Diabetes

by Peter Lavelle

Diabetes occurs when something interferes with the action of the hormone insulin, which controls blood sugar levels. In Type 1 diabetes, the body does not make enough insulin. In Type 2, it doesn't work properly.

Background

"The life is disgusting and painful; thirst unquenchable; excessive drinking, which however is disproportionate to the large quantity of urine for more urine is passed; and one cannot stop them either from drinking or making water. Or if for a time they abstain from drinking, their mouth becomes parched and their body dry; the viscera seem as if scorched up; they are affected with nausea, restlessness, and a burning thirst; and at no distant term they expire."

No, this isn't a discarded verse from 'The Pub With No Beer'. It's a description of diabetes, written sometime in the second to third century AD. The author was Greek physician Areteus the Cappadocian: the disease was well known to the ancients, who named it after the Greek word for 'siphon' because those who had it seemed to urinate so often. They gave it the full name diabetes mellitus to distinguish it from diabetes insipidus, a superficially similar but much rarer disease.

Nearly two millennia later, we know a lot more about diabetes than Areteus did, and though we can't cure the disease any more than he could, we can treat it successfully.

Blood sugar levels

We know, for instance, that the unquenchable thirst (polydipsia) and the excessive urination (polyuria) are caused by too much glucose in the urine (which explains something that also puzzled the ancients – why insects were so fond of it). Excess glucose in the urine causes the kidney to excrete more water than usual, hence the thirst, and the body therefore becomes dehydrated.

We also know there is excess glucose in the blood, not just the urine. In other words, diabetes is really a disease in which the normal mechanisms for regulating sugar in the body are not working.

Normally, glucose levels in the blood are kept within a fairly narrow range – between 3.5 and 8 millimoles per litre. After a meal, as glucose is absorbed through the intestine and enters the bloodstream, it will rise to about 10 mmol/l. This triggers a release of the hormone insulin from the pancreas (where it is made), which in turn causes glucose to be taken up by the liver for storage, and by the cells foruse. Thus, glucose levels go back down to fasting levels, where they stay until the next meal.

If glucose levels go much above or below these baseline fasting levels – especially for long periods of time – a series of biological misadventures occur inside the body. Along with the loss of fluid, thirst and dehydration described by Areteus are many others. But before we can understand what they are and why they happen, we have to understand how sugar is used by the body, and why and how the body keeps glucose levels within these narrow limits.

Glucose metabolism

Glucose is as essential to life as water and oxygen. Cells use it as a source of energy to power a wide range of biochemical reactions.

In nature, glucose exists in a stored form, in carbohydrates like starches and sugars. The human body has to ingest carbohydrates, break them down to simple sugars like glucose, absorb these in the small intestine, then store them in the liver. From the liver, glucose is gradually released into the bloodstream, to be taken up as needed by cells throughout the body.

The whole process is controlled by hormones – in particular a hormone called insulin, which controls blood glucose levels via a classic feedback loop. If the levels of glucose rise higher than needed, insulin is released from the pancreas (where it is made) which puts glucose into storage in the liver. When glucose levels fall too low, less insulin is released from the pancreas, and glucose is more readily converted from storage in the liver back into the bloodstream (this takes place via another hormone called glucagon).

In diabetes, something happens to interfere with this mechanism. Insulin is either not made in sufficient quantities, or it is made in sufficient quantities but just doesn't work.

The distinction between these two mechanisms of failure of insulin function is important, because they lead to two very different types of diabetes. These two types are called, rather unimaginatively, Type 1 (or juvenile-onset) and Type 2 (mature-onset or adult-onset) diabetes

Type I diabetes

This is the rarer but more severe type of diabetes, accounting for about 10 per cent of new diabetic cases annually. It's called juvenile-onset diabetes because it usually comes on in childhood or adolescence, though it can strike at any age.

Type 1 diabetes develops when the insulin-producing cells in the pancreas have been destroyed, so they are no longer able to produce insulin. Why the pancreas is attacked in this way isn't understood, but it's thought to be an auto-immune disease, one of a group of diseases in which the body's own immune system attacks and destroys its own tissue – in this case, specifically the cells in the pancreas that manufacture insulin.

When this happens, insulin levels fall back to almost zero, and glucose reaches very high levels. The person suffers all the symptoms described by Areteus the Cappadocian: they urinate frequently and in large amounts, they become dehydrated and drink excessively, but their thirst is never quenched. They lose weight, because the sugar that normally would go into the cells is being lost, and in advanced cases, their body starts breaking down its own fats to fuel cell metabolism. A by-product of this breakdown of fats is the production of poisonous keto-acids, giving rise to an acetone smell to the breath. Coma and death rapidly follow.

