Finally I understand the basics of energy in metabolism

[Juddog]

I think I finally get it; correct me if I'm wrong here. This may seem like a long rambling thought but it all finally clicked together in my brain and I just wanted to write it out.

So when you eat a meal, looking at post-prandial glucose levels, you get an insulin response from your pancreas, which breaks down the extra glucose into glycogen (stored in liver and muscles) and triglycerides (stored in fat cells). Once the glucose levels are low, the pancreas lowers it's amount of insulin until it's no longer needed. Since muscles act as direct stores of glycogen, for a quick fuel source, this explains why people that are very muscular generally can eat a much larger amount of food; their muscles are snatching up the glycogen directly and using it straight away when lifting.

When energy is needed, which generally is 8-12 hours after the insulin stops being secreted (glucose becomes too low), then glycogen phosphorylase is released, along with glucagon, whereupon the glycogen stored in the liver is broken down and re-converted over to Glucose to be used by the body (glycogenolysis).

This is why the intermittent fasting technique works; because unless you have that 8-12 hour period after insulin is no longer being secreted, then the glycogen stores will never be broken down unless you exercise like crazy, and then you just continuously replete your glycogen stores when eating, with the rest getting dumped into triglycerides, which gets stored in adipose (fat tissue).

To not trigger the starvation process, the leptin levels have to be kept above a certain value, and as long as that's done, the conversion of glycogen to glucose should occur without the mechanisms of starvation taking place. For the triglycerides to actually leave the fatty tissues, the insulin levels have to be low; this is why working out at the end of a period of not eating (e.g. a short fast) is more effective than eating and then working out a little bit later (in which case you just burn off the energy you eat, without tapping into your reserves at all).

Since leptin itself is created from fatty tissues, then that means the more fatty tissues there are, the higher the levels of leptin that would be created during times of high insulin levels. This would imply that the more fat you have, the more hungry you will get during times when insulin is low / not being emitted and triglycerides are being converted from existing fat tissue deposits.

This explains why people that are really fat actually get more hungry, quicker, than people who are skinny, over a period of time with lower levels of glucose in the blood stream. So basically the more fat you are, the more used to high leptin levels you are, which flood the hypothalamus after eating and tell the brain that it's not hungry. Which means that it's actually harder to lose weight (mentally speaking) for fat people than it is for skinny people, because responding to the hypothalamus is instinctual in nature.

To sum it all up; if you're specifically trying to burn into the fat reserves without triggering a starvation response, you have to wait at least 8-12 hours after your last meal, and then work out. After figuring out all this in my head, intermittent fasting makes total sense to me now, at least the variety of 8 hrs where you eat all the food in a day and 16 hours of not eating any food.

 

[Saylick]

Very intriguing. I'm naturally skinny myself but now that I think about it, I really only eat within an 8-hour window on a day-to-day basis, i.e. lunch and dinner only. I wonder if I've been doing IF without even realizing it all this time...

 

[Java Cafe]

I am not sure I quite follow all this, just having completed my weight training after a 14-hour fast. My brain is all fuzzy. ;-) Regardless, for obvious reasons, I love your conclusions!

:-D

 

[SociallyChallenged]

There are some flaws in your basic explanation of the relation of insulin to blood glucose. After you eat, you begin breaking down the meal into its constituents. As your blood glucose begins to rise from breaking down carbohydrate, insulin is secreted to assist in transport of blood glucose across most cells' phospholipid membranes. There are many insulin dependent and a few insulin independent glucose transport proteins. As glucose transporters stimulated by insulin allow flow of glucose into cells from the capillaries, blood glucose begins to reduce and lower to normal levels. Usually toward the end of that process (but technically throughout), as cells begin to get their fill of glucose, the process shifts toward glycogen synthesis. The glucose molecules are essentially attached one by one in a complex structure (i.e. glycogen in the liver and in skeletal muscle). Glucose will also be broken down Acetyl-CoA via the Tricyclic Acid cycle. From there, Acetyl-CoA will be converted into fatty acids and further into triglycerides.

It's been a while since I've taken biochemistry and bioenergetics, but I do not believe it takes 8-12 hours for glucagon to increase. Also, fat metabolism is the primary source of energy at rest, regardless of depletion of liver/muscle glycogen. Fatty acid flux provides more calories at rest than glycogenolysis. In addition, what you're saying about leptin is incorrect. You're right in that it is secreted by adipose tissue, but its response is actually the opposite of what you're saying. As leptin increases, appetite is suppressed and satiety increases due to its effect on hypothalamic nuclei. The fatter you are, technically, the lower your appetite should be, as affected by leptin. However, eating behavior is multifactorial and leptin is not the sole hormone affecting hunger.

