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INHALED INSULIN:    

Alternative Insulin Delivery Systems:
Ever since insulin was first identified as the key to restoring normal glucose levels in people with diabetes, doctors and patients have been hoping for an alternative to insulin injections. Don't get us wrong, injecting insulin works pretty well. Many people have been able to lead relatively normal lives because of it. The new technology has pretty advanced syringe and needle technology and insulin pens and pumps have made getting insulin into the body even easier. Even so, the quest continues to find an alternative way of administering insulin.

Scientists have been working on a number of new advances in insulin administration.

Transdermal (through the skin):
TransdermalOur skin is a remarkable organ. It's very good at letting almost nothing in, and letting just a few selected things out. Patches to help people quit smoking have made it seem almost easy to deliver a drug through the skin. In fact, nicotine is a small molecule that is readily absorbed into the skin. It only takes a tiny amount to have an effect on the body. Insulin on the other hand, is far too large to get through the skin without a lot of help. Trying to change that is tough.

Scientists have been working on patches using electrical currents, ultrasound waves, and chemicals to help transport insulin through the skin. Although some companies are hoping to develop products that could provide boluses of insulin through the skin for mealtime, any success for transdermal delivery is likely to come with basal delivery of relatively small amounts over time. Either way, we have a while to wait before insulin patches might be available in pharmacies.

Buccal:
BuccalBuccal insulin is similar to inhaled insulin in some ways. Buccal or delivery into the mouth, involves a device that delivers a spray of insulin like what you'd get out of a can of spray paint. Instead of going into the lungs, the insulin is absorbed in the lining at the back of the mouth and throat. The good part is that it avoids any problems from putting large amounts of insulin in the lungs. The problem is that even more of the insulin gets wasted.
Other than that, research shows that buccal insulin works about as well as inhaled insulin.

Oral:
oralYou probably already know that insulin taken as a pill is quickly broken down in the stomach, just like the food you eat. That makes it useless for lowering blood glucose levels.
So insulin can't be taken by itself in a pill form. Some scientists are trying to "package" insulin using special coatings, or by altering the insulin structure to get it through the stomach. Like inhaled insulin and insulin sprays, it's likely that a lot of the insulin will be wasted before it gets where it's going. It would probably also take a long time to start working after you swallowed the pill. Not much research has been done on insulin pills so far.

Inhaled insulin:
inhaled insulinFor over 80 years exogenous insulin has been given by injection. The injection devices have improved-disposable syringes and pen injection devices are more convenient and less traumatic than the boil to sterilize, use until too blunt devices of yesteryear-but patients and healthcare professionals remain uneasy about the concept of injections.
Yet the evidence based drive for increasingly tight glycemic control means that more patients should be offered more injections Inhaled insulin is probably what you've been hearing the most about lately.
Several products are being created in laboratories and have shown success at controlling blood glucose levels. Some of these are in phase 3 clinical trials (the final phase of testing before you can submit a device for FDA approval), but only one has been approved for use. And that one is only approved for adults.
In clinical trials, the inhaled insulin, managed blood glucose levels as well as injected fast-acting insulin. Inhaled insulin does not replace longer-acting insulin, so those would still need to be injected.
Insulin can be effective given by inhalation. This was first shown in 1971, although the early work was not pursued, and it was not until 2000 that the modern era of inhaled insulin began. The bioavailability is 10-15% and the dose equivalent about three times that of injected insulin.
 
The pharmacodynamic of inhaled insulin offer an action profile with a fast onset (although slightly longer run-off) closely related to that of rapid acting insulin analogues given subcutaneously, which in studies have shown better postprandial glucose control and less tendency to nocturnal hypoglycemia.

In patients with type 2 diabetes, adding inhaled insulin to oral hypoglycemic regimens does improve control more than doing nothing. This is important-apart from patients' comfort-an expensive new insulin could have huge potential advantage if it encouraged adherence and resulted in more patients with diabetes achieving treatment targets. Sadly, the published data on patients' satisfaction, superficially encouraging, are difficult to interpret, as invariably patients have been comparing a new treatment with an old one. When a specially designed questionnaire was used, treatment satisfaction improved significantly in patients with type 1 and type 2 diabetes on taking part in the trials, irrespective of whether the mealtime insulin they took were injected or inhaled.

