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Post by sla55 on Feb 7, 2018 8:59:26 GMT -5
www.abstractsonline.com/pp8/#!/4482/presentation/7197 Authors Swashti Agarwal, MD, Meenal Gupta, MD, Sheila Gunn, MD. Baylor College of Medicine, Houston, TX, USA. Disclosures S. Agarwal: None. M. Gupta: None. S. Gunn: None. Abstract Subcutaneous insulin resistance syndrome (SIRS), a rare entity, is characterized by increased resistance to subcutaneous (subQ) insulin, normal sensitivity to intravenous (IV) or intramuscular (IM) insulin with no increase in circulating insulin antibodies. Not much is known about its patho-physiology, but it has been suggested to occur due to rapid subcutaneous degradation of insulin. Multiple treatment modalities have been used in the past including IV or IM insulin, intra-peritoneal implants, human recombinant hyaluronidase and protease inhibitors. We illustrate a similar case here and describe the challenges in management with different modalities, eventually using inhaled insulin, which was recently FDA approved for use in adults with Type 1 diabetes. Our patient was a 17 years old non-obese (BMI: 24.6kg/m2) Caucasian female diagnosed with Type 1 Diabetes Mellitus four years ago and well controlled (HbA1c ~ 7.5%) on Aspart insulin via pump at home. She initially presented with Diabetes Ketoacidosis (DKA) at an outside hospital, which resolved within 24 hours of starting IV insulin drip. They encountered difficulties transitioning her but finally discharged her on regular insulin via pump. She presented with ketosis two days later, failed to respond to multiple correction boluses of subQ insulin leading to DKA. This resolved with IV insulin and fluids. Various subQ insulin formulations were tried and metformin added, however she developed DKA again. She was then transferred to our center for further management. DKA was initially managed with IV insulin. To transition, we tried subQ Novolin-R insulin since patient's mother reported that it was the only insulin formulation that she had responded to. Blood sugars trended up and ketosis developed within 10 hours of starting this regimen despite increasing doses to 5.6 units/kg/day. Insulin antibodies were 4.5U/mL (ref: less than 0.4U/mL) - not significantly elevated. Given suspicion of SIRS, we started IIM (intensive insulin management) regimen using IM insulin (Lantus and Lispro). This improved glycemic control however, necessitated 5 painful IM injections per day leading to patient dissatisfaction. Hyaluronidase injection at the pump site was used to facilitate increased absorption of insulin however patient failed to respond and developed ketosis. While awaiting approval and availability of inhaled insulin, hyperglycemia was managed with IM/IV insulin. With inhaled insulin (Afrezza) and IM lantus use, blood glucose remained in 90-130mg/dL range and she was discharged home on this regimen after total of 3.5 weeks of hospitalization. SIRS is a difficult condition leading to prolonged hospital stay, patient frustration and carries a serious risk of recurrent DKA. We report this case to create awareness about this entity and the use of inhaled insulin, and to provide insight into the challenges faced while managing this condition.
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Post by peppy on Feb 7, 2018 9:12:58 GMT -5
she needed the phase one.
hmmmm.
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Post by agedhippie on Feb 7, 2018 9:44:52 GMT -5
she needed the phase one. hmmmm. It's not phase 1 that was the problem, it's that she could not absorb insulin if it was given subcutaneously. I know someone who has the same problem and they had to have an implanted pump which is difficult because there are currently no FDA approved implanted pumps (they went to Europe). Afrezza is perfect for this use case because it bypasses the absorption issue. It is good to see doctors finally publishing papers about the use of Afrezza. That's the sort of thing that influences opinion. |
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Post by peppy on Feb 7, 2018 10:37:07 GMT -5
she needed the phase one. hmmmm. I know someone who has the same problem and they had to have an implanted pump which is difficult because there are currently no FDA approved implanted pumps (they went to Europe). Afrezza is perfect for this use case because it bypasses the absorption issue. It is good to see doctors finally publishing papers about the use of Afrezza. That's the sort of thing that influences opinion. quote: It's not phase 1 that was the problem, it's that she could not absorb insulin if it was given subcutaneously. reply: Subcutaneous insulin resistance syndrome (SIRS), a rare entity, is characterized by increased resistance to subcutaneous (subQ) insulin, normal sensitivity to intravenous (IV) or intramuscular (IM) insulin with no increase in circulating insulin antibodies. No chit sherlock? quote: on Aspart insulin via pump at home.