So the end of your argument is faulty. Also, physiology of bioenergetics does not always go hand in hand what macro-research shows. The complexity of the body is vast and the interactions between insulin, glucagon, leptin, ghrelin, growth hormone, and more are not linear. In addition, it varies heavily based on each individual due to thyroid activity, hypothalamic sensitivity, etc. Research has not well validated intermittent fasting. It may work, but there are also better researched methods that have both physiologic and research support.

 

[Juddog]

There are some flaws in your basic explanation of the relation of insulin to blood glucose. After you eat, you begin breaking down the meal into its constituents. As your blood glucose begins to rise from breaking down carbohydrate, insulin is secreted to assist in transport of blood glucose across most cells' phospholipid membranes. There are many insulin dependent and a few insulin independent glucose transport proteins. As glucose transporters stimulated by insulin allow flow of glucose into cells from the capillaries, blood glucose begins to reduce and lower to normal levels. Usually toward the end of that process (but technically throughout), as cells begin to get their fill of glucose, the process shifts toward glycogen synthesis. The glucose molecules are essentially attached one by one in a complex structure (i.e. glycogen in the liver and in skeletal muscle). Glucose will also be broken down Acetyl-CoA via the Tricyclic Acid cycle. From there, Acetyl-CoA will be converted into fatty acids and further into triglycerides.

So basically the food gets broken down and distributes the energy to where it's needed. The excess is broken down into glycogen and triglycerides along with other fatty acids.

It's been a while since I've taken biochemistry and bioenergetics, but I do not believe it takes 8-12 hours for glucagon to increase. Also, fat metabolism is the primary source of energy at rest, regardless of depletion of liver/muscle glycogen. Fatty acid flux provides more calories at rest than glycogenolysis.

Interesting data about fatty acid flux providing more calories at rest; will make a note of it.

In addition, what you're saying about leptin is incorrect. You're right in that it is secreted by adipose tissue, but its response is actually the opposite of what you're saying. As leptin increases, appetite is suppressed and satiety increases due to its effect on hypothalamic nuclei. The fatter you are, technically, the lower your appetite should be, as affected by leptin. However, eating behavior is multifactorial and leptin is not the sole hormone affecting hunger.

If you re-read what I wrote about leptin, what I was saying was that the hypothalamus becomes used to the huge levels of leptin if you have a lot of extra fat, and I never said that it was the sole hormone affecting hunger. If your hypothalamus becomes used to large levels, then when those levels go down, your hypothalamus will react via showing hunger symptoms. Thus people with large reserves of fat become more hungry than regular people.

So the end of your argument is faulty. Also, physiology of bioenergetics does not always go hand in hand what macro-research shows. The complexity of the body is vast and the interactions between insulin, glucagon, leptin, ghrelin, growth hormone, and more are not linear. In addition, it varies heavily based on each individual due to thyroid activity, hypothalamic sensitivity, etc. Research has not well validated intermittent fasting. It may work, but there are also better researched methods that have both physiologic and research support.

I know that it gets more complicated and nuanced, and that individuals have specific reactions to the way their body works. My general point was to understand why exercising at the end of a fasting cycle was more effective than exercising soon after eating; in other words in the morning before you eat anything. Your hypothalamus doesn't have to be very sensitive if it's being flooded by leptin; it's the same thing as an alcoholic getting used to huge levels of alcohol in their system. If you have a large amount of something, your body becomes used to things being at that level - so people with large amounts of leptin from the excess of adipose tissue are going to be used to that elevated level. As soon as that level drops, they will have a stronger reaction to hunger. It goes along the lines of insulin resistance as well in people that consume too much sugar; the body becomes so used to the insulin reaction.

 

[Raghu]

Are you trying to explain how low-carbohydrate diets work?

 

[Juddog]

Are you trying to explain how low-carbohydrate diets work?

No - I was trying to specifically place together the macro-scale energy work of the body and how it functions.

As SociallyChallenged pointed out, my current understanding still has some gaps to be filled in as far as the micro-scale goes, but in general I believe I have fleshed out the energy mechanisms of the body in terms of macro nutrition, which is something I was struggling with for a while.

One of the things I had struggled with understanding was why when people are overweight, do they have such an incredible hunger, but once I found out that adipose tissue acted as part of the endocrine system, suddenly it made sense. In the same way that people become insulin-tolerant (meaning their mind is no longer reacting to the insulin levels in the blood), the hypothalamus becomes leptin-tolerant.

The way I like to think of it is a sliding window; once your brain becomes used to certain levels of something, it generally tries to keep things at that level.

