Case Report: Avoidance of Hospitalization for DKA Using TI

[mango]

Amazing new paper published April 9, 2020

Case Report: Efficient Avoidance of Hospitalization for Diabetic Ketosis Utilizing Technosphere Inhaled Insulin


Abstract

We describe the use of inhaled insulin for the therapy of diabetic ketosis/ketoacidosis in a patient with type 1 diabetes. In this situation high insulin levels are needed to metabolize ketone bodies and avoid hospitalization. Technosphere inhaled insulin (TI) may be an alternative to subcutaneously injected fast-acting insulins, not only because of its rapid onset of action but also lack of stacking leading to late-onset hypoglycemia. In conclusion, TI may well be more efficacious and safer in the outpatient management of diabetic ketosis/ketoacidosis than standard subcutaneously injected rapid-acting insulin.


link.springer.com/article/10.1007/s13300-020-00809-x

PDF: link.springer.com/content/pdf/10.1007/s13300-020-00809-x.pdf

[hopingandwilling]

Thanks for the link--however, I have one question. Since this patient was already dosing Afrezza up to six times a day--why did she develop this condition? What am I missing?

<<A 64-year-old woman with a history of type 1 diabetes diagnosed at age 5. Her current diabetic therapy included once daily degludec insulin and inhaled TI 3–6 times daily. She had excellent glycemic control (most recent HbA1c 6.8%) without severe or frequent hypoglycemia. Her only diabetic complication was mild distal symmetrical polyneuropathy.>>>

[goyocafe]

Apr 10, 2020 10:27:08 GMT -5 hopingandwilling said:

Thanks for the link--however, I have one question. Since this patient was already dosing Afrezza up to six times a day--why did she develop this condition? What am I missing?

<<A 64-year-old woman with a history of type 1 diabetes diagnosed at age 5. Her current diabetic therapy included once daily degludec insulin and inhaled TI 3–6 times daily. She had excellent glycemic control (most recent HbA1c 6.8%) without severe or frequent hypoglycemia. Her only diabetic complication was mild distal symmetrical polyneuropathy.>>>

Maybe she forgot to dose her basal insulin.

[mango]

Apr 10, 2020 10:27:08 GMT -5 hopingandwilling said:

Thanks for the link--however, I have one question. Since this patient was already dosing Afrezza up to six times a day--why did she develop this condition? What am I missing?

<<A 64-year-old woman with a history of type 1 diabetes diagnosed at age 5. Her current diabetic therapy included once daily degludec insulin and inhaled TI 3–6 times daily. She had excellent glycemic control (most recent HbA1c 6.8%) without severe or frequent hypoglycemia. Her only diabetic complication was mild distal symmetrical polyneuropathy.>>>

Following a Christmas party, she developed severe gastroenteritis and uncontrolled vomiting which progressed to severe ketosis (urinary ketone bodies, acetoacetate, and acetone exceeding 160 mg/dl) and severe dehydration. Once her vomiting was corrected with promethazine suppositories (every 4 h) and dehydra- tion improved, the severe ketosis persisted in spite of serum glucose levels in the 90–120 mg/ dl range.

With the patient regaining her ability to absorb and maintain oral intake, she was started on inhaled TI, four units every hour. Her glu- cose was monitored with the Dexcom G6 con- tinuous glucose monitoring device with a goal of 90–150mg/dl. She was advised to inhale 8 units if her glucose read over 150 mg/dl. After 4 h, no urine ketones were reported, her serum glucose was 105 mg/dl, and she resumed her usual diabetic regimen. In addition, she did not experience any hypoglycemic episodes during the hourly inhaled TI.

[mango]

Key Summary Points

• Diabetic ketoacidosis frequently requires hospital admission which is costly and disruptive to patients.

• Outpatient treatment can be risky because of erratic subcutaneous insulin absorption and stacking.

• We report a patient treated successfully for diabetic ketoacidosis/ketosis with inhaled insulin in the outpatient setting.

• This unique use for inhaled insulin needs to be tested in a randomized controlled trial.

[veritasfiliatemporis]

Apr 10, 2020 10:27:08 GMT -5 hopingandwilling said:

Thanks for the link--however, I have one question. Since this patient was already dosing Afrezza up to six times a day--why did she develop this condition? What am I missing?

<<A 64-year-old woman with a history of type 1 diabetes diagnosed at age 5. Her current diabetic therapy included once daily degludec insulin and inhaled TI 3–6 times daily. She had excellent glycemic control (most recent HbA1c 6.8%) without severe or frequent hypoglycemia. Her only diabetic complication was mild distal symmetrical polyneuropathy.>>>

She was  way too enthusiastic at the Christmas party....

