Ketones: the good, the bad, the… misunderstood

This is going to be a long blog post… but I woke up today feeling like I had to write it because I see so many people not understand the subject. And it’s important for people with diabetes — and parents of children with type 1 diabetes especially — to know what’s going on when ketones are present.

I see a lot of parents saying that high blood sugars and ketones go hand in hand, and that if you let your child’s blood sugar get high, they will have ketones. This is actually not true. So what I want to accomplish with this post is to clear up a few misunderstandings when it comes to what’s happening when your child (or you, if the person with diabetes = the person in the mirror) shows ketones. You’ll have to forgive me for saying “your child” a lot in this post because I’m a parent of a CWD and I’m going to talk as if this is about parenting, but it goes for people who are caring for their own diabetes as well, naturally.

First, some background on me: I’m a science/medical editor, and I review and research a wide range of topics. Diabetes, of course, is required reading, but I do a lot in cardiology, renal medicine (kidneys), oncology (cancer medicine), and pediatrics. So I know a great deal more than your average Joe or Jane, but I wouldn’t call myself an expert. An advanced beginner, maybe. I have, however, worked with a lot of experts — the most notable being my son’s endocrinologist, who heads a clinic that treats not only kids with type 1 diabetes but kids with adrenal disorders and cystic fibrosis. He and I, plus a Nurse Practitioner/CDE on his clinic’s staff, wrote this book together … and it was in the course of this project that I learned what I know about ketones.

A mini lesson in metabolism and physiology
Some of this may be familiar territory, but please take a minute to read through it anyway so we’re on the same page.

We all know (hopefully) that insulin’s job is to open the door to a cell to let glucose inside so the glucose can be used to fuel the cell. And of course, we all know that type 1 diabetes = no insulin (or not enough) to accomplish this task — don’t feel left out, type 2s, I’ll get to you in a minute! What I sense many of us don’t know is where the ketones come from, and that’s key to understanding what’s happening and how to fix it.

In diabetes, we're conditioned to think "ketones = bad" but they actually are part of a normal bodily function. (It's just that, in diabetes, many normal functions are off kilter because good old insulin is central to everything!) In a person without diabetes who is burning glucose in their cells the usual way, there are times they need more glucose than is circulating currently in their blood to keep up the level of activity or energy use they have going on. So they eat food with carbohydrates (or fats), their pancreas pumps out insulin, the food is broken down into glucose, the insulin transfers that glucose into the cells, and viola, cells have glucose to use for energy.

But if the person doesn’t eat — they're too sick to eat, they're sleeping, or they just don't have the ability to eat right now — they can still get glucose one of two ways. First, their liver can release glycogen, which is stored sugar, directly into the blood — quick, but limited; it’s usually used by the body to keep blood glucose levels consistent while we’re sleeping. The other method is (and I’m going to gloss over a lot of the details here), the liver releases chemical signals that tell the body to convert fats into glucose. And the conversion of fatty acids into glucose is what produces ketone bodies or ketones. They are basically a waste product of the “fat burning” conversion process.

The thing is, this process exists for a reason. When food is available, you don’t need to break down body fat for glucose unless you’re doing a lot more work than the glucose in the food you eat can support. But when food isn’t available, “burning fats” is a great backup to keep your body, and especially your brain, supplied with energy. This is why ketones are considered a sign of “starvation” — they only appear when the body lacks energy from food. And in small amounts, they’re harmless. It’s normal, for instance, for a person to produce ketones if they're on a weight loss program that is based around exercise and calorie restrictions, because that’s kind of the whole goal — to induce your body to use up the glucose stored in fat because you need more energy (glucose) than you take in via food.