This was the inevitable and tragic outcome of juvenile diabetes until 1921, when a Canadian surgeon, Dr Frederick G. Banting, and a medical student, Charles H. Best, injected a gravely ill 11-year-old diabetic boy in Toronto, Canada, with a blended extract of animal pancreas. The boy recovered, and with daily injections of this new wonder drug – insulin – lived into adulthood. Banting was awarded the Nobel Prize for Medicine and knighted. Ever since, ketoacidosis, coma and death from diabetes have become relatively infrequent events.

Type 2 diabetes

Type 2 diabetes is called mature-onset diabetes because it usually first appears in middle-aged or elderly people, although it is occurring with increasing frequency in younger people, including children.

In this type, the pancreas produces normal levels of insulin, but the body cells do not respond to the insulin. It happens slowly and insidiously, and a person can have diabetes for many years without knowing it. In Australia, it's been estimated that more than 900,000 people have Type 2 diabetes, and about half of them are unaware of it.

People who are overweight are particularly likely to develop Type 2 diabetes. It tends to run in families and in Australia, it is more common in Aboriginal and Torres Strait Islanders, Pacific Islanders, Asian Indians and Chinese people than in Australians of European origin (Australian Aborigines have the fourth highest prevalence of Type 2 diabetes in the world).

People with Type 2 diabetes usually have it for many years before they first develop the classic symptoms of thirst, frequent passing of urine, hunger and weight loss. But while it's less dramatic in onset than Type 1 diabetes, its effects can be just as deadly over time.

This is because high blood glucose levels can cause all sorts of damage to body tissues and organs.

• Poor healing. Infections are more likely, they last longer and are more difficult to treat. Skin wounds and ulcers form more easily and take longer to heal.
• Atherosclerosis. This is narrowing and hardening of the arteries, and diabetics are especially prone to it. It can cause strokes, heart attacks, and peripheral vascular disease (poor circulation to legs and feet).
• Small artery disease. Diabetes causes a special type of arterial disease that affects small arteries in important organs – especially the kidneys, the retina (the light-sensitive part of the back of the eye) and the nerves. Blindness, kidney failure and peripheral neuropathy (disease of nerves causing paralysis and loss of sensation) are common in advanced diabetes

Whether – and how fast – these complications develop is in direct proportion to how long a person has had the disease, and how uncontrolled the blood glucose levels have been. Smoking, high blood pressure and cholesterol, and a heavy alcohol intake all accelerate these complications.

How diabetes effects the body

Eyes – Some eye conditions are more common in people with diabetes, such as cataract – clouding in the lens of the eye.

Retina – Disease of the small arteries of the eye causes areas of the retina to die, causing loss of vision. These show up as pale areas in the retina.

Kidneys – The small blood vessels in the arteries of the kidneys are damaged, which can eventually cause the kidneys to fail.

Heart – Damaged arteries can disrupt the blood supply to important organs such as the heart, causing part of the heart muscle to die (a myocardial infarction, or heart attack).

Feet – People with diabetes often have poor circulation and lack of sensation in the feet, and are prone to foot ulcers.

Arteries – People with diabetes are more likely to get atherosclerosis, which causes narrowing of the arteries. They are also prone to peripheral arterial disease, causing poor circulation in the legs. This can give rise to numbness, pain, and in severe cases, gangrene.

Diagnosis

Sometimes a person is first diagnosed as a diabetic after developing the classic symptoms of urination, thirst and hunger. Very rarely, they may have become dangerously ill and have fallen into a coma.

But it's more usual to be diagnosed by a blood glucose test taken as part of a routine check-up, or during the course of a blood test for some other illness. Since a person's blood glucose normally rises for a couple of hours after a meal, the test is taken after the person has fasted for at least eight hours. Alternatively, a series of blood tests may be performed over a two-hour period following a standard glucose drink. This is called a glucose tolerance test.

Treatment

Diabetes can't be cured (yet), but it can be controlled. A person who is careful about managing their condition will live a pretty normal life, with some restrictions on their lifestyle.

