought greater benefits are diet and exerciseAs I do loads of exercise, wat low carb and take Metformin, my numbers are consistently in non diabetic levels, I am not sure which of the above are most beneficial or if they all work together. Good luck.


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## Eddy Edson (Jul 21, 2019)

Docb said:


> Amen to that Eddy.



So as far as I can make out from clueless biochemistry-moron-level digging in the research, T2D is generally thought to be associated with insulin resistance in a variety of different ways, with different BG effects. 

The most important IR effect is often said to be interference with the regulation of gluconeogenesis in the liver.  That's not glucose production from carbs, as I understand it, but from other nutrients via a number of different mechanisms. Normally that gets suppressed when there's plenty of BG, but with IR, the suppression doesn't happen and the liver keeps gluconeogenesis-ing away, leading to elevated BG.  T2D's typically have much higher rates of gluconeogenesis.

From the patient's point of view, the impact is supposed to be on fasting levels, mainly. And the major mechanism of Metformin is supposed to be reduction in gluconeogenesis. From which it is inferred that Met's main benefit is to bring fasting levels down. It's not a mechanism you would expect to have much impact on post-prandial levels.

On the other hand, peripheral (ie skeletal muscle) IR is also a factor for T2D's, and Met is also supposed to help with that.  This is a post-prandial kind of thing, but it's supposed to be a secondary factor.

On the other hand, some well-credentialed researchers (ie not Yahoo gurus etc) seem to take issue with this view. They say that gluconeogenesis problems are only really a big thing when BG is chronically quite highly elevated, say > 10. In better controlled subjects, peripheral IR is the main factor, and the benefits of taking Metformin are seen mainly post-prandially.

I've probably screwed that little summary up one way or another. But it does illustrate a surprising lack of absolute expert consensus about fundamental things to do with T2D and Metformin ...


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## Eddy Edson (Jul 21, 2019)

Sharron1 said:


> Really interesting. It is an experiment that I have often thought about.  I have also wondered about the effectiveness of metformin. From my understanding I thought greater benefits are diet and exerciseAs I do loads of exercise, wat low carb and take Metformin, my numbers are consistently in non diabetic levels, I am not sure which of the above are most beneficial or if they all work together. Good luck.



Hey, happy to be the guinea pig!

Seriously, I'm really only doing it because maybe Met interacts with things arising from my peripheral artery disease when I walk a lot. Kind of like symptoms of over-exercise, when really you haven't done that much. If you don't find anything like that then it's probably not worth fiddling around with the Met/exercise/diet formula, I'd say.


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## Docb (Jul 21, 2019)

Northerner said:


> Surely you'd only start doing that after you'd switched it off, then switched it back on again?
> 
> I think there are a lot more variables at play with human beings, as diabetes has so many factors and influences it can't be boiled down to a 'this' or 'that', so HCPs follow treatment paths that suggest courses of action and medication. You can have insulin insufficiency or impairment, or both, plus there may be many more individual influencing factors. I don't think we're quite at the stage yet where Bones McCoy can just sweep a red light over us and pinpoint a solution, although things are progressing  Probably just too expensive at the moment to perform the suite of tests that could narrow things down, far cheaper to just use relatively informed guesswork.



Understand that logic Northerner, but is the complete absence of attention to the issue, at least as far as I can find, that I find a bit grating.   I suppose the current method keeps lots of people in a job.  Its the great benefit of doing something inefficiently!

See where you have got to Eddy Edson.  The simple idea that metformin makes your insulin work better, which you tend to see in basic info, is not reflected in the technical literature.  It is a hell of a lot more complicated and there is no consensus about what is what.  It does work, and works well for some, but I suspect there are a lot for whom it doesn't and who are putting it away because the book says so and not because it is efficacious in bringing down blood glucose.


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## Eddy Edson (Jul 21, 2019)

Docb said:


> The simple idea that metformin makes your insulin work better, which you tend to see in basic info, is not reflected in the technical literature



Well, I'm not sure that's true. Everything I've read points to Met reducing IR, it's just that the question of what that actually means is complicated, so that it'll be different strokes for different folks. Which isn't surprising and I would expect general advice to present a simplified picture - what else could it do? Particularly since it's not completely understood by experts.

