Although diabetes mellitus, or, more commonly, just ‘diabetes’, is a condition (or, technically, a group of conditions) affecting over 382 million people worldwide, it is a condition which many people don’t know much about. In this article, I will explore type 1 diabetes mellitus (T1DM) as well as a potential stem cell treatment for it.
So what exactly is T1DM? Put simply, it is a metabolic disorder leading to chronic hyperglycaemia (high blood glucose levels for prolonged periods). Unlike type 2 diabetes, it results from the autoimmune destruction of the beta cells of the islets of the Langerhans in the pancreas. Beta cells are the cells which produce insulin (the hormone which regulates the uptake of glucose into cells) – this means that people with T1DM are insulin-deficient. It doesn’t take a genius to work out that without insulin, glucose uptake into cells is going to be affected.
T1DM usually develops in children, although the exact cause isn’t known. The most common symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). There is no cure – however, if left untreated, T1DM can lead to some serious chronic complications.
The main 3 chronic complications arise from microangiopathy (damage to small blood vessels) due to high blood glucose concentrations. Diabetic retinopathy, which is damage to the retina, can cause macular edema (swelling of the macula) and, ultimately, blindness. This is actually the leading cause of blindness in non-elderly adults. Damage to the kidney, known as diabetic nephropathy, can lead to chronic renal failure, eventually requiring dialysis. Finally, diabetic neuropathy, the most common complication, is damage to nerves in the body, affecting movement, touch, and the autonomic nervous system (the nerves serving vital organs such as the heart, lungs and gastrointestinal system to name a few). This is just a selection of complications; if you have diabetes, the risk of cardiovascular disease is doubled.
To minimise the risk of such complications, people with T1DM undergo a strict treatment regime to manage their condition. First and foremost, at-least-daily insulin injections are used with the goal of lowering the blood glucose level to the normal level, avoiding the aforementioned complications. Additionally, it is frequently recommended that patients suffering from diabetes lead a healthy lifestyle (ie maintaining a healthy weight and exercising frequently).
Although this treatment is usually successful, research is being undertaken into the use of human embryonic stem cells (hESCs) to treat T1DM. Previous attempts didn’t lead to much – researchers used human pluripotent stem cells (hPSCs) to produce beta cells. In spite of that, they lacked the characteristics of bona fide beta cells (normal beta cells found in non-diabetics). However, researchers at Harvard University have had a breakthrough – they have managed to develop a technique to generate large quantities of glucose-responsive beta cells from hPSCs in vitro. These are very similar to mature beta cells – they have the flux Ca2+ response (the mechanism used to secrete insulin), and they can package insulin into granules for secretion, just like in humans. When exposed to glucose in vitro, they secreted insulin in quantities comparable to adult beta cells. Additionally, when tested in mice, human insulin was secreted into the serum, improving the hyperglycaemia in the mice. Currently, 40 patients are undergoing a clinical trial to test this potential treatment – hopefully it will be successful!
As ever with embryonic stem cells, there are certain ethical issues which need to be considered. Previously, unused embryos from IVF were donated for research. However, embryos are now being produced for research purposes – these can’t be implanted into the womb anyway. Some organisations, such as the Catholic Church, see the use of embryos as murder since life starts at conception. However, such ethical issues need to be balanced against the benefits of the research and the treatment – in this case, millions of people around will have something to gain from this research. There may also be alternatives, for example, induced pluripotent stem cells (pluripotent stem cell derived from adult somatic cells), however this phenomenon deserves it’s own article!
Diabetes affects many people around the world and has the potential to cause serious complications. However, with the right research, hopefully a new, long-term treatment for diabetes can be developed.