There is a paper on it here:
http://ajcn.nutrition.org/content/early/2011/12/26/ajcn.111.012385.full.pdf

In reading the paper, basically they were giving people that were previously overweight extra leptin to see if it brought them to the same satiety levels that they were at before they lost the weight; in other words it was bringing to their hypothalamus the same levels of leptin that they previously were used to from the continuous release from adipose tissue.

In essence, once the leptin was repleted, the subjects felt more satieted from food intake. This means that once someone who is overweight loses weight, they will be more hungry than someone who was at a healthy weight was, at that same weight. This explains why when overweight people lose weight, they oftentimes gain it back - their brain is used to these high leptin levels and so it makes the body urge to eat more to bring it back to that state where it once was.

 

[Raghu]

Well then, you inadvertently did explain LCHF

I will add one more - the absence of insulin is the most important factor in allowing mobilization of stored fats into the blood stream (lipolysis).

Does the hypothalamus regain leptin sensitivity if its exposed to long periods of normal leptin levels? Does the body regain insulin sensitivity if its exposed to long periods of normal insulin/glucose levels?

 

[SociallyChallenged]

So basically the food gets broken down and distributes the energy to where it's needed. The excess is broken down into glycogen and triglycerides along with other fatty acids.

Interesting data about fatty acid flux providing more calories at rest; will make a note of it.

If you re-read what I wrote about leptin, what I was saying was that the hypothalamus becomes used to the huge levels of leptin if you have a lot of extra fat, and I never said that it was the sole hormone affecting hunger. If your hypothalamus becomes used to large levels, then when those levels go down, your hypothalamus will react via showing hunger symptoms. Thus people with large reserves of fat become more hungry than regular people.

I know that it gets more complicated and nuanced, and that individuals have specific reactions to the way their body works. My general point was to understand why exercising at the end of a fasting cycle was more effective than exercising soon after eating; in other words in the morning before you eat anything. Your hypothalamus doesn't have to be very sensitive if it's being flooded by leptin; it's the same thing as an alcoholic getting used to huge levels of alcohol in their system. If you have a large amount of something, your body becomes used to things being at that level - so people with large amounts of leptin from the excess of adipose tissue are going to be used to that elevated level. As soon as that level drops, they will have a stronger reaction to hunger. It goes along the lines of insulin resistance as well in people that consume too much sugar; the body becomes so used to the insulin reaction.

Also, it's something minor, but I think it will assist with your understanding. You keep saying glucose gets broken down into glycogen. It doesn't get broken down whatsoever, but instead built up. Glucose is attached to glucose is attached to glucose and it makes glycogen. For fatty acids, there's a portion where glucose is broken down, but again once it's Acetyl-CoA and you don't need more energy it gets built up into triglycerides.

I don't believe the hypothalamus actually works like that. In terms of insulin, it does work like that a little bit in that if you have high insulin levels, you develop a bit of resistance. I'm not sure it's the same (or even if it's well studied enough to say one way or the other) with leptin. I've never read of leptin resistance and the brain is does not typically build up a resistance to hormones. Therefore saying that people with high leptin should be hungrier because it's higher on average is not really based in science. From all we know, as leptin goes up, appetite goes down. Period. Even if you have chronically high leptin.

First of all, are you talking about exercising after a fasting period being effective in terms of weight loss? Or in what terms? For performance, it is actually significantly less effective to exercise at the end of a fasting period due to lack of carbohydrate available. For weight loss, it ultimately depends on caloric deficit. You can exercise until you turn blue in the face while doing intermittent fasting, but if you are eating at caloric maintenance, your body will actively replenish carbohydrate and fatty acid stores that were utilized to perform the exercise. I've read research that shows that exercising after depleting glycogen stores is more effective in increasing future glycogen stores if paired with vigorous aerobic exercise. So in that sense, yes, exercising after fasting is more effective for improving future performance. However, from all the research I've read on intermittent fasting, it may only be marginally more effective for fat loss when compared to other similar caloric deficit diets.

 

[Juddog]

Well then, you inadvertently did explain LCHF

I will add one more - the absence of insulin is the most important factor in allowing mobilization of stored fats into the blood stream (lipolysis).

This is true - normally the adipose tissue is a revolving door when it comes to storing or releasing stored fats, but in general it releases much less while insulin is present in the blood. So really you don't start utilizing those fat stores until your insulin levels are low.

This directly made me understand why I used to work out later on in the day, and wasn't losing any weight at all; basically my insulin levels were still high because I had eaten a few hours earlier, so the adipose tissue wasn't doing much in terms of burning up the stored triglycerides. Instead all that was happening was my muscles were burning up the glycogen stores while I was exercising anaerobically, and potentially burning up some glycogen from my liver stores as well, once the internal glucose levels were used up.

