Tag Archives: glucagon vs insulin

the blood glucose, glucagon and insulin response to protein

  • The food insulin index data indicates that there is both a blood sugar and an insulin response to the glucogenic component of protein. [1]
  • A higher protein intake tends to lead to better blood sugar control, increased satiety and reduced caloric intake.
  • Digested amino acids from protein circulate in the bloodstream until they are required for protein synthesis, gluconeogenesis or the production of ketones.
  • The release of glucose from protein via gluconeogenesis is a demand-driven process that is smoother and slower compared to carbohydrate.
  • Someone who is insulin resistant and/or whose pancreas is not producing adequate insulin may benefit from higher protein with lower carbohydrate (LCHP) to smooth out the blood sugar response while still obtaining adequate protein.

background

Protein doesn’t significantly raise blood sugars, at least compared to carbohydrates.

At the same time, it is generally acknowledged (at least by people with Type 1 Diabetes) that protein requires insulin to metabolise.  Managing the blood glucose response to protein is a challenge for diabetics, particularly if they are minimising carbohydrates and hence may have a higher protein intake.

Recently, an increasing number of people trying to achieve nutritional ketosis have found that they need to moderate protein in addition to limiting carbohydrates to reduce insulin to the point where significant levels of ketones can be measured in the blood.

My aim here is not to criticise protein, but rather to better understand the insulin and glucose response to protein in light of the food insulin index data.

My wife Monica has Type 1 Diabetes, anything information that can help refine insulin dosing or help inform food choices that will lead to more stable blood sugars is of interest to me.

Personally, I have a family tendency towards obesity and pre-diabetes (based on my 23andMe testing and a lifetime of personal experience trying to keep the weight off), so I am also interested in how I can optimise my blood sugars and insulin levels.  I would also love to dodge the weight creep that seems to come with middle age for most people.

This has been a challenging topic to get my head around.  It is complex, and there is a lack of definitive research to provide clear guidance.  Hopefully, more data and discussion can help to progress the understanding and the practical application of the theory.

I do not claim to have all the answers, but rather plenty of observations and questions.  I hope that by documenting some of these, I can help move this discussion forward.

the blood glucose response to protein

The food insulin index data contained in Clinical Application of the Food Insulin Index to Diabetes Mellitus by Kirstine Bell (Sept 2014) [2] intrigues me.  There is a lot to be learned from looking at the body’s insulin response to food and the interrelationship to other parameters such as fat, protein, carbohydrates, fibre or blood glucose.

The data points on the right-hand side of the chart below [3] indicate that high protein foods (e.g. fish, tuna and steak) cause a small rise in blood glucose.  However, the blood sugar response to protein is still small relative to the high carbohydrate foods on the left-hand side of the plot.

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For most people, the discussion ends there.  Protein does not raise blood sugar much, therefore it is a non-issue. !

But is it really that simple?  What does the expanded food insulin index data set tell us?

the insulin response to protein

One of the challenges I see for type 1 diabetics is that, even if they eat a low carbohydrate diet, they still struggle with blood sugar control after a high protein meal.

Type 1s who have a continuous glucose monitor know that they need to watch out for a rise in their blood glucose three or four hours after a high protein meal and apply correcting doses of insulin to keep their blood sugar from going too high.

Looking at the plot of protein versus insulin index below, we can see that the insulin response to protein is more significant than the blood glucose response to protein.

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For instance, the insulin index score for whitefish is 42%, however, it only receives a 20% glucose score (note: the percentage scores are relative to pure glucose which has a glucose score and a food insulin index score of 100%).

Maybe there is something going on that can’t simply be explained by the blood sugar response alone?

If we plot the glucose score versus the insulin index we see that glucose and insulin are not directly proportional.

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Low carbohydrate high protein foods such as chicken, cheese, tuna and bacon require a lot more insulin than would be anticipated if insulin was directly proportional to the blood glucose response.

