How SGLT2 inhibitors promote ketones

[Oldvatr]

Now it seems that these meds trigger lipolysis, but restrict the excretion of ketones in the urine, thus leading to acid buildup in the blood. You;ve seen this I have seen it too. I am not on insulin, but I am on orals. My diet at the time was not keto and my sugatr levels were normal (6.2 mmol/l)

The patient leaflet says this med is contraindicated to Low Carb Diets. Looking at the mechanism described above, then this should be no worse than dietary ketosis, so ketones less than 4 mmol/l. But the inhibit on ketone excretion obviously can make this worse. So a level of 8mmol/l in my urine was a sign of severe ketosis in the blood.

If so then IMO any activity that triggers lipolysis to occur should also be contraindicated too. So this med would appear to be incompatible with fasting, with eating disorders, with sickday rules in place, also out would be long distance running, most athletic sports, HIIT, cardio workouts. In fact anything that raises epinephrine (eg cortisol) triggers lipolysis. Stress and inflammation too. These can all end up with fat burnng energy mode. Raising epinephrine also turns off insulin since they work in antithesis.

 

[Oldvatr]

I forgot to add ID T2D missing or late with an injection.

 

[Sugarstre]

Now it seems that these meds trigger lipolysis, but restrict the excretion of ketones in the urine, thus leading to acid buildup in the blood. You;ve seen this I have seen it too. I am not on insulin, but I am on orals. My diet at the time was not keto and my sugatr levels were normal (6.2 mmol/l)

The patient leaflet says this med is contraindicated to Low Carb Diets. Looking at the mechanism described above, then this should be no worse than dietary ketosis, so ketones less than 4 mmol/l. But the inhibit on ketone excretion obviously can make this worse. So a level of 8mmol/l in my urine was a sign of severe ketosis in the blood.

If so then IMO any activity that triggers lipolysis to occur should also be contraindicated too. So this med would appear to be incompatible with fasting, with eating disorders, with sickday rules in place, also out would be long distance running, most athletic sports, HIIT, cardio workouts. In fact anything that raises epinephrine (eg cortisol) triggers lipolysis. Stress and inflammation too. These can all end up with fat burnng energy mode. Raising epinephrine also turns off insulin since they work in antithesis.

If possible, can you obtain a blood ketone meter. In my own experience, the levels of ketones in my blood are significantly lower than those in my urine, sometime by an order of magnitude.

 

[saky]

As I said- spanner in the works jobbie. It actually lowers insulin levels from the pancreas by boosting glucagon so overrides the normal control mechanisms. ( so sugar levels dropping would normally slowly turn off insulin to prevent hypo. This drug forces lipolysis (ie ketosis) instead so glucose does not drop due to insulin, but by excretion.) The drug not only stops glucose being recycled via the kidneys, it interferes with the filtering out of ketones epecially the butyrate one hence the buildup in the blood. It is strongly contraindicated in patients who have renal impairement.

Not sure what the effect is for exogenous insulin users. It seeems to be safe, but the drug itself is only approved and validated for T2D non insulin users. It seems that SGLT2 may require reduction of insulin dose. There does seem to be an associaton of an increased risk of DKA in T2D insulin users. There is an association of increased incidence of GTI in insulin users with this med.

With dpp4 inhibitors... Linagliptin... Caused many problems for my mother. Vomitting / nauseous after eating food esp eating more food. Glucose in urine. Since she has end stage renal failure it made her more sick. She was having gastrointestinal intestinal issues for years. After checking with gastroenterologist - they said nothing wrong. It didn't do much to improve her sugars.

 

[Oldvatr]

If possible, can you obtain a blood ketone meter. In my own experience, the levels of ketones in my blood are significantly lower than those in my urine, sometime by an order of magnitude.

The fact that i am seeing 8mmol/l anywhere is a danger sign. I should not be seeing those sort of readings at all. I am not on a ketogenic diet. Weestix may be inaccurate but in terms of gross effect those readings were gross.I was obviously having an 'episode' that day since the levels are now back at almost zero. No idea why I suddenly flared up, but I did feel generally off at the time which is why I tested in the first place. But my leukocytes registered zero, so no infection was showing. All the other test parameters on my 10 parameter strip were normal except for the ketones and the glucose. My doctor refused to supply blood test strips even though he acknowledges euDKA is a possiblility, This is a cost decision since each strip costs the NHS over £3 a pop, and the pack of 10 only lasts a few months before they need to be ditched. The CCG has put a price cap of £9.50 for 50 strips for any meter they supply consumables for.

 

[Sugarstre]

The fact that i am seeing 8mmol/l anywhere is a danger sign. I should not be seeing those sort of readings at all. I am not on a ketogenic diet. Weestix may be inaccurate but in terms of gross effect those readings were gross.I was obviously having an 'episode' that day since the levels are now back at almost zero. No idea why I suddenly flared up, but I did feel generally off at the time which is why I tested in the first place. But my leukocytes registered zero, so no infection was showing. All the other test parameters on my 10 parameter strip were normal except for the ketones and the glucose. My doctor refused to supply blood test strips even though he acknowledges euDKA is a possiblility, This is a cost decision since each strip costs the NHS over £3 a pop, and the pack of 10 only lasts a few months before they need to be ditched. The CCG has put a price cap of £9.50 for 50 strips for any meter they supply consumables for.

I have on multiple events seen 16mmol/L on the urine test strips (the highest range there), only to have <1.5 mmol/L in the blood. My doc has asked me to monitor my blood ketone levels as that is what he is concerned with.

Such a different viewpoint, when all healthcare comes from your government, The meter here is about $50 and each strip is $0.50 or so.