For exercise to be the most efficient, it needs to occur at the end of a fasting cycle, where the lipolysis is already naturally occurring.

Does the hypothalamus regain leptin sensitivity if its exposed to long periods of normal leptin levels? Does the body regain insulin sensitivity if its exposed to long periods of normal insulin/glucose levels?

That's a good question; the studies were on people that used to be overweight but had lost it but didn't really state how long ago that was, so I'm not sure how long it would take for the hypothalamus to get back to a normal level. I would think that insulin / leptin sensitivity should eventually return to a healthy level given enough time, since my uncle for example used to be overweight for a long time and ended up losing a lot of weight and keeping it off, but it seems in his case it took several years to get over the hunger that he constantly felt.

 

[Juddog]

Also, it's something minor, but I think it will assist with your understanding. You keep saying glucose gets broken down into glycogen. It doesn't get broken down whatsoever, but instead built up. Glucose is attached to glucose is attached to glucose and it makes glycogen. For fatty acids, there's a portion where glucose is broken down, but again once it's Acetyl-CoA and you don't need more energy it gets built up into triglycerides.

Fairly noted; I guess I should change the phrasing from being broken down to something like "converted", since it would be inefficient for the liver to store energy in it's glucose form; the glycogen store is a much more efficient way to store it, and triglycerides even more efficient still.

I don't believe the hypothalamus actually works like that. In terms of insulin, it does work like that a little bit in that if you have high insulin levels, you develop a bit of resistance. I'm not sure it's the same (or even if it's well studied enough to say one way or the other) with leptin. I've never read of leptin resistance and the brain is does not typically build up a resistance to hormones. Therefore saying that people with high leptin should be hungrier because it's higher on average is not really based in science. From all we know, as leptin goes up, appetite goes down. Period. Even if you have chronically high leptin.

I'll repost the studies shown here which shows that people do become used to a certain leptin level; keep in mind this is a fairly recent study (2011):
http://ajcn.nutrition.org/content/early/2011/12/26/ajcn.111.012385.full.pdf

First of all, are you talking about exercising after a fasting period being effective in terms of weight loss? Or in what terms?

In my case, specifically for weight loss purposes. The goal for me is to lose weight while holding onto my existing skeletal muscle for that "lean" look. As soon as the exercise is done, I almost immediately drink a protein shake to make sure that the muscle tissues have the building blocks they need so to not lose any muscle mass.

For performance, it is actually significantly less effective to exercise at the end of a fasting period due to lack of carbohydrate available.

I agree; my post is mostly for people that are overweight and have excess fat stores they want to burn into. Once you are at a balanced level, e.g. 5-10% bodyfat, then there is no need to continue to dip into the fat stores to this extent.

For weight loss, it ultimately depends on caloric deficit. You can exercise until you turn blue in the face while doing intermittent fasting, but if you are eating at caloric maintenance, your body will actively replenish carbohydrate and fatty acid stores that were utilized to perform the exercise. I've read research that shows that exercising after depleting glycogen stores is more effective in increasing future glycogen stores if paired with vigorous aerobic exercise. So in that sense, yes, exercising after fasting is more effective for improving future performance. However, from all the research I've read on intermittent fasting, it may only be marginally more effective for fat loss when compared to other similar caloric deficit diets.

I'll agree to disagree on this one; I have been consistently losing weight over the past 6 months using intermittent fasting without losing any muscle mass, in fact I am stronger now than when I started this routine, which is one of the things that shocked me about it.

In the past, all the diets I had tried resulted in the loss of muscle mass. Yes I lost more weight that way, but I didn't like the fact that I had to rebuild the muscle over again. My goal is to maintain a good amount of muscle while working on reducing my fat stores. Performance is secondary at the moment; when i get to the ideal I'm going for, then I'll start eating for performance, but right now I just want to maximize the "burn".

-- edit for clarification --

I agree that a caloric deficit is necessary; what I am trying to say is that specifically "maxing out" the energy conversion from energy stores (triglycerides and glycogen) is best done via exercise at the end of a fasting cycle instead of a period within a few hours of eating. Specifically speaking, I used to exercise a few hours after eating dinner and while I gained muscle it had basically zero effect in terms of fat loss. So really what I'm aiming for is the "most effective" approach; if that means only a small increase in effectiveness over traditional methods, then so be it. By understanding the macro-scale energy cycle, it helps me specifically to plan out my meals / workouts.

 

[SociallyChallenged]

Fairly noted; I guess I should change the phrasing from being broken down to something like "converted", since it would be inefficient for the liver to store energy in it's glucose form; the glycogen store is a much more efficient way to store it, and triglycerides even more efficient still.