On the lower side of the trend line, we have high carbohydrate foods from whole food sources such as raisins, wholemeal pasta, brown rice and water crackers having less of an insulin response than would be anticipated from the blood glucose response.

diabetic versus normal response to protein

The figure below compares the blood sugar and insulin response to 50g of protein (200 calories) in type 2 diabetics (yellow lines) and healthy non-diabetics (white lines). [4]  We can see that:

  • Blood glucose remains relatively stable for healthy people after eating 50g of protein. However when someone with Type 2 Diabetes eats a high protein meal the insulin secreted seems to bring the blood sugar down from elevated levels!
  • Insulin is elevated for more than five hours after ingestion of protein, particularly for the insulin resistant type 2 diabetic. There’s definitely something going on with insulin in response to high protein foods, even if we don’t see a sharp increase in blood sugar.
  • The diabetic requires a lot more insulin to deal with the same quantity of protein and it takes a lot longer for the insulin levels to peak and comes down.

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We can also see from the insulin response that protein takes more than three hours to digest and metabolise.  It is possible that the food insulin index data (which is based on the measurement of insulin over only three hours) underestimates the insulin response to protein-containing foods and that the insulinogenic demand of protein is actually higher than predicted by the food insulin index data (i.e. protein requires more than 56% of the insulin relative to carbohydrate).

what happens when we eat a lot of protein?

The question of what happens to ‘excess’ protein that is not required for muscle growth and repair is controversial, and the science is not exactly clear.

Does the energy from unused protein magically disappear?  If it did, then protein would be the ultimate macro nutrient that everyone should eat to lose weight.  We could effectively ignore calories from protein.

Does it turn into nitrogen and get excreted in the urine?

Or does it turn into glucose ‘like chocolate cake’?

There is limited authoritative information on this topic. However, some helpful guidance that I’ve found on the subject is outlined below:

  • Richard Feinman says that “…after digestion and absorption, amino acids not used for protein synthesis may be trashed.  The nitrogen is converted to ammonia which is converted to urea and excreted.  The remaining carbon skeleton can be utilized for energy either directly or converted to ketone bodies, particularly on a very low carbohydrate diet.” [5]
  • Richard Bernstein says “Dietary protein is not the only source of amino acids.  The proteins of your muscles continually receive amino acids from and return them to the bloodstream.  This constant flux ensures that amino acids are always available in the blood for conversion to glucose (gluconeogenesis) by the liver or to protein by the muscles and vital organs.” [6]
  • According to David Bender “In fasting and on a low carbohydrate diet as much of the amino acid carbon as possible will be used for gluconeogenesis – an ATP-expensive, and hence thermogenic, process.” [7]

So it appears that amino acids circulate in the bloodstream and can be used as required for protein synthesis or to stabilise blood glucose levels.

The figure below [8] shows a comparison of the blood glucose response to ingestion of glucose and 600g of lean beef (i.e. a huge serving of steak!).

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During the more than eight hour period that the steak takes to digest you can see the nitrogen levels continue to rise.  Meanwhile, blood glucose rises only slightly until around four hours after the meal and comes back down.

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What appears to be happening here is that the amino acids from digestion are being progressively released into the bloodstream (over a period of digestion of more than eight hours) but are not immediately converted to blood glucose.  Thus the digestion of protein does not cause a sharp rise in blood glucose.

It is said that gluconeogenesis is a demand-driven process, not a supply-driven process.  What I think this means is that the body can draw on the amino acids circulating in the bloodstream for muscle growth and repair (protein synthesis) or to balance the blood sugar (via gluconeogenesis) depending on requirements from moment to moment.

The fact that we don’t see a sharp rise in blood glucose in response to protein indicates that excess protein does not immediately turn into glucose.  Gluconeogenesis occurs slowly over time with the amino acids being used up as required.

However as noted by David Bender above, if we are fasting or minimising carbohydrates then our body will maximise the use of protein to produce glucose via gluconeogenesis.  Conversely, if we eating more carbs and less protein the body doesn’t need to rely on protein as much for glucose.

do amino acids spill over into glucose in the bloodstream?

Most people aren’t eating so much protein that their amino acid stores in their blood are full to overflowing like peoples’ livers and are typically overflowing with glucose from a higher carbohydrate diet.

It would be interesting to see what happens in someone whose bloodstream became saturated with amino acids from long-term consistently high protein consumption.

Would we see more protein excreted or perhaps a larger amount removed from the blood via gluconeogenesis with subsequent conversion to fat using insulin?

By comparison, when carbohydrate is eaten we typically see glucose causing an immediate rise in blood sugar because the liver is often already full.

glucagon response

A healthy non-diabetic person will release both insulin and glucagon in response to a high protein meal.

Insulin helps to metabolise the protein and grow and repair muscles (i.e. insulin is ‘anabolic’).   Glucagon helps to keep blood sugar stable and prevent it from going too low due to the action of the insulin used in the muscle growth and repair process.