I want the Dr McCoy scanner! Medical researchers should get off their butts and invent it already


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## Sharron1 (Jul 21, 2019)

Eddy Edson said:


> Hey, happy to be the guinea pig!
> 
> Seriously, I'm really only doing it because maybe Met interacts with things arising from my peripheral artery disease when I walk a lot. Kind of like symptoms of over-exercise, when really you haven't done that much. If you don't find anything like that then it's probably not worth fiddling around with the Met/exercise/diet formula, I'd say.


Believe me I am the seriously over cautious type no fiddling for me. Loads of thinking and even over thinking Good luck.


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## Eddy Edson (Jul 21, 2019)

Day 3 ....

Waking BG: 5.0.  Stomach still a bit iffy. Metformin withdrawal symptoms, no doubt 

After carby b'fast (fruit+melon+big soy flat white+chia) and 30 min walking plus bout of brain-work & a meeting:  6.5. 

So far today, all consistent with pre-experiment levels. Walking continues to be easier.

Update: After late lunch (pumpernickel, avocado, raspberries, strawberries, lemon juice, soy flat white, chia) and no exercise: 7.4

A bit high, but maybe to the point, stomach went squiffy again so ...?  I hope I haven't developed a food allergy? If I had to give up almonds, walnuts, soy or seeds I'd be at a loss - have to start eating beef or dairy or something  Eating enough is hard enough as it is: weighed in at 62.7kg this morning, so failed to hold at 63kg & getting close to BMI = 19, which is just too low. No matter how much I enjoy being skinny (my efforts to get people to call me "Slim Eddy" haven't been at all successful but I live in hope.)


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## Eddy Edson (Jul 22, 2019)

For reference, this piece from last month is worth a look: https://blogs.sciencemag.org/pipeline/archives/2019/06/24/metformin-and-exercise

Talking about recent research showing that Met and exercise can interfere with each other, for some people.

_Metformin looks far more plausible as almost anything else – a fertilizer additive, a component of marine paint to keep barnacles from attaching to ship hulls, a veterinary deworming agent. Anything other than a multibillion dollar diabetes drug.
...
The authors (a multicenter team in Illinois, Colorado, and Oklahoma) studied patients in their early 60s who had no chronic disease but had at least one risk factor for Type 2 diabetes, and who had never taken metformin. For twelve weeks, they engaged in a program of aerobic exercise, and took either metformin or a placebo along with that.

Exercise comes out looking good, as it generally does in such studies. Participants in the placebo group (exercise alone, in other words) lost fat mass, improved their oxygen handling, and decreased their fasting insulin levels. The metformin-plus-exercise group was a bit different, though: some of these metabolic measures improved, but in some cases by not as much, and there was a lot more scatter in the data. Indeed, when they gave participants an oral glucose tolerance test at the end of the study, the exercise group improved across the board, whereas the metformin-plus exercise group had about half the participants improve but the others actually get worse compared to the start of the trial.

Looking down at the cellular level (muscle biopsies, ouch), the differences became even more apparent. Exercise caused an increase in mitochondrial respiration in skeletal muscle, as advertised, but the metformin treatment definitely seemed to interfere with that process (as determined by a number of measures, and especially apparent in ADP titration experiments). The effect seems to be via some intrinsic mitochondrial function(s), rather than on protein synthesis. _


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## Eddy Edson (Jul 23, 2019)

Day 4 ...

Experiment interrupted when batteries ran out & I couldn't find the spares I thought I had. (For clarity, batteries for my meter, not for me 

Before dinner, after so far a relatively low-ish carb day for me & ~7km walking:  6.4.

That looks high versus pre-experiment expectation. But one thing I've noticed is that BG elevations are pretty closely associated with the stomach bloat-y issues I'm having at the moment - BG goes up when the bloat starts. And these issues aren't very closely associated with carbs.  In fact, it's looking like almonds might be the culprit, which would be really annoying if it persists.

I assume this is a coincidence - can't see any reason why stopping Met would cause almond intolerance?

Bah!

Anyway, had my first appointment with the exercise physiologist today. She didn't have a pill to increase upper-body strength without tedious strength training, unfortunately, and didn't really have any exercise suggestions beyond the obvious kind of thing.  Didn't have anything to say about Met interfering with exercise.  Did have a few interesting things to say about fatigue and general expectations for how much exercise to do etc, which generally confirmed that my current walking strategy is OK.

