Treatment and Prevention of Diabetes in the United Kingdom

In the treatment and management of patients with diabetes, individual needs and risk factors must be considered, and strategies must be tailored to the specific patient. For patients with type 1 diabetes, factors such as insulin delivery methods, frequency of injections, and insulin pharmacological profile must be considered alongside patient adherence, target control, severity of disease, and risk factors for hypoglycaemic episodes and other diabetic complications.[1],[2] Emerging forms of insulin, improved insulin delivery (eg, pens, pumps, and inhaled insulin) and blood glucose monitoring technology, as well as solid pancreas and islet cell transplantation, have the potential to increase the effectiveness and convenience of treatment regimens in future.[1]

Currently in the United Kingdom (UK), there are many forms of human insulin and human insulin analogues available, though a very small percentage of patients continue to opt for animal insulin, noting that the switch from porcine to human insulin predicated in them a lack of awareness of hypoglycaemia.[1] Table 1 details various forms of insulin currently available, as well as their manufacturers, sources and delivery methods.

Table 1. Insulins available in the UK.[3]

*Formerly known as CP Pharmaceuticals

For patients with type 2 diabetes, dietary and lifestyle modifications are the initial treatment in less severe disease, followed by metformin, sulphonylureas (SUs), and thiazolidinediones (TZDs). Insulin therapy is used in more severe or chronically uncontrolled patients.[1] The National Institute for Clinical Excellence (NICE) treatment algorithm for the management of blood glucose presents clinicians with options for the individualised treatment of patients (Figure 1).[4] Of those patients who have been diagnosed with type 2 diabetes, approximately 20% are treated with lifestyle modifications alone, 50% with lifestyle modification and oral medication, and 30% with lifestyle modification and insulin.[5]

Figure 1. Treatment algorithm for the management of blood glucose in type 2 diabetes.[4]

There is overwhelming evidence that the effective care of patients with diabetes in general should include glycaemic control, lifestyle modification and maintenance, and control of cardiovascular risk factors such as hypertension and lipid levels.[1] The British Medical Association (BMA) points to 2 specific major clinical trials that have considerably influenced efforts to prevent complications and delay progression of disease in patients with type 1 and type 2 diabetes.[1] The Diabetes Control and Complications Trial (DCCT) showed that intensive therapy improved glycaemic control and slowed the onset and the progression of complications (diabetic retinopathy, nephropathy, and neuropathy) in patients with type 1 diabetes.[1],[6] Patients received either conventional diabetes management or intensive insulin therapy administered either via an insulin pump or multiple daily injections. The latter group also received education and extensive backup support to assist them in achieving target glycaemic control.[1],[6] However, this positive effect was diminished by as much as a 3-fold increase in severe hypoglycaemia. In addition, the study’s design did not allow for separation of the effects of education versus insulin therapy.[1],[6] The United Kingdom Prospective Diabetes Study (UKPDS)examined the role of glycaemic and blood pressure control in patients with type 2 diabetes.[1],[4],[7] In the glycaemic control component of the study, the intensive control group, treated with a sulphonylurea, insulin, or metformin, aimed for a fasting plasma glucose (FPG) <6 mmol/L, while conventional control, treated primarily with dietary modifications, aimed for an FPG of <15 mmol/L.[4],[7] Similarly, blood pressure was tightly maintained with captopril or atenolol and a target of <150/85 mm Hg, or less tightly controlled, without ACE inhibitors or beta-blockers, and a target of <180/105 mm Hg.[4],[7] Intensive glycaemic control reduced the risk of major diabetic eye disease by 25%, and early kidney damage by 33%, while tighter blood pressure control reduced the risk of death from long-term complications of diabetes by 33%, strokes by more than 33%, and serious deterioration of vision by more than 33%.[7] Key points from this study appear in Table 2.

