Metformin Blocks Benefits of Aerobic Exercise on Insulin Sensitivity and VO2 max

[DragonBits]

That’s not really how that works. Fasting and carb restriction help to REDUCE your insulin resistance, meaning your body doesn’t need to churn out as much for the same effect. Think of it like developing a tolerance to alcohol - if you chug constantly it takes more to feel drunk, but if you go a year without drinking you turn into a lightweight.

As for “prolonged insulin response” - with reactive hypoglycemia many people report becoming symptomatic about 2 hours after eating. It’s thought this is because their body doesn’t register to stop producing insulin and keeps producing a steady amount even though glucose levels have hit fasted levels.

I dealt with this a lot when I was younger. I was anorexic thin up until my mid 20s. The thickest part of my arms was my elbow and it was next to impossible for me to put on weight. Even after a meal, my glucose levels would sit around 60 mg/dL. This is low for someone in a fasted state, much less for someone with a recent meal. Most of the time the only thing I noticed were persistent headaches and minor tremors to my hands. But on the other hand, I needed to eat something small about every two hours or I got nauseaus, weak, clammy skin, and mental status changes that eventually would progress to loss of consciousness. It took quite a bit of time to figure out what was going on with me. I was eventually told that if I weren’t careful this would lead to type 2 diabetes because my body would develop insulin resistance. Dietary changes have allowed me to avoid that, but years later it’s really no surprise I’m having additional endocrine issues.

Did you find out what was causing you to be so thin and a BG of 60 mg/dl?

I think people with very normal blood glucose control can pretty much do any kind of diet and do OK.

Otherwise it seems like dueling experts. As in intermittent fasting Vs not skipping breakfast.


"Eating Breakfast Every Day Can Lower Your Risk for Type 2 Diabetes
Experts say skipping breakfast occasionally can even raise your risk"

Eating Breakfast Every Day Can Lower Your Risk for Type 2 Diabetes

I am not advocating any side here, just it seems like you find very conflicting advice about this subject.

 

[Tad1979]

Did you find out what was causing you to be so thin and a BG of 60 mg/dl?

I think people with very normal blood glucose control can pretty much do any kind of diet and do OK.

Otherwise it seems like dueling experts. As in intermittent fasting Vs not skipping breakfast.


"Eating Breakfast Every Day Can Lower Your Risk for Type 2 Diabetes
Experts say skipping breakfast occasionally can even raise your risk"

Eating Breakfast Every Day Can Lower Your Risk for Type 2 Diabetes

I am not advocating any side here, just it seems like you find very conflicting advice about this subject.

We never did figure it out. Reactive hypoglycemia isn’t a common diagnosis and as many of us have learned here, finding the right doctor is key. As a teenager/20something I simply didn’t have the experience or resources to push harder for help or information.

I’m sorry, but you do seem to have some very sketchy concepts overall, like when you talk about metformin “impeding the absorption of carbs”. Again, that’s not how it works - it works by affecting insulin resistance. Over and over again insulin resistance has been shown to be an issue for people - this is the root mechanism for type 2 diabetes and all treatments for it attempt to address that resistance in some way - metformin, glipizide, or biduriun to lower resistance or more insulin to overcome it (which perversely only makes the issue worse and is why type 2 diabetics end up on progressively more insulin). Even weight loss, the very first thing advocated for pre-diabetics and type 2 diabetics targets this concept because as we low T patients know, fat impedes hormone health.

I’m not trying to be condescending here, but reading everything you’ve said in this thread I fear for your safety. You really need to sit down with a medical provider and have a detailed Q&A session.

 

[Ardoc2]

From everything I have read there is still a lot of debate on Metformin's mechanisms of actions, with many experts admitting they don't fully understand the way it works. This excerpt from fda.gov shows some of the ways it works, and in fact lists reduced glucose absorption as one of the benefits?
Considering the number of people taking Met with little if any side effects I would doubt his safety is a concern?