I finally took the plunge and ordered a couple of Libre sensors. Some might call it indulgence but I call it Science, which continues its forward march.  (I had to tell a fib & say I'm on insulin for the order to go thru.)

Update: Before bed reading = 6.4 after late dinner of berries+lemon juice+peanuts+chia/soy flat white. A point or so "too high", but stomach probs persist, so who knows? Tomorrow starts the no-more-almonds leg of the experiment; will have to scrounge those calories from somewhere else.

10km+ walking today, pretty easy.


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## Eddy Edson (Jul 23, 2019)

Ya Sham said:


> Good luck!
> 
> I also decided to drop Metformin and try something new I heard about. It's called CuraLin- have any of you heard of it and can give advice?



On a quick look, it's a supplement manufactured in India whose ingredients include bitter lemon (Monmordica charantia) and a bunch of other stuff I don't recognise.  This has some info on bitter lemon: https://www.medicalnewstoday.com/articles/317724.php

My summary: At most a small improvement in BG, maybe nothing.

I wouldn't take it without my doc's approval and as with any other unregulated supplement, you can't be sure of exactly what's going to be in any batch of it.


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## Sharron1 (Jul 23, 2019)

Oh no. Bad luck if the almonds aren't playing ball. I eat loads of them. I didn't realise they fill me up so much


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## Drummer (Jul 23, 2019)

For me the meter always showed carbs make a whoosh, low carbs go ambling along no concerns or worries. Some carb types did a super whoosh - so they got the boot - but the key for me is diet - not pills supplements or concoctions but simply not eating myself into a condition requiring them.


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## Eddy Edson (Jul 24, 2019)

Day 5 ...

No almonds & stomach much better. I guess almonds were the issue, damn it.

Waking 5.2, high 8.9 after carby b'fast, time-weighted average over the day ~6.5.  Walked 11km+.

Compared to pre-experiment, waking is at the top end of the range, peaks are about 1 higher, elevations last longer, troughs are not quite as low and the time-weighted avg is also about 1 higher.  That's pretty consistent I think with a picture in which my liver is doing its gluconeogenesis thing in a fairly "normal" way, hence fairly normal waking levels not much affected by dropping Metformin.  Peripheral insulin sensitivity is not terrible but could do better and Met does seem to have an impact there.  

Anyway, it's a hypothesis. It would seem to be consistent with the Roy Taylor et al view on things - by losing weight I've cleared my liver of fat, so reducing hepatic insulin resistance and allowing normal gluconeogenesis, but in the absence of muscle-building the peripheral IR benefits have not been as great. 

Subjectively, the walking-fatigue situation is noticeably better. I also see some signs that dropping the Met improves peripheral IS after walking in the absence of food.

If this kind of picture holds up it would be consistent with an HbA1c of around 5.7% / 39, the top-end of what I consider "normal".

Taking it all together, suggests a possible strategy of dropping the Met permanently and adding strength training to build muscle and improve peripheral IS with or without food. The main advantage of dropping the Met in this strategy would be fatigue reduction, but also maybe longer term better peripheral IS as muscle builds.

I think I should get my Libre sensors tomorrow - exciting! The plan is to keep doing this for a week hopefully with added BG insight from the Libre, then go back on the Met for say 3 weeks and compare as closely as I can (to allow 1 week for it to build up + 2 weeks real experiment).


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## Eddy Edson (Jul 25, 2019)

Day 6 ...

Waking 5.5, high of 7.2 after lunch, time-weighted avg ~6.3. Walked 9km+.

That waking read is the highest for months, at the very top end of what I think is "normal". If it continues to rise, my "normal gluconeogenesis" hypothesis gets torpedoed; we'll see.

Through lunch-time I had a pretty low carb-y time & also walked for an hour +, so I'm not sure why BG went up - not that it's a big deal. The more interesting thing is that my base pre-prandial level now seems to hover around in the low 6's, versus high 4's and low 5's pre-experiment. I guess this might also be a sign that the gluconeogenesis engine is running a bit fast.

Apart from that, not much difference vs yesterday.

The delivery company was supposed to leave my Libre sensors at the door but this didn't happen for some reason; have to pick them up from somewhere tomorrow, if I have time. Interesting that there's no availability issue here in Oz - maybe we've been dumped with last-gen surplus or something.

