2 Clinical need and practice

2.1

Diabetes mellitus is a chronic metabolic disorder caused by insufficient activity of the hormone insulin and a subsequent loss of control of blood glucose levels. There may be a lack of the hormone itself or resistance to its action. Insulin is produced by the beta cells of the pancreas in response to rising blood glucose levels and mainly regulates the metabolism of carbohydrates, but also of proteins and fats. There are two types of diabetes mellitus. Type 1 diabetes mellitus is caused by the destruction of insulin-producing cells, leading to an absolute lack of the hormone. Type 2 diabetes mellitus is characterised by insulin resistance and is often associated with obesity. In type 2 diabetes mellitus, the pancreas initially responds by increasing insulin production, but over time this excess production cannot be maintained, leading to a decrease in insulin production and a lack of insulin. Both types of diabetes mellitus are characterised by hyperglycaemia – an elevation of blood glucose levels above normal.

2.2

The onset of type 1 diabetes mellitus usually occurs in children and young adults, with an estimated prevalence in the UK in 2005 of 0.42% (approximately 250,000 people). The incidence has been increasing over time, with the greatest increase in children younger than 5 years. Type 2 diabetes mellitus occurs in adults and usually begins after the age of 45 years. The current prevalence in England is estimated to be 4.3% (approximately 2.5 million people). The incidence is rising and expected to rise further because of an ageing population and an increasing prevalence of obesity. There is also an increasing incidence of type 2 diabetes mellitus in children.

2.3

Diabetes mellitus can cause short- and long-term complications. Short-term complications are acute metabolic emergencies that can be life-threatening: diabetic ketoacidosis, which is a consequence of high blood glucose levels (hyperglycaemia); and low blood glucose levels (hypoglycaemia) caused by treatment. Mild hypoglycaemia can be corrected by oral intake of sugars. Severe hypoglycaemia is defined by the need for assistance from another person for recovery. Severe hypoglycaemia can cause convulsions, coma and, very occasionally, death. In children, especially those younger than 5 years, severe hypoglycaemia can cause long-term cognitive impairment. Fear of recurrent hypoglycaemia not only decreases quality of life but can also hinder adherence to treatment and the achievement of good glycaemic control. The long-term microvascular and macrovascular complications of chronically elevated blood glucose levels include retinopathy and blindness, nephropathy and renal failure, ischaemic heart disease, stroke, neuropathy, and foot ulceration and amputation. Uncontrolled diabetes in pregnancy is associated with adverse pregnancy outcomes.

2.4

Diabetes mellitus is a lifelong condition in which both morbidity and treatment affect quality of life. On conventional (that is, injection) insulin regimens, daily life activities need to be arranged around a relatively inflexible structure of meal times and insulin injections. Diabetes is a source of stress for all members of an affected person's family and in the case of children can cause intense parental anxiety. As the length of time with diabetes increases and with the onset of complications, people with diabetes may experience occupational difficulties because of disabilities as well as requiring prolonged and frequent medical attention.

2.5

Type 1 diabetes mellitus requires lifelong treatment with insulin. Type 2 diabetes mellitus is initially managed by lifestyle change, including diet and weight loss if necessary. If this is insufficient, oral glucose-lowering drugs are introduced. Over time, many people will need insulin to control their blood glucose levels. There are various types of insulin, distinguished by their rate of onset and duration of action. Insulin requirements change depending on food intake, exercise or intercurrent illness. Insulins with varying times to onset and durations of action are combined in treatment regimens, which are then delivered by multiple injections timed to coincide with insulin requirements. Achieving good control of blood glucose through an intensive regimen reduces the risk of complications. Intensive insulin regimens attempt to reproduce the normal secretion of insulin by the pancreas. However, exogenously administered insulin lacks the feedback mechanism that the pancreas uses to regulate insulin secretion, whereby insulin production decreases as blood glucose levels fall. Therefore, people taking insulin need to check their blood glucose levels regularly by using a monitor (glucometer). Regular measurements enable short-term control of blood glucose levels by adjusting the insulin dose. Long-term monitoring of control is achieved by measuring glycosylated haemoglobin (HbA1c) levels, which reflect average blood glucose levels over the preceding 3 months. Good control is indicated by a value of less than 7.5% (the normal range for people who do not have diabetes is 4.5% to 6.1%).