Diabetes is a common condition. It develops when the amount of glucose in the blood is too high because the body can’t use it properly. Diabetes can lead to serious conditions such as stroke, circulation problems, and damage to the kidneys and eyes.
Medically known as Diabetes Mellitus, symptoms include thirst, a frequent need to pass urine (especially at night), extreme tiredness, weight loss, genital itching or regular episodes of thrush, and blurred vision. There are three main types: 1, 2 and gestational. If diagnosed early enough, most people with diabetes can handle their condition by a combination of lifestyle and medical interventions. But there is no doubt medical advances need to be made.
What is diabetes?
Diabetes occurs because some people do not make, or cannot respond to, their natural hormone insulin. Hormones help us control the way our bodies work. Insulin’s specific job is to regulate the body’s use of glucose, our main fuel source. We get glucose, a form of sugar, from the food we eat. It is also made by the liver
In Type 1 diabetes very little or no insulin is made and lifestyle changes cannot alter the condition. Patients need to monitor their blood glucose levels and administer insulin injections several times daily. This type of diabetes generally develops in younger people, and affects both sexes equally.
Type 1 diabetes develops when cells that make insulin have been destroyed by the body’s own immune system. There is a genetic risk to diabetes – it tends to run in families. The environmental factors that might trigger such a destructive process, possibly viral, are not well understood.
Type 2 diabetes
In type 2 diabetes, either the body makes some, but not enough, insulin or it cannot use the insulin it does make. Patients may not need insulin injections.
Type 2 diabetes is associated with lifestyle factors such as increased weight and a sedentary lifestyle. It used to be called ‘late onset’ because it usually appears in middle-aged or elderly people. It’s also been wrongly described as ‘mild’ diabetes. There is no such thing. All diabetes should be taken very seriously.
At least three quarters of the estimated 150 million diabetics world-wide have Type 2. It is increasing alarmingly. The World Health Organisation expects numbers to double to over 300 million by 2025.
Pregnancy affects blood glucose levels in all women and, as its name suggests, gestational diabetes is linked to pregnancy. If diagnosis is made during the first three months, then the expectant mother was most probably diabetic already. However, when the diabetes starts after three months, it is thought to be other hormones from the placenta interfering with insulin action.
Diabetes in animals
Insulin, the hormone at the heart of diabetes.
Roughly one in every 500 dogs or cats has diabetes. Onset is usually in older animals, typically over seven for dogs and over five for cats. Burmese cats are known to be genetically predisposed to diabetes. One in ten over eight years’ old will develop the disease. Guinea pigs and rabbits also contract the condition. Like humans, some diabetic animals can improve with insulin and a controlled diet. Others need medicines, the ones that were first developed for humans.
What happens when the body cannot control glucose production?
Our bodies digest sugar and starchy foods to make glucose. This glucose is released into the blood and stimulates the pancreas to make insulin. Insulin controls the amount of glucose in the blood by allowing it to move out of the blood into cells. Once inside cells, glucose is converted to energy, either to be used immediately or stored.
Insulin, the hormone at the heart of diabetes
People with diabetes do not have enough insulin or it does not work properly, so their ability to convert glucose into energy is impaired. The body recognises it lacks energy and stimulates the liver to make more feed-stock for energy – glucose. But the patient’s insulin problem means this extra glucose still cannot be converted. The next option for the body is break down its stores of protein to try and release yet more, but unfortunately still unusable, glucose. This is why untreated diabetics often feel tired and lose weight. The body gets rid of glucose in the urine, which explains the need to pass large amounts of urine and the extreme thirst from the dehydration that follows.
The impact of diabetes
Foot problems are among the many serious complications that can result from diabetes. Nerve sensations in a patient’s foot being tested.
People with diabetes are significantly more likely to develop serious health problems like heart disease, stroke, high blood pressure, circulation problems, nerve damage, and damage to the kidneys and eyes. Disease of their leg arteries greatly increases the risk of exercise pain, gangrene and amputation. Kidney damage, for example, may develop in about one-quarter of all people with the condition, and this can lead to kidney failure and the need for dialysis or kidney transplantation. Diabetes is the single most common cause of blindness in adults of working age. The risks are made even worse if the patient is overweight, smokes or is not physically active. According to one study, diabetes accounts for some 9 per cent of the annual NHS budget.
Thanks are due to Professor Frances Ashcroft (Oxford University), Professor Anthony Barnett (Birmingham Heartlands Hospital), Professor Don Chisholm (Garvan Institute) and Diabetes UK.
Diabetes – Current Treatment All diabetics can reduce the risk of complications by controlling blood glucose and blood pressure levels, healthy eating practices, maintaining physical activity, and by regular medicals.
