Dr Alan Begg highlights points for primary care relating to the NICE guideline on managing hyperglycaemia in acute coronary syndromes

In October 2011, NICE published Clinical Guideline (CG) 130 on managing hyperglycaemia in acute coronary syndromes (ACS).1 The recommendations cover patients admitted to hospital with a suspected episode of ACS, the spectrum of occlusive coronary heart disease ranging from unstable angina to all forms of myocardial infarction (MI).

The NICE guideline provides advice on the use of intensive insulin therapy in the first 48 hours after admission in those with a blood glucose level >11 mmol/l.1 This cut-off point was based on consensus within the Guideline Development Group (GDG) and is in line with the published evidence used to inform the recommendations. Although not immediately apparent, the guideline is of relevance to primary care. Hyperglycaemia at the time of admission in patients with ACS is a strong predictor of poor survival and results in an increased risk of complications.1

The main NICE recommendation is that patients with ACS and hyperglycaemia should be considered for a dose-adjusted insulin infusion, with regular monitoring of blood glucose levels to ensure that levels are kept below 11 mmol/l.1

The NICE guideline illustrates the difficulty of formulating precise guidance when the evidence base is conflicting, which can result in variation in clinical practice. The recommendations were underpinned by evidence from three trials:2–4

  • DIGAMI 1 (Diabetes mellitus Insulin and Glucose infusion in Acute Myocardial Infarction)
  • DIGAMI 2
  • HI5 (Hyperglycemia: Intensive Insulin Infusion In Infarction).

The DIGAMI 1 trial recruited 602 patients with suspected acute MI and known diabetes and a blood glucose level >11 mmol/l or a level >11 mmol/l, but without known diabetes.2 This study showed that an insulin glucose infusion followed by a multidose insulin regimen resulted in improved long-term prognosis in patients with acute MI and diabetes, with significant mortality benefit at 1 year compared with conventional therapy: after 1 year, 57 subjects (18.6%) in the infusion group had died compared with 82 subjects (26.1%) in the control group giving a relative mortality reduction of 29% (p=0.027).

The follow-up DIGAMI 2 trial of 1253 patients investigated whether long-term insulin therapy was beneficial in patients with diabetes and an MI.3 However, the results did not reveal any additional benefit and it was concluded that insulin therapy was not required beyond the first 24 hours unless clinically indicated. Nevertheless, there was a clear message from the DIGAMI 2 trial that glycated haemoglobin (HbA1c) and blood glucose levels were significant independent mortality predictors in patients who had experienced an MI, in addition to traditional risk factors.

The HI5 study recruited 240 subjects with acute MI and a blood glucose level ?7.8 mmol/l who either had known diabetes or were not diabetic.4 Participants were treated with insulin/dextrose infusion therapy for at least 24 hours, but no reduction in overall mortality was demonstrated, either at the inpatient, 3-month, or 6-month stage. However, mortality was lower in people who achieved a mean blood glucose level of ?8 mmol/l in the first 24 hours compared with a level >8 mmol/l (2% versus 11% at 6 months, p=0.02).

Overall, the NICE GDG did not believe that intensive insulin therapy had a significant effect on overall mortality despite the results of DIGAMI 1, which it felt was underpowered. The GDG also highlighted that ACS is now managed very differently compared with when the trial was performed, particularly with regard to the extensive use of antiplatelet and statin therapy and coronary revascularisation.5 It was on this basis that NICE made the additional secondary recommendation that intensive insulin therapy should not be offered routinely to manage hyperglycaemia unless clinically indicated.1

Additionally, the guideline recommends that patients without known diabetes should have tests for fasting blood glucose and HbA1c levels within 4 days following onset of ACS.1 Although these tests should be performed before discharge, they should not delay it, so the burden of testing is likely to fall on general practice. If these results are within the normal range, a routine oral glucose-tolerance test does not need to be offered to the patient.1

Appropriate long-term care and follow up after discharge need to be arranged for people with ACS and hyperglycaemia. The NICE guideline recommends that lifestyle advice be provided on healthy eating, increased physical activity, weight management, smoking cessation and alcohol consumption. General practitioners should offer at least annual monitoring of HbA1c and fasting blood glucose levels but checking both these parameters in these patients may overcome the present controversy over how we should confirm a diagnosis of diabetes.


