By A Sweet Life
Karmel Allison | August 05, 2010
As a child with diabetes, one of the most frightening reminders of the danger of the disease was the emergency glucagon kit. Not only was it a symbol of the terrifying risk of severe hypoglycemia, it also had a giant needle. And as I look at the kit today, which I found after digging through some drawers, I have to agree with my childhood self; that’s one big needle!
Glucagon kits are part of the emergency arsenal for diabetics; Novo Nordisk and Eli Lilly each manufacture the kits, which come in bright red or orange cases and contain a disposable syringe pre-filled with liquid and a vial with 1 milligram of glucagon powder. The glucagon powder has the same chemical formulation as human glucagon, but has been preserved through lyophilization (freeze-drying).
Glucagon kits are not designed for quotidian lows, but for severe hypoglycemic incidents, in which a diabetic’s blood sugar gets so low that she becomes unconscious or has a seizure. In the event of severe hypoglycemia, a friend, family member, or emergency responder would remove the syringe and glucagon vial from the case. The responder would then remove the cap from the needle, remove the cap from the vial, and inject the liquid contained in the syringe into the glucagon vial. The liquid and freeze-dried glucagon would have to be mixed within the vial and subsequently drawn back up into the syringe. Finally, the responder would inject the newly mixed solution into the diabetic’s leg or abdomen.
Why is the procedure so complex, and the needle so threatening? Glucagon, like insulin, is an unstable protein when dissolved in solution. At a moment’s notice, glucagon forms amyloid fibrils, or tightly woven chains of proteins made up of the individual glucagon peptides. And, as soon as glucagon begins to fibrilize, it becomes useless when injected, as the glucagon cannot be absorbed and used in the body.
This amyloid fibril formation can happen very quickly, and within a few days, glucagon in solution becomes noticeably viscous . Clearly, this would be a problem for anything designed to be used in emergencies; can you imagine having to replace your glucagon kit every week, or, pulling out a glucagon kit from your purse in an emergency and discovering that after only a few days of jostling around it had become cloudy and useless?
Without the invention of a chemical formulation of glucagon that is more stable, the available alternative is to freeze-dry the glucagon peptide. This prevents the protein molecules from changing form, and therefore allows glucagon to be kept on hand and stored at room temperature for about two years . So despite the complexity of assembling the glucagon kit in an emergency, the user and the patient can at least be confident that the solution will still be potent and effective at the moment it is needed.
As to the length of the needle, it is important to know that glucagon can be injected intravenously, intramuscularly, or subcutaneously, however, the three types of injection do not all achieve the same results. Intravenous injections work the most quickly, but require an IV and trained personnel to administer. Having to wait for emergency medical teams before using glucagon could delay the treatment, and would defeat the purpose of having a kit for immediate response from home.
Friends and family would be able to administer either subcutaneous or intramuscular injections, and of the two, intramuscular injections work more rapidly, achieving maximum effect in less than 30 minutes, while subcutaneous injections can take 30 – 45 minutes [2,3]. The length of the needle, then, serves to ensure that any untrained person is able to inject the diabetic patient with glucagon, and to get far enough into the patient’s tissue that the glucagon begins to take effect within a short period of time.
Despite these complexities, it is surprising that there is not a more user-friendly glucagon kit available. It is crucial for the unconscious diabetic that the response be immediate and effective, but the difficulties inherent in the glucagon kit make such a response harder for untrained friends and family. The more steps required before the glucagon is circulating in the patient’s blood stream, the more opportunity there is for error and failure.
So why isn’t there something better, easier, faster, and simpler? Well, fortunately, there may be soon. Enject, Inc., a Washington-based biotech start-up, has announced that they’ve completed prototypes of – and are moving forward with – a novel way to inject glucagon in emergencies: the GlucaPen.
The GlucaPen is designed to be the entire glucagon kit, rolled into a single pen-needle. The pen cartridge contains both the freeze-dried glucagon powder and the liquid for mixing. In an emergency, users would rotate the base of the pen to engage an integration process within the pen that automatically mixes the two elements. Then the user need only uncap the needle, and inject the solution into the diabetic patient.
This simplified injection process seems a good way to improve the success rates of emergency treatment for hypoglycemia, but there are many open questions, especially given the fact that the product is still in an early stage of development. I was happy to be able to ask Dick Rylander, CEO of Enject, some of my questions directly, and to get some promising answers:
Why is glucagon necessary in the treatment of diabetics?
It’s necessary if and when their blood sugar drops low enough, fast enough, that they lose consciousness and can slip into a diabetic coma, have seizures, suffer brain damage or die. This degree of hypoglycemia is defined as severe because it requires the assistance of another. Because the patient is unconscious, oral sugar/glucose is not an option. The injected glucagon signals the liver to release its stored glucose into the blood thereby returning the patient to consciousness where additional measures can be taken.
What is wrong with current glucagon kit systems?
They are cumbersome, require numerous steps (12-15 depending on who’s counting), are prone to damaged needles, risk of secondary needle sticks, loss of liquid due to handling, dropping, etc. Caregivers are under stress, agitated, prone to making mistakes, and frequently fear seeing the needle and the act of giving the injection (despite the fact that the patient is unconscious, and assuming they make no errors).
How is the GlucaPen™ better than the current kits?
Read how: http://asweetlife.org/feature/glucagon-kits-g...
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