Excerpt from;
Mechanism of Action Pharmacokinetics - FDAhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021748s002lbl.pdf

CLINICAL PHARMACOLOGY
Mechanism of Action
Metformin is an antihyperglycemic agent, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

 

[DragonBits]

I’m sorry, but you do seem to have some very sketchy concepts overall, like when you talk about metformin “impeding the absorption of carbs”. Again, that’s not how it works - it works by affecting insulin resistance. Over and over again insulin resistance has been shown to be an issue for people - this is the root mechanism for type 2 diabetes and all treatments for it attempt to address that resistance in some way - metformin, glipizide, or biduriun to lower resistance or more insulin to overcome it (which perversely only makes the issue worse and is why type 2 diabetics end up on progressively more insulin). Even weight loss, the very first thing advocated for pre-diabetics and type 2 diabetics targets this concept because as we low T patients know, fat impedes hormone health.

I’m not trying to be condescending here, but reading everything you’ve said in this thread I fear for your safety. You really need to sit down with a medical provider and have a detailed Q&A session.

Amazing then how you can be condescending without even trying.

I didn't make up what I said about metformin. I was just repeating what the NIH has discovered. And my first statement was that Met "increases the sensitivity of muscle cells to insulin ". It's just not the only thing it does.

"Metformin reduces the rate of small intestinal glucose absorption in type 2 diabetes."

Metformin reduces the rate of small intestinal glucose absorption in type 2 diabetes. - PubMed - NCBI

My saving grace is that I have a mild problem with blood glucose, usually not very high blood glucose. I do think it's odd how I can go fairly low on BG a few hours after a meal, and honestly the 40 shocked me, but I had casually seen that even 10 years ago I tended to be pretty low 2-3 hours after a big meal. Just never seen that low.

 

[dnfuss]

Amazing then how you can be condescending without even trying.

I didn't make up what I said about metformin. I was just repeating what the NIH has discovered. And my first statement was that Met "increases the sensitivity of muscle cells to insulin ". It's just not the only thing it does.

"Metformin reduces the rate of small intestinal glucose absorption in type 2 diabetes."

Metformin reduces the rate of small intestinal glucose absorption in type 2 diabetes. - PubMed - NCBI

My saving grace is that I have a mild problem with blood glucose, usually not very high blood glucose. I do think it's odd how I can go fairly low on BG a few hours after a meal, and honestly the 40 shocked me, but I had casually seen that even 10 years ago I tended to be pretty low 2-3 hours after a big meal. Just never seen that low.

Let's start with the fact that the mechanisms of action of metformin are only grossly understood, more deduction from results than fully mapped-out biochemistry. When anyone, including the NIH, makes statements regarding such they must be taken as likely hypotheses rather than gospel.

But putting that aside, you can both be correct in certain aspects of your statements without the need for any ad hominem arguments.

DragonBits,
Metformin does reduce the rate of glucose absorption in the intestine. That is not exactly the same as blocking carbohydrate digestion, which is the mechanism of action of other oral agents, such as Acarbose. And even so, the effect is fairly weak. Diabetics on metformin who continue on a Standard American Diet will see at best quite modest reductions in postprandial and fasting serum glucose, and almost inevitably not down to the level of truly normal blood sugars. If a change is made to a very low-carbohydrate diet together with metformin, normal blood sugars may be achieved if the diabetes is mild enough.

Kudos to you for your statement to the effect that those with naturally truly normal lifetime blood sugars (my extremely rough guess would be somewhere between 40% and 65% of the adult population, but that's just pure speculation) can pretty much eat any diet and pursue any exercise plan (or none at all) with no adverse effect on blood sugars. They will never develop diabetes (or pre-diabetes). Those of us who are not as fortunate are well-advised to monitor our blood sugars and do whatever is necessary (and fasting is usually not helpful in this regard) to maintain truly normal blood sugars despite our genetic proclivity to the contrary. Even so-called pre-diabetes (i.e., mild diabetes) over the years demonstrably increases morbidity and mortality. E.g., pre-diabetics experience serious cardiovascular events at significantly higher rates than do those with truly normal blood sugars.

