Insulin resistance

[Shenpen]

Lets say that you have snack of 50 gram delicious 76% Feodora dark chocolate. This is contains some fat (stearic acid) but also 32 grams of carbohydrate, for a total of 1000 kcal. Let say that after ingestion the carbs will result in your blood-sugar being slightly elevated. So now some of that glucose needs to be cleared away for you to get back to a blood sugar level within normal range. You pancreas are up the job and know that this takes insulin. So insulin is squirted out - more and more until the job is done. Some of the insulin makes the muscles take up the exes glucose.

But some of the insulin is not doing anything with your glucose, but instead makes your adipose tissue take up free fatty acids from the blood and store it as triglycerids. 20 grams of FFAs gets stored away as unattractive blubber round you belly. Off course you can later burn that, as soon as there is no insulin to stop your hormone sensitive lipase (HSL) from getting it out of the lipoproteins and into FFAs.

Back when you were 21 and had normal insulin sensitivity this would take say 0.1 mmol/l insulin. But you are now middle aged, have bad knees. And after taking glycosamin on and off for two years, your insulin sensitivity have dropped quite a bit. So now it takes 0.2 mmol/l of insulin to get the exes glucose shoved into muscle tissue. Guess what happens to fat-storage at this point....

Yes, as you probably guessed, more fat gets stored away to inaccessible adipose sites, and less is available for your muscles to burn. Quite a bit of the ingested energy got into muscle tissue and can be burned while you lift some iron. But at the same time you lost some of your available energy to storage. If you stored fat worth 400 kcal of energy, then you only got around 600 kcal of useful energy to play with. So if your plan was to do some heavy lifting with a budget of 800 kcal, you now have to choose between doing 25% less heavy lifting and eating something that will supply 200 kcal extra as your blood-sugar drops. This is all a bit contrived and somewhat simplified. But i trust that you get the point. This is not like choosing between Yolandi Visser and Janelle Monea for some quality time. As soon as your energy goes to storage it means that you will sacrifice one way or the other.

This is hardly news to you, but the key point is that your insulin resistance determines the actual size of your sacrifice.

Question is: What drives insulin resistance up?

[Iusedtobefat99]

Question is: What drives insulin resistance up?

Eating like everyone else on this board, outside of the keto sub-forum.

[Shenpen]

This is from Ronald A. Codario: "Type 2 Diabetes, Pre-Diabetes, and the Metabolic Syndrome":

One of the most critical effects of insulin is its effects on glucose disposal. As the result of impaired muscle glucose uptake, glucose disposal is significantly reduced resulting in impaired glycogen synthesis, glucose oxidation, and tissue glucose uptake. Glucose transport is rate limiting for overall disposal under most normal physiologic conditions. Of the five types of glucose transporters identified, the GLUT-4 protein is referred to as the insulin sensitive glucose transporter. This transporter is found in high concentrations in adipose cells, skeletal and cardiac muscles and is primarily responsible for glucose uptake and its effects. The GLUT-4 proteins are housed in intracellular vesicles and translocate to the cell surface inserting into the plasma membrane upon insulin stimulation. This causes glucose to enter the cell. Type-2 diabetics usually have normal GLUT-4 levels, but impaired glucose transport. This may indicate that a flaw exists in the insulin influence translocation of GLUT-4 to the cell surface. This defective signaling pathway between the receptor and the transport stimulation results in insulin resistance in these patients [5].


Free fatty acids released from adipose cells due to enhanced lipolysis may also contribute to insulin resistance by inhibiting glucose transport and phosphorylation followed by reduced rates of glucose oxidation and glycogen synthesis, as well as increasing apolipoprotein B secretion and increased hepatic lipase activity. Chronically elevated free fatty acid levels inhibit insulin secretion from the beta cell, and decrease insulin sensitivity in the muscle and the liver [9].