The treatment revolves around keeping blood glucose levels as close as possible to normal. There are several ways of doing this:

• Diet. The ancient Greeks knew about the importance of diet in treating diabetes: a certain Paul of Aegina recommended pot-herbs, endive, lettuce, rock-fishes, juices of knotgrass, elecampane in dark-coloured wine and decoctions of dates and myrtle. Try taking that list to the supermarket! These days dieticians like to keep it simple. The aim is to lose weight and to carefully manage carbohydrate intake: plenty of whole grains, vegetables, fruit, nuts, and seafood, small amounts of meat and meat products, and a reduced intake of animal fats.
• Exercise. Physical activity increases the body's consumption of glucose from the blood and also helps with weight loss. For those with very mild diabetes, diet plus weight loss plus exercise may be enough to keep blood glucose within reasonable levels.
• Drugs. If not, the next step is drug treatment. There are two different classes of drugs given to lower blood sugar. The most powerful is insulin, which is used to treat people with Type I diabetes and cases of Type 2 diabetes when tablets become ineffective. It's available in several different forms; synthetic human insulin is the most commonly used and the best tolerated.

Insulin can't be taken by mouth because it is destroyed in the stomach. So it is injected (usually by the diabetic him/herself) under the skin into the fat layer, usually in the abdominal wall (commonest), arm, or leg.

Insulin is available in short-acting, intermediate-acting and long-acting forms. The aim is to get enough in the body over a 24-hour period to cover meals and keep glucose levels within the desired range. A small percentage of people find that a single morning injection of insulin is enough, but most people with Type 1 diabetes are now on four injections a day. Finding the right combination and timing of injections is a matter of trial and error.

People with unstable diabetes, or those requiring many injections a day, may benefit from an insulin pump which is worn on the body (on a belt for instance) and delivers a continuous infusion of insulin via a needle implanted into the body.

Insulin has also recently become available in a puffer form – inhaled through the mouth into the lungs. It's been licensed under the trade name Exubera for use in the US and Europe, but not yet Australia. It's being promoted as the "first new insulin delivery option introduced since the discovery of insulin in the 1920s" – but it does have some disadvantages. Trials have shown it can cause breathing problems, and it's not recommended for smokers or people with lung diseases like asthma and bronchitis. Also, it may not be useful for suffers of Type 1 diabetes, who must have very precise dosages consistently delivered into the bloodstream; using a puffer, dosage delivery is very variable. So for now, it's likely to be useful as a possible way of reducing the amount of insulin needed to taken by injections, rather than replacing insulin injections altogether.

In Type 2 diabetes, the drugs used are mostly oral preparations (taken by mouth). There are several different types, and they are usually used in conjunction with diet and exercise. Some, like the so-called sulfonylurea drugs (such as glibenclimide, gliclazide, and glipizide) lower the blood sugar level by stimulating the pancreas to release insulin. Metformin does it by increasing the body's response to the insulin already circulating in the blood. Another drug, called acarbose, works by delaying the absorption of glucose in the intestine. A new class of drugs, the glitazones (pioglitazone and rosiglitazone) have recently been released in Australia and they reduce the insulin resistance characteristic of Type 2 diabetes.

For every person with diabetes the diet, recommended level of exercise, and the type and dosage of drug will be different, and changes in treatment may be needed during pregnancy, illness, or during and after surgery.

People with diabetes must continually monitor their own glucose levels, preferably through blood testing (urine testing is unreliable). A small plastic device is used that takes a pin-prick droplet of blood from a finger. The blood is applied to a test strip, which is then inserted into a machine that reads the blood glucose level. The person keeps a record of his or her blood sugar levels, and from this, the doctor decides whether the treatment is adequate or needs to be changed.

Anyone who keeps their blood glucose levels lower than 8 millimoles per litre most of the time is doing very well. Between 8 and 10 millimoles per litre is fair; over 10 millimoles per litre is poor.

Sometimes, because of too much medication, a missed meal, or too much exercise, the blood glucose level gets too low. This is called hypoglycaemia, or often, just a 'hypo'. The person feels faint, dizzy, hungry, has a rapid heartbeat and will sweat. This is a dangerous situation, and they must be given sugar immediately. Most diabetics carry sweets, glucose tablets or a glucose drink with them at all times. Frequent episodes of hypoglycaemia may mean that their diet, exercise plan and/or drug treatment needs to be changed.

It's a good idea for people with diabetes to wear or carry an identification card, bracelet or neck tag in case they become unconscious due to hypoglycaemia. That way they can be recognised in an emergency and treated with an injection of glucose.

They should also take special care to avoid foot infections, and be careful taking other medications as these may interfere with their diabetic medication. An annual vision check is recommended because damage to the retina (also called diabetic retinopathy), can eventually lead to blindness, but can be treated if identified early.

Reviewed by Professor Paul Zimmet AO, International Diabetes Institute

Originally published 19/12/2002; Last modified 16/01/2007