Tad1979,
The etiology of type 2 diabetes mellitus is quite complicated to say the least. While many, maybe the majority of, type 2 diabetics are quite insulin resistant, many are not. They may simply have, e.g., insufficient first phase insulin response. That leads to very high post-prandial blood sugars while still retaining normal or near-normal fasting glucose (this is in fact how a great many type 2 diabetics remain undiagnosed for many years). And sometimes the body tries to compensate for this with an overly-robust second-phase insulin response (which in those with truly normal blood sugars is a very mild fine-tuning of blood sugars following a robust first-phase insulin response). This is generally the pattern leading to reactive hypoglycemia. It is very commonly, although not always, associated with the early stages of diabetes. It can be controlled, like all diabetes, with the proper therapy. Begin with a low-carbohydrate diet and exercise, if insufficent add oral agents as indicated, if still insufficient add the correct regime of injected insulin.

You are quite correct that the most dramatic perceived result of metformin therapy appears to be better glucose uptake/less hepatic and muscular insulin resistance. However, I must take issue with the thought that type 2 diabetes inevitably worsens and requires ever-increasing amounts of insulin. This is only true if one follows the recommendations of the ADA, eating a high-carbohydrate diet and allowing blood sugars to remain at constantly elevated levels. And insulin, used properly, certainly does not worsen diabetes, but can actually help preserve beta cell function. Diabetics (including Type 1s) who follow the practices laid out in the last sentence of the previous paragraph and constantly maintain truly normal blood sugars can expect to live full life-spans and maintain a consistent insulin dosage through their lives (and occasionally even reduce their dosage under the right conditions).

 

[Tad1979]

Let's start with the fact that the mechanisms of action of metformin are only grossly understood, more deduction from results than fully mapped-out biochemistry. When anyone, including the NIH, makes statements regarding such they must be taken as likely hypotheses rather than gospel.

But putting that aside, you can both be correct in certain aspects of your statements without the need for any ad hominem arguments.

DragonBits,
Metformin does reduce the rate of glucose absorption in the intestine. That is not exactly the same as blocking carbohydrate digestion, which is the mechanism of action of other oral agents, such as Acarbose. And even so, the effect is fairly weak. Diabetics on metformin who continue on a Standard American Diet will see at best quite modest reductions in postprandial and fasting serum glucose, and almost inevitably not down to the level of truly normal blood sugars. If a change is made to a very low-carbohydrate diet together with metformin, normal blood sugars may be achieved if the diabetes is mild enough.

Kudos to you for your statement to the effect that those with naturally truly normal lifetime blood sugars (my extremely rough guess would be somewhere between 40% and 65% of the adult population, but that's just pure speculation) can pretty much eat any diet and pursue any exercise plan (or none at all) with no adverse effect on blood sugars. They will never develop diabetes (or pre-diabetes). Those of us who are not as fortunate are well-advised to monitor our blood sugars and do whatever is necessary (and fasting is usually not helpful in this regard) to maintain truly normal blood sugars despite our genetic proclivity to the contrary. Even so-called pre-diabetes (i.e., mild diabetes) over the years demonstrably increases morbidity and mortality. E.g., pre-diabetics experience serious cardiovascular events at significantly higher rates than do those with truly normal blood sugars.

Tad1979,
The etiology of type 2 diabetes mellitus is quite complicated to say the least. While many, maybe the majority of, type 2 diabetics are quite insulin resistant, many are not. They may simply have, e.g., insufficient first phase insulin response. That leads to very high post-prandial blood sugars while still retaining normal or near-normal fasting glucose (this is in fact how a great many type 2 diabetics remain undiagnosed for many years). And sometimes the body tries to compensate for this with an overly-robust second-phase insulin response (which in those with truly normal blood sugars is a very mild fine-tuning of blood sugars following a robust first-phase insulin response). This is generally the pattern leading to reactive hypoglycemia. It is very commonly, although not always, associated with the early stages of diabetes. It can be controlled, like all diabetes, with the proper therapy. Begin with a low-carbohydrate diet and exercise, if insufficent add oral agents as indicated, if still insufficient add the correct regime of injected insulin.

