What is Diabetes?

Diabetes is a condition which is characterised by a high blood sugar level. Normally the blood sugar level is maintained at a value of between 4 and 7mmol/l throughout. However, in patients with diabetes the body is unable to control the blood sugar level, either due to a deficiency of the hormone insulin which regulates blood sugar levels or due to a resistance to the action of insulin in the body.

There are two main forms of diabetes, the first is called insulin dependent diabetes and affects children and young people, usually up to the age of 30 years. This condition often results in weight loss with a tendency to infections, blurring of vision but also increasing thirst and passing of large volumes of water and getting up at night to pass water. In some situations if not diagnosed the patient can go into a coma. It is an extremely serious condition which needs to be diagnosed immediately and which needs to be treated with insulin. There is no alternative treatment other than insulin for this condition. The key priorities in the treatment of patients with type 1 diabetes are to obtain good blood sugar levels but also to make sure that other factors such as blood pressure and cholesterol are controlled in order to prevent any damage to the circulation.

The commonest form of diabetes however, is called type 2 diabetes or late onset maturity diabetes. This occurs in patients as they get older and usually occurs in patients over the age of 50 years of age. It is frequently related to weight gain and obesity. This type of diabetes also causes the same symptoms as type 1 diabetes but can usually be controlled with diet and tablets. There are several different forms of tablets which can be used to control blood sugar levels in type 2 diabetes and we often start with one drug and then increase the dosage and then add additional drugs as time passes, dependent on the level of control of the sugar levels. It is very important that patients stick to an appropriate diet, avoid sugar and refined carbohydrates and instead having a diet which is high in fibre and roughage and also at the same time low in cholesterol. Losing weight is a very helpful and important part of the treatment of patients with type 2 diabetes as well as exercise which also lower blood sugar levels as the glucose is used by muscles.

There are other forms of diabetes as well but these are rarer. These include maturity onset diabetes of the young which is a genetic condition in which patients develop what appears to be type 2 diabetes but at a much younger age. There is often a strong family history of diabetes occurring in patients in their 20s and 30s which can be easily controlled with tablets rather than insulin. This condition can be linked to specific genetic abnormalities affecting the way in which glucose is controlled in the liver.

There are also what we call secondary causes of diabetes and largely these occur as a result of damage to the pancreas, so patients with pancreatitis or even carcinoma of the pancreas can develop diabetes. There are other conditions such as an overload of iron (haemochromatosis) and other hormonal conditions including Cushing's syndrome and acromegaly which may also contribute to the development of diabetes.

We also know that there are several tablets that increase the risk of diabetes and these include steroids such as Prednisolone.

The Genetics of Diabetes

There are strong genetic influences in the development of both type 1 and type 2 as well as in MODY diabetes.

In type 1 diabetes we know that patients develop a susceptibility to diabetes through the genes which control and regulate the immune response. These are referred to technically as the HLA DR3 and DR4 and DQB haplo types.

The function of these genes is to produce proteins which help to regulate the immune response. We know that in the case of type 1 diabetes that damage to the insulin producing cells in the pancreas occurs as a result of the immune system attacking the insulin producing cells such that there is a progressive fall in the amount of insulin that patients are able to make. We know that in 98% of patients with type 1 diabetes, that the HLA, haplo types DR3 and DR4 are present but these are also found in approximately 50% of the general population. Therefore the genetics of type 1 diabetes is such that it makes diabetes more likely but it is not specifically a genetically related disease. We know therefore that there are other factors that contribute to the development of diabetes and there have been several theories as to what these may be. These include some factor which damages the insulin producing cells such as viruses which may directly infect the insulin producing cells. The commonest virus to be implicated is referred to as the Coxsackie virus and there is quite a lot of evidence to suggest this might be involved. In addition there are theories that certain forms of food, such as smoked meat may contribute to diabetes or possibly chemicals. There is also a link with Vitamin D levels and in some scientific articles it has been suggested that artificial milk given to children can contribute. There is evidence for example that breast feeding tends to protect against type 1 diabetes and there is a possible association with diabetes and the bovine serum albumin which is found in cows milk.