Increases in plasma glucose concentrations by 50–100 mg/dl for as little as 24 h can cause downregulation of the glucose transport system in the muscle GLUT-4) significantly increasing insulin resistance. With the progression of time, insulin resistance peaks and then plateaus, while increases in plasma insulin compensate to maintain the glycemic state.

Diabetic patients may be prone to enhanced effects of glucosamine on the PAI-1 promoter, subsequently activating PKC isoforms. Hence Type -2 diabetics should be cautioned about using glucosamine because of this potential complication, although its use in diabetic patients has not been shown to induce insulin resistance or insulin sensitivity. Glucosamine is an endogenous amino monosaccharide that is utilized for the biosynthesis of glycosaminogly-cans and lycoproteins. One of the most popular dietary supplements, it is synthesized from glucose and present in practically all human tissues with the highest concentrations found in cartilage. Glucosamine can be found in many forms – hydrochloride, sulfate, N-acetylglucosamine, or chlorohydrate salt and is approximately 90% absorbed when taken orally. Diabetics should monitor their blood glucose levels when taking this product.


summary
Abnormalities and disruptions of several glucose control mechanisms contribute to the etiology of type-2 diabetes: decreased tissue response and resistance to insulin, impaired insulin production and secretion due to deficient non autoimmune beta cell function, increased hepatic glucose production induced by prolonged islet alpha cell glucagon secretion, and a deficiency in secretion and response to gut hormones called incretins. An appreciation of these pathophysiologic mechanisms and the natural history of the disease are crucial to understanding the therapeutic maneuvers, treatment plans, outcome data, and risk reduction strategies for the diabetic patient.

My take: Not even close to explaning the specifics of how insulin resistance is changed.

[DannySampsonite]

Eating like everyone else on this board, outside of the keto sub-forum.

God shut up retard. The number one cause of insulin resistance is obesity. Who here is obese?

The number one booster of insulin sensitivity is exercise. Who here exercises?

Yeah, you do the math you parroting ketard

[DannySampsonite]

This is from Ronald A. Codario: "Type 2 Diabetes, Pre-Diabetes, and the Metabolic Syndrome":

One of the most critical effects of insulin is its effects on glucose disposal. As the result of impaired muscle glucose uptake, glucose disposal is significantly reduced resulting in impaired glycogen synthesis, glucose oxidation, and tissue glucose uptake. Glucose transport is rate limiting for overall disposal under most normal physiologic conditions. Of the five types of glucose transporters identified, the GLUT-4 protein is referred to as the insulin sensitive glucose transporter. This transporter is found in high concentrations in adipose cells, skeletal and cardiac muscles and is primarily responsible for glucose uptake and its effects. The GLUT-4 proteins are housed in intracellular vesicles and translocate to the cell surface inserting into the plasma membrane upon insulin stimulation. This causes glucose to enter the cell. Type-2 diabetics usually have normal GLUT-4 levels, but impaired glucose transport. This may indicate that a flaw exists in the insulin influence translocation of GLUT-4 to the cell surface. This defective signaling pathway between the receptor and the transport stimulation results in insulin resistance in these patients [5].


Free fatty acids released from adipose cells due to enhanced lipolysis may also contribute to insulin resistance by inhibiting glucose transport and phosphorylation followed by reduced rates of glucose oxidation and glycogen synthesis, as well as increasing apolipoprotein B secretion and increased hepatic lipase activity. Chronically elevated free fatty acid levels inhibit insulin secretion from the beta cell, and decrease insulin sensitivity in the muscle and the liver [9].

LOLWUT. Type II diabetes is defined by insufficient insulin PRODUCTION. The issue is B-islet dysfunction that is simply worsened or caused by insulin resistance. Insulin resistance cannot be equated with diabetes...at all. 99% of obese people have insulin resistance...only about 1-5% have type II diabetes.

[DannySampsonite]

Eating like everyone else on this board, outside of the keto sub-forum.

Your signature is beyond stupid:

"Ketosis: Because initiating lipolysis during a cut is obviously a terrible thing."