I'll repost the studies shown here which shows that people do become used to a certain leptin level; keep in mind this is a fairly recent study (2011):
http://ajcn.nutrition.org/content/early/2011/12/26/ajcn.111.012385.full.pdf

In my case, specifically for weight loss purposes. The goal for me is to lose weight while holding onto my existing skeletal muscle for that "lean" look. As soon as the exercise is done, I almost immediately drink a protein shake to make sure that the muscle tissues have the building blocks they need so to not lose any muscle mass.

I agree; my post is mostly for people that are overweight and have excess fat stores they want to burn into. Once you are at a balanced level, e.g. 5-10% bodyfat, then there is no need to continue to dip into the fat stores to this extent.

I'll agree to disagree on this one; I have been consistently losing weight over the past 6 months using intermittent fasting without losing any muscle mass, in fact I am stronger now than when I started this routine, which is one of the things that shocked me about it.

In the past, all the diets I had tried resulted in the loss of muscle mass. Yes I lost more weight that way, but I didn't like the fact that I had to rebuild the muscle over again. My goal is to maintain a good amount of muscle while working on reducing my fat stores. Performance is secondary at the moment; when i get to the ideal I'm going for, then I'll start eating for performance, but right now I just want to maximize the "burn".

-- edit for clarification --

I agree that a caloric deficit is necessary; what I am trying to say is that specifically "maxing out" the energy conversion from energy stores (triglycerides and glycogen) is best done via exercise at the end of a fasting cycle instead of a period within a few hours of eating. Specifically speaking, I used to exercise a few hours after eating dinner and while I gained muscle it had basically zero effect in terms of fat loss. So really what I'm aiming for is the "most effective" approach; if that means only a small increase in effectiveness over traditional methods, then so be it. By understanding the macro-scale energy cycle, it helps me specifically to plan out my meals / workouts.

I'll check out the link - I've haven't been reading as many nutrition articles as I used to. Thanks.

While I agree that intermittent fasting can be effective to modify eating behaviors, there are other programs that allow for maintenance of muscle mass under a caloric deficit. Approaching it from a different perspective, strength training biases weight loss more toward fat mass than muscle mass with or without intermittent fasting. Aerobic exercise alone is notorious for allowing people to lose weight, but staying at a similar body fat percentage.

Either way, I respect your decision. It's definitely not wrong. I tend to run the middle ground in most things and I like to eat throughout the day, not just during a feeding window. I also like to propose alternative methods for individuals who are/were in your situation where you felt like you lost muscle mass.

What kind of workout program are you currently completing? I imagine that intermittent fasting + heavy strength training would give you the biggest bang for your buck in addressing fat-specific weight loss.

Currently, I focus a bit more on my sports performance so I have shifted away from the "get as shredded as possible" mentality. That may also be because I'm between 10-12% body fat and think it's evolutionarily fit to have a little bit of fat to live on in a worst case scenario. I've been happy to have this discussion with you - haven't had anybody to chat about metabolism of nutrients, hunger hormones, etc in a while.

 

[Juddog]

I'll check out the link - I've haven't been reading as many nutrition articles as I used to. Thanks.

While I agree that intermittent fasting can be effective to modify eating behaviors, there are other programs that allow for maintenance of muscle mass under a caloric deficit. Approaching it from a different perspective, strength training biases weight loss more toward fat mass than muscle mass with or without intermittent fasting. Aerobic exercise alone is notorious for allowing people to lose weight, but staying at a similar body fat percentage.

Either way, I respect your decision. It's definitely not wrong. I tend to run the middle ground in most things and I like to eat throughout the day, not just during a feeding window. I also like to propose alternative methods for individuals who are/were in your situation where you felt like you lost muscle mass.

What kind of workout program are you currently completing? I imagine that intermittent fasting + heavy strength training would give you the biggest bang for your buck in addressing fat-specific weight loss.

Currently, I focus a bit more on my sports performance so I have shifted away from the "get as shredded as possible" mentality. That may also be because I'm between 10-12% body fat and think it's evolutionarily fit to have a little bit of fat to live on in a worst case scenario. I've been happy to have this discussion with you - haven't had anybody to chat about metabolism of nutrients, hunger hormones, etc in a while.

Well a bit of history; as I mentioned earlier, I used to be dumb with my training in that I'd get out of work, eat dinner, then a couple hours later I'd hit the gym. I found myself gaining more and more muscle but not losing the fat. For a while I was up to about 2 hours of exercise in a session, but I just never seemed to lose any weight as ridiculous as that sounds.

