Diabetes - Questions & Answers

Type 1
Inflammation occurs in the islet cells Islet beta cells are destroyed Antibodies to islet cells present Due to interaction of environmental factors with inherited predisposing genes Not directly inherited Accounts for an estimated 10-25 per cent of cases of diabetes.

Type 2
No islet inflammation apparent Beta cells retain some secretory function No such antibodies Susceptibility genes increase vulnerability, but they differ from those in type 1 Strong familial trend Accounts for 75-90 per cent of cases of diabetes.

Diabetes mellitus is a chronic disorder in which the body’s ability to use sugars is reduced. This can cause raised levels of glucose in the blood and its excretion in the urine. In more severe acute cases, this can lead also to a loss in the balance of water and minerals in the body. These changes are the result of a deficiency of the pancreatic hormone, insulin. There are two main types of diabetes: type 1 or insulin-dependent diabetes mellitus (IDDM), an autoimmune disease, and type 2 or non-insulin-dependent diabetes mellitus (NIDDM). In type 1 diabetes especially, there may be a production of chemicals called ketones, which can make the breath smell of acetone, and ultimately, if not treated, cause coma. In a few cases, diabetes can be caused by factors including diseases of the pancreas, some medications and other hormonal conditions.

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The pancreas is an elongated gland, 5-6 inches long, situated in a loop of the small intestine and lying behind the stomach. It is called a mixed gland, because it has distinct parts with different functions. It has a major role in digestion – accounting for about 99 per cent of its weight – and releases digestive juices into the small intestine through a small duct. The other 1 per cent, comprising the islets of Langerhans, is involved with the making and storing of hormones, including insulin, and releasing them directly into the blood stream.

In an adult, there are from 200,000 to 2 million pancreatic islets scattered throughout the gland, each containing four different kinds of specialised cells acting in combination to regulate digestion and glucose balance. The two most important in diabetes are called alpha and beta cells. Alpha cells produce a hormone called glucagon that raises blood glucose by triggering its release from glycogen stores in the liver. Glucagon is also involved in the utilisation of fats and protein constituents by the body. Beta cells secrete insulin, which lowers blood glucose. It is clear that glucagon and insulin do opposite things. In fact, glucagon is referred to as hyperglycaemic (glucose raising) while insulin is called hypoglycaemic (glucose lowering).

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What is insulin?

Chemically, insulin is made of amino acids, the building blocks of protein. It is synthesised in the islet cells in a form called proinsulin, which is broken down before release into the blood into a small piece called C-peptide, and insulin. The insulin itself consists of two chains (A and B) linked together by sulphur-containing bridges. Both C-peptide and insulin (and some proinsulin) are packaged together in the islet cells into granules prior to release and all three are detectable in the blood of people who do not have diabetes. Though drawn in the illustration for convenience as two straight chains, the structure of insulin is in fact coiled up into a three-dimensional ball. The amino acids on the outside interact with the cell’s insulin receptors. It has proved possible to modify insulin by changing its size and amino acid composition to produce novel insulin-type medicines.

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What are the differences between type 1 and type 2 diabetes?

This division is important because it affects the clinical assessment of the patient and subsequent treatment. The mechanisms of the two differ, though they both culminate in an inability to regulate glucose properly.

Type 1: Though less common, this form has a sudden onset, usually before the age of 40, but can occur at any age. Insulin treatment is essential for the survival of people with type 1 diabetes and will always have to be taken. Without insulin, blood glucose levels become too high and fat is broken down as an alternative source of energy. This results in the production of ketone bodies which, if they accumulate, can lead to ketoacidosis. This in turn can cause nausea, vomiting and drowsiness, and can lead to diabetic coma.

Type 2: This is the form that most people with diabetes have. In contrast to type 1, it affects mostly people over the age of 40 and has a slow onset that may go undiagnosed. People with type 2 diabetes still secrete insulin, though there is almost always some reduction in the quantity produced. In type 2, three main types of abnormality may account for the development of the condition:

• the receptors on cells may fail to be stimulated by insulin, a condition known as peripheral insulin resistance. This type is especially common in people who are overweight and is characterised in some people by a compensatory over-production of insulin
• insulin production may be too low
• the insulin produced may be chemically abnormal and not properly functional

Although type 1 and type 2 are clinically distinct from each other, some people with type 2 may develop a need for insulin in order to manage their diabetes effectively.

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What are the symptoms of diabetes?

The ‘classical’ symptoms of both types of diabetes are thirst, tiredness, itching or rash in the genital areas caused by yeast-like infections of glucose-rich urine, over-production of urine (especially at night) and weight loss. In type 1, less frequent symptoms are cramps, constipation, blurred vision, and skin infections. In type 2 diabetes, the onset of symptoms may be so gradual that they go unnoticed. People with type 2 diabetes who have remained undiagnosed for some years may eventually be diagnosed because they go to the doctor complaining of deteriorating eyesight or with foot ulcers or pain in the limbs, which are some of the signs of complications of diabetes.