The body secretes both glucagon and insulin in response to a high protein meal (as shown in the figure below [9]).  In a healthy insulin-sensitive non-diabetic person the glucagon will cancel out the insulin response to the protein used for protein synthesis.  Hence we see a flat line blood glucose response in the insulin-sensitive non-diabetic.

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In a diabetic, particularly type 1s, we often see blood sugar rising after a high protein meal due to the initial glucagon response and then gluconeogenesis as some of the protein converts to glucose.  In the diabetic, the insulin response is either inadequate (due to poor pancreas function) or ineffective (due to high insulin resistance) and therefore the blood sugar does not remain stable as it would in a metabolically healthy person.

By contrast, after we eat a high carbohydrate meal glucagon decreases as the insulin increases and the body moves into fat storage mode as shown in the following figure. [10]  The primary thesis of Protein Power is that we want to do whatever we can to maximise glucagon which promotes fat burning rather than insulin which leads to fat storage.

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Even though glucagon offsets the insulinogenic effect of protein used for protein synthesis, it seems that the glucogenic portion of protein requires insulin.

I haven’t found any data on the subject, but I wonder if the body does not secrete glucagon to negate the effect of the ‘excess’ protein over and above the body’s requirement for protein synthesis (say 7 to 10% of calories)?

If this were the case, then the glucogenic proportion of excess protein will behave largely like a carbohydrate with no glucagon to counteract the insulin?

glucagon, the antidote to insulin?

The observation that glucose does not rise significantly in response to protein is often taken to mean that protein is a non-issue.  [11]  [12]

This may be largely true for someone who is insulin sensitive. However, diabetics with impaired pancreatic function may not be able to secrete adequate insulin to offset the effects of glucagon and keep their blood sugars stable.

If you are a type 2 diabetic or someone with impaired insulin sensitivity I suggest that it would be better to keep your carbohydrate AND protein intake to the point where your body can keep up and maintain normal blood sugars?

The image below shows the continuous glucose monitor (CGM) plot of a type 1 diabetic after ingestion of a protein shake (46.8g protein and  5.6g of carbs).

Without insulin, there is a blood sugar rise over a period of more than eight hours, not dissimilar to what you would see from carbohydrates.

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Is this blood glucose rise from gluconeogenesis of the protein or is the blood glucose rise from glucagon in response to the ingested protein or a bit of each?  It’s hard to know.

What we do know is that there is a rise in blood glucose that needs to be managed if we are going to achieve optimal blood sugar control.

letting your pancreas keep up

For a diabetic who is insulin resistant and/or whose pancreas is not producing adequate insulin, the issue is that the total insulin load of their diet (from carbohydrates and the glucogenic component of protein) is more than their body’s ability to keep blood glucose under control.

From the insulin index data, we know that the body’s blood sugar and insulin response are proportionate to carbohydrate plus about half of the ingested protein.

So potentially we can balance our blood glucose response by managing the glucogenic inputs, that is, by moderating protein and keeping carbohydrates adequately low.  And by doing this, we can minimise, or perhaps eliminate, the need for insulin or other medications.

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the high protein ‘hack’ for diabetics

To some extent, obtaining glucose from protein rather than carbohydrate is a beneficial ‘hack’ for someone who is not able to manage their blood sugars given:

  • eating higher levels of protein will ensure that the body’s needs for essential amino acids are met or exceeded;
  • the blood sugar rise from protein is much slower than it is for carbohydrate foods and hence it is easier to keep blood sugars under control;
  • protein takes more energy to convert to glucose than using carbohydrate directly. Hence there is additional energy lost in the process (i.e. a calorie of protein is not really a calorie if you have to convert it to glucose before it can be used), [13] and
  • protein is more satiating than carbohydrates.

Paul Jaminet argues that obtaining glucose from protein is not ideal given that it’s not as energy efficient as getting it directly from carbohydrates.

However, I think that the optimal approach is to ensure that you maximise vitamins, minerals, fibre and amino acids from carbohydrate and protein containing foods while at the same time not overwhelming your body’s ability to maintain optimal blood sugars due to excess glucose from either carbohydrates or excess protein.

To some extent, it’s a balancing act between gaining adequate nutrition from things that will raise blood glucose while at the same time not overwhelming the ability of your pancreas to produce insulin to keep blood sugars in the ideal range.