I see you're enjoying some normal summer weather there in the UK for a change


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## Eddy Edson (Jul 26, 2019)

Day 7 ...

Waking 4.9, high of 8.4 after carb-y b'fast (fruit, melon, chia+soy flat white), time-weighted avg ~6.5. Walked ~4km.

So waking level back in the pre-experiment range, but the rest of the day in-line with the last few days.  Fairly stressful - intense meeting, pressure to get a project finished. 

No real time for walking, which means no fatigue data, the main point of this little experiment. It's so easy to get sucked into focusing too much on BG - I wish I had a fatigue-o-meter to give some numbers of that.

Didn't have time to pick up the Libre sensors - do it on Monday.


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## Eddy Edson (Jul 27, 2019)

Day 8 ...

Waking 5.2 after not enough sleep, high of 8.3 after relatively low-carb-ish b'fast, in the 5's after ditto lunch, 4.9 after evening walk. Time-weighted avg ~6.0. Walked 10.5km.

Apart from walking, still buried in a project for a robotics start-up all day. General impression is that walking really doesn't zap me as much for fairly intense thinking, compared to pre-experiment.  

Better BG numbers today probably linked to fewer carbs - no melon, no pumpernickel, less soy flat white - about 120g. Not a huge deal. Does seem to remain the case that BG takes longer to fall from post-prandial highs.

Niece's birthday - preparing birthday lecture covering deportment, nutrition, ethics and political history, lucky girl.


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## Leonora (Jul 27, 2019)

Fascinating...as Spock would say. Are you eating the same foods every day on this experiment and will you be getting your a1c checked after it?


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## Eddy Edson (Jul 27, 2019)

Leonora said:


> Fascinating...as Spock would say. Are you eating the same foods every day on this experiment and will you be getting your a1c checked after it?



The idea was to eat generally the same way I ate pre-experiment. But it's interesting the way frequent measuring tends to move you unconsciously towards lower carb, a Pavlovian slave to the meter. Reminds me of when I was first measuring and wrangling levels down. 

I really don't want to change my pre-experiment eating habits very much. It'd be a reason for resuming the Met, if I couldn't eg fit good quantities of fruit & melon into the picture.

I'm supposed to be getting my next HbA1c in September.


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## Sharron1 (Jul 28, 2019)

Eddy Edson said:


> Day 8 ...
> 
> Waking 5.2 after not enough sleep, high of 8.3 after relatively low-carb-ish b'fast, in the 5's after ditto lunch, 4.9 after evening walk. Time-weighted avg ~6.0. Walked 10.5km.
> 
> ...


You missed out chastity.


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## Eddy Edson (Jul 28, 2019)

Sharron1 said:


> You missed out chastity.



I don't feel that I'm qualified to lecture on that topic


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## Eddy Edson (Jul 28, 2019)

Day 9 ...

Waking 5.0 after once again not enough sleep, peak of 6.4 after lunch, 5's and 6's all day, time weighted avg of ~5.8. Walked ~8km.

That puts me dead on the mean of what the data I benchmark against says is a "normal" avg daily BG level and generally the profile over today looked like a typical day pre-experiment. Fairly typical eating day, ~185g gross carbs.

Maybe my poor old bod has adjusted to doing without the Metformin crutch? We'll see ...

Still buried in this project & limited time for walking but generally the fatigue thing does seem to be better. I'm pretty toasted right now but that's from a few 12+ hour working days in a row and not enough sleep - it's a different kind of fatigue.

Bed calls - early meetings tomorrow.


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## Eddy Edson (Jul 29, 2019)

Day 10 ...

Waking early to 4.7, peak of 7.4 after fairly carby b'fast, time weighted avg 5.8 once again. Walked 10km.

Again a "normal" profile, on a 200g+ carb day. Neat!

For reference , the "normal" daily values I use as a benchmark, from a couple of CGM studies (+/- one standard deviation):

Low: 4.6 +/- 0.3
High: 8.0 +/- 1.3
Time-weighted average: 5.8 +/ 0.6
HbA1c: 5.3% +/- 0.3% or 34 +/- 4

Not one of my very "good" days for walking - a bit of a struggle; maybe put that down to still not having caught up on sleep.

