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Issue 23 Science Shoutout

The Need, the Needle or the Needless?

🕒 7 min

Among the deadliest diseases worldwide is diabetes. Despite the exhausting public health campaigns designed to raise awareness of the fatal complications that develop within one year of untreated diabetes, one in ten people around the world suffer from it. The “hidden” sugar is added to virtually every soda, not to mention the abundance of sweets in our everyday diet. Kids as young as two years old are exposed to such high sugar food in every social encounter and there’s no way to protect them from it, even if we want to. The fact that so many of us have become accustomed to the taste of sugar is scary if not alarming already and is starting to cost us not only money, but lives. Lives of so many lost over a little 6 carbon ring molecule.

However, not all of it is our fault. According to their literature, even the ancient Greeks and Egyptians noticed a sweet taste of their urine. The term diabetes was first used over 2000 years ago and the first medical texts describing it appear in 1425 in Britain. The diabetes mellitus they talked about is, as we call it today, of type 1. The onset of the type 1 diabetes is usually already in childhood, due to genetics and congenital pancreatic insufficiency. With the modern world came the type 2 – caused by the overconsumption of sugar and carbohydrates, usually starting later in the adult life. The difference is – in type 1 diabetes pancreatic cells produce very little or no insulin due to the organ dysfunction, whereas in type 2 it’s either all other cells in our body stop recognizing the insulin our pancreas produces and become blind to it in a way, or the pancreas stops producing the insulin because of the exhaustion caused by constant high blood sugar levels.

The needle

While there are weekly injections and oral medicine available for those suffering from type 2, the only clinically tested and approved treatment for type 1 is insulin therapy. There are 4 types of artificial insulin that can be administered. The short-acting insulin starts working around 30 minutes after injection and the effects last for about 4-6 hours. The rapid-acting starts working within 15 minutes after injection and is usually taken just before the meal. Intermediate-acting starts working within 1-3 hours and lasts for 12-24 hours. Long-acting and ultra-long-acting insulin is released slowly from the albumin and its’ effects last for up to 40 hours. There are different injection regimes that the patients need to follow, and different insulin types can be combined to achieve the best glucose level in every patient. For example, some people take only one injection of a long-acting insulin in the morning and then take a rapid-acting one before every meal. Others might take an intermediate-acting in the morning and a long-acting in the evening. Two things that are the same regardless of the regime: the patients need to inject themselves at least once daily and they are advised to check for the glucose levels every day. Both involve needles and blood. Imagine you must prick yourself with a needle 2-6 times a day.

It has been reported that the biggest reasons behind low long-term adherence to insulin therapy are the fear of needles or blood and the unpleasant feeling of needle injection. Because insulin is a growth factor, its’ constant administration under the same part of the skin promotes cell replication and growth of connective or musculoskeletal tissues. The result is thickened skin that can sometimes feel uncomfortable. In order to postpone this process (which is nevertheless inevitable), we advise patients to change the injection position and use the same spot only every 2-3 days. Even with all those attempts to make the insulin therapy more bearable, many still boycott it. If one fails to adhere to insulin therapy, blood sugar levels remain high and eventually cause micro- and macrovascular problems including kidney failure, blindness, limb amputation, high blood pressure, heart attack, stroke and ultimately, premature death.

The needless

There are several reasons why we decided to look for other options, with the money being the main one, as usual. Complications caused by untreated diabetes cost the public health far more then the production of potential medicine alternative to insulin. In countries where health care is completely privatized, the biggest push came from the patients who need to pay unjustifiably high prices of insulin. Therefore, the tables started shifting and we might soon have several options for diabetes treatment that involve less or no needles at all.

We first thought that the only option to persuade people to take their insulin is to make pills. Orally administered medicine has far bigger adherence rates, it is easier, quicker, less painful, and simpler. Unfortunately, making an insulin pill is a lot harder than it might seem. Insulin is a hormone, a protein – big molecule that gets torn to pieces in our stomach before it even reaches its’ transporters in the duodenum. Naturally, the first thought was to try and make a formulation that would protect insulin molecules from a strong gastric acid. Usually, this problem is easily solved by gastro-resistant tablets that are coated with film insoluble in gastric acid.

The new oral insulin

Last year researchers at NYU Abu Dhabi developed a new oral system that consists of ultrathin nanosheets with hexagonal pores. Insulin molecules are stored between the stacked layers of nanosheets. This technology not only protects the insulin from the digestive tract and allows it to reach the bloodstream, but also regulates the rate at which it is released. Once there’s enough glucose molecules in the blood, they fill the system’s pores and displace the insulin. In that way, the level of glucose determines how much insulin will be released, lowering the risk of hypoglycemia. Although this system is still in testing and the only available results are those from the animal tests, it looks promising.

Earlier this month, researchers at the University of British Columbia offered a slightly different solution. Instead of swallowing the insulin pill, why don’t we dissolve it in our mouth? The absorption via buccal mucosa is one of the fastest ways of administration and is used for some emergency medicine like trinitrate for the acute treatment of a heart attack or angina pectoris attack, as well as in some psychiatric drugs like olanzapine for psychotic episodes in schizophrenia. In the tests they performed in rodents, they found that nearly 100% of the insulin administered buccally reached the rodents’ livers. This means virtually no wasted insulin per pill and therefore lower price.

A different kind of insulin injection

Although the idea of orally administered insulin is appealing, there is still the problem of transporter desensitization. Basically, with time, the transporters that move the insulin through the intestine wall can become less sensitive and need higher concentrations of insulin in order to start moving it towards the blood stream. Because this is a hard problem to tackle, we never really abandoned the idea of subcellular administration of insulin.

The UT Southwestern Medical Center announced last year that a weekly insulin treatment for type 2 diabetes was proven as effective as daily insulin in two clinical trials. Their synthetic insulin remains bound to the albumin in the bloodstream for up to seven days and is being released in a slow and steady manner, avoiding the hypoglycemia. Their product entered third phase of clinical trial last year and is being tested for both type 1 and type 2 diabetes.

Surprisingly, once we move away from the insulin, the magic starts. As it turns out, we do have the cure for type 1 diabetes – transplantation of pancreatic islet cells or the entire pancreas from a donor with healthy pancreas – a method that has been proven effective and irreversible, but also far from practical. There’re only so many donors of a healthy pancreas, and far more people in need of one. Where transplantation medicine fails, the stem cells come to rescue. In December last year, a single patient with type 1 diabetes was infused with the pancreatic islet cells that were grown in the laboratory from the embryotic stem cells. Once the cells entered his bloodstream, they started producing insulin and, even more importantly, remained in the system by multiplying. This one time treatment could save hundreds of thousands of lives once it’s proven effective and safe in bigger clinical trials. Hopefully, soon enough.

The Romans always turn out to be right

The journey from needles to needless is far more complicated than just a little snake-like letter. While many can’t be blamed for the diseases they inherited or simply developed by bed luck, the rest of us can. Why is it so hard for so many of us to take actions for our health and respect the only body we’ve got? So often do we perceive the colorful pills as plan B and rely on it so much that plan A never stands a chance. Whatever happened to “An apple a day keeps the doctor away” and “Mens sana in corpore sano”.

By Đesika Kolarić

Đesika is a pharmacist with an exceptional love for science. Apart from clinical pharmacy, her biggest love is computational biology, which she's currently pursuing through a predoctoral training at Medical university Graz. She loves long walks accompanied by her dog and a good beer.

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