When to use fasting glucose to diagnose people with type II diabetes

Fasting plasma glucose should only be used to test for type II diabetes in situations when the use of HbA_1c is inappropriate.¹ The two primary situations where HbA_1c may be inaccurate are when serum glucose levels have risen too quickly for glycation rates to provide an accurate picture, or where a condition is present that will affect the accuracy of HbA_1c over the long term. Where serum glucose has risen quickly, HbA_1c should not be used. In clinical situations where HbA_1c may be misleading, measuring glycation rates may still be useful, although consideration should be given to using fasting plasma glucose.

Where serum glucose levels have risen rapidly, do not use HbA_1c

A recent UK consensus statement recommended that HbA_1c should not be used in the following patients or situations where blood glucose levels may have risen too fast to affect HbA_1c:⁵.

• All children and young people or anyone with suspected type I diabetes, regardless of age
• People with a short duration of diabetes symptoms
• Women who are pregnant or have been pregnant in the previous two months
• People at high risk of diabetes who are acutely unwell (HbA_1c ≥ 50 mmol/mol confirms pre-existing diabetes, but a value < 50 mmol/mol does not exclude it in an unwell patient and such patients should be retested once the acute episode has resolved)
• People taking medicines that may cause rapid glucose rise, e.g. corticosteroids or antipsychotics (for two months or less). HbA_1c can be used in people taking such medicines long-term (over two months) who are not clinically unwell.
• People with acute pancreatic damage or who have had pancreatic surgery

In these situations, where symptoms have only been present for a short period (less than three months) and glycation of haemoglobin is unlikely to have occurred, it is more appropriate to request fasting plasma glucose than HbA_1c.⁵ In addition, in some clinical settings self-monitoring blood glucose (SMBG) measurement, may be indicated to establish glucose levels to guide an acute intervention, such as hospital admission, in patients with suspected hyperglycaemia.

Table 1: Factors influencing HbA_1c results, modified from Gallagher^6,7

In clinical conditions where HbA_1c may be misleading, use with caution

Certain clinical conditions may also affect the accuracy of an HbA_1c test - the HbA_1c may be falsely low and lead to false-negative results, or falsely elevated and lead to a false-positive result for type II diabetes. Some conditions have variable effects on HbA_1c results and may increase or decrease HbA_1c levels. Table 1 lists the most common conditions and factors that affect HbA_1c. HbA_1c may still be useful in these situations, but it should be used with caution, and consideration given to using fasting plasma glucose.

These conditions need to be viewed within the clinical context of the patient. For many, the degree of effect on HbA_1c results is modest. For example, iron deficiency tends to modestly raise HbA_1c for unknown reasons.¹¹ However, if the rate of blood loss is enough to cause anaemia then HbA_1c will typically fall due to increased red blood cell turnover, i.e. HbA_1c will be falsely low, rather than high. A similar situation exists with patients who undergo venesection for haemochromatosis where HbA_1c results can be very low. In general, HbA_1c will still be useful, however, results should be viewed with caution and when there is clinical suspicion about the validity of the HbA_1c result, discussion with a clinical biochemist (pathologist) may be appropriate.

Note that there is also a possible age-related effect when using HbA_1c, which rises approximately 0.3% each decade in people with normal glucose tolerance.¹² This does not limit the use of HbA_1c in older people, but clinicians should be aware of the possible effect.

Where HbA_1c results are borderline or further investigation of the result is necessary, such as in a patient with two discrepant HbA_1c results, a fasting plasma glucose test may be useful if the result would change the management of the patient. However, waiting six months before retesting HbA_1c, with lifestyle interventions in the interim, would generally be the recommended management strategy.

If a fasting plasma glucose test is indicated, rather than HbA_1c, this can be undertaken and interpreted in accordance with previous type II diabetes testing guidance.

Patients are required to fast (i.e. no caloric intake) for at least eight hours, but ideally 12 hours, prior to testing.¹³ Advise patients that they may drink water during the fasting period.