You obviously don't understand what ketosis is.

[ArchangelEST]

Keep going Danny.

I came here looking to add something, but found you already cleaned house. Nice.

[ArchangelEST]

Back when you were 21 and had normal insulin sensitivity this would take say 0.1 mmol/l insulin. But you are now middle aged, have bad knees. And after taking glycosamin on and off for two years, your insulin sensitivity have dropped quite a bit. So now it takes 0.2 mmol/l of insulin to get the exes glucose shoved into muscle tissue. Guess what happens to fat-storage at this point....

Yes, as you probably guessed, more fat gets stored away to inaccessible adipose sites, and less is available for your muscles to burn. Quite a bit of the ingested energy got into muscle tissue and can be burned while you lift some iron. But at the same time you lost some of your available energy to storage. If you stored fat worth 400 kcal of energy, then you only got around 600 kcal of useful energy to play with. So if your plan was to do some heavy lifting with a budget of 800 kcal, you now have to choose between doing 25% less heavy lifting and eating something that will supply 200 kcal extra as your blood-sugar drops. This is all a bit contrived and somewhat simplified. But i trust that you get the point. This is not like choosing between Yolandi Visser and Janelle Monea for some quality time. As soon as your energy goes to storage it means that you will sacrifice one way or the other.

This is hardly news to you, but the key point is that your insulin resistance determines the actual size of your sacrifice.

Question is: What drives insulin resistance up?

I hope you do realize that Insulin Resistance can also affect Fat Cells?
In many cases, people with Insulin resistance have LOWERED fat storage rate, despite higher Insulin in their system. Simply because their fat cells are also losing sensitivity to the insulin.

And I don't even understand what the rest of your babble is all about.

Fat gets stored away to inaccessible adipose sites? Where would those be? Why inaccessible? I hope you do realize that your body will always burn fat for energy, even when lifting hard in the gym. Glucose is never the only source for energy. I don't have specific numbers at hand, but most likely you burn a very large percentage of fat during any work-out in the gym. Glucose is mainly used in high-intensity actions - which is most of the reps. But you don't just rep non-stop at the gym. No, usually you spend more time between sets, resting or carrying weights or whatnot. That's major fat burning time right there.

Let's not even go into how your body can synthesize glucose from proteins and whatnot.

[Shenpen]

I hope you do realize that Insulin Resistance can also affect Fat Cells?
In many cases, people with Insulin resistance have LOWERED fat storage rate, despite higher Insulin in their system. Simply because their fat cells are also losing sensitivity to the insulin.

And I don't even understand what the rest of your babble is all about.

Fat gets stored away to inaccessible adipose sites? Where would those be? Why inaccessible? I hope you do realize that your body will always burn fat for energy, even when lifting hard in the gym. Glucose is never the only source for energy. I don't have specific numbers at hand, but most likely you burn a very large percentage of fat during any work-out in the gym. Glucose is mainly used in high-intensity actions - which is most of the reps. But you don't just rep non-stop at the gym. No, usually you spend more time between sets, resting or carrying weights or whatnot. That's major fat burning time right there.

Let's not even go into how your body can synthesize glucose from proteins and whatnot.

You are totally right that during exercise, energy stored in adipose tissue is not inaccessible. The main point however is that most people have insulin resistance (and elevated blood-sugar and elevated insulin), which will hinder hormone sensitve lipase from exporting the stored fat as FFAs. And they don't spend enough time exercising to make this glorious exception the main scenario.

The issues surrounding insulin resistance are complicated and poorly understood and its hard to always make clear the context that is relevant when you try to put the story together in short form.

[Shenpen]

LOLWUT. Type II diabetes is defined by insufficient insulin PRODUCTION. The issue is B-islet dysfunction that is simply worsened or caused by insulin resistance. Insulin resistance cannot be equated with diabetes...at all. 99% of obese people have insulin resistance...only about 1-5% have type II diabetes.