My current strategy, as of about a half year ago and reading about IF on the bodybuilding forums, was to try to switch my routine around so that I would exercise in the morning first thing, then slam a protein shake (whey, frozen berries, and ice, 200 calories per shake), then go to work. I work out less nowadays than I used to, roughly a half hour to an hour per day, but it's been more effective for me so far. I found it's also easier to plan out my meals and calorie totals per day when I only have a limited window to eat; before I would find myself constantly snacking throughout the day because my hunger was out of control.

When I eat a big meal now after not eating anything for 12 hours, I find myself feeling stuffed a lot easier. I think IF has worked better for me in terms of psychologically being easier to do, since I now control the time window I eat in, if I find my mind wandering to food I just say "it's past 6 PM" and then I can go find something else to occupy my mind.

My current exercise routine is basically hit the exercise bike in the morning and follow up with some extremely basic weight training, but I plan on stepping it up once I get a gym membership again. I recently moved into a new house about a year ago so most of my weights are scattered about and I don't have a good workout area yet. I know that my exercise routine right now is severely lacking and so now that I finally have started to understand (at the marcro level) of how my metabolism works, I can start adding more and more into my weight training and diet routine.

I enjoy having this discussion also; to me amazing at how much is continuously being discovered as far as how the body works and that we're still making all these new advances in what we know.

 

[OSULugan]

Good, now let's talk about what's different in a Type 1 Diabetic's metabolic cycle with the inability of the body to produce insulin and glucagon on its own.

 

[SociallyChallenged]

Good, now let's talk about what's different in a Type 1 Diabetic's metabolic cycle with the inability of the body to produce insulin and glucagon on its own.

I don't think it technically has all that much to do with the metabolism itself (the act of breaking down/processing energy sources), but moreso with the transport mechanisms. If given insulin, their body metabolizes everything in a near-normal fashion, which hints it's not an issue with the metabolic process.

I know that type I diabetes mellitus results in altered insulin production and alters glucagon secretion, but are you sure it modifies the pancreas' ability to produce glucagon? I have read about a blunted glucagon response, especially as it related to responses to recurrent hypoglycemia (insulin induced), but not about truly altered production.

 

[OSULugan]

I know that type I diabetes mellitus results in altered insulin production and alters glucagon secretion, but are you sure it modifies the pancreas' ability to produce glucagon? I have read about a blunted glucagon response, especially as it related to responses to recurrent hypoglycemia (insulin induced), but not about truly altered production.

While the type 1 diabetic's immune system doesn't kill the glucagon producing alpha cells, without their beta cell counter-parts, the glucagon production is severely hampered (as you allude to). Everything I've read (and experienced) points to a lack of appreciable production. This is why there have been multiple studies and attempts to "close the loop" with insulin pump therapy by using a CGM, and taking the results to help run a secondary infusion pump providing glucagon to help prevent hypoglycemic episodes.

What brought me into this thread, and the reason for the previous statement, is to hope for that "a-ha" moment including a hampered endocrine system to how metabolism, energy production, and the interaction with the fatty liver energy stores and general fat cells. With a hampered glucagon production, I have a hard time understanding how a diabetic harnesses the fat tissue stores of energy, especially going by the OP's explanation of the metabolic response.

 

[Juddog]

While the type 1 diabetic's immune system doesn't kill the glucagon producing alpha cells, without their beta cell counter-parts, the glucagon production is severely hampered (as you allude to). Everything I've read (and experienced) points to a lack of appreciable production. This is why there have been multiple studies and attempts to "close the loop" with insulin pump therapy by using a CGM, and taking the results to help run a secondary infusion pump providing glucagon to help prevent hypoglycemic episodes.

What brought me into this thread, and the reason for the previous statement, is to hope for that "a-ha" moment including a hampered endocrine system to how metabolism, energy production, and the interaction with the fatty liver energy stores and general fat cells. With a hampered glucagon production, I have a hard time understanding how a diabetic harnesses the fat tissue stores of energy, especially going by the OP's explanation of the metabolic response.

Glucagon helps converts glycogen to glucose, from the stores in the liver; it doesn't affect adipose tissue in terms of converting triglycerides to a usable form (hydrolysis of triglycerides into free fatty acids). Adipose begins the hydrolysis process when insulin levels are low, not when glucagon levels are high, at least from my understanding of it.

There is also glycogen stored in muscle tissue itself which seem to be able to be burned off directly by the muscles during the initial heavy burst of activity when it's needed. Therefore it's feasible to say that someone who has an issue producing glucagon levels in the pancreas could still find ways to pull energy from their reserves, it would just be harder in particular to pull the faster form of energy from the glycogen stores in the liver in particular.

A two-pump system (one pump produces insulin, the other glucagon) wouldn't be able to fully regulate the entire metabolic system of a person's body, in my opinion; rather it would specifically regulate the metabolism as it pertains to the liver storing or releasing energy via either stacking glucose into glycogen or breaking down glycogen into glucose, along with the other effects of insulin. It would avoid hypoglycemia from occurring, but it is far from a perfect system.