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What is hypoglycaemia and what are its telltale signs?

Hypoglycaemia is the medical term for a blood glucose level which is too low, often referred to as a ‘hypo’. A hypo happens in people with diabetes because there is insufficient glucose to fuel the essential activities of the brain and other organs. The lack of glucose may arise after an insulin injection, after taking oral diabetes medicines such as a sulphonylurea (e.g. if the dose is too high or there is a build-up in the body as a result of kidney disease), a delayed or missed meal, insufficient carbohydrate foods, strenuous exercise or drinking alcohol without food. The signs of an impending hypo vary between individuals but may include sweating, anxiety, irritability, blurred vision, hunger, pallor, tingling lips and palpitations. By recognising these signs and taking appropriate measures to boost glucose levels, a hypo can be avoided.

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Are hypoglycaemic episodes dangerous?

If corrective action is not taken, unconsciousness may result, but the body will take emergency action to raise glucose levels so that consciousness is regained. However, a person may be in a dangerous environment and need help, so it is important to take special measures when appropriate (e.g. driving) and to inform friends and workmates of the condition and what to do if help is needed. Death from a hypo is very rare.

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What causes diabetes?

Although both types of diabetes culminate in a failure to regulate glucose properly and have a genetic predisposition, there are clear distinctions between them.

Type 1: In this form we know that the body produces antibodies against itself (an autoimmune reaction) that destroy the beta-cells in the pancreas, but it is still uncertain what triggers this reaction. Various possibilities have been proposed, including infections with some specific types of virus, infections with bacteria of the mycobacterium group, food-borne chemical toxins and exposure as a very young infant to cow’s milk - a component of which may cross into the baby’s circulation and cause an immune response that cross-reacts with the beta-cells ‘by mistake’. However, there is not enough conclusive evidence to implicate any of these suggestions.

Type 2: Here the beta cells are preserved and there are no antibodies or autoimmune attack. Genetic factors determine susceptibility in most cases and common trigger factors are excessive energy intake in food leading to obesity, physical inactivity, and increasing age. Of these, obesity is of enormous importance: 80 per cent of people with type 2 diabetes are overweight. Other infrequent causes include some medicines, gestational diabetes, and other illnesses in which hormones that counter the action of insulin are produced.

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Obesity is one of the fastest-growing medical epidemics affecting people in Britain. Over half of the UK population is overweight and about one-sixth is clinically obese. In 1980, about 6 per cent of men and 8 per cent of women were obese. By 1991, the figures had doubled. Obesity greatly increases the risks of many diseases, including high blood pressure, kidney disease, and type 2 diabetes. It has been estimated that the diseases caused by obesity cost the National Health Service over £2 billion each year.

It appears that in obese individuals (especially those with much fat in the trunk), the cells in the body begin to develop a resistance to insulin. They then fail to use blood glucose properly and glucose intolerance develops. Some obese individuals initially produce more insulin in compensation, but this also soon fails and diabetes results. Hence it is very important to try and maintain a reasonable weight. This can be estimated by calculating the Body Mass Index which also indicates the degree of risk for different ranges of BMI.

 

Are you overweight or obese? Clinically, obesity can be defined in terms of a number called the BODY MASS INDEX or BMI. To calculate your own BMI, measure your weight (in kilogrammes) and your height (in metres). Then divide your weight by the square of your height as shown in the example below, and read off your BMI from the table, i.e.: BMI = Weight (in kilos) ÷ height2 (in metres) e.g. A person weighs 78kg and is 1.6 metres tall, then the BMI is 78 ÷ 1.62 = 30.4. From the table below, it is evident that this person is on the borderline between overweight and becoming clinically obese. BMI and relative risk of diabetes less than 20 –underweight/very low risk 20 to 25 – ideal/very low risk 25-30 – overweight/significant risk above 30 – clinically obese/high risk above 40 – extremely obese/very high risk

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Who does diabetes affect?

Type 1 and type 2 have very different patterns of onset. Type 1 begins most commonly in childhood with a peak onset between the ages of 11 and 13, though it can develop at any age. It accounts for about 10-25 per cent of all cases of diabetes in the UK. It has been estimated that there are at least 20,000 people under the age of 20 with diabetes in the UK and almost all have type 1.

Type 2 is much more common and accounts for 75-90 per cent of diagnosed cases. It usually begins after the age of 40, although prevalence increases with age.

In Asian and African-Caribbean people, there is a three to four times greater risk of diabetes compared with Caucasians. Diabetes affects men more often than women, in a ratio of about 3:2.