Im just trying to find good information about insulin resistance. The books about nutrition that mentions insulin resistance tend to be even more vague and unspecific than this book on diabetes and "syndrome x".

[ArchangelEST]

You are totally right that during exercise, energy stored in adipose tissue is not inaccessible. The main point however is that most people have insulin resistance (and elevated blood-sugar and elevated insulin), which will hinder hormone sensitve lipase from exporting the stored fat as FFAs. And they don't spend enough time exercising to make this glorious exception the main scenario.

The issues surrounding insulin resistance are complicated and poorly understood and its hard to always make clear the context that is relevant when you try to put the story together in short form.

Well, you are basically using fancy language to conclude that people are fat cause they don't exercise.

Insulin Resistance is usually brought upon through various means like lack of exercise, excessive caloric intake and the increased weight. And it's true we don't understand the mechanisms completely, which is a shame indeed.

While insulin resistance can hinder HSL from expressing itself it is only one part of the whole picture. It is not the only player in town that is responsible for fatty acid release. ATGL seems to play a huge part as-well.

Now even when fat store fat release is hindered through IR, the total daily nutrition and activity can still make it a fairly moot point in terms of burning fat in general over a longer period of time. As far as I understand the usual need for fat for energy is low enough, that the needs can be met even in a hindered state. Meaning that in the case of a negative caloric balance, the fat stores will still be mobilized effectively enough to cause expected fat loss.

I imagine that IR people may not make particularly effective marathon runners, but in terms of simply losing weight - there shouldn't be an issue. After all, countless people have lost ridiculous amounts of fat mass, even without any exercise - being in a caloric deficit is quite enough to use up stored Fats, even if their release is hindered through IR.

Im just trying to find good information about insulin resistance. The books about nutrition that mentions insulin resistance tend to be even more vague and unspecific than this book on diabetes and "syndrome x".

I wouldn't rely on books too much. They tend to be a collection of the author's(s) views, which may or may not be backed by relevant up to date science. I'd suggest reading actual unbiased scientific research instead to keep up to date on the specifics and make your own opinion based on that evidence. - It's hard work, often very hard to read through the dry science and mess of numbers and other data - but it will often paint a more factual picture.

[Grifts]

I tend to think of insulin resistance similar to how one might develop a drug tolerance/resistance. As insulin resistance develops, you need larger and larger amounts of insulin for it to work properly, for the same amount of carb loads. Your cells have become resistant and need a larger insulin stimulus to react to insulin the way it had previously at lesser amounts.

So...what drives it up: Chronically elevated insulin levels.

[Iusedtobefat99]

Your signature is beyond stupid:

"Ketosis: Because initiating lipolysis during a cut is obviously a terrible thing."

You obviously don't understand what ketosis is.

"Ketogenesis begins with the lipolysis of fat by the enzyme lipases in which fat is cleaved into 3 fatty acid chains and 1 glycerol molecule."

Quoted DIRECTLY from this sticky on this board. Why the f*** are you so mad ?

[ArchangelEST]

"Ketogenesis begins with the lipolysis of fat by the enzyme lipases in which fat is cleaved into 3 fatty acid chains and 1 glycerol molecule."

Quoted DIRECTLY from this sticky on this board. Why the f*** are you so mad ?

Probably because you don't need Ketogenesis for it to happen. Nor does Keto offer any magical long term fat burning benefits. It may be preferable to some people purely as a personal preference kind of thing, but the number of individuals to whom I'd actually recommended Keto is pretty damn close to zero.

[KLMARB]

Too funny. Lipolysis causes ketosis. No ketosis, no lipolysis. Simple biochemistry. Not advocating ketosis means not advocating lipolysis. Fine, unless you'd actually like to burn fat and lose adipose. Insulin resistance is caused by a chronically lipogenic state. Chronic overcompensation of glycogen, as well as eating carb-fat food combinations that synergistically increase insulin production. This is an adaptive process resulting in a rise in anorexigenic hormonal resistance.