Although the improvement was greater with inhaled insulin, the injected insulin treatment was identical to pre-trial treatment limiting the potential for improvement. Notably, improvement in treatment satisfaction correlated with improved glycemic control.

Might greater satisfaction have been obtained with injected regimens if these had been optimized effectively? Were the studies just too short to show the biomedical gains one might anticipate from a treatment expressly designed to support compliance, or do the problems of insulin therapy extend beyond a dislike of needles?

Inhaled insulin has potential problems:
The new inhaled insulin does not come without limitations:

Patient have to inhale a lot of insulin to get the amount your body needs. This is because only a small percentage of the inhaled insulin actually reaches the bloodstream and lowers blood glucose. So, a lot of it is "wasted." Because of that, the cost of inhaled insulin is fairly high - the waste must be paid for.

There are also questions about the safety of delivering insulin to the lungs. After all, that's what you're doing when you inhale the insulin. You send it straight to the lungs. Many scientists think the lungs are a great place to deliver a drug because of the large surface area and ready absorption. There have been concerns about possible long term effects of insulin on lung structure and function, although current published trials report no deleterious effects over the short-term. The fact remains:" that is not what lungs were designed to do".

Although inhaling insulin has proven safe in short-term studies, the long-term safety remains a question.
 
The bioavailability is affected by asthma (decreased) and smoking (increased). If patients really dislike injections so much inhaled insulin might make its biggest impact on complications of diabetes if it were to be available only to proved non-smokers.

Formation of anti-insulin antibodies is higher with inhaled insulin, and although this is dismissed as not affecting insulin requirement over time, older diabetologists will remember the drive to reduce insulin antibody formation, with the fears that antibodies delay and render unpredictable insulin absorption and even that antibody-antigen complexes may increase risk of micro-vascular disease.

Few people like injections and some are so terrified they refuse appropriate treatment for diabetes. Many are discouraged by previous experience of injections-none of whom will have used current insulin injection devices-and by healthcare professionals using injection therapy as a threat in a (vain) attempt to improve adherence.
For patients with established type 1 diabetes lack of freedom to eat or not eat and the demand for (painful) blood glucose testing may be much more of an issue than injection therapy itself.
In one study only 14% of injections were missed because they were injections. In this group healthcare providers will need more robust evidence of patients' preference than is currently available. Where inhaled insulin could really have an impact (in the developed world) will be if healthcare professionals and patients start to use insulin much earlier and more aggressively in type 2 diabetes, affecting the progression of diabetic complications.
Meanwhile, all patients are waiting to see if the new inhalations are safe. If they are, and if they are cheap enough, at least one barricade to better diabetes treatment may fall.

Is Inhaled Insulin as Good as Insulin Injection?
Because people with type 1 diabetes can't make insulin and need to take it, they usually need more than one type of manufactured insulin to control their diabetes.

The different types of insulin work at different rates and for different amounts of time. Three commonly used types of insulin are "short-acting," "intermediate-acting," and "long-acting."
A-"Short-acting" insulin works much faster than intermediate- or long-acting insulin, and it is used around mealtime. Short-acting insulin should be taken about 30-45 minutes before eating, and it peaks at about 2-3 hours. It can keep working for as long as 6 hours.

B-"Intermediate-acting" insulin is insulin mixed with a substance that makes the body absorb the insulin more slowly. It takes longer to start to work, and it stays in your body for a longer time. NPH is a type of intermediate-acting insulin that usually begins to work about 2-4 hours after injected. It peaks 4-10 hours after injection, and it keeps working for 10-16 hours.

C-"Long-acting" insulin starts to work in 6-10 hours and can stay in the body for 20 hours or more. It has a peak, but its top speed looks a lot like its normal speed. Like intermediate-acting insulin, it is usually taken in the morning or before bed.
People with type 1 diabetes can often keep their glucose levels under control by taking shots of intermediate-acting or long-acting insulin in the morning or before bed, as well as taking shots of short-acting insulin before meals. However, even though this type of routine has been shown to work for people with type 1 diabetes, many patients often stray from this routine, probably because of the burden of taking so many shots.

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