This is where the "acid" part comes in

The one drawback is that ketones are acids, and we humans have a fairly limited tolerance of acidity in our blood and tissues. If ketones accumulate in the body to a point of reducing our bodily pH past the minimum tolerated level of 7.35, we get sick — metabolic acidosis develops, which, if it’s caused by diabetes-related ketones, is known as diabetic ketoacidosis or DKA. When this happens, we have to start using up all sorts of stored minerals (calcium, potassium) to “buffer” the acids and get us back into the range our body likes (pH over 7.35 but below 7.45), and we also use up a lot of fluids because the only way to remove the excess acids is to process them through the urine. Dehydration and electrolyte imbalance are the immediate result; if it’s not corrected quickly, many other serious and life-threatening problems happen down the line.

Luckily for those of us without diabetes, and for the most part for those with type 2 diabetes, the body has a solution to prevent ketone/acid accumulation, too: the glucose released into the blood by “fat burning” triggers a release of insulin, and insulin in even small amounts stops the signal to convert fat to glucose because it enables the cells to have the fuel they need. The ketones produced by the temporary period of starvation get peed out, and off we go on our way.

But, as you know, people with type 1 diabetes can’t produce adequate insulin to meet their needs. Even people with type 2 diabetes who are capable of producing insulin may not be able to produce enough insulin to halt ketone production, because there has to be enough insulin present so that most of the body's cells get glucose and stop yelling to the liver that they're starving — and if you're very insulin-resistant, the amount needed may be more than your pancreas can put out (particularly since stress hormones increase insulin resistance). This is why a type 2 diabetic who is under severe physical stress, like an illness, can develop DKA, contrary to popular wisdom that DKA only happens in T1s.

In either case, T1 or stressed/sick T2, without putting artificial insulin into the system, there is no way to stop the “burn fats” signal — and thus, ketones accumulate and produce ketoacidosis.

The connection between ketones and high blood sugar

Now, obviously, if the body is burning fatty acids and producing ketones, it’s also producing glucose. That’s kind of the point, right? And if there’s no insulin, the glucose isn’t getting used, and the cells are still “starving” even though there’s glucose coming out your eyeballs at this point — that’s only a slight exaggeration, by the way — you get accumulation of glucose along with the accumulation of ketones. High ketones = high glucose, in this situation.

But that’s not always the case. If you’ve ever had a T1 child or other PWD with a stomach virus, you know what I mean — the blood sugar is low because no food is going in, so you have to cut back the insulin to prevent catastrophe because the kid can’t eat anything, but the ketones are high because, obviously, body still needs energy to fight off the illness and so it’s burning fats — yet the three things needed to cushion against DKA (fluids, electrolytes, insulin) can’t be used without making the kid yack and/or go low.

As I mentioned earlier, it takes a very small amount of insulin to put a stop to ketone production — a lot less than it takes to move high concentrations of glucose out of the blood and into the cells. And ketones start up when cells can't get enough glucose from the blood — which can be either not enough insulin or not enough glucose present, or both at the same time. That means that you can have ketones without high blood sugar or vice versa. In other words: high blood sugar doesn’t cause ketones or DKA. You can have ketone production leading to DKA with either high or low blood sugar, depending on the situation. Remember, ketones come about because cells aren't getting glucose, not because the glucose is missing but because the insulin isn't there. Ketones are produced because of a lack of insulin to move the glucose into cells, not because of the excess of blood glucose.

This means that if your type 1 diabetic is getting some insulin — my endo said the amount is equivalent to 10% of what the body actually needs — he or she won’t start or keep burning fats and generating ketones, but may still have high blood sugar.

High blood sugar can happen even when there’s insulin available for a lot of reasons with nothing to do with ketones:

  • If you eat more carbs than you bolused for, then obviously your BG will be high; you’ve taken in more glucose than you have insulin to move it, but you still have enough glucose moving into cells to prevent a starvation response.
  • Stress hormones produce insulin resistance, which means even a correctly bolused meal makes your BG go high — and stress can be physical (you’re catching a cold and your body is fighting it off, for instance) or mental (tests at school, a fight with your spouse, parent, friend, or sibling, even a mass attack of Creepers in Minecraft… and YES, I HAVE SEEN THAT ONE.)
  • Growth hormone in children also produces insulin resistance; a major cause of consistent highs in kids is growth spurts, and it’s why you get consistent highs at night in elementary-age kids and in early morning in teens.