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How widespread is diabetes?

This has been difficult to determine accurately, because about half the people with diabetes do not know they have it. Population studies based on the assessment of medical records, prescription patterns and postal questionnaires suggested an overall prevalence of about 1-1.5 per cent in the UK. However, this may be an underestimate, because a survey in 1993 by the Office of Population Census and Surveys, in which over 16,500 people were interviewed, revealed a prevalence of 3 per cent over the whole age range. If this is extrapolated to the over 16 population, the total of people with diabetes is just under 1.4 million in the UK. Of these, from 1-1.25 million will have type 2.

Attempts to determine the incidence of diabetes have produce varied results ranging from 16 to 100 new cases per 100,000 of the population per year.

In global terms, the diabetes problem is massive and is growing rapidly. A detailed study estimated that in 1997, there were 124 million people in the world with diabetes, of whom 97 per cent had type 2. By the year 2010, the number of people with diabetes has been projected to rise to 221 million, largely as a result of adverse lifestyle changes in developing countries in Asia and Africa leading to obesity and inactivity.

There are very large differences in the number of cases of both type 1 and type 2 diabetes in different countries. Thus the incidence of type 1 varies from about 30 cases per 100,000 per year in Finland to only 1 per 100,000 per year in Japan. The UK figure is around 10. The prevalence of type 2 also varies.

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Is diabetes a serious condition?

Before the discovery of insulin, type 1 diabetes was fatal, but today the condition can be treated. Though a cure is not yet possible, a high quality of life is enjoyed by most people and complications can be minimised. Though not initially needing insulin, people should not regard type 2 diabetes as a ‘mild’ condition: without proper treatment complications can develop and life expectancy reduce. Active management is required to prevent the development of complications in both types 1 and 2 diabetes. This requires not only medicines but also the active involvement of the individual in his/her own monitoring and a high degree of motivation and commitment. This can be very disruptive of everyday activities but must be encouraged, because the long-term benefits are so great.

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What are the possible long-term complications of diabetes?

It is important to be aware that if diabetes is well controlled by diet and/or medicines, then in many cases no complications may develop even after 30 or more years. This has just been re-emphasised with the release of the results of the 20-year UK Prospective Diabetes Study. This involved 5,000 people with type 2 diabetes in 23 clinical centres. It showed that the rigorous management of blood glucose levels and blood pressure substantially minimised long-term complications. It showed that better blood glucose control reduced the risk of diabetic eye disease by a quarter and early kidney disease by a third.

Most important, it also showed that control of blood pressure to near normal levels resulted in:

• a reduction in death from the long-term complications of diabetes by a third
• one third fewer strokes
• a reduction in serious sight defects by one third

The intensive therapy that people in this study were given did not impair life quality, though some people gained weight and others had more frequent hypos. Overall, it was concluded that ‘...a substantial improvement in health of people with type 2 diabetes can be obtained’. These data provide motivation and incentive for people with diabetes to manage their condition better, in the knowledge that improved health and fewer complications will result.

Despite this encouragement, many people do experience problems, especially after many years of living with diabetes. These often arise through damage to blood vessels. If the blood vessels damaged are small (i.e. capillaries), then blood supply to the eyes, kidneys and various nerves may become restricted. Over time, this can lead to damage to the retina in the eye and to impaired sight (retinopathy), to kidney disease that can further complicate the maintenance of the body’s chemical balance (nephropathy), and to pain (sometimes severe) and loss of sensation, especially in the legs and feet (neuropathy). The combination of blood vessel and nerve damage predisposes some people to foot problems such as diabetic ulcers and even gangrene. Less commonly, neuropathy can also affect other parts of the body such as the arms, hands, face or internal organs, depending on which nerves are affected. If large blood vessels are damaged, then there will be an increased risk of circulatory disorders such as hypertension and heart disease.

 

Complications in diabetes BLOOD VESSELS AND HEART coronary heart disease is 2-3 times higher in men and 4-5 times higher in pre-menopausal women. It accounts for more than 55 per cent of deaths from diabetes, mostly in type 2 there is a 2-3 fold increase in the risk from stroke blood clots in the limbs can result in amputation. Lower limb amputation is 15 times more likely in people with diabetes EYE diabetes is a leading cause of blindness in the UK KIDNEY kidney damage/failure is especially a problem in type 1 diabetes, but often occurs in type 2 as well, when blood glucose and blood pressure are not well controlled NERVES & BRAIN pain or loss of sensation can cause foot problems and ulceration other forms of nerve damage may affect other parts of the body or internal organs. Impotence is a common example

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Does diabetes follow the same course in all people?

Type 1: In type 1, there are people who have used insulin for over 50 years and have enjoyed a long and a satisfying life. However, some are less fortunate and experience a more rapid progression of their condition.