[Shenpen]

1. Well, you are basically using fancy language to conclude that people are fat cause they don't exercise.

2. Insulin Resistance is usually brought upon through various means like lack of exercise, excessive caloric intake and the increased weight. And it's true we don't understand the mechanisms completely, which is a shame indeed.

3. While insulin resistance can hinder HSL from expressing itself it is only one part of the whole picture. It is not the only player in town that is responsible for fatty acid release. ATGL seems to play a huge part as-well.

4. Now even when fat store fat release is hindered through IR, the total daily nutrition and activity can still make it a fairly moot point in terms of burning fat in general over a longer period of time. As far as I understand the usual need for fat for energy is low enough, that the needs can be met even in a hindered state. Meaning that in the case of a negative caloric balance, the fat stores will still be mobilized effectively enough to cause expected fat loss.

5. I imagine that IR people may not make particularly effective marathon runners, but in terms of simply losing weight - there shouldn't be an issue. After all, countless people have lost ridiculous amounts of fat mass, even without any exercise - being in a caloric deficit is quite enough to use up stored Fats, even if their release is hindered through IR.



6. I wouldn't rely on books too much. They tend to be a collection of the author's(s) views, which may or may not be backed by relevant up to date science. I'd suggest reading actual unbiased scientific research instead to keep up to date on the specifics and make your own opinion based on that evidence. - It's hard work, often very hard to read through the dry science and mess of numbers and other data - but it will often paint a more factual picture.

1. A lot of people draw exactly that conclusion, but it is not what i'm driving at. While it might be correct at some level, it is not a conclusion that lend itself easily to practical application, ie. most people cant just find more time to do more exercise in. I'm interested in strategies where choice of macro nutrients make a difference, even when the amount of exercise remains constant. This will offer an alternative to the often quoted axiom of "calories in = calories out", which is again correct at some level, but does not afford you a lot of practical application in real life. I will for sure get around to this in a lot more detail later. Please be patient.

2. There are people working on exactly this, but it is hard for me to understand their working theories without a recap of the history of what is the current view.

3. Interesting indeed. Please post links to articles if they are available online.

4. If you are saying that enough exercise will burn of the flabber, i'm with you. But it is interesting to look at the factors that make people do more or less "exercise", either as gym-time or as movement driven by acutal purpose.

5. I would need to know what exactly you mean by "being in a caloric deficit" to answer this.
If you are just saying that people will burn their calories when moving, i'm with you. But in many cases it is a counterfactual statement and it still doesn't answer why it is so.

6. You are preaching to the choir: I'm totally with you when it comes to reading the actual research literature. I'm just not ready for it on this particular subject. But i don't share your faith in the research being unbiased. I acutally find that a lot of the research on the subject is biased to a degree, that i need to know specifically what kind of orthodoxy the researchers would tend to try to defend while they rapport their results.
Regarding the quoted book, you will find that the "my take" remark is quite sceptical about the presented view.

[KLMARB]

"Ketogenesis begins with the lipolysis of fat by the enzyme lipases in which fat is cleaved into 3 fatty acid chains and 1 glycerol molecule."

Quoted DIRECTLY from this sticky on this board. Why the f*** are you so mad ?

Here's the problem with that statement. Ketosis does not begin until the glycerol molecule goes to the liver, where it is used as the substrate for ketogenesis as well as hepatic gluconeogenesis. What the above statement deals with is lipolysis, which also requires glucagon secretion. No lipolysis, no ketosis..

[Mickqc1]

The more I seem to read about insulin sensitivity, resistance and ins secretion the more I get confused and the less I seem to understand.
After reading lots of posts and articles I came to the conclusion that I'm resistant to insulin and have good insulin sensitivity.
Then I read some more and question my deductions.
Maybe this is only something one can work out by using yourself as the guinea pig.

