The new NICE guideline takes a stepwise approach to achieving optimal blood glucose control in type 2 diabetes, as Professor Philip Home and Aileen McIntosh explain


 

Type 2 diabetes is a relatively common condition, affecting an estimated 1.4 million individuals in the UK.1 The condition and its complications consume around 9% of NHS expenditure. The number of individuals affected is increasing and by 2010 an estimated 3 million people in the UK may have the condition.1 Two-thirds of them will die of a diabetes-related complication.

Type 2 diabetes is best thought of as a progressive condition, requiring steadily more intensive management from the time of diagnosis. The number and severity of the associated microvascular and macrovascular complications are likely to increase as the disease progresses.

The need for guidelines

Mortality and morbidity is higher for individuals with type 2 diabetes than for health individuals of similar age and sex. Heart disease is the main cause of death in type 2 diabetes. It has been estimated that men with type 2 diabetes have a two- to three-fold increase in risk of ischaemic heart disease, and premenopausal women a four- to five-fold increase. The risk of stroke may be two to three times higher.

The goals of effective management in type 2 diabetes are thus to avoid premature mortality and to reduce morbidity, in particular from cardiovascular disease. Good blood lipid and blood pressure control are essential, as are other approaches to cardiovascular risk management -aspects considered in NICE inherited guideline H.2

There is a wealth of good epidemiological data showing the relationship between blood glucose levels and complications.3 Extrapolation from trial data, such as the United Kingdom Prospective Diabetes Study (UKPDS), also supports this relationship.4 Accordingly, the reduction of blood glucose to levels as near normal as possible has long been an intermediate objective in diabetes care.

The management of type 2 diabetes is complex and requires both careful clinical management advice from healthcare professionals and ongoing self-management by patients. As self-management affects many aspects of normal life, in particular diet, patient education is a major component of diabetes care.

However, while initially management may involve diet and lifestyle changes, the natural history of the condition in most individuals requires escalating pharmacological therapy, as the patientÍs condition deteriorates, starting within 1-3 years of diagnosis. This ïstep upÍ process requires careful consideration of what further action to take and when to take it. The new guideline on blood glucose management aims to help both healthcare professionals and patients map out these steps.

How robust is the evidence?

The guideline development process is detailed in the full guideline.5 As with other NICE guidelines, the levels of evidence are graded from Ia to IV and the recommendations from A to D, according to the strength of the underlying evidence (see Table 1 and 2, below).

Table 1: Levels of evidence

Reproduced from Management of type 2 diabetes - management of blood glucose. NICE Inherited Clinical Guideline G, by kind permission of the National Institute of Clinical Excellence

Table 2: Grading of evidence

Reproduced from Management of type 2 diabetes - management of blood glucose. NICE Inherited Clinical Guideline G, by kind permission of the National Institute of Clinical Excellence

The development group started with key clinical questions that were to be addressed by the research evidence and the professional knowledge and experience of group members (Box 1, below).

Box 1: Key questions
  • What are acceptable and unacceptable blood glucose levels?
  • What levels should be aimed for and achieved, to reduce risks of:
    • microvascular disease
    • arterial disease?
  • What methods can be supported?
    • pharmacological interventions
    • lifestyle interventions

Extensive formal searching and appraisal of research evidence was undertaken and findings presented to the multidisciplinary guideline development group. Although type 2 diabetes is relatively common and the complications devastating, in some areas there is a paucity of good quality research evidence to point the way to effective management.

Glucose control: targets and monitoring

The evidence for the relationship between poor blood glucose control and adverse health outcomes is good, although the evidence for microvascular complications is more abundant and robust than for macrovascular disease. The group was therefore able to set targets for blood glucose levels with some confidence.

However, the evidence for which biochemical measures to use, how often to measure blood glucose, and by what means was relatively poor. The group concluded that as there was evidence that standardised HbA1c can indicate the risk of developing complications, and is the measure used in the major outcome studies, it was the most useful measure clinically to assess overall blood glucose control.

Targets are a difficult issue in progressive disease management, as they are quite often unattainable in a significant proportion of individuals. However, the guideline group recognised that many people would be able to reach optimum targets with modern therapy and that it would be wrong to deny them the protection that offered.

In practice, a target becomes the level at which attempts to intensify therapy should start in those with deteriorating blood glucose control, and the level at which further intervention was not required for those responding to therapy. The fact that some patients would be unable to reach targets despite maximum personal and professional effort was not felt to be a significant barrier to setting targets.