You are quite correct that the most dramatic perceived result of metformin therapy appears to be better glucose uptake/less hepatic and muscular insulin resistance. However, I must take issue with the thought that type 2 diabetes inevitably worsens and requires ever-increasing amounts of insulin. This is only true if one follows the recommendations of the ADA, eating a high-carbohydrate diet and allowing blood sugars to remain at constantly elevated levels. And insulin, used properly, certainly does not worsen diabetes, but can actually help preserve beta cell function. Diabetics (including Type 1s) who follow the practices laid out in the last sentence of the previous paragraph and constantly maintain truly normal blood sugars can expect to live full life-spans and maintain a consistent insulin dosage through their lives (and occasionally even reduce their dosage under the right conditions).

If you look back over my previous responses in this thread you’ll notice I talk about controlling carbohydrate intake for diabetes management - we’re not in disagreement here. My wording about type 2 diabetics needing progressively more insulin could have been better - the intention wasn’t to lump all type 2 patients together. With the exception of actual insulin administration, the treatment modalities you’re talking about preserve/enhance insulin sensitivity, which logically would mean you don’t need to increase insulin dosage.

Regardless of which points we disagree on, OP has made multiple comments about INCREASING carbohydrate intake (which is something we agree needs to be managed properly) in addition to some other statements that may or may not stem from correct understanding of material. Is suggesting he sit down with a provider for clarification instead of “experimenting” really bad advice?

 

[DragonBits]

If you look back over my previous responses in this thread you’ll notice I talk about controlling carbohydrate intake for diabetes management - we’re not in disagreement here. My wording about type 2 diabetics needing progressively more insulin could have been better - the intention wasn’t to lump all type 2 patients together. With the exception of actual insulin administration, the treatment modalities you’re talking about preserve/enhance insulin sensitivity, which logically would mean you don’t need to increase insulin dosage.

Regardless of which points we disagree on, OP has made multiple comments about INCREASING carbohydrate intake (which is something we agree needs to be managed properly) in addition to some other statements that may or may not stem from correct understanding of material. Is suggesting he sit down with a provider for clarification instead of “experimenting” really bad advice?

I think your posting style is causing confusion.

First, it appears you are talking about me, BUT misunderstand the meaning of OP.

OP is the original poster, or the poster that started the thread, which would be Vergil.

Second, it seems you misunderstand my position on several things. Lowering carbohydrates is one of the most important aspects to controlling blood glucose levels in a type 2 diabetic. Followed by exercise and drugs to control diabetes.

Moving to someone that isn’t already a diabetic.

Intermittent fasting has become a popular meme for losing weight and increasing health, and some small studies have shown it to significantly improved insulin sensitivity.

Yet other studies show skipping breakfast can lead to greater insulin resistance.

My conundrum was how do you reconcile those two studies?

Thirdly, if you have ever read the story of Richard K. Bernstein MD, who is a legend in being able to control his type 1 diabetes, you should note if he had sat down with his doctors, followed their advice and NOT experimented he would have been dead a long time ago.

I respect doctors while also knowing that as a group they all tend to promote whatever is the conventional medical thinking they were trained to believe, and they also tend to treat people as “typical” meaning if you are outside the norms they tend to treat you like you are every other patient. Doctors also don’t have a lot of time to focus on just your problem, so unless you have a more critical problem they then tend to treat by the numbers and what works for 90% of their patients.

Another problem I have seen with doctors and other professionals. They tend to “see” problems that are aligned with their own problems or their own specialties. Urologist will look towards preventing prostate cancer / prostate problems while ignoring that their treatment might make you less healthy overall. Doctors at hormone clinics will tend to think hormones are the answer, while nutritional experts will look first to diet, etc.

Myself personally, my doctor wouldn’t have much time to devote in discussing esoteric diabetic issues with me since the highest ever in my life that my A1C was measured was 5.8. Fasting blood glucose was once 113 back in 2009, the next year after that it was 77. But I don’t know how rigorous I was in fasting for the blood test in 2009. There is no measure by which I am diabetic, and I must eat a high carb diet to even get into the prediabetic camp. 18 months ago, I was going through a 50 lb. bag of popcorn in 3 months, often I would eat a 12-quart bowl of popcorn as dinner. Without added butter, it’s not a huge number of calories, lots of fiber, but it does add a huge carb burden to your diet. During that time, if I was restless in the middle of the night, I would have a bowl of pasta which tends to make me sleep better. It’s that sort of diet that got my A1C to 5.8.