The food ranking and meal ranking systems have been designed around this approach.

what is the optimum amount of protein and carbohydrates?

I find Steve Phinney’s well formulated ketogenic diet chart helpful when it comes to understanding how to optimise protein and carbohydrate intake.

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  • The minimum protein intake is around 10% of calories or 0.8g/kg body weight. [14] At this point the vast majority of the protein will go to muscle growth and repair.  Based on the guidance given by the WFKD triangle you might even be able to tolerate up to 20% carbohydrates and stay in nutritional ketosis if you were to keep your protein levels low.  At this point, you won’t have to worry too much about gluconeogenesis messing up your blood sugars because all of the protein will be used up in protein synthesis.
  • If you are active, then you will likely want higher levels of protein, with 1.2 to 1.7g/kg body weight recommended for athletic performance. [15] Higher levels of protein will ensure that you have enough amino acids for optimal physical and mental function rather than just being adequate.
  • As we move to higher levels of protein above the minimum 10% of calories we should consider also reducing carbohydrate and increasing fat, due to the fact that the glucogenic portion of the protein that is over and above the basic needs for growth and repair will likely be turned into glucose, requiring increased levels of insulin which will work against you if your goals are reducing your insulin load in order to stabilise blood sugars or to lose weight.

I have discussed the concept of balancing glucose load from protein and carbohydrates with your body’s ability to produce insulin in more detail in the article the Goldilocks glucose zone.  However, if you are keeping track of your food intake you can use the formula below to calculate and track your insulin load.

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If you are not yet achieving normal blood sugar levels you could try winding back your insulin load.  Most people find that they will achieve stable blood sugars and nutritional ketosis with an insulin load of around 125g, however, your mileage may vary, and you will likely have to tweak this level to find your optimum based on your goals and your situation.

What do you think of all this?  I would love to hear your response in the comments below.

 

 

 

references

[1] See http://en.wikipedia.org/wiki/Glucogenic_amino_acid,   https://www.dropbox.com/s/4dkl03mz2fci71v/The%20metabolism%20of%20%E2%80%9Csurplus%E2%80%9D%20amino%20acids.pdf?dl=0 and http://www.medschool.lsuhsc.edu/biochemistry/Courses/Biochemistry201/Desai/Amino%20Acid%20Metabolism%20I%2010-14-08.pdf

[2] http://ses.library.usyd.edu.au/handle/2123/11945

[3] Glucose score is the area under the curve of the rise in blood glucose response over three hours relative to pure glucose tested in healthy non-diabetics.

[4] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC524031/

[5] Chapter 5 of The World Turned Upside Down: The Second Low Carbohydrate Revolution.

[6] Dr Bernstein’s Diabetes Solution, page 96.

[7] https://www.dropbox.com/s/4dkl03mz2fci71v/The%20metabolism%20of%20%E2%80%9Csurplus%E2%80%9D%20amino%20acids.pdf?dl=0

[8] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC424828/pdf/jcinvest00541-0071.pdf

[9] https://books.google.com.au/books?id=3FNYdShrCwIC&printsec=frontcover&dq=marks+basic+medical+biochemistry&hl=en&sa=X&ei=-ctaVcivOJfq8AXL84CAAw&redir_esc=y#v=onepage&q=glucagon&f=false

[10] https://books.google.com.au/books?id=3FNYdShrCwIC&printsec=frontcover&dq=marks+basic+medical+biochemistry&hl=en&sa=X&ei=-ctaVcivOJfq8AXL84CAAw&redir_esc=y#v=onepage&q=glucagon&f=false

[11] http://caloriesproper.com/dietary-protein-does-not-negatively-impact-blood-glucose-control/

[12] http://www.ketotic.org/2013/01/protein-gluconeogenesis-and-blood-sugar.html

[13] See chapter 15 of Richard Feinman’s The World Turned Upside Down: The Second Low Carbohydrate Revolution for an in depth discussion of this topic.

[14] This is based on the point where at least half of the population has adequate protein!  Not exactly an ideal goal to be shooting for!

[15] https://www.dropbox.com/s/zelfo3n0q8kvtfx/Paoli%20et%20al.%20(2015)%20The%20Ketogenic%20Diet%20and%20Sport%20A%20Possible%20Marriage.pdf?dl=0

 

post updated July 2017