Working towards a day without Type 1 Diabetes

You have been feeling very thirsty, and even though you are eating enough, you feel quite hungry. You are losing weight. The visits to the toilet, to urinate, more and more often. You feel tired, sometimes you even experience blurry vision. You have wounds that take long to heal. This is all unusual, and you decide that it is time to go to the doctor. He tells you that you have high sugar levels in your urine, and the diagnosis is quick: you have type 1 diabetes mellitus.

In ancient Greek, diabetes (diabainein) means “pass-through” – referring to the frequent urination –, and mellitus, “sweetened with honey” – referring to the sugar found in this urine. The first known mention of symptoms associated with this conditions is dated from 1552 B.C. At the same time, ancient healers observed that ants seemed to be attracted to people’s urine with this condition. It does have sugar as the core cause, but being diagnosed with type 1 diabetes has nothing to do with sweetness.

The sugar I so much talk about has a fancier name: glucose. Glucose comes from the Greek “sweet,” and it is a type of sugar you get from all types of foods you eat. Your body uses it as fuel to generate energy. When glucose travels through your bloodstream, ready to enter your cells, we called it blood glucose or blood sugar. Many cells can also use fat or protein as an energy source. But others, such as the brain and the red blood cells, can “only” use glucose. Glucose metabolism is a complex topic, and we will talk about it in another post!

Type 1 diabetes is an autoimmune disease that results in the destruction of one specific cell type, the insulin-producing cells, or beta-cells. They are part of a structure in our pancreas called islets of Langerhans. The hormone insulin, produced by these cells only, is a critical hormone that has the primary function of regulating our blood sugar levels. This must be kept in a very narrow range to ensure the body’s energy balance and, therefore, survival.

Type 1 diabetes, unlike type 2 diabetes which tends to be a lifestyle disease (not always, but it tends to be more of a lifestyle-related condition), comes without warning; it can occur in children or adults and it is a chronic (life-long) condition. A century ago, a patient diagnosed with type 1 diabetes at age 10 would live up to 13 years old. If diagnosed at age 30, up to 36 years-old. That is an incredibly low life expectancy, and I do not think that I need to elaborate on quality of life: terrible.

Everything changed in 1921 when Dr. Frederick Banting, Charles Best, and John Macleod announced that they could isolate insulin from the pancreas of a dog. To prove its efficacy, the scientist used insulin to treat Marjorie, a lovely female dog. Marjorie was the first being with diabetes that ever received insulin. Her treatment showed that this was a way to control blood sugar levels. This discovery not only led the scientists to receive a Nobel Prize in 1923, but it also quickly expanded insulin as a therapy for patients with type 1 diabetes.

Type 1 diabetes went from a life sentence disease to a chronic, treatable condition, with the establishment of insulin therapy as a treatment. The treatment also included the patients’ continuous management of blood sugar levels by measuring it and injecting the right amount of insulin units to keep its balance (what is a normal blood sugar level?). They also needed to keep track of their diet, the practice of physical activity, and the development of potential complications such as kidney, heart, and vascular problems. If the condition and symptoms per se were not enough, more salt to the wound was added when we found out that these complications may occur even with careful management of the disease.

According to the IDF (International Diabetes Federation), it is estimated that 98,200 children under 15 years develop T1D worldwide annually. This increases to 128,900 if we consider all patients under 20 years. There are an estimated 600,900 children under 15 years living with type 1 diabetes worldwide, with this figure almost doubling to 1,110,100 for under 20 years. Most people with type 1 diabetes die from the secondary complications such as heart or kidney disease.

Beyond type 1 is a nonprofit organization that supports global efforts and programs working to educate, advocate and cure type 1 diabetes. You can check some very interesting insights regarding type 1 diabetes statistics (and much more!) on their website. A super recent report about the topic is also very much recommended, as well as this one.

That was all 100 years ago, but even nowadays we have not really changed the way we treat type 1 diabetes. We do basically the same thing: we measure, we inject, we track. What has changed is that we now offer patients better ways to measure their blood sugar levels, better insulin compositions, and better methods to administer the insulin. But we are still doing basically the same thing. Today, men with type 1 diabetes have an average life expectancy of 66 years old and women, 68. This is still, on average, more than a decade less than people without type 1 diabetes.