The genetics of type 2 diabetes is very complex and appears to link to the two fundamental defects in type 2 diabetes, namely the lack of insulin that occurs but also the resistance to insulin which develops. There are also genetics factors which are implicated in the development of diabetes and also other factors which indicate that the hormone systems related to GLP1 may be contributing in some individuals to type 2 diabetes. GLP1 is an intentional hormone which increases with the effect of insulin. We also know that within families specific genetics types tend to run true and that there are therefore multiple separate influences on the development of type 2 diabetes. The genetic studies which have looked at the human Genome have indicated that there are several different areas of the chromosomal pattern which can link to the development of type 2 diabetes. For example in some patients we know that there are abnormalities of the insulin gene but in the majority of patients with type 2 diabetes insulin itself is produced in an entirely normal way.

The Treatment of Diabetes

For patients with type 1 diabetes we know that insulin has to be given and this is the only effective form of treatment. However, there are different ways of giving insulin. We can use mixtures of insulin which include short acting and longer acting insulins. These can be given twice daily, firstly before breakfast and then subsequently before the evening meal. The other widely used regime for giving insulin is known as the basal bolus regime in which patients have a long acting insulin injection, usually at night or in the late evening with injections of short acting insulin given just before each meal. The dosage of insulin that is required should match the amount of carbohydrate taken in each meal and this allows greater flexibility but also overall better control for patients on this particular regime. The difficulty with this however is that patients need to take four injections of insulin a day rather than two injections with the other regimes. We do know how important it is that blood sugar levels are maintained satisfactorily in order to reduce the risk of future development of complications.

Several different insulin companies manufacture insulin. Many of these are based on the human insulin molecule although some of the newer forms of insulin have slight modifications so that they will work more quickly or slowly and therefore help to mimic the natural production of insulin and the response to meals.

Some patients continue to be treated with insulin derived from animal sources including pork insulin. The use of animal insulins is declining progressively.

Medication

There are several different tablets we can use to treat patients with type 2 diabetes, the commonest is Metformin which is a drug from the Biguanide group of agents which increases sensitivity of the body to insulin and therefore helps the body's natural insulin to reduce blood sugar levels. This drug also helps to encourage weight loss and is helpful for many patients although it does have unfortunate side effects which include tummy troubles such as diarrhoea and also indigestion. In general however, Metformin is a very helpful and useful drug.

Gliclazide and other sulphonylureas are shorter acting agents which increase the stimulation to the pancreas to produce more insulin. This means that, following food, greater amounts of insulin are made and this therefore lowers the blood sugar level. Many patients however on Gliclazide and sulphonylureas experience occasional lowering of the blood sugar levels to produce hypoglycaemic episodes (hypos) and therefore the dose of sulphonyurea needs to be adjusted carefully to prevent this happening.

Other groups of drugs used relate to the hormone system called GLP1 and these drugs include Sitagliptin, Vildagliptin and the GLP1 agonist such as Exenatide and Laraglutide. These drugs work by enhancing the body's ability to respond to insulin and also have effects on appetite. Patients on Exenatide and Laraglutide often lose weight when on treatment and these are becoming increasingly popular. The difficulty with this treatment is that it is given by injection and therefore may not be suitable for all patients.

Glitazones are agents which again improve the sensitivity of the body to insulin and which lower blood glucose levels. The one that is usually most commonly prescribed is referred to as Pioglitazone which is effective in lowering the long term blood glucose levels and it is a very effective drug. However, other examples of drugs in this field have been withdrawn from the market following the development of complications and these include Rosiglitazone which was associated with fluid retention in some patients with heart failure. This drug therefore is no longer used.

Metabolic Targets

We try to ensure that patients achieve the following targets in relation to control of their blood sugar levels and other factors.

HbA1C or glycosylated haemoglobin

we like to see this level below 7.0% as we know that from large scale research studies that if the HbA1C is below 7.0% patients are much less likely to develop complications such as vascular disease including retinopathy and kidney damage.

Cholesterol

Again more recently the advisory bodies in the United Kingdom have suggested that the total cholesterol should be below 4.0mmol/l with a low density lipoprotein cholesterol below 2, in order to reduce the risk of vascular disease such as heart attacks and peripheral vascular disease.

Blood Pressure

Blood pressure is also an important target in the treatment of patients with diabetes and should be below 140/80 although in many patients with renal disease an even lower level of below 130/80 would be required.