[Shenpen]

The more I seem to read about insulin sensitivity, resistance and ins secretion the more I get confused and the less I seem to understand.
After reading lots of posts and articles I came to the conclusion that I'm resistant to insulin and have good insulin sensitivity.
Then I read some more and question my deductions.
Maybe this is only something one can work out by using yourself as the guinea pig.

I have read so many references to insulin resistance with no full explanation or even a sketchy overview of the big picture. My curiosity has been steadily rising for a few years, and I think i have found some good sources for a complete picture, but i will need to put it together slowly.

[Mickqc1]

I have read so many references to insulin resistance with no full explanation or even a sketchy overview of the big picture. My curiosity has been steadily rising for a few years, and I think i have found some good sources for a complete picture, but i will need to put it together slowly.

A few years!!
I've got no chance of understanding then!!
I thought at first it was cut and dry, I'm naturally a skinny person who can gain some muscle slowly but will never be a giant. I can also lose weight without much effort.
When I was younger I used to eat 600g carbs a day on a bulk, I would gain at first but then these would slow right down.
I went through a stage of having 400g oats a day, major stomach probs.
But as you get older everything seems to change, hence the keto diet for me.

[DannySampsonite]

"Ketogenesis begins with the lipolysis of fat by the enzyme lipases in which fat is cleaved into 3 fatty acid chains and 1 glycerol molecule."

Quoted DIRECTLY from this sticky on this board. Why the f*** are you so mad ?

Yeah, and you know what feedback regulates HSL and perilipin? Insulin and epinephrine. Thus, the phenomenon of lipolysis has absolutely no specificity to ketosis and everything to do with total food consumption and exercise.

[DannySampsonite]

Here's the problem with that statement. Ketosis does not begin until the glycerol molecule goes to the liver, where it is used as the substrate for ketogenesis as well as hepatic gluconeogenesis. What the above statement deals with is lipolysis, which also requires glucagon secretion. No lipolysis, no ketosis..

Well, in the case of ketosis, it actually has nothing to do with the glycerol either, which is gluconeogenic at the level of triose phosphates.

Ketosis is an overflow pathway whereby so much lipolysis and b-oxidation has occurred that acetyl-CoA levels are too high in the liver. The liver does not use the acetyl-CoA for energy because it doesn't need it, and the presence of acetyl-CoA blunts other pathways (e.g. pyruvate decarboxylase). So, in an effort to get rid of the excess acetyl-CoA, the liver converts them to ketone bodies and exports them to tissues with high metabolic demand.

[DannySampsonite]

I have read so many references to insulin resistance with no full explanation or even a sketchy overview of the big picture. My curiosity has been steadily rising for a few years, and I think i have found some good sources for a complete picture, but i will need to put it together slowly.

It's very complex, I just happen to have done some research in the area. A big component of it is genetic with about 30 or so loci already having been identified.

Interestingly, the 6 meals a day BBer diet was inadvertently used as a model for the development of insulin resistance in rats

[Shenpen]

It's very complex, I just happen to have done some research in the area. A big component of it is genetic with about 30 or so loci already having been identified.

Interestingly, the 6 meals a day BBer diet was inadvertently used as a model for the development of insulin resistance in rats

Any insights or references or both would be highly appreciated!

[FemmeFatale]

God shut up retard. The number one cause of insulin resistance is obesity. Who here is obese?

The number one booster of insulin sensitivity is exercise. Who here exercises?

Yeah, you do the math you parroting ketard

It is my understanding that the number one booster of obesity is insulin resistance, not vise versa.

[Shenpen]

I used to have the energy to dig up sources but all my accounts end up getting banned because moderators dislike unpopular opinions. Plus, learning how to do your own research is good for you!



That is incorrect. The number one factor in obesity is overeating (this is fact at this point). Genetics, exercise, etc are all secondary.

If insights are based on empirical research they are no longer just "opinions". They might still be unpopular I will grant.

There was never a slight bit of hubris involved in getting banned?