Having set targets, the issue of how often blood glucose should be measured needed to be considered. Twice-yearly measurement of HbA1c was recommended because patients can deteriorate rapidly in some circumstances. However, the evidence to underpin this was group consensus based on epidemiological data.

The evidence for self-monitoring of blood glucose by patients was quite robust, despite the lack of evidence to show that self-monitoring per se affects blood glucose levels. Self-monitoring is part of the process of enabling individuals to manage their own condition, for example by seeing the impact of dietary change.

Patient education

Patient education is a crucial part of self-management in individuals with type 2 diabetes, as changing behaviour has the potential to improve critical aspects of diabetes management, such as controlling blood glucose levels, lipid levels and body weight, and preventing foot complications.

The partnership based on information shared between patients and professionals is widely seen as an essential element of the effective management of diabetes.

However, while the evidence suggests that it is beneficial to provide education, we could discern no clear evidence about which type of patient education, mode of delivery or professional group was most effective in delivering educational interventions. Thus the guideline recommendations were to offer education and to try a range of approaches to suit the individual patient.

There was also a lack of robust research evidence relating to lifestyle and, again, the most concrete recommendation that could be made was to try different approaches until the desired outcomes were achieved. Although several systematic reviews and meta-analyses have been undertaken in these fields, they were of mixed quality, as data were often pooled inappropriately.

Pharmacological interventions

As might be expected, the evidence to underpin pharmacological intervention was, on the whole, more methodologically robust. However, even here there were significant gaps.

Some older therapies lacked evidence that would be considered methodologically acceptable today. So, for drugs such as tolbutamide, there was little research evidence but decades of clinical experience.

In the case of metformin, however, its recent introduction in the USA means that there are several recent randomised controlled trials and meta-analyses. Moreover, metformin was used in a subpopulation of the UKPDS.

There is a lack of evidence for some new drugs; however, we were able to draw upon some recent NICE technology appraisals for the thiazolidinediones (commonly referred to as glitazones) and anti-obesity agents.

For areas such as insulin regimens and insulin delivery devices, robust evidence to support established clinical practice is largely absent. For insulin therapy in combination with oral glucose-lowering drugs it is rather better.

Other important issues such as concordance of therapy (for example choice of once daily or multiple dosing in patients on 3-15 different drug types) are also poorly supported. In many areas the lack of head-to-head trials (most were placebo trials) created difficulties in decisions about comparative effectiveness.

How will the guideline improve patient care?

The blood glucose guideline is the third in a series of four recently published by NICE.2 These include clinical practice guidelines covering the early management of retinopathy, renal disease, lipid and blood pressure management. Foot care was covered in an earlier guideline published by the Royal College of General Practitioners6 and is being updated by NICE for issue in late 2003.

It is hoped that this series of guidelines will provide a framework of practice recommendations to help prevent complications, delay their onset or ensure that effective interventions are delivered. All of these can help to lessen the burden of disease for the NHS and for patients.

Each NICE guideline contains an algorithm (see Figure 1, below) which provides a useful summary of key recommendations (see Box 2, below). Patient information has also been produced to foster partnership, which is the keystone to effective care for patients with type 2 diabetes.

Figure 1: Algorithm for the management of blood glucose in adults with type 2 diabetes
Reproduced from Management of type 2 diabetes - management of blood glucose. NICE Inherited Clinical Guideline G, by kind permission of the National Institute of Clinical Excellence
Box 2: Key recommendations and grades of evidence
  • Individuals with type 2 diabetes should have ongoing structured evaluation of microvascular and cardiovascular risk and the development of complications (C)
  • Haemoglobin A1c (HbA1c) should be measured at 2-6 monthly intervals, depending upon levels of control and stability, and changes in therapy (D)
  • For each individual, a target HbA1c (DCCT-aligned) should be set between 6.5% and 7.5%, based on the risk of macrovascular and microvascular complications (B)
  • Weight loss and increased physical activity should be encouraged in those who are overweight or obese (B)
  • Patient education should be offered on an ongoing basis. Different approaches should be tried until the best methods for the patient are identified from the attainment of desired outcomes (A)
  • In individuals who are overweight (BMI >25kg/m2) and whose blood glucose is inadequately controlled using lifestyle interventions alone, metformin* should normally be used as the first-line glucose-lowering therapy (A)
  • Metformin should be considered as an option for first line or combination therapy for individuals who are not overweight (A)
  • Insulin secretagogues should be used in combination with metformin in overweight or obese individuals when glucose control becomes unsatisfactory (A)
  • Insulin secretagogues should be considered as an option for first-line therapy when:
    • metformin is not tolerated or is contraindicated (A)
    • individuals are not overweight (A)
  • Individuals should be offered a thiazolidinedione as oral combination therapy if:
    • they are unable to take metformin and insulin secretagogues as combination therapy (A), or
    • the HbA1c remains unsatisfactory despite adequate trial of metformin with insulin secretagogues (A)
  • Insulin therapy should be offered to individuals with diabetes with inadequate blood glucose control on optimised oral glucose-lowering drugs (A)
  • When transferring an individual from a combination of metformin and another oral agent to insulin therapy, continue with metformin (B)
  • When transferring an individual from a combination of sulphonylurea plus another oral agent (metformin not tolerated or contraindicated) to insulin therapy, continue the sulphonylurea (B)

