It's not just infusion sites. One of the greatest unknowns in T1 is injection sites and there is a lot of work going on looking at this as well.Agree, but at present we just dont know - the sciencedirect article references a whole lot of interesting studies, and by following the references in some of these I have realised how much more complex the infusion site issues in particular may be, especially over the long term, and how much they are being studied.
And given the percentage of T1s using CSII compared with the number using injections, it will remain a low priority. As it stands, this is a first world problem with limited value in large amounts of investigation. I'm sure it will continue but I don't expect fast progress.
That is a good question, I would just add one important detail- the costs. From experience in a process industry, engineers are always pushed to lower the operative costs and increase the yields. Different separation resins are probably more expensive.The question is whether it removes the proteins in a way that they can be reused in insulin in an effective manner.
Gosh, this is all rather depressing! I think I'll stay naive to the additives/cancer risk possibilities et al
Depends on how much bacteria 'flow' in the air. Besides, we can think about 'ready for use sterile reservoairs' already filled with insulin.If you consider that the method for using insulin from a 10ml phial is to inject the same amount of air into the phial as you will withdraw insulin, every time you do this, you are injecting bacteria into the phial. As all injectable insulins are made with this delivery mechanism in mind, would you prefer to inject a sterile insulin or a non-sterile insulin containing who knows what bacterial cultures? That's effectively what the Phenol and Cresol prevents.
Depends on how much bacteria 'flow' in the air. Besides, we can think about 'ready for use sterile reservoairs' already filled with insulin.
Hi, after some time I'm back on the same topic. Why? Because one more issue with the commercially available insulins: their onset and duration of action.Great but the same insulin is used in both sterile and non-sterile environments, and I'd rather inject low levels of toxins than bacteria that can multiply. The phenol and m-cresol also maintains the stability of the hexamer form which makes non-human insulin effective.
@Nnora The faster acting insulins (Apidra, Humalog and NovoRapid) are all Monomeric.
You are aware I hope that your original link was to something produced by Novo Nordisk in their development of Novorapid? And that the monomer insulin it refers to is the insulin analogues you were not impressed with where the links between the dimers and hexamers have been replaced with Amino Acids using recombinant DNA? The tricky bit with insulin in general is that its structure dictates that it forms dimers and hexamers and keeping it out of that form is not something that has yet been achieved?Hi, thank you for your reply. According to:
Setter SM, et al. Ann Pharmacother. 2000.
Insulin aspart: a new rapid-acting insulin analog
"Insulin aspart exists as hexamers that rapidly dissociate into monomers and dimers on subcutaneous injection."
The above mentioned, NovoRapid and other are so-called rapid-acting insulin analogs. In the presence of phenolic group, and because the natural tendency to form hexamers, they stay active during 3-5 hours after the injection.
I share my thoughts openly and criticize what I think is wrong. Diabetes, with or without me is a nation of nearly 300 mil. people, but without any government and institutions. Nation of such a size could afford for a proper research, to find a way to improve the quality of life?
Respect to all the people here with a positive attitude; my experience with diabetes is different...
Actually it is a bit more complicated rather than simple. Phenolic preservatives are included in insulin formulation to keep bacteria from growing in the vial and to kill any bacteria that you might inject through the skin. To have "bacterial efficacy" means that you will kill all of the common skin bacteria that you might get on your needle before you inject. Sadly there are very few anti-bacterial compounds that are both safe for insulin (meaning that it won't cause the insulin to either clump together or denature to an ineffective form) and safe for human tissue. Injection site or infusion site infections can be very nasty and hard to treat.
As for monomeric insulin, it has been tried and the time to peak for a pure monomeric insulin such as described by Jens Brange show that insulin concentration is more important than state of aggregation for time to peak studies. It is true that the current fast insulins (lispro, aspart and apidra) are not really monomeric but the fact that phenolic preservatives help stabilize them in the vial is completely fortuitous. From a study by Kang and colleagues
"The absorption rate of insulin aspart is not statistically significantly different from a purely monomeric analogue such as AspB9, GluB27 [96]. To get to faster time to peak i.e. to help the possibility of a true AP we will need to figure out how to better put insulin into people. Putting insulin into the peritoneum is indeed much faster but making implantable pumps work well is a big job.
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