[DannySampsonite]

If insights are based on empirical research they are no longer just "opinions". They might still be unpopular I will grant.

There was never a slight bit of hubris involved in getting banned?

Nope, I just have an uncanny ability to expose and demean supplement companies who exploit the consumer.

[FemmeFatale]

That is incorrect. The number one factor in obesity is overeating (this is fact at this point). Genetics, exercise, etc are all secondary.

Well, from what I've read and watched (which has been a lot, albeit not as in depth as some of the people discussing Keto science) - overeating is being caused by, or at least stimulated by said insulin resistance, (as opposed to fat people just being ONLY lazy biatches shoving tons of food in their faces). That whole "eating more because you're getting fatter," versus "getting fatter because you're eating more" thing.

I really think that a lot of us are more prone to our metabolisms "breaking" when it comes to carbs than others, which is why some lucky folks can eat lots of carbs (regardless of calories) and be non-diabetic/insulin-resistant, often non-overweight for life --- and why some people get very fat very young, and why some folks eat "normally" and are fine until a point later in life when their bodies just can't handle it anymore.

I, for one, am SO insulin resistant that eating "normal" macros and non-insane weight-loss levels of calories makes me gain weight like CRAZY. I'm sure I can't be the only one on Earth that previously had to flat-out starve to lose *any* weight at all. Though I'm wondering if, among that group, I'm one of the only ones that found ketogenic eating and later metformin to help me.

[Shenpen]

Well, in the case of ketosis, it actually has nothing to do with the glycerol either, which is gluconeogenic at the level of triose phosphates.

Ketosis is an overflow pathway whereby so much lipolysis and b-oxidation has occurred that acetyl-CoA levels are too high in the liver. The liver does not use the acetyl-CoA for energy because it doesn't need it, and the presence of acetyl-CoA blunts other pathways (e.g. pyruvate decarboxylase). So, in an effort to get rid of the excess acetyl-CoA, the liver converts them to ketone bodies and exports them to tissues with high metabolic demand.

Needs a picture:

[DannySampsonite]

Well, from what I've read and watched (which has been a lot, albeit not as in depth as some of the people discussing Keto science) - overeating is being caused by, or at least stimulated by said insulin resistance, (as opposed to fat people just being ONLY lazy biatches shoving tons of food in their faces). That whole "eating more because you're getting fatter," versus "getting fatter because you're eating more" thing.

I really think that a lot of us are more prone to our metabolisms "breaking" when it comes to carbs than others, which is why some lucky folks can eat lots of carbs (regardless of calories) and be non-diabetic/insulin-resistant, often non-overweight for life --- and why some people get very fat very young, and why some folks eat "normally" and are fine until a point later in life when their bodies just can't handle it anymore.

I, for one, am SO insulin resistant that eating "normal" macros and non-insane weight-loss levels of calories makes me gain weight like CRAZY. I'm sure I can't be the only one on Earth that previously had to flat-out starve to lose *any* weight at all. Though I'm wondering if, among that group, I'm one of the only ones that found ketogenic eating and later metformin to help me.

Again, this is incorrect. Insulin has an appetite-suppressing effect in the brain. In fact, some people theorize that insulin resistance and obesity are so connected (and reversible) because insulin resistance increases blood insulin levels, which is a way that the body re-attains homeostasis (more insulin -> less food consumption -> less body fat). This is all mediated by adiponectin which drops (thus reducing insulin sensitivity) once adipocytes get saturated.

Also incorrect is that you "eat more because you are fatter." The gain of bodyfat actually further reduces appetite via leptin signaling and various neuropeptides.





If metformin is helping you, then you may not have insulin resistance: you may have type II diabetes. If a ketogenic diet is helping you lose weight so easily, then it is even more likely that you are diabetic or pre-diabetic. You should probably get a glucose tolerance test done. Type II diabetes at age 24 isn't unheard of, but it's incredibly rare.