I appreciate your concern about “double diabetes” in the conclusion. A lot of people look to medicine and scientific research for a replacement of doing the hard work to stay healthy, i.e. a health promoting diet, exercise, glucose control. While a cure for T1D would definitely remove a burden from nearly 10 million people globally, it does not even come close to the problem of T2D. Which do you think would be easier to cure? T1D or T2D?
To your question about which is easier to "cure," T1D has a single cause, whereas T2D can result from one (or more) metabolic dysfunctions that result in elevated glucose levels. The ways in which the body has trouble maintaining glucose levels are incredibly vast, so if any one of them trips up, it can lead to perpetual hyperglycemia---hence, T2D.
For this reason, one doesn't "cure" T2D, though there certainly could be curative therapies that may address any one or more of the pathologies, but it doesn't make sense to use the phrase "cure T2D."
Coming full circle, everything I just described above can -- and DOES -- happen to T1Ds as well. Though the initial onset of T1D is autoimmune-related, the conditions and circumstances that lead to T2D happen to T1Ds more often than not. It's just that we don't call it T2D because we already have the elevated glucose levels. But if you look carefully into any given T1Ds metabolic functions whose had it longer than a few years, you'll find many other disorders that were triggered by similar conditions that non-T1D individuals experience.
"Insulin resistance" is one such condition that spans both T1 and T2 populations, and that kind of pathology is not solely due to obesity. It can be caused by a large number of factors, the most common one being hyperinsulinemia -- that is, an excess amount of insulin is required to bring glucose levels down. The more insulin that's required to reduce glucose levels, the greater the insulin resistance, which leads to a progressively longer chain of metabolic disorders. Both T1s and T2s share this problem.
My next article will be touching upon this subject.
as you know, this is well outside the topic of a 'cure,' which is defined as a state where no exogenous insulin is required at all.
Nevertheless, while I love the IDEA of glucose-sensitive insulins, it's one of those technologies that has been researched for decades, and likely always will be. The primary problem is that there saccharides (the chemical family that comprises glucose) is very wide and overlapping, and there are many non-glucose chemicals that will activate the insulin because they look like sugar.
The second problem with the whole idea---which is far more important---is that glucose is essential to a healthy exercise regimen, and because T1Ds cannot [efficiently] produce sufficient glucagon to provide glucose when blood sugars are low, we need to eat glucose in sufficient quantities for exercise. Muscles take up glucose WITHOUT insulin mediation, which is why we need to reduce the amount of insulin prior to exercise. The "smart insulins" are not intended for short-term doses the way fast-acting insulins are intended to be used, so I cannot possibly imagine how T1Ds will even get sufficient aerobic exercise using smart insulins. You'll just never get your glucose levels high enough for sustained aerobic activity.
and yes, I know my posts are long. As Mark Twain once said, "I'm sorry this letter is so long. I didn't have time to make it shorter."
Seriously, it's a trade-off between publishing something short and easy that's more widely read, and writing quality material that holds up. I'd rather be critiqued for posts being too long than being inaccurate.
I prefer to write about larger, more comprehensive topics that are more foundational to the general knowledge about T1D---topics that are evergreen, that could be read anytime in the future and they'd still be relevant. "Smart insulin" by itself is not such a topic.
However, I do have an article in the pipeline about insulin absorption variability, how and why it happens, and ways to use these nuances to make better timing and dosing decisions for better glycemic control. I have a section that describes the different ways insulin formulations achieve different onset and duration of efficacy, and this is where mention of glucose-sensing or glucose-responsive insulins would be mentioned.
As for Novo's investment and their "belief" in the technology, that's to be expected. As my recent article on a "cure" points out, science advances iteratively from prior research and development. Having a broad portfolio of intellectual property allows of intermixing of ideas, techniques and resources to move things along under a larger interactive tent. We wouldn't have what we use today were it not for similar investments back in the 1980s and 90s.