I’ve seen this in action before many times: my son will have sky-high BG because I’ve under-dosed or because the insulin flow from his pump is occluded (but not stopped completely), yet he has no ketones because he’s gotten/getting enough insulin to prevent the starvation response. This is also why type 2 diabetics don’t get DKA very often, because even when their blood sugars are sky high, they usually have enough insulin present to move enough glucose into cells to prevent fat burning, but not enough to overcome insulin resistance completely (but that’s a different metabolic issue altogether from what T1s have).

Bottom line:

So if you’re a parent whose child is showing high blood sugar and ketones, you’re looking at two problems resulting from one cause: You have ketone production because cells are still starving, regardless of how much glucose there is in the blood; and you have high blood sugar because there’s not enough insulin to move the glucose into cells to give them the energy they need. These problems have the same solution: give more insulin so the glucose goes where it's needed and the perceived need to provide more glucose by breaking down fats goes away.

The reason I think it’s important to recognize this distinction is that I worry that parents may resist letting blood sugar get “too high” in a sick child who is showing ketones, thinking that keeping blood sugar lower will help avoid DKA, when in fact, when children are ill, it’s better to maintain blood sugar at higher levels so you can give enough insulin to avoid ketones and DKA. Given the two possibilities, working to avoid ketones is a much higher priority than striving for lower blood sugar.

I hope this has been helpful.

I,ve learned a lot, thank you.

Thanks for your explanation! I'm sure it can help many. The idea of 10% insulin being enough to keep from producing ketones is quite incredible. Of course, all depends on your diabetes, sickness, etc I understand that a person should look at the overall situation not just the fixed number.

In YOUR experience, what level of ketones should a person feel concerned?

I see your book was published in 2012 I'm sure lots of newly diagnosed parents would be interested in reading it. Is it mentioned on the site as a reference for newcomers? I don't know if that possible..... Congratulations on the book anyway!

Wow - that is absolutely the BEST explanation of the whole process that I've ever read. Thanks for putting it all together, and in such an understandable way.

Ruth

Good job!

Yes, Mari, of course, Your Diabetes Will Vary...

In days of routine activity, any time ketones are above the "trace" level (0.0-0.3, for those who have blood ketone meters) there's potential concern, particularly in someone on a pump. There may be 50 ways to say goodbye but there seem to be a thousand ways to screw up insulin flow in a pump with tubing... and my understanding is that within 2 hours of stopping insulin flow, the ketones will start being generated, usually. Although if you're lucky enough that you got a bolus in before the pump site became blocked, or got torn out, or developed big bubbles, or got a crimped cannula, or any of the other 996 ways, you *may* get 4 hours without ketones.

If there's significant exercise going on — running a marathon, for instance — or you have a sickie who can't eat, you might be OK to see ketones in the "small" level (0.3-0.6), but anything above that is bad news because of the potential effects of metabolic acidosis. This is why GI bugs are so freaking scary — no food = low BG + potential for ketones. The ketones are a sign that the body is generating more glucose to support the cells while there's no food around, but you can't provide the insulin needed to mobilize the glucose and stop the ketones until the blood sugar gets high enough that you don't risk a serious low. This is when Zofran and glucagon are our best friends.

So when my toddler had high ketones due to sickness, but not high BG (it was normal), I was told it was due to dehydration. Does that fit with this? not sure I understand all of it... but I think it's important for parents to know that sickness can cause high ketones w/o high BG. We ended in the ER for rehydration a few times due to this.
thanks

Dehydration factors into it in that it throws off electrolytes, and the electrolytes are what buffer the acids. Potassium salts and sodium are pretty commonly used in oral and IV rehydration. There are all kinds of home remedies for oral rehydration solutions but I find PediaLyte mixed with non-glycemic drink mix like Crystal Lite works pretty well (you can't just give it straight because it tastes horrible).

