3 ms·

No, there isn't a hardware problem and such systems exist. Several trials[1-3] dating back several years have looked at "bionic pancreas" or a closed loop bihor

No, there isn't a hardware problem and such systems exist. Several trials[1-3] dating back several years have looked at "bionic pancreas" or a closed loop bihormonal system. Inreda (a Dutch company) has a CE-marked device[4] that can be clinically used but one limitation has been glucagon stability (has to be replenished daily). Tandem in the US was working on this as well but I haven't heard anything about them in a while, not sure how far along they are. The Inreda product is still in the early stages of testing but fully functional. Small crossover trials seem promising (defined by more time in euglycemic state). There is a competing approach with "intelligent insulin" or a self-regulating glucose sensitive insulin formulation that has different bioavailability depending on circulating glucose levels rather than relying on a monitor, this is farther out from clinical use. One of the reasons bihormonal pumps haven't entered mainstream use yet is that it's more expensive/complicated and the current techniques of algorithmic predictions of hypoglycemic episodes and insulin delivery suspension are already very good that hypo isn't much of a problem with modern devices like Tandem's offering. Medtronic has added a meal detection algorithm[5] that's really good too (the best on the market I'm told by my endo colleagues) and they say we're getting close to not needing meal announcement anymore, this practically eliminates carb counting. It's the first such algorithm to be in clinical use so we're not there yet but the expectation is that this approach will get us there. The question (for glucagon) then becomes how clinically useful more time in euglycemia is as the hypo episode problem is essentially solved, we'll need more data to draw any conclusions and it will take a while for this particular question as many of the outcome measures are long-term (i.e. what are the long-term sequela of mild intermittent hyperglycemia, it's somewhere between nothing and uncontrolled diabetes but how far along on that line is the billion dollar question). [1] https://pubmed.ncbi.nlm.nih.gov/28007348/ https://pubmed.ncbi.nlm.nih.gov/28007348/ [2] https://jamanetwork.com/journals/jamasurgery/article-abstract/2795853 https://jamanetwork.com/journals/jamasurgery/article-abstrac... [3] https://pubmed.ncbi.nlm.nih.gov/24931572/ https://pubmed.ncbi.nlm.nih.gov/24931572/ [4] https://www.inredadiabetic.nl/en/discover-the-ap/ https://www.inredadiabetic.nl/en/discover-the-ap/ [5] https://www.medtronicdiabetes.com/products/minimed-780g-insulin-pump-system https://www.medtronicdiabetes.com/products/minimed-780g-insu...

nahsra 3y ago
It's not clear from their site whether the Inreda product also has CGM built into it, or if it must be paired with one? Glucose-responsive insulin also seems like science fiction as this point, but would be extremely powerful tool. I'm very familiar with one of the most popular, closed-loop system combinations in the USA and I definitely don't feel the hypoglycemia problem is anywhere near "solved". There is too much volatility dictating a person's insulin sensitivity that even today's smartest systems will regularly give too much insulin, requiring treatment, or too little, resulting in prolonged hyperglycemia. I agree that time-in-range is incredible today with the technology, comparatively, but there's still lots and lots of room for improvement.
- haldujai 3y ago
  Inreda integrates the CGM, [1] has more details on the setup. > I'm very familiar with one of the most popular, closed-loop system combinations in the USA and I definitely don't feel the hypoglycemia problem is anywhere near "solved". I should have been clearer, the moderate to severe hypoglycemia (level 2 and 3) problem is essentially solved with the newest generation of closed loop systems. Hypoglycemia in general is trending towards being solved particularly with the newest Medtronic devices, both from studies and what endocrinologists are seeing. In some of the recent studies (which again are still small as these devices are new) I've come across there are no severe hypo episodes reported and % time in moderate hypoglycemia was (picking one study) ~0.3%[2]. The belief is that further iterations of these algorithms will continue to improve this hence why I said "solved" as in there is no strong need for a large treatment paradigm shift on the basis of moderate-severe hypoglycemia. > There is too much volatility dictating a person's insulin sensitivity that even today's smartest systems will regularly give too much insulin, requiring treatment, or too little, resulting in prolonged hyperglycemia. Hyperglycemia is a different discussion altogether that is not addressed by insulin delivery suspension or glucagon. The MiniMed 780G is probably the most advanced system out there with minimal patient input and time in target range is being reported as ~80% which is certainly getting there. [1] https://diabetesjournals.figshare.com/articles/figure/Fully_Closed_Loop_Glucose_Control_With_a_Bihormonal_Artificial_Pancreas_in_Adults_With_Type_1_Diabetes_An_Outpatient_Randomized_Crossover_Trial/13283912 https://diabetesjournals.figshare.com/articles/figure/Fully_... [2] https://www.nejm.org/doi/10.1056/NEJMoa2004736?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed https://www.nejm.org/doi/10.1056/NEJMoa2004736?url_ver=Z39.8...

nahsra 3y ago

It's not clear from their site whether the Inreda product also has CGM built into it, or if it must be paired with one? Glucose-responsive insulin also seems like science fiction as this point, but would be extremely powerful tool. I'm very familiar with one of the most popular, closed-loop system combinations in the USA and I definitely don't feel the hypoglycemia problem is anywhere near "solved". There is too much volatility dictating a person's insulin sensitivity that even today's smartest systems will regularly give too much insulin, requiring treatment, or too little, resulting in prolonged hyperglycemia. I agree that time-in-range is incredible today with the technology, comparatively, but there's still lots and lots of room for improvement.

haldujai 3y ago
Inreda integrates the CGM, [1] has more details on the setup. > I'm very familiar with one of the most popular, closed-loop system combinations in the USA and I definitely don't feel the hypoglycemia problem is anywhere near "solved". I should have been clearer, the moderate to severe hypoglycemia (level 2 and 3) problem is essentially solved with the newest generation of closed loop systems. Hypoglycemia in general is trending towards being solved particularly with the newest Medtronic devices, both from studies and what endocrinologists are seeing. In some of the recent studies (which again are still small as these devices are new) I've come across there are no severe hypo episodes reported and % time in moderate hypoglycemia was (picking one study) ~0.3%[2]. The belief is that further iterations of these algorithms will continue to improve this hence why I said "solved" as in there is no strong need for a large treatment paradigm shift on the basis of moderate-severe hypoglycemia. > There is too much volatility dictating a person's insulin sensitivity that even today's smartest systems will regularly give too much insulin, requiring treatment, or too little, resulting in prolonged hyperglycemia. Hyperglycemia is a different discussion altogether that is not addressed by insulin delivery suspension or glucagon. The MiniMed 780G is probably the most advanced system out there with minimal patient input and time in target range is being reported as ~80% which is certainly getting there. [1] https://diabetesjournals.figshare.com/articles/figure/Fully_Closed_Loop_Glucose_Control_With_a_Bihormonal_Artificial_Pancreas_in_Adults_With_Type_1_Diabetes_An_Outpatient_Randomized_Crossover_Trial/13283912 https://diabetesjournals.figshare.com/articles/figure/Fully_... [2] https://www.nejm.org/doi/10.1056/NEJMoa2004736?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed https://www.nejm.org/doi/10.1056/NEJMoa2004736?url_ver=Z39.8...