Table 2. Key points from the UKPDS.[1]

The National Health Service (NHS) NICE guidelines, as well as the recommendations of Diabetes UK and the BMA, stress the importance of focussing upon glycaemic control and cardiovascular risk factors in the treatment and management of patients with diabetes, in order to delay progression of disease and prevent the development of associated complications. Glycated haemoglobin has been demonstrated to be an effective indicator of average glycaemia over the previous 60-day period (Table 3).[1] As mentioned previously, both the UKPDS and the DCCT have demonstrated the importance of controlling blood glucose levels by targeting glycated haemoglobin A1C (HbA1C) levels for both type 1 and type 2 patients. Based on these studies, the BMA suggests:

• An HbA1C of around 7% is associated with a significantly reduced risk of developing microvascular complications[1]

• Reducing the HbA1C below 7% may reduce the risk of diabetic eye disease further[1]

• In those with established retinopathy, the maintenance of good glycaemic control is essential to delay progression of the disease[1]

• In the primary prevention of cardiovascular disease there appears to be no level of glycaemic control that confers a reduction in risk[1]

• The evidence for good glycaemic control in patients with established diabetic nephropathy (as judged by the presence of microalbuminuria) is less convincing. In type 1 diabetes there appears to be no clear benefit[1]

Table 3. Relationship between HbA1C and approximate blood glucose levels.[1]

In type 1 patients, NICE recommendations call for the measurement of HbA1C levels every 2-6 months, dependent upon achieved level of blood glucose control, stability of blood glucose control, or change in insulin dose or regimen.[2] Further, NICE guidelines state:

• Where there is evidence of increased arterial risk (identified by a raised albumin excretion rate, features of the metabolic syndrome, or other arterial risk factors), people with type 1 diabetes should be advised that approaching lower HbA1C levels (for example, 6.5% or lower) may be of benefit to them[2]

• Where target HbA1C levels are not reached in the individual, adults with diabetes should be advised that any improvement is beneficial in the medium and long term, and that greater improvements toward the target level lead to greater absolute gains[2]

• Undetected hypoglycaemia and an attendant risk of unexpected disabling hypoglycaemia or of hypoglycaemia unawareness should be suspected in adults with type 1 diabetes who have:
• Lower HbA1C levels, in particular levels in or approaching the normal reference range[2]
• HbA1C levels lower than expected from self-monitoring results[8]

• Where experience or risk of hypoglycaemia is significant to an individual, or the effort needed to achieve target levels severely curtails other quality of life despite optimal use of current diabetes technologies, tighter blood glucose control should not be pursued without balanced discussion of the advantages and disadvantages[2]

References

1. British Medical Association. Diabetes mellitus: an update for professionals. Available at: http://www.bma.org.uk/ap.nsf/Content/Diabetes/$file/diabetes.pdf. Accessed February 2006.
2. National Institute for Clinical Excellence (NICE). Type 1 diabetes: diagnosis and management of type 1 diabetes in children, young people and adults. Clinical Guideline 15, July 2004. Available at: http://www.nice.org.uk/pdf/CG015NICEguideline.pdf. Accessed February 2006.
3. Insulin available in the UK. Diabetes UK. Available at: http://www.diabetes.org.uk/products/insulin.htm. Accessed April 2006.
4. NHS MeReC briefing. Type 2 diabetes (part 1):the management of blood glucose. Available at: http://www.npc.co.uk/MeReC_Briefings 2003/ Briefing%20 No%2025%20press%20RGB.pdf. Accessed February 2006.
5. Diabetes UK. Diabetes in the UK 2004; October 2004. Available at: http://www.diabetes.org.uk/infocentre/reports/in_the_UK_2004.doc. Accessed February 2006.
6. The Diabetes and Complication and Complications Trial Research Group (1993). The effect of intensive treatment of diabetes on the development and progression of long term complications in insulin dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.
7. UK Prospective Diabetes Study. Available at: http://www.dtu.ox.ac.uk/index.html?maindoc=/ukpds/. Accessed February 2006.
8. NHS MeReC briefing. Type 2 diabetes (part 2): the management of cardiovascular risk factors. Available at: http://www.npc.co.uk/MeReC_Briefings/2003/briefing%20no%2026%20press%20RGB.pdf. Accessed February 2006.