I appreciate your concern about “double diabetes” in the conclusion. A lot of people look to medicine and scientific research for a replacement of doing the hard work to stay healthy, i.e. a health promoting diet, exercise, glucose control. While a cure for T1D would definitely remove a burden from nearly 10 million people globally, it does not even come close to the problem of T2D. Which do you think would be easier to cure? T1D or T2D?
To your question about which is easier to "cure," T1D has a single cause, whereas T2D can result from one (or more) metabolic dysfunctions that result in elevated glucose levels. The ways in which the body has trouble maintaining glucose levels are incredibly vast, so if any one of them trips up, it can lead to perpetual hyperglycemia---hence, T2D.
For this reason, one doesn't "cure" T2D, though there certainly could be curative therapies that may address any one or more of the pathologies, but it doesn't make sense to use the phrase "cure T2D."
Coming full circle, everything I just described above can -- and DOES -- happen to T1Ds as well. Though the initial onset of T1D is autoimmune-related, the conditions and circumstances that lead to T2D happen to T1Ds more often than not. It's just that we don't call it T2D because we already have the elevated glucose levels. But if you look carefully into any given T1Ds metabolic functions whose had it longer than a few years, you'll find many other disorders that were triggered by similar conditions that non-T1D individuals experience.
"Insulin resistance" is one such condition that spans both T1 and T2 populations, and that kind of pathology is not solely due to obesity. It can be caused by a large number of factors, the most common one being hyperinsulinemia -- that is, an excess amount of insulin is required to bring glucose levels down. The more insulin that's required to reduce glucose levels, the greater the insulin resistance, which leads to a progressively longer chain of metabolic disorders. Both T1s and T2s share this problem.
My next article will be touching upon this subject.
Thank you for your clear and concise explanations.
WOW! thankyou
as you know, this is well outside the topic of a 'cure,' which is defined as a state where no exogenous insulin is required at all.
Nevertheless, while I love the IDEA of glucose-sensitive insulins, it's one of those technologies that has been researched for decades, and likely always will be. The primary problem is that there saccharides (the chemical family that comprises glucose) is very wide and overlapping, and there are many non-glucose chemicals that will activate the insulin because they look like sugar.
The second problem with the whole idea---which is far more important---is that glucose is essential to a healthy exercise regimen, and because T1Ds cannot [efficiently] produce sufficient glucagon to provide glucose when blood sugars are low, we need to eat glucose in sufficient quantities for exercise. Muscles take up glucose WITHOUT insulin mediation, which is why we need to reduce the amount of insulin prior to exercise. The "smart insulins" are not intended for short-term doses the way fast-acting insulins are intended to be used, so I cannot possibly imagine how T1Ds will even get sufficient aerobic exercise using smart insulins. You'll just never get your glucose levels high enough for sustained aerobic activity.
For more on glucose and exercise, see my article https://danheller.substack.com/p/the-paradox-of-low-carb-diets-a1c-vs-metabolic-health
and yes, I know my posts are long. As Mark Twain once said, "I'm sorry this letter is so long. I didn't have time to make it shorter."
Seriously, it's a trade-off between publishing something short and easy that's more widely read, and writing quality material that holds up. I'd rather be critiqued for posts being too long than being inaccurate.
I prefer to write about larger, more comprehensive topics that are more foundational to the general knowledge about T1D---topics that are evergreen, that could be read anytime in the future and they'd still be relevant. "Smart insulin" by itself is not such a topic.
However, I do have an article in the pipeline about insulin absorption variability, how and why it happens, and ways to use these nuances to make better timing and dosing decisions for better glycemic control. I have a section that describes the different ways insulin formulations achieve different onset and duration of efficacy, and this is where mention of glucose-sensing or glucose-responsive insulins would be mentioned.
As for Novo's investment and their "belief" in the technology, that's to be expected. As my recent article on a "cure" points out, science advances iteratively from prior research and development. Having a broad portfolio of intellectual property allows of intermixing of ideas, techniques and resources to move things along under a larger interactive tent. We wouldn't have what we use today were it not for similar investments back in the 1980s and 90s.