 

[Juddog]

Good, now let's talk about what's different in a Type 1 Diabetic's metabolic cycle with the inability of the body to produce insulin and glucagon on its own.

I don't know that this will ever be able to be fixed; from what I understand diabetes mellitus type 1 is caused by someones immune system attacking the insulin producing cells of the pancreas; even if one were able to somehow use a 3d printer to create a framework and use stem cells to assume beta pancreatic cell properties to regrow a healthy pancreas from scratch (I'm talking future tech here), planting the regrown organ into a patient would still likely result in another attack by the autoimmune cells and breakdown of those beta cells once again.

The only fix would be a combination of fixing the auto-immune response and regrowing the organ; that might be possible 50 years from now when medical researches figure out how to control what the autoimmune system attacks or doesn't attack, but right now I don't see how it's possible.

 

[SociallyChallenged]

While the type 1 diabetic's immune system doesn't kill the glucagon producing alpha cells, without their beta cell counter-parts, the glucagon production is severely hampered (as you allude to). Everything I've read (and experienced) points to a lack of appreciable production. This is why there have been multiple studies and attempts to "close the loop" with insulin pump therapy by using a CGM, and taking the results to help run a secondary infusion pump providing glucagon to help prevent hypoglycemic episodes.

What brought me into this thread, and the reason for the previous statement, is to hope for that "a-ha" moment including a hampered endocrine system to how metabolism, energy production, and the interaction with the fatty liver energy stores and general fat cells. With a hampered glucagon production, I have a hard time understanding how a diabetic harnesses the fat tissue stores of energy, especially going by the OP's explanation of the metabolic response.

Well, fatty acid metabolism is regulated by a vast number of hormones. Those that stimulate fatty acid metabolism (other than glucagon) include epinephrine, norepinephrine, growth hormone, vasopressin, ACTH, cortisol, thyroid hormone, testosterone, TNF-alpha, estrogen, nitric oxid, and leptin. The paper that has a pretty good explanation of this is located here: http://www.ingentaconnect.com/conte...4247b592c2b414c3e763568293c62207d673f582f6bd5. I'm not sure if it's a free article so PM me if you're curious about what is actually says. People tend to oversimplify metabolism into glucagon vs insulin, when in actuality it is vastly complex. There are a lot of ways to get around it. Type 1 diabetics aren't typically skinny because they are effective at metabolizing fat, but rather because they are so inefficient at getting nutrients into their cells from dietary resources.

 

[Raghu]

Turns out proteins are also used as a source of glucose. Before the body turns to stored fat (which usually more than 2 days of fasting), it tends to burn muscles for glucose.

http://www.nbs.csudh.edu/chemistry/faculty/nsturm/CHE452/24_Glucose Homeostas.htm

^ Very good explanation of body response to fasting and other nutritional information. I tend to get a feeling that fasting->exercise damages muscles more because the body has depleted most of stored glycogen and burns proteins for generating glucose. This particular quote from wiki

"The body's rate of protein loss is greatest during the first 72 hours (of fasting). After several days of starvation the body adapts and starts to conserve protein."

http://en.wikipedia.org/wiki/Starvation_response

Consequently, if you are in ketosis you are conserving proteins since you are always using fats (stored or dietary), and there is no need to make glucose from alanine. The protein requirement of the body is ketosis is lesser than normal because not as much muscles are being broken down.

 

[Juddog]

Turns out proteins are also used as a source of glucose. Before the body turns to stored fat (which usually more than 2 days of fasting), it tends to burn muscles for glucose.

http://www.nbs.csudh.edu/chemistry/faculty/nsturm/CHE452/24_Glucose Homeostas.htm

^ Very good explanation of body response to fasting and other nutritional information. I tend to get a feeling that fasting->exercise damages muscles more because the body has depleted most of stored glycogen and burns proteins for generating glucose. This particular quote from wiki

"The body's rate of protein loss is greatest during the first 72 hours (of fasting). After several days of starvation the body adapts and starts to conserve protein."

http://en.wikipedia.org/wiki/Starvation_response

Consequently, if you are in ketosis you are conserving proteins since you are always using fats (stored or dietary), and there is no need to make glucose from alanine. The protein requirement of the body is ketosis is lesser than normal because not as much muscles are being broken down.

Using carbs, protein, and fat, are all part of the basic consumption of energy in terms of the macro level.