Fetched my Libre sensors but then discovered my iPhone 6 can't run the app. Doh! I guess that means it's time to upgrade, which means I have to go a phone shop tomorrow & deal with a phone shop youth. For some reason dealing with tech-shop youth always spikes my misanthropy index (first world problems, never mind ...).

Snooze time ...


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## Eddy Edson (Jul 30, 2019)

Just to triangulate on those "normal" benchmarks ... This is one of my favourite pics:



From https://www.ncbi.nlm.nih.gov/pubmed/30735238 published recently, assessing a new model for predicting how normal people's BG will react to different food based on a bunch of factors including their gut microbes. I think probably a really important piece of research, mentioned as such in the recent update to the ADA's dietary guidelines.

Anyway, the pic shows how six different non-diabetics' BG reacted to a standardised bagel+cream cheese meal. Each colour shows how a particular individual reacted on two different occasions. Pretty consistent over the two occasions for each individual; wide variations between individuals.

Eyeballing the peaks and 2 hour post-prandial values and dividing by 18 to convert from US-style mg/DL to mmol/L, I get:

Peak: Average 8.1, standard deviation 1.4.
2 hour: Average 7.0, standard deviation 1.7.  [EDIT: fixed a typo.]

The peak calculation agrees very well with the 8.0 +/ 1.3 benchmark (which comes from other data), increasing my confidence in it.  Message: Don't stress if you peak above 9. Lots of non-diabetics do too.

The 2 hour calculation is interesting to compare with the various numbers for 2-hr post-prandial you see floating around: no more than 7.8, no more than 8, no more than 8.5, no more than 10.  Overall, I think it's a pretty weak metric to look at - much better to look at time-weighted average and peak, to the extent you can - but if you do track it and you're a T2 trying to be one-standard-deviation "normal", this data seems to support the 8.5 target more than the others.


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## Eddy Edson (Jul 30, 2019)

Day 11 ...

Waking 5.3, peak 7.4 after carb-y b'fast, time-weight avg 5.9. Walked 12.5km.

Don't see much interesting data from today, except to note that everything continues to be "normal" on a 200g+ carb day, although a tiny smidgen higher BG-wise than pre-experiment expectation. Walking a bit of a struggle early on, much easier by the end of the day and little residual fatigue - continuing the general pattern with this experiment.  Peripheral IS signal post-walking maybe a bit improved also.

I've ordered a Libre reader. Apparently I'm locked into a phone plan which means it would cost $gadzillion to replace my iPhone 6.  I can't really blame the phone-shop youth for this, so I've decided to blame the one I bought my current phone and plan from, for not ignoring me when I said I didn't want to upgrade. Plus he had a goatee.


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## Eddy Edson (Jul 31, 2019)

Day 12 ...

Waking 5.1, peak 7.9 after non-carby lunch, time weighted avg 5.8. Walked 13.7km. ~200g carbs.

Another pretty boring, "normal" BG day, still maybe a little bit higher than pre-experiment.

The big thing was being able to walk 13.7km at avg of ~5.4km/h with no probs, as if I didn't have a blocked artery at all. And no particular fatigue. Fab!

I am now Libre'd! Really very cool, how easy and plug'n'play the whole thing is. On a few tests, the readings seem within +/- 0.3 of my meter so far, better than I expected. Well done, Abbott.

As part of the experiment, what I'm looking forward to is getting more insight into what happens during and after exercise & what that might mean for my peripheral IS, comparing with what things look like when I do the back-on-Metformin leg.  

And for curiosity, what happens to my BG over night. I'm guessing nothing very interesting, but I really have no idea.


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## Ya Sham (Aug 8, 2019)

Eddy Edson said:


> On a quick look, it's a supplement manufactured in India whose ingredients include bitter lemon (Monmordica charantia) and a bunch of other stuff I don't recognise.  This has some info on bitter lemon: https://www.medicalnewstoday.com/articles/317724.php
> 
> My summary: At most a small improvement in BG, maybe nothing.
> 
> I wouldn't take it without my doc's approval and as with any other unregulated supplement, you can't be sure of exactly what's going to be in any batch of it.