- presented with Diabetes Ketoacidosis (DKA)..... so blood glucose is high. cells have no/minimal intracellular glucose. ketones produced by the liver from fatty acids during periods of low food intake (fasting), carbohydrate restrictive diets, starvation -IV insulin drip. They encountered difficulties transitioning her but finally discharged her on regular insulin via pump. -. She presented with ketosis two days later, failed to respond to multiple correction boluses of subQ insulin leading to DKA. This resolved with IV insulin and fluids. - Various subQ insulin formulations were tried and metformin added, however she developed DKA - DKA was initially managed with IV insulin - IM insulin (Lantus and Lispro). This improved glycemic control however, necessitated 5 painful IM injections per day. - With inhaled insulin (Afrezza) and IM lantus use, blood glucose remained in 90-130mg/dL range and she was discharged home on this regimen after total of 3.5 weeks of hospitalization. So this individual needed insulin delivered to the blood stream, unable to absorb insulin through fat and barely absorb insulin through muscle? The delivery from muscle much quicker than subq. So aged and all, what cases this? |
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Post by kc on Feb 7, 2018 10:41:24 GMT -5
www.abstractsonline.com/pp8/#!/4482/presentation/7197 Authors Swashti Agarwal, MD, Meenal Gupta, MD, Sheila Gunn, MD. Baylor College of Medicine, Houston, TX, USA. Disclosures S. Agarwal: None. M. Gupta: None. S. Gunn: None. Abstract Subcutaneous insulin resistance syndrome (SIRS), a rare entity, is characterized by increased resistance to subcutaneous (subQ) insulin, normal sensitivity to intravenous (IV) or intramuscular (IM) insulin with no increase in circulating insulin antibodies. Not much is known about its patho-physiology, but it has been suggested to occur due to rapid subcutaneous degradation of insulin. Multiple treatment modalities have been used in the past including IV or IM insulin, intra-peritoneal implants, human recombinant hyaluronidase and protease inhibitors. We illustrate a similar case here and describe the challenges in management with different modalities, eventually using inhaled insulin, which was recently FDA approved for use in adults with Type 1 diabetes. Our patient was a 17 years old non-obese (BMI: 24.6kg/m2) Caucasian female diagnosed with Type 1 Diabetes Mellitus four years ago and well controlled (HbA1c ~ 7.5%) on Aspart insulin via pump at home. She initially presented with Diabetes Ketoacidosis (DKA) at an outside hospital, which resolved within 24 hours of starting IV insulin drip. They encountered difficulties transitioning her but finally discharged her on regular insulin via pump. She presented with ketosis two days later, failed to respond to multiple correction boluses of subQ insulin leading to DKA. This resolved with IV insulin and fluids. Various subQ insulin formulations were tried and metformin added, however she developed DKA again. She was then transferred to our center for further management. DKA was initially managed with IV insulin. To transition, we tried subQ Novolin-R insulin since patient's mother reported that it was the only insulin formulation that she had responded to. Blood sugars trended up and ketosis developed within 10 hours of starting this regimen despite increasing doses to 5.6 units/kg/day. Insulin antibodies were 4.5U/mL (ref: less than 0.4U/mL) - not significantly elevated. Given suspicion of SIRS, we started IIM (intensive insulin management) regimen using IM insulin (Lantus and Lispro).  This improved glycemic control however, necessitated 5 painful IM injections per day leading to patient dissatisfaction. Hyaluronidase injection at the pump site was used to facilitate increased absorption of insulin however patient failed to respond and developed ketosis. While awaiting approval and availability of inhaled insulin , hyperglycemia was managed with IM/IV insulin.With inhaled insulin (Afrezza) and IM lantus use, blood glucose remained in 90-130mg/dL range and she was discharged home on this regimen after total of 3.5 weeks of hospitalization . SIRS is a difficult condition leading to prolonged hospital stay, patient frustration and carries a serious risk of recurrent DKA. We report this case to create awareness about this entity and the use of inhaled insulin, and to provide insight into the challenges faced while managing this condition. Amazing abstract.... Hopefully somebody will pay attention to the presentation.
Think about the cost of 3.5 week hospital stay for patient and the insurance carrier or for the Medicare or Medicaid system.
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Post by centralcoastinvestor on Feb 7, 2018 16:13:39 GMT -5
This is a very significant abstract in my opinion. What is important is that this isn’t any study pushed by MannKind. It is normal doctors trying to help a Type 1 patient that is in crisis. Everything else failed except painful intramuscular shots or Afrezza. And guess what, they could send the patient home with Afrezza. Wow.