Type 2: Here the rate of progress of complications can be dependent on when diagnosis is made – the earlier the better – and also on the rigorous control of blood glucose levels and blood pressure.

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Do the genes we inherit play any part in diabetes?

Type 1: This form is not inherited through the transfer of a single gene, but some people have genes that increase their likelihood of getting it. Several studies have shown that in identical twins (who have identical genes), only 25-60 per cent of both individuals get diabetes, thus strongly indicating that there are other non-inherited factors involved. Overall, a child with a mother with type 1 has a small increased risk of developing diabetes, amounting to 3 per cent, 9 per cent if it is the father. If both parents are affected, then the risk is significantly higher.

Type 2: This form tends to run in families more strongly than type 1. Detailed studies have shown that the chance of both identical twins developing diabetes can approach 100 per cent when followed over their lifetime. There are also a few well-studied families who pass on the disorder to some of their children through a dominant gene. This type of diabetes is called MODY, or Mature Onset Diabetes of the Young. In these cases, the disorder often emerges in childhood and has been linked to specific genes.

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What are the main types of medicines used in diabetes?

Type 1: These individuals cannot survive without some form of insulin replacement and this is the mainstay of their treatment. Some of the many different kinds of insulin are described later.

Type 2: Though people with type 2 diabetes may eventually require insulin, other oral medicines can be used, especially in the early years. These are:

• sulphonylureas
• biguanides
• the alpha glucosidase inhibitors
• the glitazone group, which may soon be re-introduced in the UK

In addition, many people require medicines to control blood pressure (ACE inhibitors, beta-blockers, diuretics), and blood fats and cholesterol (statins). These are mentioned later but are not discussed in detail in this booklet.

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When are these medicines likely to be used?

Type 1: As soon as this form of diabetes is diagnosed, a person will receive insulin. Occasionally this protects the few remaining beta cells and may result in a temporary remission (honeymoon period). However, this is invariably short and people with type 1 diabetes will need some form of insulin, coupled with dietary control, throughout their lives.

Type 2: In a person with impaired glucose tolerance or type 2 diabetes, the first approach to management will often be to regulate the diet and modify the life-style. A low-fat, high carbohydrate diet (coupled with reduction in calories for the overweight) will be combined with increased physical activity. If these measures prove inadequate, then medicines will be added in a cascade fashion to achieve control.

About 60-70 per cent of people with type 2 diabetes take oral medication, and rather fewer with type 1. The doctor may prescribe a medicine that stimulates insulin secretion, such as one of the sulphonylureas. In some people, especially those who are very overweight, the biguanide metformin is usually the first choice. An alpha-glucosidase inhibitor such as acarbose may also be prescribed, as this reduces the absorption of glucose in the intestines and hence its uptake into the blood.

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Are there any medicines to treat the complication of diabetes?

Though not the primary purpose of this booklet, a short description of some of the approaches available and in development for diabetic complications are described later. These include medicines that reduce high blood pressure and have a protective effect towards the kidneys, and medicines that lower blood cholesterol and help reduce weight and the risk of heart disease and/ or stroke. Other novel agents are directed towards preventing or treating nerve damage, and treating foot ulcers – including the development of synthetic skin to speed healing.

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Do medicines used to treat diabetes have side effects?

Very few medicines (including insulin) are entirely devoid of side effects and it is important to take only the dosage prescribed and to report any strange, unexplained effects to the doctor. However, medicines used in diabetes are generally well tolerated and the side effects of the widely used sulphonylureas are well documented and largely mild in nature. The early biguanides were associated with some deaths due to an accumulation of lactic acid (called lactic acidosis) and were withdrawn. The glitazones are new and generally well tolerated products. The adverse effect on the liver of troglitazone is under investigation, but it is too soon yet to say whether it will also be a characteristic of other glitazone compounds still in clinical trials.

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Are there forms of treatment for diabetes other than medicines?

In the early stages of diabetes, modifications to the diet may be sufficient to control excess glucose, at least for some months or even years. Learning what and what not to eat and when to eat (and drink) is also very important. Increased fibre may help in some people and bulking agents can be prescribed as a supplement to diet and/or medicines. Information on these aspects can be obtained from the British Diabetic Association (BDA), whose address is at the end of this booklet, or will be provided by your doctor or local clinic. The aim overall is to individualise treatment to promote optimal diabetic control for the individual.

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What kind of general support is available for people with diabetes?

Diabetes will have a significant impact on lifestyle and will also place many demands on the individual, families and friends in terms of understanding what is wrong and how to cope with it. Patient education will be necessary and will vary depending on the stage of the condition. This may be provided by nurses, dietitians and other health care professionals at the local diabetic clinic. Additional information is available from the BDA, or by reference to the local support groups which operate throughout the country.

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