 

[Oldvatr]

I have on multiple events seen 16mmol/L on the urine test strips (the highest range there), only to have <1.5 mmol/L in the blood. My doc has asked me to monitor my blood ketone levels as that is what he is concerned with.

Such a different viewpoint, when all healthcare comes from your government, The meter here is about $50 and each strip is $0.50 or so.

Agree with the statement that blood ketones are a sign of possible DKA. I am not generating ketones by myself, and any significant sign of ketones emanating from my body is a sign of either something seriously wrong with my insulin production, or the med itself by forcing ketosis. Since this med inhibits excretion of the said ketones, then there will be a buildup in the bloodstream, so I would not expect the urine output to be higher than the blood level. Maybe it was a final flush when the SGLT2 relinquished its stranglehold on my kidneys. But I was testing because I felt like c**p. I survived the incident without needing the blulight taxi, so in that instance the event was shortlived and not dangerous. But I do not know what caused it, and if it comes again, will it be more severe?

As you point out, weestix are a poor alarm system, but my doctor is not able to supply blood test strips. however a DKA event would remove my SGLT2 access (immediate and permanent stop on SGLT2 according to CCG rules, as well as loss of driving licence, and by that token, removal of my monthly test strip (glucose) support) so its win-win for the GP and the CCG. Its the Hospital budget that gets clobbered if i have an admission for DKA.

 

[Sugarstre]

Agree with the statement that blood ketones are a sign of possible DKA. I am not generating ketones by myself, and any significant sign of ketones emanating from my body is a sign of either something seriously wrong with my insulin production, or the med itself by forcing ketosis. Since this med inhibits excretion of the said ketones, then there will be a buildup in the bloodstream, so I would not expect the urine output to be higher than the blood level. Maybe it was a final flush when the SGLT2 relinquished its stranglehold on my kidneys. But I was testing because I felt like c**p. I survived the incident without needing the blulight taxi, so in that instance the event was shortlived and not dangerous. But I do not know what caused it, and if it comes again, will it be more severe?

As you point out, weestix are a poor alarm system, but my doctor is not able to supply blood test strips. however a DKA event would remove my SGLT2 access (immediate and permanent stop on SGLT2 according to CCG rules, as well as loss of driving licence, and by that token, removal of my monthly test strip (glucose) support) so its win-win for the GP and the CCG. Its the Hospital budget that gets clobbered if i have an admission for DKA.

Are you able to purchase blood testing supplies yourself as I have? This morning my urine testing shows 8mmol/L. My blood testing is 0.7mmol/L. I was told by my doc urine concentrations can be higher as urine pools over time in the bladder.

 

[Oldvatr]

Are you able to purchase blood testing supplies yourself as I have? This morning my urine testing shows 8mmol/L. My blood testing is 0.7mmol/L. I was told by my doc urine concentrations can be higher as urine pools over time in the bladder.

I had one ketone test strip that came as a sample in a replacement meter kit that perchance landed on my doormat the same day as my incident. When my urine strip was saying 3.9 mmol/, the meter reading was 3.1 mmol/l.

I am a pensioner, and today my fuel bill landed in my intray. I have used almost exactly half what I used in the same month last year, but I have been charged twice what I paid this time last year. So, no, I do not have the luxury of being able to purchase these strips at the moment. I buy my glucose strips at discount, so I have just paid out for 500 test strips to reduce the effect of the P&P charge. That makes each glucose test 11p per test, but the ketone test cost is over £3 per shot and no discounts. Whether I test once or 10 times, the cost to me is over £30 as the strips need to be replaced every 3 months.

 

[Sugarstre]

Interesting. According to this study, SGLT2i cause increases in glucagon and ketone levels ONLY in diabetic patients. The rise in ketones was not seen in normal controls.

Empagliflozin caused a significant increase in mean plasma glucagon, free fatty acid (FFA) and ketone concentrations in T2DM subjects. However, empagliflozin did not cause a significant change in mean plasma insulin, glucagon or ketone concentrations in non-diabetic subjects.

Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients - PubMed

Results of the present study demonstrate that SGLT2 inhibition exerts different metabolic effects in non-diabetic individuals as compared to diabetic patients.

pubmed.ncbi.nlm.nih.gov

 

[Oldvatr]

Interesting. According to this study, SGLT2i cause increases in glucagon and ketone levels ONLY in diabetic patients. The rise in ketones was not seen in normal controls.

Empagliflozin caused a significant increase in mean plasma glucagon, free fatty acid (FFA) and ketone concentrations in T2DM subjects. However, empagliflozin did not cause a significant change in mean plasma insulin, glucagon or ketone concentrations in non-diabetic subjects.

Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients - PubMed

Results of the present study demonstrate that SGLT2 inhibition exerts different metabolic effects in non-diabetic individuals as compared to diabetic patients.

pubmed.ncbi.nlm.nih.gov

i have no eyes dear. I wil surmise that the difference is Insulin Resistsnce. Normal people will probably have insulin that works, and glucose that needs to be stored away as would normally happen , but IR means the glucose cannot go into the cells and remains high(ish) so the body starts burning lipids instead because it cannot use the glucose.

I did wonder about the glucagon. This normally ends the food insulin cycle by shutting off insulin. but it in itself does not result directly in lipolysis. But I think IR keeping insulin high (as a T2D) could trigger it especially as the med is jamming up the works and interfering with the normal processes. The alpha cells do not need SGLT2 as they have their own backup systems which kick in when hypoland is near. Normal people will use the glucose s intended, the glucose levels drop, and then the liver dumps more glucose as necessary. No probs.