My 10 year old son was diagnosed in June of this year with T1D. The past couple months his health hasn’t been what it needs to be. His symptoms include, weakness, shortness of breath, dizziness, he sometimes can’t walk he’s so weak and even his vision is sometimes affected. For awhile he was in the “honeymoon” stage and he didn’t require any fast acting insulin, only the slow acting, then his endo dr said that when his sugar would get over 300 we could just “tweek” it with a couple of units to lower it. Of course, his blood sugar gradually kept climbing day to day way over 300 on a consistent basis. I’m not sure if that messed him up or not. We started doing a 1:20 ratio with the fast acting. That made him feel even worse. His whole body seems to crash. He turns pale, has shortness of breath, dizziness, everything I mentioned above. The only way we can keep him feeling “normal” is to do a low carb diet (he doesn’t get more than 50grams a day) and with that his BG stays within range and he stills gets his long lasting insulin at night. We’ve been doing this for the past week or so and he seems to be feeling much better as far as the symptoms go that I listed above. BUT the past few days he’s been drinking and urinating a lot. His ketones were small yesterday and today they were close to moderate. I’m just not sure what to do. We’ve been looking for a pattern for months to explain his dizziness and the only thing we’ve noticed is that when he eats a large amount of carbs along with his fast acting insulin he crashes. We’ve just noticed that recently. We’ve been the to ER several times (not for the ketones but the other symptoms) and they are at a loss. They say it’s not diabetic related. So we’ve had an MRI done, seen an ENT, had chest X-rays done, blood work done to check for thyroid, and an EKG done. Everything has come back normal. We just want some consistency and for him to feel “normal”. We’ve really had a hard time. Any feedback as to why he would feel that way when given insulin with his carb intake and why he now has ketones when he’s on a low carb diet would be much appreciated. Should I be concerned that he has almost
Moderate ketones but his blood sugar is fine and he’s not sick? Other than drinking and urniating a lot he feels great!

Don’t you mean “convert fats into energy”? In humans, fat doesn’t convert to glucose except about 10% from the glycerol backbone.

I just wanted to say thank you for posting this. I’ve been thinking about this since you posted. It makes perfect sense to me now and puts my mind at ease. My DD has never had ketones (touch wood) despite having some high blood sugars at times and this explains it all perfectly. She’s on MDI and takes plenty of basal (one of the main reasons I like that she has chosen MDI over pump). I feel more prepared in the event she develops ketones in future. Thanks again.

The liver CAN convert fat into glucose through a process called Gluconeogenesis.
Why does it do this sometimes and not others? It depends.
It can really get complicated, but it might be easier to explain if you understand the primal purpose of this ability.
In the old days, and I’m talking Paleolithic times, there wasn’t any such thing as fast refined carbohydrates, So, our bodies naturally burned fat as our primary source of energy, And carbs were stored in the liver as glycogen, to provide a quick boost of energy in the event we had to run away from sabertooth tiger. Sometimes, there was not even any leafy greens or berries around to fuel this reservoir of carbs that the liver holds in reserve in case it is needed for a fast boost. Thus the super power of Gluconeogenesis, The liver is not happy when it does not have at least some carb type fuel in reserve, so it makes it from fats or protein. A truely amazing bit of chemistry.
Fast forward to modern times. Our bodies are no longer fat adapted. We are sugar burners. The body now thinks that glucose is our primary form of energy because it is so plentiful. So, when we try to become fat adapted again as in the Paleolithic, or Ketogenic diet, the body resists, and the liver MAY try to convert the fats we are now consuming on this low carb diet, to sugar, because this is what it is used to. It may take days, weeks or months to truly become fat adapted, till then, the liver is just trying to keep the blood at the BG level it has become used to.
If you want try to understand the process more, here is a link


And. Like I said, it’s complicated. Good luck.