Patients and caretakers still define the condition as a fatal disease, because it basically requires minute-to-minute regulation, a condition that makes you “spend your life not dying.” Patients have been waiting for a cure. Technology and science can be the combination to tackle the issue, and fields such as regenerative medicine and tissue engineering have been making important steps in this area.

How could we deliver more?

The main problem with type 1 diabetes is the autoimmune destruction of the beta-cells. This the first set of domino pieces to fall. Perhaps we could replace them, right?

In the year 2000, 80 years after the insulin discovery, someone replied to this inquiry. A brilliant Canadian scientist (Dr. James Shapiro) and his team showed the world that pancreatic islet transplantation was a feasible way to treat patients with type 1 diabetes. Upon isolation of islets from human cadavers, the research group could infuse them into the patients’ livers. There, the islets took up residence and started producing insulin. These patients (most of them) were insulin-independent for 5 years or a little bit longer, i.e., transitionally functionally cured.

Of course, there is a but. Islet transplantation using the liver as an infusion site has limitations. This includes 1) immune system reactions towards the new islets, 2) the non-native pancreatic environment that these cells encounter (the whole liver structure is quite different from the pancreas) and 3) the lack of appropriate blood supply for blood sugar levels’ sensing and oxygenation. Moreover, it also includes the shortage of cells (shortage of islets donors) and the price. A healthy human pancreas can contain 4 to 15 million islets, transplantation does not replenish all of them, and from 2 up to 4 donors are required to treat each recipient. Moreover, a report published in 2016 that analyzed its cost-effectiveness concluded that, although providing substantial improvements in health outcomes over conventional insulin therapy, islet transplantation is much more costly and not cost-effective.

The ambitious goal of very motivated scientists (including me!) is to overcome these limitations. We aim to develop a treatment that is closest to a cure and to make it available for the largest number of patients possible. The path includes not only scientists but also funding institutions and volunteers.

To tackle the issue “supply”, emerging technology can come to the rescue: the use of mesenchymal stem cells. These cells have a unique capacity to transform into any cell type in the body. They are considered immortal: the cells do not age, and they proliferate indefinitely.

What we (scientists) have been doing with these cells? We investigate ways to transform these cells into beta-cells to develop artificial methods to drive this transformation. We are also studying ways to safely explore their potential as supportive bodies to, for example, transplanted islets. Evidence show that mesenchymal stem cells can positively impact islet transplantation outcomes in animal studies.

There are many different types of stem cells. They can be isolated from different places in our bodies and are formed at different moments during our lives. You can check a great overview of the different types of stem cells here.

Suppose an appropriate environment is present to induce this transformation. In that case, the cells will further mature to produce insulin and other native pancreatic factors, correcting the disease. That may sound relatively straight-forward, but it takes a lot of work and investments. Some research groups have been making important steps towards it.

Having the cells is crucial, of course. However, it is only half of the challenge. We also need to develop ways to conveniently, efficiently, and safely administer these cells to the patient. For that, different strategies to build up what we call scaffolds, structures used to support the cells, are used. Made of polymers compatible with the human body, both man-made (such as the one I work with!) or natural (such as alginate, one of the most common polymers used to encapsulate islets), they show a lot of potential as new houses for transplanted islets. Injectable scaffolds, with more of a gel structure, have also gained some attention.

You can imagine that, like any other house, the material to build up its foundation is critical and all infrastructure and the neighborhood too. Where should we implant this device? The optimal site would be somewhere we can easily check or remove if it is needed. We would also be interested in a place where we can reach through a minimally invasive procedure, correct? Under the skin sounds like a good plan. Research on all of these topics is advancing fast.

That is all we want: a functional cure or, at least, a long-term functional treatment for all patients with type 1 diabetes. Instead of the multiple daily insulin injections, patients could be soon receiving a dose of pancreatic islets derived from stem cells within a device placed under the skin that could last for many years.  

“Turning type 1 into type none”. This is the JDRF, a non-profit worldwide known organization that funds type 1 diabetes research since 1970, motto. It summarizes their purpose and the one of all scientists and volunteers involved in finding a cure for type 1 diabetes.

Disclaimer: as the JDRF and Beyond type 1, other institutions fund and advocate for type 1 diabetes research. Particularly for scientists, for example, we have the the(sugar)science that aims to connect all of us working with type 1 diabetes. This post was not sponsored by none of these institutions, but all of these institutions receive donations that help them to continue to support our research. Please, inform yourself and donate.