It’s not hard to back of that sort off diet and lower my carbs a bit to get to a A1C of 5.2-5.3. If I were rigorous about diet, I think I could get to A1C of 4.9. Last night I had russet potato wrapped rockfish , my BG afterwards was 108. Often I eat pad Thai or other Thai dishes with rice. I have backed off of carbs to the degree I don't eat a lot of pretzels or munch on candy or have popcorn for dinner.

What does amaze me a bit is the stories I read about people discovering they are a diabetic when they get in a hospital and get a reading of 300+ blood glucose, or an A1C of 10, geez, how can they go for so long without being aware of what was going on? I have been tracking my own blood tests since 1992, and I don't have any health problems that cause me to do that.

 

[dnfuss]

Is suggesting he sit down with a provider for clarification instead of “experimenting” really bad advice?

Not per se, but since you're asking, the overall tone could be construed as condescending, to which you yourself alluded. Many of your other points were good, although I did disagree with some.

Myself personally, my doctor wouldn’t have much time to devote in discussing esoteric diabetic issues with me since the highest ever in my life that my A1C was measured was 5.8.

Yes, that is the problem with many of the ADA guidelines and why diabetes is grossly underdiagnosed and undertreated. An HgbA1c correlates to an average estimated glucose level of 120 mg/dl and should at least be cause for further testing (OGTT) and investigation, but most doctors will say nothing or simply suggest that you "watch your sugar intake."

What does amaze me a bit is the stories I read about people discovering they are a diabetic when they get in a hospital and get a reading of 300+ blood glucose, or an A1C of 10, geez, how can they go for so long without being aware of what was going on?

Unfortunately, this is not uncommon at all. The first symptom of diabetes is often a diagnosis of diabetes following a blood test. I.e., popular belief to the contrary, diabetics quite often do not present with unquenchable thirst, frequent urination, or other obvious physical symptoms.

 

[DragonBits]

Yes, that is the problem with many of the ADA guidelines and why diabetes is grossly underdiagnosed and undertreated. An HgbA1c correlates to an average estimated glucose level of 120 mg/dl and should at least be cause for further testing (OGTT) and investigation, but most doctors will say nothing or simply suggest that you "watch your sugar intake."

My problem would be that I pulled an 5.8% A1C once in my life 7 months ago. I agree with you, I was very concerned about an average 120 mg/dl BG and took action to correct it.

BTW, this test where I got a 5.8% I ordered myself, I informed my Primary Care Physician, he agreed that he would be willing to prescribe metformin based on those results.

He knows I already have metformin, just wanted to have my local PCP be willing to take over prescribing it.

The next three A1C tests were 5.6%, 5.2% then 5.3%, with a fasting BG of 88. But the 5.3 was without metformin, just wanted to see if dropping Metf changed my running / cardio ability. And what is my level of glycemic control now that I have lost 33 lbs from 7 months ago. It's probably also significant that I got back on TRT 9 months ago and it takes 3-12 months to maximize glycemic control.

I ordered and have taken a OGTT test. I don't have a lot of time to post labs but will do so Wed of next week.

But I have moved from insulin resistant to insulin sensitive.

Now the only significant thing I could discuss with my PCP is that my BG was perfectly normal outside of I dropped to a very low blood sugar level (40 mg/dl) before my liver started to push out more glucose. If I hadn't done a test, I would have never been aware of it, likely if I had tested 10 min later it would have looked normal.

 

[Joe Sixpack]

1200 mg Leucine + 500 mg twice per day Metformin + probably 5 -10 mg sildenafil

I was using 500 mg twice per day of Metformin. Ordered some 25 mg viagra tablets to split them in 3. That is why I have not started. I got Leucine capsules from Amazon.

I am following the metformin controversy very closely. Do have any updates on your Met usage Nelson? I WAS considering asking my doctor for it but held off until I heard more about it.

 

[madhacker]

I am following the metformin controversy very closely. Do have any updates on your Met usage Nelson? I WAS considering asking my doctor for it but held off until I heard more about it.

I'm very curious of this as well.