The liver CAN convert fat into glucose through a process called Gluconeogenesis.
Mostly not. “it is widely held that fatty acids cannot be converted to glucose in humans directly .” (https://en.wikipedia.org/wiki/Gluconeogenesis) That’s the classic view, although more research may contradict that.
Some discussion:
https://biology.stackexchange.com/questions/48300/can-the-human-body-create-glucose-out-of-fat/48322
The glycerol part of fat can be converted to glucose via gluconeogenesis.

gretchen

It can really get complicated, but it might be easier to explain if you understand the primal purpose of this ability.
In the old days, and I’m talking Paleolithic times, there wasn’t any such thing as fast refined carbohydrates, So, our bodies naturally burned fat as our primary source of energy, And carbs were stored in the liver as glycogen, to provide a quick boost of energy in the event we had to run away from sabertooth tiger. Sometimes, there was not even any leafy greens or berries around to fuel this reservoir of carbs that the liver holds in reserve in case it is needed for a fast boost. Thus the super power of Gluconeogenesis, The liver is not happy when it does not have at least some carb type fuel in reserve, so it makes it from fats or protein. A truely amazing bit of chemistry.
Fast forward to modern times. Our bodies are no longer fat adapted. We are sugar burners. The body now thinks that glucose is our primary form of energy because it is so plentiful. So, when we try to become fat adapted again as in the Paleolithic, or Ketogenic diet, the body resists, and the liver MAY try to convert the fats we are now consuming on this low carb diet, to sugar, because this is what it is used to. It may take days, weeks or months to truly become fat adapted, till then, the liver is just trying to keep the blood at the BG level it has become used to.
If you want try to understand the process more, here is a link

Chemistry LibreTexts – 2 Oct 13

Gluconeogenesis

Gluconeogenesis is much like glycolysis only the process occurs in reverse. Gluconeogenesis is the metabolic process by which organisms produce sugars (namely glucose) for catabolic reactions from …

And. Like I said, it’s complicated. Good luck.

Well, like I said, It’s complicated. And, as you indicated, there are parts of this mysterious process, that still are not well understood. I do think we would all benefit by trying to understand the liver and our own metabolic processes a little better. I personally believe, that we have to manage our own care and that Doctors, should be partners, and not dictators. There is a lot of information out there, and I think we have to observe how our own bodies behave under different scenarios.
Cheers!

I totally agree with that statement, however, at the top diabetic clinics in the world, (Joslin, Mayo, etc.) the doctors need to promote the hospital doctrine and that doctrine is heavily influenced by the pharmaceutical industry, where they get the bulk of their funding. As a doctor, you either back the hospital policies or get a job elsewhere or go out on your own. In a way that makes sense, because you would not want to go see another doctor in the same large clinic (like when yours is not available) that would give you advice contrary to what you have received in the past. On the other hand these policies which are really one size fits all, and we as diabetics are far from one size fits all, are not always what is best for us as an individual. For those of us doing our own research based on our own characteristics the best we can hope for are doctors that say they can’t side with us on certain specific issues as they relate to our particular situation, but do not take a dictatorial position that we comply or else. I have kept my endo at Joslin scratching her head for years by clearly being able to demonstrate on my Dexcom Clarity reports coupled with my lab results that hospital policies are very often not in my best interest and that I will follow a path that works best for me. We have partnered for over 20 years and we both immensely respect each other and I just hope that with advanced technologies we can continue our great partnership for many years to come.

I don’t do Keto but do eat mostly low carb foods and measure my ketones every Saturday just to keep a record and they are always in the 2.0-3.0 mg/dl range.

Thank you CJ. That’s good input, Yes and don’t get me going on Big Pharma. :slight_smile:Cheers!

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