Concern Over Euglycemic DKA & Low-Carb Diet With Type 1 Diabetes

[Oldvatr]

As a T1 I've ;always been told that DKA was caused by insufficient insulin and that high bgs and ketones were a marker. (Admittedly, my consultant was horrified when I told her a few years ago that I'd never really tested for ketones, and promptly gave me a glucometer that could test for them. (And I haven't had a DKA in 53 years of T1, don't know if that is luck or not).

So, assuming no other meds than insulin, is a T1 actually more likely to go into euDKA than a non diabetic? (Assuming that a T1 is injecting insulin to maintain their bgs and therefore presumably not low on the stuff)

https://wchh.onlinelibrary.wiley.com/doi/pdf/10.1002/pdi.1769

Non-medication causes of euDKA appear to be starvation, pregnancy or a weird metabolosm.. I'm not sure whether a T1 is more likely to have any of those than a non diabetic?

This study discusses other triggers that may be relevant. we must take on board that SGLT-2 medications are now being prescribed as a prophylactic to those at higher risk of cardio event, and this may include T1D in the future. There is also the possibility that weight loss injections may also trigger these events because they also increase glucagon levels and have reported occurrences of gastroparesis. I note that bariatric surgery is also a risk factor.

Euglycemic Diabetic Ketoacidosis - StatPearls - NCBI Bookshelf

So, users of low carb / keto diets who are insulin dependant should also be aware of possibility of euDKA , but I doubt if that message is being dispensed. It seems it is not.

The SGLT-2 experience in T2D shows that controlling to a low level of bgl can allow gluconeogenesis from ketones to reach euDKA levels and not the higher DKA levels but enough to turn the blood acidic. This same mechanism could apply to T1D. I have seen warnings from an SGLT-2 study on euDKA from it that they suggest that controlling below 7 mmol.l does increase the risk of euDKA, which is why Low Carb is contraindicated for those meds.

 

[oldgreymare]

This study discusses other triggers that may be relevant. we must take on board that SGLT-2 medications are now being prescribed as a prophylactic to those at higher risk of cardio event, and this may include T1D in the future. There is also the possibility that weight loss injections may also trigger these events because they also increase glucagon levels and have reported occurrences of gastroparesis. I note that bariatric surgery is also a risk factor.

Euglycemic Diabetic Ketoacidosis - StatPearls - NCBI Bookshelf

So, users of low carb / keto diets who are insulin dependant should also be aware of possibility of euDKA , but I doubt if that message is being dispensed. It seems it is not.

The SGLT-2 experience in T2D shows that controlling to a low level of bgl can allow gluconeogenesis from ketones to reach euDKA levels and not the higher DKA levels but enough to turn the blood acidic. This same mechanism could apply to T1D. I have seen warnings from an SGLT-2 study on euDKA from it that they suggest that controlling below 7 mmol.l does increase the risk of euDKA, which is why Low Carb is contraindicated for those meds.

Hi @Oldvatr

I'm pretty good at reading physiology and biochemistry papers but have never come across anything citing increased glucagon production in T1 diabetics, if you can provide some references that would be great.

I'm sure our experiences do differ, but pragmatically I'd refuse a SGLT-2 inhibitor even if suggested (which of course they are not recommended for T1 ).

Insulin can be a very dangerous drug but it is also extremely flexible for achieving good blood glucose control - however this also requires constant attention and re-tweeking doses and I would now be lost without my CGM to fine tune dosing. I've done a DAFNE course but could not stand the extra high insulin shots for high carbs. Low carb/keto is much easier for day to day life.

In fairness my endocrinologist last year did discuss in depth with me how would I identify eDKA give my preferred low carb/keto diet. He was reassured when I said that I would be relying on symptoms of severe acidosis, not ketones nor high bg levels - I know when to self treat and when to call 999.

Probably an area all diabetics whether T1 or T2 could use more information about.

 

[Antje77]

I'm pretty good at reading physiology and biochemistry papers but have never come across anything citing increased glucagon production in T1 diabetics

A google search got me some results.
But even if we do produce more glucagon than average, having normal BG (euglyceamic, which is what this thread is about) proves we can adjust our insulin doses for this.

This study discusses other triggers that may be relevant. we must take on board that SGLT-2 medications are now being prescribed as a prophylactic to those at higher risk of cardio event, and this may include T1D in the future. There is also the possibility that weight loss injections may also trigger these events because they also increase glucagon levels and have reported occurrences of gastroparesis. I note that bariatric surgery is also a risk factor.

Euglycemic Diabetic Ketoacidosis - StatPearls - NCBI Bookshelf

So, users of low carb / keto diets who are insulin dependant should also be aware of possibility of euDKA , but I doubt if that message is being dispensed. It seems it is not.

The SGLT-2 experience in T2D shows that controlling to a low level of bgl can allow gluconeogenesis from ketones to reach euDKA levels and not the higher DKA levels but enough to turn the blood acidic. This same mechanism could apply to T1D. I have seen warnings from an SGLT-2 study on euDKA from it that they suggest that controlling below 7 mmol.l does increase the risk of euDKA, which is why Low Carb is contraindicated for those meds.