[rfogel]

Apr 10, 2020 11:09:50 GMT -5 mango said:

Apr 10, 2020 10:27:08 GMT -5 hopingandwilling said:

Thanks for the link--however, I have one question. Since this patient was already dosing Afrezza up to six times a day--why did she develop this condition? What am I missing?

<<A 64-year-old woman with a history of type 1 diabetes diagnosed at age 5. Her current diabetic therapy included once daily degludec insulin and inhaled TI 3–6 times daily. She had excellent glycemic control (most recent HbA1c 6.8%) without severe or frequent hypoglycemia. Her only diabetic complication was mild distal symmetrical polyneuropathy.>>>

Following a Christmas party, she developed severe gastroenteritis and uncontrolled vomiting which progressed to severe ketosis (urinary ketone bodies, acetoacetate, and acetone exceeding 160 mg/dl) and severe dehydration. Once her vomiting was corrected with promethazine suppositories (every 4 h) and dehydra- tion improved, the severe ketosis persisted in spite of serum glucose levels in the 90–120 mg/ dl range.

With the patient regaining her ability to absorb and maintain oral intake, she was started on inhaled TI, four units every hour. Her glu- cose was monitored with the Dexcom G6 con- tinuous glucose monitoring device with a goal of 90–150mg/dl. She was advised to inhale 8 units if her glucose read over 150 mg/dl. After 4 h, no urine ketones were reported, her serum glucose was 105 mg/dl, and she resumed her usual diabetic regimen. In addition, she did not experience any hypoglycemic episodes during the hourly inhaled TI.

So if severe "serum glucose levels in the 90–120 mg/ dl range.," how did afrezza help relieve the ketosis?  Actually, when I think about it does that qualify as DKA?  I thought DKA, by definition, resulted in high glucose levels due to inadequate levels of insulin.

I was also a little disturbed by the phrase, "outpatient management of diabetic ketosis/ketoacidosis."  I was under the impression that DKA was a life threatening condition requiring intensive care.

[mango]

Apr 10, 2020 12:35:48 GMT -5 rfogel said:

Apr 10, 2020 11:09:50 GMT -5 mango said:

Following a Christmas party, she developed severe gastroenteritis and uncontrolled vomiting which progressed to severe ketosis (urinary ketone bodies, acetoacetate, and acetone exceeding 160 mg/dl) and severe dehydration. Once her vomiting was corrected with promethazine suppositories (every 4 h) and dehydra- tion improved, the severe ketosis persisted in spite of serum glucose levels in the 90–120 mg/ dl range.

With the patient regaining her ability to absorb and maintain oral intake, she was started on inhaled TI, four units every hour. Her glu- cose was monitored with the Dexcom G6 con- tinuous glucose monitoring device with a goal of 90–150mg/dl. She was advised to inhale 8 units if her glucose read over 150 mg/dl. After 4 h, no urine ketones were reported, her serum glucose was 105 mg/dl, and she resumed her usual diabetic regimen. In addition, she did not experience any hypoglycemic episodes during the hourly inhaled TI.

So if severe "serum glucose levels in the 90–120 mg/ dl range.," how did afrezza help relieve the ketosis?  Actually, when I think about it does that qualify as DKA?  I thought DKA, by definition, resulted in high glucose levels due to inadequate levels of insulin.

I was also a little disturbed by the phrase, "outpatient management of diabetic ketosis/ketoacidosis."  I was under the impression that DKA was a life threatening condition requiring intensive care.

They wrote, "the severe ketosis persisted in spite of serum glucose levels in the 90–120 mg/ dl range."

Nope. This patient was treated successfully and safely with Afrezza as an outpatient. 

Key Summary Points

• Diabetic ketoacidosis frequently requires hospital admission which is costly and disruptive to patients.

• Outpatient treatment can be risky because of erratic subcutaneous insulin absorption and stacking.

• We report a patient treated successfully for diabetic ketoacidosis/ketosis with inhaled insulin in the outpatient setting.

• This unique use for inhaled insulin needs to be tested in a randomized controlled trial.



As noted above, RRA subcutaneous insulins are erratic, slow absorbing and unpredictable, and come with the high cost and high risk of stacking. In other words, it is not safe with RAAs, but with Afrezza it is safe. Two completely different products, and only one is actually insulin. 

That is why the authors said a RCT should he conducted based on how successful and safe it is with Afrezza. 


Afrezza, the safest insulin in the world. 

[rfogel]

Yes, but it still doesn't make any sense. If her blood sugar is in the normal range then she should have adequate insulin levels. Ketones are produced from burning fat. She shouldn't be burning fat if she has adequate insulin.