You are correct I did consult with my doctor and she said it looks good and since it is 100% natural it can't be harmful... Look I joined the Facebook group Winning Type 2 Diabetes Together where most people there use CuraLin and are reporting amazing results not only in glucose levels but also changes with eyesight.. more energy and such. I recommend you to check it out for ourself- https://www.facebook.com/groups/261568611056436/

They also have a clnical review on their website where each ingredient is explained. For me, it works amazing so far...


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## grovesy (Aug 8, 2019)

Ya Sham said:


> You are correct I did consult with my doctor and she said it looks good and since it is 100% natural it can't be harmful... Look I joined the Facebook group Winning Type 2 Diabetes Together where most people there use CuraLin and are reporting amazing results not only in glucose levels but also changes with eyesight.. more energy and such. I recommend you to check it out for ourself- https://www.facebook.com/groups/261568611056436/
> 
> They also have a clnical review on their website where each ingredient is explained. For me, it works amazing so far...


Just because something is natural it does not mean it can't be harmful


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## Ya Sham (Aug 8, 2019)

grovesy said:


> Just because something is natural it does not mean it can't be harmful


That is true grovesy but from personal experience, the natural way is a lot less harmful than all the chemicals that are given to us in prescribed medications.. especially when I see in the group that people have been taking CuraLin for more than 2 years and are still doing great with amazing results


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## Eddy Edson (Aug 8, 2019)

Ya Sham said:


> You are correct I did consult with my doctor and she said it looks good and since it is 100% natural it can't be harmful... Look I joined the Facebook group Winning Type 2 Diabetes Together where most people there use CuraLin and are reporting amazing results not only in glucose levels but also changes with eyesight.. more energy and such. I recommend you to check it out for ourself- https://www.facebook.com/groups/261568611056436/
> 
> They also have a clnical review on their website where each ingredient is explained. For me, it works amazing so far...



I think it's great if you find it helpful but to me it looks like just another dismal snake-oil supplement scam. That FB group belongs to the company that makes it, BTW.


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## grovesy (Aug 8, 2019)

Eddy Edson said:


> I think it's great if you find it helpful but to me it looks like just another dismal snake-oil supplement scam. That FB group belongs to the company that makes it, BTW.


I am suspicious of sites like that one,


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## Eddy Edson (Aug 10, 2019)

grovesy said:


> I am suspicious of sites like that one,



With good reason, I think. How could you know if it's real people posting there, rather than just company sock-puppets?


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## Eddy Edson (Aug 10, 2019)

Experiment update ...

First, some more on "normal". The most comprehensive study I've seen looking at "normal" is this: https://care.diabetesjournals.org/content/32/7/1188  Dates back to 2009 and the population is Chinese, but I don't think either of those things is very important.

A good thing is that it looks at data grouped by age and sex:



BG values in US mg/dL - divide by 18 to get mmol/L.  "PT140" is percentage of time during the day with BG > 140 mg/dL = 7.8 mmol/L.  "PT70" is percentage of time with BG < 70 mg/dL = 3.9 mmol/L.  "P5" etc means the 5th percentile etc, so "P50" is the median.

Dead-centre "normal" is the median, so the P50 mark.  For me, a 58 year-old male, the numbers look like this:



Median is around 5.9 mmol/L, corresponding to a 5.3% / 34 HbA1c on the conventional translation, with < 2% of time above 7.8 mmol/L.  But anything up to 6.5 mmol/L, 5.7% / 39, 13% would still be within a solidly "normal" range.

According to the Libre, over the last week my avg BG is 5.8 mmol/L and I'm spending 5% of time above 7.8 mmol/L.  It's still reading a bit high versus finger-pricks:



... but getting better. Anyway, the data is enough to confirm that I don't currently "need" Metformin for any BG-related reason.

I think it's definitely the case that I have fewer fatigue issues since the start of the experiment. There's fatigue (and pain) from walking, which is subjectively better to a moderate extent; and "brain fatigue", which seems much better. I have had zero days where I was complete toast, and the other night I had to pull a frantic all-nighter getting a complex project finished, which I was able to do without getting completely destroyed.

Comparing BG levels is difficult - I wasn't testing a lot pre-experiment - but waking levels over the last few days have been in the lower 4's, versus higher 4's, and moderate walking has a big (1.5 - 2.5 mmol/L) impact on BG levels without a big bounce-back afterwards. 