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Post by dreamboatcruise on Feb 7, 2018 19:12:23 GMT -5
This is a very significant abstract in my opinion. What is important is that this isn’t any study pushed by MannKind. It is normal doctors trying to help a Type 1 patient that is in crisis. Everything else failed except painful intramuscular shots or Afrezza. And guess what, they could send the patient home with Afrezza. Wow. Maybe it will cause a spark in some medical minds that Afrezza would be beneficial in the much larger patient population that has less severe injection site issues. |
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Post by sayhey24 on Feb 7, 2018 20:01:56 GMT -5
IMO, what should be highlighted by our CMO Big Dave is the last thing they tried after everything else failed was afrezza. Good Grief! Big Dave should be screaming that the first thing they should have tried was afrezza.
What's the VDex motto with the T2s "afrezza first, afrezza always!". It should be the same with the SIRS and ALL the T1s.
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Post by agedhippie on Feb 9, 2018 22:47:43 GMT -5
So this individual needed insulin delivered to the blood stream, unable to absorb insulin through fat and barely absorb insulin through muscle? The delivery from muscle much quicker than subq. So aged and all, what causes this? Insulin antibodies. The insulin spends to long in the bodies and the antibodies attack it. The IM approach works because it gets the insulin into the bloodstream far quicker with the high blood vessel density. You can accelerate that still more by working the muscle and/or applying heat. An implanted pump works because the absorption in the peritoneal cavity is so fast. |
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Post by sayhey24 on Feb 10, 2018 19:37:44 GMT -5
The paper says "with no increase in circulating insulin antibodies. Not much is known about its patho-physiology, but it has been suggested to occur due to rapid subcutaneous degradation of insulin" I have no idea what causes this but it sounds like the presence of an insulin degrading enzyme.
I think what is import here is that there is now a clear "Standard of Care" for SIRS - give them the afrezza.
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Post by digger on Feb 11, 2018 3:03:12 GMT -5
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Post by agedhippie on Feb 11, 2018 10:35:59 GMT -5
They were never FDA approved in the US although there was a VA trial using them. It would certainly reduce insulin costs since they use Regular insulin. Having to implant the pump was never going to be a popular selling point compared to a regular pump. |
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Post by digger on Feb 11, 2018 11:48:48 GMT -5
They were never FDA approved in the US although there was a VA trial using them. It would certainly reduce insulin costs since they use Regular insulin. Having to implant the pump was never going to be a popular selling point compared to a regular pump. It's interesting that Minimed had developed a device -- www.healthline.com/diabetesmine/implantable-insulin-pumps#6 -- but it was dumped in 2007 by Medtronic after the acquisition. People that still have one have to go to France every three months to get it refilled. Every three months is probably why Medtronic didn't want the device to be a success. I imagine the cash flow wouldn't be very lucrative. |
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Post by dfarragut on Feb 11, 2018 21:30:08 GMT -5
The reality of the difficulties with the IDP (implantable drug pump) is more regulatory, specifically the FDA. Hence the EU approval and market that exist today. The barrier to approval are incredibly arduous, which simply means expensive. The device is extremely difficult to manufacture and the risks during use only compound the already strained business model. Pocket refills, or inadvertently injecting the drug (more than one type of IDP exists; there is also a pump for chronic pain) into the patient's "pocket" opposed to the pump fluid chamber can be lethal. In addition, pumps are notorious for stopping delivery due to what is believed to be mechanical issues referred to "hang up." Under delivery of insulin or morphine in the case of a pain pump, can be diagnosed and remedied fairly easily. However, sometimes doc's go off label and use an drug that is not approved, e.g. Baclofen, which must use proper titration. I sudden stop of delivery also can cause a fatality.
With those headwinds, and the unbelievable cost of getting a pump approved, it is actually quite simple why there isn't a viable business model here in the states. I know people like to think large corporations withhold treatments to patients in need because they do not provide a large enough revenue stream for a company. But from my vantage point, making the costs of development and the approval process so costly, most novel devices/medications don't really have much of a chance to see the light of day, must less get approval. Can suggest is that we try not to be overly cynical?
Just think, the few lucky enough to survive this process and get to a coveted PMA often times have little or no money left for commercialization. Sounds familiar, eh?
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Post by harryx1 on Mar 20, 2018 12:37:53 GMT -5
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This improved glycemic control however, necessitated 5 painful IM injections per day leading to patient dissatisfaction. 