And for any residual ketones left over from DKA, they -- per wikpedia -- should be "converted into acetyl-CoA, which then enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids." Afrezza certainly wouldn't help in that process. Best I can tell, based on the information they provide, I don't see that her being "started on inhaled TI, four units every hour" necessarily had anything to do with resolution of the ketosis.

Also, did I miss it or did they fail to mention the woman's blood pH? Simple ketosis does not necessarily translate into acidosis. I can find references to outpatient management of "mild" DKA but even those require measurement of blood pH and other elements: " “Mild DKA” was previously defined in the International Society for Pediatric and Adolescent Diabetes Guidelines as a pH of 7.2-7.3, a bicarbonate level of 10-15 mmol/L, a glucose >200mg/dL and ketonemia or ketonuria." Best I could tell all they did with her was check urine ketones.

[agedhippie]

Apr 10, 2020 14:40:18 GMT -5 rfogel said:

Yes, but it still doesn't make any sense. If her blood sugar is in the normal range then she should have adequate insulin levels. Ketones are produced from burning fat. She shouldn't be burning fat if she has adequate insulin.

And for any residual ketones left over from DKA, they -- per wikpedia -- should be "converted into acetyl-CoA, which then enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids." Afrezza certainly wouldn't help in that process. Best I can tell, based on the information they provide, I don't see that her being "started on inhaled TI, four units every hour" necessarily had anything to do with resolution of the ketosis.

Also, did I miss it or did they fail to mention the woman's blood pH? Simple ketosis does not necessarily translate into acidosis. I can find references to outpatient management of "mild" DKA but even those require measurement of blood pH and other elements: " “Mild DKA” was previously defined in the International Society for Pediatric and Adolescent Diabetes Guidelines as a pH of 7.2-7.3, a bicarbonate level of 10-15 mmol/L, a glucose >200mg/dL and ketonemia or ketonuria." Best I could tell all they did with her was check urine ketones.

Though it kills me to agree with rfogel he is partly right in this case.

If she is still taking her basal insulin then she cannot go into DKA and you see this reflected in the fact that her levels were normal. Basal insulin is specifically designed so that you can fast indefinitely and you will not go into DKA. However, you definitely will get ketones, just as any person would, if you fast but those are dietary ketones and they are safe.

So why did the ketosis persist? Because she wasn't eating. If you don't take in carbs you will continue to burn ketones and hence the level will remain regardless of how much insulin you take. Once she started to take in glucose ("With the patient regaining her ability to absorb and maintain oral intake, she was started on inhaled TI, four units every hour.") dietary ketones would go away and four hours for urine ketones sounds about right.

The giveaway is the normal glucose level. You cannot develop DKA at that level. I am extremely surprised this got published.

If her endo thought she really was in DKA he absolutely should have sent her to the ER because she needs to have her electrolyte balance corrected as that's what kills people, not high glucose levels. In fact dropping very elevated rates fast is dangerous in it's own right. I think there is a thread somewhere about someone being warned about this by their endo - a fast glucose drop sucks in calcium into the blood which causes cardio problem (another reason why ER only uses glucose when they have fixed everything else and controls the rate of correction.)

I think I will send the link to my endo and see what he says.

Edit: He does look like a reputable source which is confusing. I might reach out to him.

[mnkdfann]

Apr 10, 2020 15:37:09 GMT -5 agedhippie said:

The giveaway is the normal glucose level. You cannot develop DKA at that level. I am extremely surprised this got published.

The lead author is a member of the Journal's Editorial Board, but I'm sure that had nothing to do with it. 

Disclosures. David S. H. Bell is on the Speaker’s bureau of Novo-Nordisk and Mannkind Corporation. David S.H. Bell is a member of the journal’s Editorial Board.

[mango]

Apr 10, 2020 15:37:09 GMT -5 agedhippie said:

Apr 10, 2020 14:40:18 GMT -5 rfogel said:

Yes, but it still doesn't make any sense. If her blood sugar is in the normal range then she should have adequate insulin levels. Ketones are produced from burning fat. She shouldn't be burning fat if she has adequate insulin.

And for any residual ketones left over from DKA, they -- per wikpedia -- should be "converted into acetyl-CoA, which then enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids." Afrezza certainly wouldn't help in that process. Best I can tell, based on the information they provide, I don't see that her being "started on inhaled TI, four units every hour" necessarily had anything to do with resolution of the ketosis.

Also, did I miss it or did they fail to mention the woman's blood pH? Simple ketosis does not necessarily translate into acidosis. I can find references to outpatient management of "mild" DKA but even those require measurement of blood pH and other elements: " “Mild DKA” was previously defined in the International Society for Pediatric and Adolescent Diabetes Guidelines as a pH of 7.2-7.3, a bicarbonate level of 10-15 mmol/L, a glucose >200mg/dL and ketonemia or ketonuria." Best I could tell all they did with her was check urine ketones.