Even if T1s not on flozins but on insulin only are theoretically able to go into eDKA in the absence of underlying illness, does it actually happen in real life or not?
Can you find anything on T1s going into DKA on a keto type diet, insulin only, while maintaining normal BG?

 

[jonathan183]

Dr Bernstein thinks DKA is about dehydration.
High blood glucose or high ketones will accelerate dehydration. If you are constantly being sick you will be unable to rehydrate quick enough and require medical assistance.

 

[Oldvatr]

Hi @Oldvatr

I'm pretty good at reading physiology and biochemistry papers but have never come across anything citing increased glucagon production in T1 diabetics, if you can provide some references that would be great.

I'm sure our experiences do differ, but pragmatically I'd refuse a SGLT-2 inhibitor even if suggested (which of course they are not recommended for T1 ).

Insulin can be a very dangerous drug but it is also extremely flexible for achieving good blood glucose control - however this also requires constant attention and re-tweeking doses and I would now be lost without my CGM to fine tune dosing. I've done a DAFNE course but could not stand the extra high insulin shots for high carbs. Low carb/keto is much easier for day to day life.

In fairness my endocrinologist last year did discuss in depth with me how would I identify eDKA give my preferred low carb/keto diet. He was reassured when I said that I would be relying on symptoms of severe acidosis, not ketones nor high bg levels - I know when to self treat and when to call 999.

Probably an area all diabetics whether T1 or T2 could use more information about.

Your Endo has IMO given you the headsup you need and made you aware that it may be possible, and so you can take appropriate counter measures if it ever does occur. That is why I beleive this conversation should happen, but does not seem to be part of the current education. Perhaps Daphne needs updating in line of current trends and research findings.

 

[Oldvatr]

A google search got me some results.
But even if we do produce more glucagon than average, having normal BG (euglyceamic, which is what this thread is about) proves we can adjust our insulin doses for this.

Even if T1s not on flozins but on insulin only are theoretically able to go into eDKA in the absence of underlying illness, does it actually happen in real life or not?
Can you find anything on T1s going into DKA on a keto type diet, insulin only, while maintaining normal BG?

Here is a treatise on T1D and glucagon.
It is not usual for research studies to measure glucagon levels, and is generally only done in lab trials for new medications. The normal DKA is accompanied by very high levels of hyperglycemia, but one of the studies I linked earlier did report bgl levels of around 17 being found to be DKA. So where is the bottom line for definition of DKA vs the top line of euDKA - I think it is semantics.

We know from drug trial infos from SGLT-2 research that ketoacidosis can occur at levels as low as 10 mmol/l, and I am hypothesising that someone using keto to control to low levels such as can easily b obtained by keto diet (i.e. around 4 or 5 mmol/l pre meal), will be possible for moderate glucagon induced bgl generation to add on top but remain below the normal 20 mmol/l threshold used by A&E to determine DKA.

Yes T1D can adjust insulin dose to reduce glucose levels, and this may be sufficient, but there are a lot of T1D who either cannot or may not realise they need to, Not everyone is able to recognise hyperglycemia, and I personally walked around with levels above 32mmol/l and felt fit and healthy with no side effects. insulin bolus after the event takes time to act so is not the quickest route out of DKA if it starts.

British Journal of Diabetes
https://bjd-abcd.com › bjd › article › download

 

[Oldvatr]

Dr Bernstein thinks DKA is about dehydration.
High blood glucose or high ketones will accelerate dehydration. If you are constantly being sick you will be unable to rehydrate quick enough and require medical assistance.

Dehydration has the effect of increasing concentration of
(1) glucose in mmol/litre,
(2) ketones in mmol/litre
(3) level of perceived acidosis

So there is a direct mathematical relation between hydration and level of effect, But dehydration is not the cause or the trigger. it is a symptom. Also, these measurements may well be taken in A&E after vomiting and excessive peeing have been in place during the onset period of DKA prior to admission

Dehydration will affect the thresholds for dignosis and possibly the timing of distress actually being recognised, but it is the acidosis that is the harmful element. This acidosis is a result of ketone buildup in the blood, making the blood ph change. Other factors affect this. The kidney ability to filter out excess ketones (the normal daily route for all of us) or the ability of the lungs to clear ketones (keto breath) and how much we are sweating ketones. These vary from person to person, but there are some meds (e.g. SGLT-2 and DPP-4 meds) that reduce this excretion. Illness and reduced kidney function play their part too.

 

[Antje77]

one of the studies I linked earlier did report bgl levels of around 17 being found to be DKA.

17 mmol/l is definitely not seen as euglyceamic, and many T1s are told to test for ketones when above 13 or 15 for a prolonged time, not 20.

Yes T1D can adjust insulin dose to reduce glucose levels, and this may be sufficient, but there are a lot of T1D who either cannot or may not realise they need to, Not everyone is able to recognise hyperglycemia, and I personally walked around with levels above 32mmol/l and felt fit and healthy with no side effects. insulin bolus after the event takes time to act so is not the quickest route out of DKA if it starts.