A complicating factor for the comparison is that my last lab tests in May gave an HbA1 of 4.6% / 27. That would correspond on the conventional translation to an avg daily BG of 4.8 mmol/L, which is actually below the 4.9 mmol/L 5th percentile value from the study.  I'm certainly not that low now, but I'm pretty sure I also wasn't that low back in May; I suspect the low result had a lot do with changes in my red blood cell count.

Next: I do want to do the back-on-Metformin leg, starting now with a good set of comparison data in a day or two. But probably with just 500mg rather than the pre-experiment 1000mg. Will it deliver a net improvement in peripheral insulin resistance, reducing that 5% time above 7.8 mmol/L? Will it do the opposite, plus maybe bring fatigue issues back?


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## Eddy Edson (Aug 11, 2019)

Eddy Edson said:


> A complicating factor for the comparison is that my last lab tests in May gave an HbA1 of 4.6% / 27. That would correspond on the conventional translation to an avg daily BG of 4.8 mmol/L, which is actually below the 4.9 mmol/L 5th percentile value from the study. I'm certainly not that low now, but I'm pretty sure I also wasn't that low back in May; I suspect the low result had a lot do with changes in my red blood cell count.



But actually, maybe ...  Yesterday I averaged 5.0 by both Libre and finger prick, which are now agreeing excellently - avg variance less than 1% - on a day when I did hardly any walking (miserable weather).  Back in May I was walking on avg 12 km+ per day.  

Then today this happened (up until 10.30pm, the time here now):



According to the Libre my avg BG has been 4.8 today so far, with 10km+ walking.

Over night, I woke at about 4am and went back to sleep for a few hours at 6am.  While asleep, the Libre reckons I spent maybe 4 hours below 3.9, dropping as low as 3.4. Do I believe that? Who knows? Finger prick said 4.1 soon after first waking, at a point where the Libre said it was on the rise from 3.8 to 4.1. Before going back to sleep, another finger prick said 4.4 vs  Libre's 4.6 and falling. And so on - excellent agreement between Libre and a few finger pricks for the rest of the day.

(It definitely wasn't squashies and I didn't notice any hypo effects, apart from feeling like I'd just been disinterred upon waking, but that's normal  )

In the early evening I set myself to test whether I could make BG go below 3.9 by walking a few kilometres - in the last few days walking has certainly been enough to get me down to ~4.0.  According to the Libre, I was down at 3.7 after walking 5km. But I didn't get the chance to compare with finger pricks; maybe better luck next time.

It might be that getting down to very low fasting and post prandial levels with a bit of exercise is now a regular kind of thing for me & my bod has just taken a a couple of weeks to get over whatever aftershocks of dropping the Metformin. 

Or perhaps my liver's decided this whole gluconeogenesis business is bogus - hard to pronounce; nobody talks about it on Internet message boards, only experts with actual qualifications in professional papers; doesn't have anything to do with low carb so not sexy - and it's not going to make much of an effort anymore.  

Or maybe I've got a touch of some kind of hepatitis. 

Or maybe it's just random squidginess ...


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## Eddy Edson (Aug 12, 2019)

So the last day of the no-Metformin leg - how exciting!

I certainly had the squashies last night - Libre reading in the 2's - but we'll skate over that.

I've set up my spreadsheet so I can compare some metrics over different periods.



"Mean" is just the average Libre BG reading. "Avg Low" is the average low over the period.

"Avg Day Low" is the average low between midday and 11pm. I pull out this metric because it might sorta-kinda reflect peripheral IR. Hepatic IR would also be a factor here, especially for pre-prandial and bed-time levels, but I'm pretty much assuming that hepatic IR and gluconeogenesis aren't issues for me now, in which case this is a fairly interesting rough metric.

Similar the daily "Avg High" and "Avg P7.8" = percentage of time > 7.8 mmol/L are interesting peripheral IR indications.

"Avg FP-L" is a check against finger pricks, the average difference between the Libre and FP values.

In this table you can see that levels in the last week have been lower compared to the whole period including the first few days of wearing a Libre. But in the last week the Libre has on average been spot-on versus finger pricks, whereas for the whole period the Libre was reading ~0.2 high.  If you apply a rough adjustment and reduce the whole period levels by that 0.2, you get kinds-sorta similar numbers to the last week. So everything seems to hang together.