Improving diagnosis of diabetes

The challenge to general practice is how to identify new patients with diabetes and confirm the diagnosis, especially in high-risk groups. This will allow blood glucose to be controlled prior to any possible admission with ACS. Approximately 30%–50% of diabetes cases are undiagnosed and between 3% and 15% of the elderly population may have undiagnosed diabetes.6 A delay in making a diagnosis may lead to greater complications, and identification of diabetes can allow risk factors to be addressed, and ensure prompt screening for retinopathy and kidney disease. Addressing hyperglycaemia in the elderly may also improve cognition. Questioning of newly presenting patients with diabetes of all ages in one study revealed that 39% had symptoms for more than 12 months and 80% recognised the presence of one or more further symptoms when asked directly.7

At present, the quality and outcomes framework (QOF) encourages annual review of risk factors (e.g. blood pressure and smoking) in patients with coronary heart disease, with cholesterol as the only biochemical parameter that needs to be measured. There is no requirement or incentive to screen individuals for diabetes unless they are on the mental health register (MH15).8

Screening

Currently the main approach to screening for diabetes is through NHS Health Checks—a systematic and targeted programme of vascular risk assessment and management.9 These were launched by the Westminster Government in 2008 and taken over by NHS Diabetes and Kidney Care, in conjunction with the Department of Health, in April 2010. The programme aims to provide preventative checks to all people aged 40–74 years in order to help prevent heart disease, stroke, diabetes, and kidney disease. If we are to reduce the level of undiagnosed diabetes, the impetus and funding for these universal checks needs to be continued.

Diagnosis

A further area of uncertainty is how diabetes should be diagnosed. The World Health Organization (WHO) has been publishing guidance on the definition of diabetes since 1965. In 2005, the diagnostic criteria for diabetes was maintained at a fasting plasma glucose level of ?7.0 mmol/l or a 2-hour post-prandial plasma glucose level of ?11.1 mmol/l.10 Similarly, there was no change to the definition of impaired glucose tolerance, with the cut-off point for impaired fasting glycaemia remaining at 6.1 mmol/l. The criteria for impaired glucose tolerance was a fasting plasma glucose of <7 mmol/l and a 2-hour plasma glucose of ?7.8 and <11.1 mmol/l.10

Defining a normal glucose level was found to be difficult and so WHO recommends using the term ‘normoglycaemia’ in relation to glucose levels associated with a low risk of developing diabetes or cardiovascular disease.10 Identification of people with impaired glucose tolerance is beneficial as lifestyle and pharmacological interventions in this patient group can prevent or delay progression to diabetes.

Using HbA1c
WHO has now issued a report indicating that HbA1c can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to international reference values.11 It recommends an HbA1c cut-off value of 48 mmol/l for diagnosing diabetes but states that a value of <48 mmol/l does not exclude diabetes diagnosed using glucose tests.11 However, the use of HbA1c may not be suitable for all individuals (see Box 1, below).12

Box 1: Using HbA1c for the diagnosis of diabetes12

The use of HbA1c as a sole test to diagnose diabetes is not appropriate in:

  • all symptomatic children and young people
  • patients of any age with symptoms suggestive of type 1 diabetes
  • patients who have had symptoms of diabetes for less than 2 months
  • patients at high risk of diabetes who are acutely ill
  • women who are pregnant
  • those taking medication such as corticosteroids and antipsychotics, which may cause a rapid glucose rise
  • people with acute pancreatic damage or previous pancreatic surgery.