I personally try to avoid full blown ketosis for several days in a row like what occurs with the super-high protein and Atkins diets; I've tried the Atkins diet in the past and it started making me see spots in my vision (e.g. the start of a full blown migraine headache). It may work for some people, but as soon as I started getting migraines from it I quit doing it. I believe the headaches were a result of the severely low glucose levels, so basically my brain wasn't getting enough energy.

You don't need 2 days of fasting to tap into your stored fat reserves; you only need to get the insulin in your blood to a sufficiently low level to start hydrolysis which then leads to lipolysis. The adipose tissue is kind of a revolving door in terms of triglycerides; it is constantly active throughout the day and while you sleep in either storing or releasing energy. The lower the insulin levels, the more energy it begins to release.

The fact that the body does consume protein at a certain point after depleting it's stores of glycogen is one of the reasons that I like the IF technique; you basically get close to the beginning of when the body begins to start using protein for energy, but then immediately consume protein upon breaking the fast, after the workout. This stops your body from tapping into your protein reserves in your muscles, preserving muscle mass, plus your muscles will be in need of protein themselves, so it's a win / win. The typical technique used by the high protein / Atkins diet seems to like to get ketosis going full blast and keep it going; Intermittent Fasting only dips into ketosis for a little bit.

I think the whole Atkins / high protein diet thing was necessary for the public understanding of why it can be bad for some people to consume too many carbs, but ultimately it was a flawed view of diets and can lead to health issues. For instance it doesn't regulate the types of fat that is consumed, only really tells people to quit eating carbs and then eat as much protein and fat as possible. Down the road I'd see this as leading to cardiac issues and fat deposits in the blood stream. Basically you're switching from one extreme to the other - in other words going from continuously repleting glycogen into it's polar opposite of never allowing glycogen to build up. I don't really view the extremes as healthy; in general the body seems to prefer the moderate approaches.

The balanced approach, in my mind, is to replete glycogen stores so that ketosis doesn't continue indefinitely like it would with the typical high-protein / Atkins approach. The way I look at it is that the body needs balance, and optimal body usage would be to use both sides of the coin in terms of energy storage / energy release. By extending the period in between meals, you start ketosis for a tiny bit (which basically means your body is producing ketones as a result of the lipolysis kicking in, which shows that fat is directly being burned), then you replete your glycogen and protein stores as to avoid the loss of muscle mass and give your muscles some stored energy to work with. If one were to stick exclusively with ketosis then the muscles wouldn't have that extra energy stored up.

This way you still replete your glycogen on a daily basis, which is good for energy (and for me allows me to avoid migraines from lack of glucose in the brain), yet still burns away at those fat reserves. There is a higher than normal need for protein in this approach though, specifically post-workout, to avoid the protein cannibalism of muscle tissue, until the ideal is reached, but nowadays it's pretty easy to introduce via whey protein.

 

[SociallyChallenged]

In reply to the above post, you don't go into ketosis after 8-12h. You utilize liver glycogen, muscle glycogen (a much larger store than liver glycogen), and fat stores. It takes quite a while for your body to max out such that it needs to begin ketosis. That process typically takes 2-3 days. In addition, gluconeogenesis allows for the brain to run on glucose still for a short period of time between the end of glycogen stores and the beginning of ketosis so I doubt your feelings were due to low blood glucose. Even when you're literally in a starved state, blood glucose levels are still maintained. However, the body preferentially utilizes fatty acids and ketones for energy.

 

[Juddog]

In reply to the above post, you don't go into ketosis after 8-12h. You utilize liver glycogen, muscle glycogen (a much larger store than liver glycogen), and fat stores. It takes quite a while for your body to max out such that it needs to begin ketosis. That process typically takes 2-3 days. In addition, gluconeogenesis allows for the brain to run on glucose still for a short period of time between the end of glycogen stores and the beginning of ketosis so I doubt your feelings were due to low blood glucose. Even when you're literally in a starved state, blood glucose levels are still maintained. However, the body preferentially utilizes fatty acids and ketones for energy.

As soon as your body runs out of glycogen stores and begins breaking down triglycerides from your fat cells is when ketogenesis technically begins, since ketone bodies are the byproduct of fatty acids being broken down in the liver. This doesn't take 2-3 days to start the process; it might take that long to bring it to a high level.

In regards to the brain thing, studies have shown that after a long enough period the brain begins to use the ketone bodies for energy and starts to preserve glucose:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874681/

From the study:

Neurodegeneration after oxidative stress limits the recovery of tissue response and appears to be caused by impaired glycolysis. If indeed there is a defect in glucose metabolism it might be beneficial to supplement energy metabolism with an alternate substrate.

That is the period when I started to have migraines, which is why I had to stop the Atkins / no-carb diet. Maybe it's something wrong with my brain but the effect was literally crippling. That's why I avoid a high level of ketosis.

-- edited for clarification --