Briefly:

- Everything looks well within the bounds of "normal", without Metformin.
- It'd be nice but not essential to get that P7.8 lower and maybe Metformin will have an effect there.
- Unfortunately I don't have a "fatigue metric" so will just have to be subjective with that comparison.

In pics: First, hourly means for the whole period for Libre versus finger pricks.



Very close. I don't include the few overnight finger prick readings in the data base, because obviously I was awake when I took them and it's not apples-vs-apples to compare with sleeping Libre values. 

The Libre line looks smoother than any individual day, because I am not a creature of very regular habits so peaks and troughs happen at different times, to some extent cancelling each other out when you munge everything together.  But there is still a noticeable breakfast bump, reflecting my most carby meal, usually.

Second, a chart showing the hourly means for the last week versus the whole period:



In the last week, as reflected also in the table, levels have generally been coming down and the afternoon "shape" has been different, maybe reflecting a bit of peripheral IR improvement, maybe just to do with time eating/exercise timing. I'll be looking at this comparison as the back-on-Metformin leg progresses for a quick overview of any major changes.


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## Eddy Edson (Aug 15, 2019)

Day 3 of back-on-Metformin ...

Too soon to really say anything, of course, but I have to say I'm not sure about this Metformin caper.  Plus, this is the Internet, where confirmation bias is *just fine* 

First, the fatigue. Both forms are back: today I felt like I had the mental acuity and focus of an old cigarette butt & had to nap; and walking 10km was a painful chore and left me feeling for much of the day like I had over-exercised.

My BG profile looked like this:



(Blue = Libre, orange = finger pricks.) A new Libre sensor is performing excellently, so far.

The general pattern for the day:

- Post breakfast, it's smooth!
- No noticeable Met impact on overnight levels.
- Noticeably lower post-prandial levels.
- Generally higher daytime pre-prandial levels and BG reduction from walking is quite muted and transient. An afternoon nap had a bigger and more lasting impact.

Comparing the day with the no-Metformin leg:



(where I've applied crude adjustments based on finger pricks).

No significant diff in daily average BG or overnight lows.  But daytime lows are fairly significantly higher, and this combines with much lower post-prandial peaks.

If this pattern continues it's very much in line with my initial hypothesis, ie:

- I've dealt with hepatic insulin resistance via weight loss, so gluconeogenesis under control, so overnight levels completely normal and Metformin won't do anything for that.
- Metformin might still have an impact on peripheral ie muscle IR, particularly post-prandial, so it might shave peaks.
- The Metformin and exercise mechanisms for peripheral IR improvement might interfere with each other so maybe pre-prandial, post-exercise levels will be higher.

I need to run this for at least a few more days, but if I continue to feel toasted I'll probably blame it all on the Met and ditch it ... 

The strategy will then be to up my strength work from current daily average of around 78 seconds to something real, in order to build muscle and improve natural peripheral IR, finding some way to deal with the tedium.  Maybe carry weights while walking? My exercise physiologist is supposed to be looking into that.


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## Eddy Edson (Aug 17, 2019)

Experiment terminated!

Two days of brain fog and walking pain//fatigue is enough. Obviously I can't be certain that these are to do with Metformin, but it sure feels that way, and I simply have too much on my plate to spend time in zombie-mode, so anything which might cause it needs to go.

Based on the no-Metformin leg, dropping it shouldn't take my BG outside of a "normal" range, and this includes post-prandial peaks which it seems Metformin might shave - the peaks are within normal bounds, even without shaving.

The potential non-BG benefits of Met are too nebulous to justify the fatigue, and it seems to me that there's a better chance of being able to improve peripheral IR without it, along with putting some muscle on my scrawny frame.

I'm interested now in whether lactic acid build up has anything to do with the fatigue and brain-fog. It doesn't seem stupid to my (admittedly pretty clueless) thinking. Met does promote lactic acid; my blocked leg artery means I start building up the stuff with not very much walking; there seem to be some well-recognised brain-foggy effects from it.  But really only of academic interest for now ...


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## Eddy Edson (Aug 17, 2019)

FWIW, to wrap up, comparing the no-Metformin leg with the few days back on Met, after a couple days build-up:



No significant difference in avg BG.  Pre-prandial lows lower and post-prandial peaks higher without Met.


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