 

[Nelson Vergel]

The fatigue it caused after a few weeks and my loss of muscle pump made me discontinue it.

 

[madhacker]

The fatigue it caused after a few weeks and my loss of muscle pump made me discontinue it.

Thanks for your response Nelson.

I trialed Metformin as well and noticed the same things as you. I looked less full, lost my pump and had crippling fatigue.

As you mentioned before, Metformin + Leuicine supplementation may be worth a trial.

 

[Nelson Vergel]

As you mentioned before, Metformin + Leuicine supplementation may be worth a trial.

Yes, I have both. I should try this combo plus a tiny dose of viagra as shown in this study:

Weight Loss Combo: Effect of Leucine plus Metformin and Sildenafil Combination on Weight and Metabolic Parameters

 

[Joe Sixpack]

My doctor was fine giving me a script for Metformin 500mg Extended release. I was worried about side FX, so instead of taking a full 500mg, I cut up a pill and took that. I would guess that the small amount I took was 50-75mg. It gave me wicked diarrhea. I had heard that it might take a few weeks to get past the gastro upset. But seeing as how such a small amount gave me problems, I am not optimistic that I would ever be able to take a therapeutic dose. I haven't decided if I will try it again. We'll see.

 

[madhacker]

Yes, I have both. I should try this combo plus a tiny dose of viagra as shown in this study:

Weight Loss Combo: Effect of Leucine plus Metformin and Sildenafil Combination on Weight and Metabolic Parameters

I was hoping you may had tried this combination already. That's what I was curious about.

I'm going to start the combination of the Metformin, Leucine and Sild. sometime this week. I'll have pre/post labs done and post them here. If you have any suggestions on labs that would help us, let me know.

 

[DragonBits]

My doctor was fine giving me a script for Metformin 500mg Extended release. I was worried about side FX, so instead of taking a full 500mg, I cut up a pill and took that. I would guess that the small amount I took was 50-75mg. It gave me wicked diarrhea. I had heard that it might take a few weeks to get past the gastro upset. But seeing as how such a small amount gave me problems, I am not optimistic that I would ever be able to take a therapeutic dose. I haven't decided if I will try it again. We'll see.

Cutting up an extended release Metformin changes it into quick release. Quick release tends to have more negative side effects.

 

[Joe Sixpack]

Cutting up an extended release Metformin changes it into quick release. Quick release tends to have more negative side effects.

AGreed. But you have to understand that I took a small portion of the pill, probably 50-75mg worth out of a 500mg pill. If THAT small of a dose gives me horrible diarrhea, I am not going to take the chance that a full pill would not. The full pill is 8-10x the dose that I took. A typical therapeutic dose is 1000-2000mg. I took about 1/15-1/20th the therapeutic dose. Some day if I have absolutely nothing on my calendar I might try taking a full pill to see if I tolerate it. Pretty unlikely that I can stand it tho.

 

[DragonBits]

AGreed. But you have to understand that I took a small portion of the pill, probably 50-75mg worth out of a 500mg pill. If THAT small of a dose gives me horrible diarrhea, I am not going to take the chance that a full pill would not. The full pill is 8-10x the dose that I took. A typical therapeutic dose is 1000-2000mg. I took about 1/15-1/20th the therapeutic dose. Some day if I have absolutely nothing on my calendar I might try taking a full pill to see if I tolerate it. Pretty unlikely that I can stand it tho.

why are you wanting to take metformin? Blood Gluscose problems or general health benefit?

 

[Guided_by_Voices]

Regarding the impact on exercise, Ben Greenfield recently had an anti-aging person on his podcast and her belief was that since each dosage remains in the body for a fairly short amount of time (the half-life is around 6 hours) that taking it away from exercise was a way to mitigate any performance issues while still retaining the anti-aging and other benefits. My thought on that was that this may be true, but that compounds that have signaling functions can continue to have an affect long after they are out of the body, but this may not be the case with Metformin. Anyway, it is something to consider for those who are concerned about it. I have never taken it near exercise and it seems to have a slight fat reduction affect with no impact on exercise, however affects on either may be so small as to not be relevant and I can't be sure exactly what it is doing.