* Metformin is contraindicated in those with renal impairment (serum creatinine >130µmol/l) and those at risk of sudden deterioration of renal function (C)

Audit criteria have also been presented to provide a starting point for improving the quality of care provided, with the aim of moving from the auditing process to a consideration and measurement of outcomes.

The guidelines also provide a list of key areas for future research (Box 3, below).

Box 3: Key areas for future research
  • Studies of relative effectiveness of different insulin secretagogues
  • Studies of forms of blood and urine self-monitoring in individuals using oral glucose-lowering drugs
  • Studies of the impact of providing a summary of the assessments and management plan for the individual
  • A long-term outcome study of metformin in non-obese patients
  • Outcome studies of earlier initiation of insulin therapy
  • Studies of different insulin regimens in individuals with type 2 diabetes
  • Economic assessment of the impact of different strategies to reduce arterial event risk in individuals with diabetes, and find optimally cost-effective approaches to this
  • Studies that investigate which measures should be used in the assessment of blood glucose levels

Integrating activity: promoting best practice

The diabetes guidelines advocate measuring, classifying, acting on, and assessing the result in a continuing cycle of care to manage all aspects of the condition equally and efficiently. In the past, diabetes has been seen as a condition of blood glucose control, rather than one of vascular risk management for both arterial and small vessel disease.

There is robust evidence that the multiple intervention approach to vascular risk management can extend the healthy-life expectancy of individuals with type 2 diabetes. A useful exercise here is for health professionals to calculate the evidence-based gains for a high risk smoker with type 2 diabetes, treated with glucose lowering, blood pressure lowering, lipid lowering, antiplatelet and smoking cessation interventions.

The guideline on blood glucose management did not assess the cost utility of many of the interventions. However, the most expensive of these therapies have been the subject of NICE technology appraisals, which found them affordable by conventional NHS criteria, largely because of the high costs of preventable complications.

National Institute for Clinical Excellence. Management of type 2 diabetes - management of blood glucose. NICE Inherited Clinical Guideline G. London: NICE, September 2002 can be downloaded from the NICE website: www.nice.org.uk

This work is undertaken by ScHARR, University of Sheffield, which received funding from the Royal College of General Practitioners on behalf of the National Institute for Clinical Excellence. The views expressed in this article are those of the authors and not necessarily those of either the Royal College of General Practitioners or the National Institute for Clinical Excellence.

References

  1. Audit Commission. Testing Times: A Review of Diabetes Services in England and Wales. London: Audit Commission, 2000.
  2. National Institute for Clinical Excellence. Management of type 2 diabetes – management of blood pressure and blood lipids. NICE Inherited Guideline H. London: NICE, 2002. www.nice.org.uk
  3. Laakso M. Hyperglycaemia as a risk factor for cardiovascular disease. In Marshall SM, Home PD, Rizza RA (eds): The Diabetes Annual/12. Amsterdam: Elsevier Science, 1999. p. 317-28.
  4. Stratton IM, Adler AI, Neil HA et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Br Med J 2000; 321: 405-12.
  5. McIntosh A, Hutchinson A, Home PD et al. Clinical guidelines and evidence review for Type 2 diabetes: management of blood glucose. Sheffield: ScHARR, University of Sheffield: 2002. www.nice.org.uk
  6. Hutchinson A, McIntosh A, Feder G, Home PD et al. Clinical Guidelines for Type 2 Diabetes – Prevention and Management of Foot Problems. London: Royal College of General Practitioners, 2000.

Guidelines in Practice, December 2002, Volume 5(12)
© 2002 MGP Ltd
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