First, people with diabetes need to eat a healthy diet that contains the right balance of foods. People with type 1 diabetes also need daily injections of insulin for the rest of their lives. If diet and regular physical activity does not control type 2 diabetes, there are several different sorts of tablets to help. Some, such as the sulphonylurea drugs and prandial glucose regulators, stimulate the pancreas to produce more insulin. Metformin helps to stop the liver making new glucose and also makes insulin more effective. Acarbose slows down the absorption of starchy foods and, therefore, the rise in glucose level after a meal. While the newest class, the thiazolidinediones, overcome resistance to insulin. More than one kind of medicine may be needed to control the amount of glucose in the blood, and, like people with type 1 diabetes, type 2 sufferers may eventually need insulin injections.
How did we get these treatments?
Without treatment, diabetes is a long-lasting, wasting disease that inevitably leads to death. That inevitability began to change in 1921 when insulin, and its ability to treat diabetes, was discovered. Insulin was found to lower blood glucose in a dog that had been given diabetes by removing its pancreas. Once the medical value of insulin had been established in the dog, attention turned to purifying it so it could be given safely to patients. Insulin has been used to treat diabetes ever since. For a long time, insulin was purified from cows and pigs killed for food. It was not until the 1980’s that human insulin, genetically engineered from bacteria or yeast, became available.
The first class of oral diabetes medicines was discovered, unexpectedly, at the time of the second world war. Several typhoid patients died who had been given a new antibiotic. The cause was found to be low levels of sugar in the blood. Studies in dogs showed that the antibiotic had decreased glucose levels. Though clearly fatal for some, this might, it was thought, be beneficial for people with diabetes.
The antibiotic was not suitable to become a diabetes medicine, so the search was on to find similar-acting chemicals. Candidate molecules were tested first in animals and then humans until, in 1956, a sulphonylurea usable against diabetes – tolbutamide – was identified. As understanding grew as to how sulphonylureas produce insulin and reduce blood sugar levels, more of them were developed.
The next advance came via the herb Goat’s Rue or French Lilac. This had been known for centuries to have natural benefits for diabetics but it is too toxic to make a satisfactory medicine. The active ingredient in Goat’s Rue – guanidine – was the inspiration for Metformin. Metformin became available for diabetics in the 1970s, it is often of particular value for obese patients. Driving the development of the thiazolidinedione class was the need to enhance the action of insulin for type 2 diabetics.
In addition to understanding how the body makes insulin normally and uses it to convert glucose into energy, there was research into how the disease itself strikes. A great deal of this work can be done with cells and tissues, but at some point researchers will need to have insights into how the part of the disease they are examining proceeds in a living creature.
Although insulin and today’s medicines make a huge difference to patients’ lives, blood glucose levels can still fall too far, causing ‘sugar lows’ (hypoglycaemia).
Symptoms including feeling shaky, sweating, tingling in the lips, going pale, heart pounding, confusion and irritability can result. If hypoglycaemia is not treated with a quick sugar ‘fix’ and a more substantial snack, it can lead to loss of consciousness. Therefore, ongoing research is looking both to understand how insulin operates normally and in disease and for better treatments for diabetes.
An ideal treatment for diabetes might be to provide new pancreas islets, (these are where the beta cells that make insulin are found). Some patients have already received cell transplants from donors. But there are two problems: not enough donors and patients need to receive immunosuppressive drugs for the rest of their lives.
Genetically engineering the patient’s beta cells and putting them back in the pancreas might offer an alternative. A different approach is to convert liver cells into pancreas cells. Another possibility is to use stem cells. These are the relatively non-specialist cells found, for example in bone marrow, that become specialised. There has been some success in making beta-like cells that produce insulin in response to glucose. We are a long way from using engineered cells in treatment. One vital aspect will be to understand how the pancreas, the insulin factory, develops.
It has been know for some 20 years now that the protein Ptf1a is involved in the development of the pancreas. By comparing normal mice and mice bred without this protein it has been found Ptf1a helps cells to decide what they will become. It is turned on very early in all the cells that will eventually form the pancreas and then switches off in those pancreas cells that will eventually go on to make hormones like insulin.
Perhaps Ptf1a could be used to turn stem cells into pancreas cells, which would form part of the cell transplant process for diabetics.
Other research is concentrating on new targets for medicines for example, what hinders the beta cells in the pancreas from releasing insulin? One culprit is an enzyme called DPP-IV which breaks down proteins that stimulate the release of insulin. Therefore, a medicine that inhibited DPP-IV might be able to treat diabetes in a new way. Finding chemicals that stop DPP-IV from working in the test tube is reasonably easy. But that does not mean in a patient they will be any good.
Medicines have to be swallowed or injected, they have to travel to their target, they have to avoid being turned into something toxic or into something that loses its effectiveness.