Though it kills me to agree with rfogel he is partly right in this case.

If she is still taking her basal insulin then she cannot go into DKA and you see this reflected in the fact that her levels were normal. Basal insulin is specifically designed so that you can fast indefinitely and you will not go into DKA. However, you definitely will get ketones, just as any person would, if you fast but those are dietary ketones and they are safe.

So why did the ketosis persist? Because she wasn't eating. If you don't take in carbs you will continue to burn ketones and hence the level will remain regardless of how much insulin you take. Once she started to take in glucose ("With the patient regaining her ability to absorb and maintain oral intake, she was started on inhaled TI, four units every hour.") dietary ketones would go away and four hours for urine ketones sounds about right.

The giveaway is the normal glucose level. You cannot develop DKA at that level. I am extremely surprised this got published.

If her endo thought she really was in DKA he absolutely should have sent her to the ER because she needs to have her electrolyte balance corrected as that's what kills people, not high glucose levels. In fact dropping very elevated rates fast is dangerous in it's own right. I think there is a thread somewhere about someone being warned about this by their endo - a fast glucose drop sucks in calcium into the blood which causes cardio problem (another reason why ER only uses glucose when they have fixed everything else and controls the rate of correction.)

I think I will send the link to my endo and see what he says.

Edit: He does look like a reputable source which is confusing. I might reach out to him.

Reach out to him and post the exchange here, please.

[sayhey24]

Apr 10, 2020 10:27:08 GMT -5 hopingandwilling said:

Thanks for the link--however, I have one question. Since this patient was already dosing Afrezza up to six times a day--why did she develop this condition? What am I missing?

<<A 64-year-old woman with a history of type 1 diabetes diagnosed at age 5. Her current diabetic therapy included once daily degludec insulin and inhaled TI 3–6 times daily. She had excellent glycemic control (most recent HbA1c 6.8%) without severe or frequent hypoglycemia. Her only diabetic complication was mild distal symmetrical polyneuropathy.>>>

"Following a Christmas party, she developed severe gastroenteritis and uncontrolled vomiting which progressed to severe ketosis (urinary ketone bodies, acetoacetate, and acetone exceeding 160 mg/dl) and severe dehydration."

With the severe dehydration I would suspect her basal absorption was completely messed up which led to severe ketosis - but thats a total guess.

[agedhippie]

Apr 13, 2020 11:19:56 GMT -5 sayhey24 said:

Apr 10, 2020 10:27:08 GMT -5 hopingandwilling said:

Thanks for the link--however, I have one question. Since this patient was already dosing Afrezza up to six times a day--why did she develop this condition? What am I missing?

<<A 64-year-old woman with a history of type 1 diabetes diagnosed at age 5. Her current diabetic therapy included once daily degludec insulin and inhaled TI 3–6 times daily. She had excellent glycemic control (most recent HbA1c 6.8%) without severe or frequent hypoglycemia. Her only diabetic complication was mild distal symmetrical polyneuropathy.>>>

"Following a Christmas party, she developed severe gastroenteritis and uncontrolled vomiting which progressed to severe ketosis (urinary ketone bodies, acetoacetate, and acetone exceeding 160 mg/dl) and severe dehydration."

With the severe dehydration I would suspect her basal absorption was completely messed up which led to severe ketosis - but thats a total guess.

I guess it's possible because the Tresiba forms a depot in the sub q fat which then leaches out. If that was slowed enough...

The official approach is to increase doses by 20% which may be a reflection of this.

[rfogel]

Apr 13, 2020 11:19:56 GMT -5 sayhey24 said:

Apr 10, 2020 10:27:08 GMT -5 hopingandwilling said:

Thanks for the link--however, I have one question. Since this patient was already dosing Afrezza up to six times a day--why did she develop this condition? What am I missing?

<<A 64-year-old woman with a history of type 1 diabetes diagnosed at age 5. Her current diabetic therapy included once daily degludec insulin and inhaled TI 3–6 times daily. She had excellent glycemic control (most recent HbA1c 6.8%) without severe or frequent hypoglycemia. Her only diabetic complication was mild distal symmetrical polyneuropathy.>>>

"Following a Christmas party, she developed severe gastroenteritis and uncontrolled vomiting which progressed to severe ketosis (urinary ketone bodies, acetoacetate, and acetone exceeding 160 mg/dl) and severe dehydration."

With the severe dehydration I would suspect her basal absorption was completely messed up which led to severe ketosis - but thats a total guess.

Regardless, the author shouldn't claim it's "ketoacidosis" without measuring the [atient's blood pH.