WHO has also included factors and conditions that may also affect HbA1c and its measurement, such as anaemia, altered haemoglobin, chronic alcohol problems, and chronic renal failure, which may affect glycation.11

There is concern that the WHO-simplified criteria for the diagnosis of diabetes may increase the number of diagnosed people, but as the majority of them will be identified at an early stage, they will be initially controlled by diet alone. Intensive diet and lifestyle changes that are instituted when a diagnosis is made earlier will reduce progression and long-term complications. WHO highlights that the diagnosis of diabetes in an asymptomatic person should not be made on the basis of a single abnormal value, and at least one additional value in the diabetic range should be obtained.11 It has been suggested that this should be carried out after a period of 2 weeks using the same laboratory.12

What should GPs do in the meanwhile? For patients deemed to be at high risk of diabetes such as those with ACS (as referred to in NICE CG130), screening for HbA1c on an annual basis, as part of the regular QOF review for coronary heart disease, would be appropriate. At present, measurement of HbA1c has not been formally adopted in the UK for the diagnosis of diabetes, but we look forward to further guidance at a local or national level.13,14

Conclusion

The initial management of hyperglycaemia in patients with an ACS event is the responsibility of secondary care, but general practice is expected to provide post-discharge assessment and ongoing monitoring. General practice also has an important role in population screening for diabetes and identifying other individuals at high risk of developing the disease. Despite controversy on the current approach to confirming a diagnosis of diabetes, identifying patients earlier allows effective management, reduction of long-term side effects, and improved outcomes from coronary events.

  • The NICE guidance on managing hyperglycaemia in people admitted to hospital for acute coronary syndromes is very specific to a small group of patients
  • Commissioners and secondary care clinical colleagues should be able to agree a simple care pathway for this group of patients and include it in local contracts
  • This should specify follow-up tests in hospital for those with hyperglycaemia, where time allows
  • However, as some admissions for acute coronary syndromes can be very short, clear guidance for primary care on glucose monitoring should be detailed in the discharge summary
  • Regular audit of this patient group against the pathway can demonstrate quality.
  1. National Institute for Health and Care Excellence. Hyperglycaemia in acute coronary syndromes: management of hyperglycaemia in acute coronary syndromes. Clinical Guideline 130. London: NICE, 2011. Available at: www.nice.org.uk/cg130
  2. Malmberg K, Rydén L, Efendic S et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment
    in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol 1995; 26 (1): 57–65.
  3. Malmberg K, Rydén L, Wedel H et al. DIGAMI 2 Investigators. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 2005; 26 (7): 650–661.
  4. Cheung N, Wong V, McLean M. The Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5) study: a randomized controlled trial of insulin infusion therapy for myocardial infarction. Diabetes Care 2006; 29 (4): 765–770.
  5. National Institute for Health and Care Excellence. Hyperglycaemia in acute coronary syndromes: management of hyperglycaemia in acute coronary syndromes. Full Guideline 130. London: NICE, 2011. Available at: www.nice.org.uk/cg130
  6. Croxson S. Diabetes in the elderly: diagnosis, testing and screening. In: Sinclair A, Finucane P, editors. Diabetes in old age. 3rd edition. Chicester: John Wiley & Sons, 2009: pp.21–38.
  7. Singh B, Jackson D, Wills R et al. Delayed diagnosis in non-insulin dependent diabetes mellitus. BMJ 1992; 304 (6835): 1154–1155.
  8. British Medical Association. NHS Employers. Quality and outcomes framework guidance for GMS contract 2011/12. London: BMA, NHS Employers, 2011. Available at: www.bma.org.uk/employmentandcontracts/independent_contractors/quality_outcomes_framework/qofguidance2011.jsp
  9. NHS Health Check website. NHS Health Check. www.healthcheck.nhs.uk/ (accessed 25 January 2012).
  10. World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Geneva: WHO, 2006. Available at: whqlibdoc.who.int/publications/2006/9241594934_eng.pdf
  11. World Health Organization. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. Geneva: WHO, 2011. Available at: www.who.int/diabetes/publications/report-hba1c_2011.pdf
  12. John G, Hilson R, Alberti G. Use of HbA1c in the diagnosis of diabetes: the implementation of WHO guidance 2011. Diab Primary Care 2011; 13 (6): 333–334.
  13. Diabetesbible website. Type 2 diabetes mellitus. www.diabetesbible.com/condition/type-2-diabetes-mellitus/investigation (accessed 26 January 2012).
  14. Diabetes UK website. New diagnostic criteria for diabetes (Jan 2011). www.diabetes.org.uk/About_us/Our_Views/Care_recommendations/New_diagnostic_criteria_for_diabetes_/ (accessed 26 January 2012).G