You're still talking about diabetics with hyperglyceamia and DKA, not eDKA.
T1's as a rule do not rely on how they feel to recognise a high level, we test. And many of us use CGM and we'll get an alarm when we rise.

 

[Oldvatr]

17 mmol/l is definitely not seen as euglyceamic, and many T1s are told to test for ketones when above 13 or 15 for a prolonged time, not 20.

You're still talking about diabetics with hyperglyceamia and DKA, not eDKA.
T1's as a rule do not rely on how they feel to recognise a high level, we test. And many of us use CGM and we'll get an alarm when we rise.

And you are talking about healthy T1D able to dose adjust, and using copious monitoring, including the new and expensive CGM. Are you sure this applies to the majority of T1D? It is not what my T1D friends experience.

I have no problem with T1D using low carb. Even keto provided they have sufficient support and education to enable them to understand the abnormal use of diet with insulin which is not as far as I am aware part of the Daphne or Desmond teachings.

One of the papers I linked listed many other triggers for eDKA. Gastroparesis for a start. Some mental health drugs, and (from experience of caring for my late wife) some Parkinsons medications which can significantly increase ketone levels.

There are some also using fasting with keto diets, and while these are safe for most people ( and religious groups like monks), they also could be a factor for eDKA Again, if you know what you are doing then you should be able to deal with your condition without problem.

You asked for evience of T1D and euDKA. Here is one I found,

Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma

Euglycemic diabetic ketoacidosis (EDKA) is a clinical triad comprising increased anion gap metabolic acidosis, ketonemia or ketonuria and normal blood glucose levels <200 mg/dL. This condition is a diagnostic challenge as euglycemia masquerades ...

www.ncbi.nlm.nih.gov

I have not found evidence of keto diet being a causal factor so it may be a rare event.

But with T1D now being prescribed SGLT-2 meds for heart and kidney health, this is still a possibility for T1D to become aware of

The apparent rarity of this is clear, but can we guarantee that this possibility will never, ever EVER become reality for someone? So far we have had T2D drugs like the Gliflozins, the DDP-4's and now the Glutide meds that are contraindicated for T1D, but are increasingly being used off label and now prescribed to T1D so this problem is likely to increase and can no longer remain primarily a T2d problem.

It remains to be seen if keto diets join in the fray, but as pointed out in many papers in this thread, the use of keto diet by T1D is possibly linked to eDKA and may increase the risk. They must have some reason for making that declaration, and just because you and I have not found a paper proving this should not allow us to say it will be without risk.

As a matter of interest, the term euDKA was first coined in 1973 as a result of T1D patients admissions and not a T2D in sight. The causes of the DKA are not mentioned in this abstract but may be in the full text.

Euglycaemic diabetic ketoacidosis - PubMed

Of a series of 211 episodes of diabetic metabolic decompensation 37 had severe euglycaemic ketoacidosis (a blood sugar level of less than 300 mg/100 ml and a plasma bicarbonate of 10 mEq/1. or less). All were young insulin-dependent diabetics, only one being previously undiagnosed. Vomiting was...

pubmed.ncbi.nlm.nih.gov

 

[oldgreymare]

Your Endo has IMO given you the headsup you need and made you aware that it may be possible, and so you can take appropriate counter measures if it ever does occur. That is why I beleive this conversation should happen, but does not seem to be part of the current education. Perhaps Daphne needs updating in line of current trends and research findings.

There is a lot about DAFNE that I feel needs review/updating (but in fairness it has taught me a few things and improved my carb & protein counting/bolusing). Also the course coordinator was the one that had me issued a ketone meter once she knew I favoured low carb.

Totally agree that there needs to be broader education and understanding re euDKA and probably DKA generally for all diabetics. I did find this interesting article -

Euglycemic diabetic ketoacidosis: a potential pitfall for the emergency physician

www.ceemjournal.org

Pragmatically we all need to be taught warning signals of acidosis, namely -
"Patients with eu-DKA typically present with symptoms such as malaise, dyspnea, nausea, vomiting, and abdominal pain, similar to patients with conventional DKA".

After 3 hospital admissions for DKA, I am always on the lookout for incipient acidosis (as mentioned previously for me symptoms take priority over BG and ketone readings) - pragmatically I know for me it is aways associated with dehydration and since since my last DKA admission in 2014 I have been able to self treat with hydration and extra insulin if indicated by BG levels - but I'm always conscious that I may need to call 999 if not improving within 1-2 hours.


Edited for another interesting article -

https://www.wjgnet.com/1948-9358/full/v12/i5/514.htm

 

[Oldvatr]

Just to add this recent post regarding DKA in T2D Insulin dependant person using low carb diet.

DKA diabetic ketoacidosis in type 2 diabetes

I’m writing this to inform of what can happen . My husband ha type 2 diabetes and is insulin dependent. Just over a month ago I woke to find him what I thought was drunk. He rarely drank alcohol but I thouhjt he was behaving like I’d seen before. Anyway by the morning he hadn’t “sobered “ up...

www.diabetes.co.uk