In symptomatic people a single fasting plasma glucose result of ≥7.0 mmol/L can be considered diagnostic of type II diabetes for the majority of people.¹ Repeat testing is recommended where the result is borderline or there is clinical doubt about symptoms.

In asymptomatic people a fasting plasma glucose result of ≥7.0 mmol/L strongly indicates type II diabetes; however, a second test is required for confirmation.¹ The test should be performed on a separate occasion,¹³ ideally within two weeks.⁵ Lifestyle interventions should be encouraged during the waiting period. If the second result is discordant, repeat testing again in three to six months is recommended, with lifestyle interventions continuing in the interim.

The diagnostic criteria for type II diabetes¹

* Requesting both HbA_1c and fasting plasma glucose together in at-risk, asymptomatic people is unnecessary and discouraged.⁵ However, if HbA_1c and fasting plasma glucose are measured together, and results are discrepant with regards to a diagnosis of diabetes, the test above the diagnostic cut point should be repeated after three to six months.¹

Who should be screened for type II diabetes?

Current recommendations are for asymptomatic men aged over 45 years and women aged over 55 years to be screened for type II diabetes as part of a joint diabetes/cardiovascular risk assessment. Screening of asymptomatic Māori, Pacific and Indo-Asian people should begin at age 35 years for men and age 45 years for women.

Screening should be undertaken every three to five years depending on risk.

New Zealand Guidelines recommend screening ten years earlier in people with multiple risk factors:¹

• A family history of early onset type II diabetes (more than one first-degree relative)*
• A history of gestational diabetes*
• Known ischaemic heart disease, cerebrovascular disease, or peripheral vascular disease*
• Central obesity or increased BMI (BMI > 30 or >27 kg/m² for Indo-Asian people)*
• Long-term steroid or antipsychotic treatment*
• Intermediate hyperglycaemia on previous assessment, e.g. HbA_1c 41 - 49 mmol/mol or fasting plasma glucose 6.1 - 6.9 mmol/L
• An adverse lipid profile, e.g. TC/HDL ratio ≥7.0
• High blood pressure, e.g. ≥160/95 mm Hg
• Polycystic ovary syndrome
• Current smoker (or have quit within the last twelve months)

NZSSD also recommends that children and young adults with BMI >30 (or >27 kg/m² in Indo-Asian children) should be screened if:

• There is a family history of early onset type II diabetes or;
• They are of Māori, Pacific or Indo-Asian ethnicity

* Screening should be undertaken from age 25 years in people with multiple high risk factors, as indicated

All people with type II diabetes should have regular follow-up in general practice to monitor glycaemic control, risk level and disease progression. HbA_1c is the recommended test for measuring glycaemic control during follow-up. In the presence of the co-morbidities discussed in Table 1, HbA_1c may not accurately reflect the level of glycaemic control. Alternative methods for assessing control may be more appropriate, such as fasting plasma glucose and a series of self-monitoring blood glucose measurements for people using insulin. If therapeutic changes are being considered and there is clinical concern of the validity of the HbA_1c test, discussion with a diabetologist is recommended. Measurement of fructosamine may be an alternative option for some people, however, the availability of this test varies, so it should be discussed with a clinical pathologist or diabetologist first. Fructosamine is a glycated protein that indicates glycation levels over the preceding 14 - 21 days.¹⁸

How regularly should follow-up occur

Follow-up of people with type II diabetes should occur at least annually. In people with multiple co-morbidities or where regular medicine adjustments are being made to achieve appropriate control, more frequent consultations and testing e.g. three to six monthly, should be considered.

A full list of risk factors and the regularity of required follow-up can be found in the "New Zealand Primary Care Handbook 2012", available from: www.health.govt.nz

Follow-up should include measurement of HbA_1c (or an alternative method when HbA_1c is not appropriate), blood pressure and lipid levels, an assessment of diabetes related complications including cardiovascular disease (CVD) risk assessment, kidney disease assessment and checks for foot and retinal complications.¹⁹ In addition, educational material and advice on diet, exercise and smoking cessation should be discussed and provided at each follow-up visit, as applicable. N.B. Some factors, e.g. retinopathy will only need to be assessed annually, even in the highest risk groups.