Glucose monitoring

HbA1c has been the gold standard for monitoring long-term glycaemic management since 1976, and it is one method used to diagnose diabetes. HbA1c testing should be performed routinely at initial assessment. Monitoring is usually recommended at three-month intervals (four per year); however, with stable diabetes, a six-month interval may be appropriate. 

HbA1c measurement and natural test variation 

HbA1c can be measured and reported using two different standards: 

• as a percentage measure of the glycated N‐terminal residue of the β-chain of haemoglobin (eg 7%) 
• in units of mmol/mol, according to the International Federation of Clinical Chemistry (IFCC) standardised reporting (eg 53 mmol/mol). 

In Australia, the variability in laboratory HbA1c test results is acceptably low.⁶ However, there may be some variability,^7,8 which needs to be considered when monitoring long-term glucose management and that there are limitations to the utility of HbA1c in accurately reflecting day-to-day or week-to-week glycaemic variability. Conditions that affect HbA1c results also need to be considered (see below). 

Conditions that affect HbA1c results 

A number of conditions can cause HbA1c discordance, where HbA1c does not accurately reflect mean blood glucose. 

Any condition that shortens erythrocyte survival or decreases mean erythrocyte age will falsely lower HbA1c test results, regardless of the assay method used. 

The presence of abnormal haemoglobin variants can occur in people of Mediterranean, African or South-East Asian heritage. Screening for haemoglobinopathies before HbA1c testing should be considered.⁸ If a haemoglobinopathy is suspected, then haemoglobin electrophoresis is suggested. 

Some important clinical situations may indicate the presence of a haemoglobinopathy, such as when: 

• results of SMBG have a poor correlation with HbA1c results 
• an HbA1c result is discordant with measured alternative laboratory glycaemic values 
• an HbA1c result is >15% or <4% 
• a person’s HbA1c test result is radically different from a previous test result following a change in laboratory HbA1c measurement methods. 

Other causes of HbA1c discordance are presented in Box 1. 

Alternative forms of diabetes monitoring, such as SMBG, CGM and flash glucose monitoring (refer to ‘Use of technology in type 2 diabetes management’), should be considered for people with conditions that can affect HbA1c results. 

Note that fructosamine as an alternative longer-term glucose measure may not be suitable in people with iron deficiency anaemia, because this condition raises both HbA1c and fructosamine; conversely, iron infusion spuriously lowers both HbA1c and fructosamine.^9–11 

The shorter fructosamine time window is not sufficient for determining a long-term prognosis.¹ The fructosamine test measures glycated proteins (not glycated haemoglobin) that circulate in the blood for only 14–21 days. Anything affecting serum proteins may invalidate the test.¹² 

Advantages and limitations of HbA1c 

Clinical management of diabetes has been using HbA1c as a marker for healthy goals, complication prevention and management. However, HbA1c may be affected by various clinical physiological and pathological conditions, and this measure may lack sensitivity related to in-day and between-day glucose variability. Because HbA1c only provides an ‘average’ measure related to HbA1c over the past two to three months, various glycaemic excursion patterns may lead to the same HbA1c result, thus not accurately reflecting periods spent in hypoglycaemia and hyperglycaemia.^15–18 

The general target in (non-pregnant) people with type 2 diabetes is HbA1c ≤7% (≤53 mmol/mol).¹ 

In the vast majority of (non-pregnant) people with diabetes, optimising their blood glucose management may improve specific short- and long-term health outcomes. However, what is ‘optimal’ will vary, depending on the balance between benefits and risks and the individual’s priorities (Figure 1). Thus, there is no single glycaemic target that suits all people. 

For example, HbA1c targets may vary in selected people as follows:² 

• A more stringent target of 6.5% (48 mmol/mol) might be appropriate for people with short disease duration, long life expectancy and no significant cardiovascular disease, if this can be easily and safely achieved without hypoglycaemia or other adverse effects of treatment. The HbA1c target should be determined after assessment of hypoglycaemia risk and be re-evaluated in pregnancy and with the person’s characteristics.⁵ 
• If adults with type 2 diabetes reach an HbA1c level that is lower than their target and they are not experiencing hypoglycaemia, encourage them to maintain it. Be aware that there are other possible reasons for a low HbA1c level (eg deteriorating renal function or sudden weight loss).³ 
• Less stringent targets might be more appropriate for people with reduced life expectancy or extensive comorbid conditions; those who have difficulty attaining targets despite intensive self-management education, repeated counselling and effective doses of multiple glucose-lowering agents (including insulin); or those at risk of hypoglycaemia. 
• Investigate unexplained discrepancies between HbA1c and other glucose measurements. Seek advice from a team with specialist expertise in diabetes or clinical biochemistry.³ 

Diabetes symptoms (eg polydipsia, polyuria) are related to increasing glycaemia, as measured by HbA1c levels above 8% (64 mmol/mol).¹⁹ 

Figure 1. Approach to individualising HbA1c targets²⁰  

SMBG in people with type 2 diabetes is recommended:^2,4 

• for people on insulin and sulfonylureas, which can cause hypoglycaemia 
• for people not on insulin who are having difficulty achieving their glycaemic target (the person and their healthcare providers should be trained in methods to modify health behaviours and glucose-lowering medications in response to SMBG values) 
• when monitoring hypo-/hyperglycaemia arising from intercurrent illness (refer to ‘Medical management of glycaemia’, ‘Managing risks and other impacts of type 2 diabetes’ and ‘Type 2 diabetes sick-day management plan – template’) 
• during prepregnancy and pregnancy management for people with established diabetes or gestational diabetes 
• when there is a clinical need for monitoring, such as during changes in management or lifestyle, or for conditions or medications (such as corticosteroids) that require data on glycaemic patterns that HbA1c cannot provide 
• when HbA1c estimations are unreliable (eg haemoglobinopathies). 

Routine SMBG for people with type 2 diabetes who are considered low risk and who are using non-insulin glucose-lowering drugs (with the exception of sulfonylureas) is not recommended.^21–25 

The method and frequency of monitoring need to reflect individual circumstances and therapeutic aims. SMBG is most effective where the person with diabetes and their healthcare providers have the knowledge, skills and willingness to incorporate SMBG and therapy adjustments into diabetes care plans. 

Targets for self-monitored glycaemic management in type 2 diabetes (where stringent glycaemic management is recommended) are presented in Table 1. 

The National Diabetes Services Scheme (NDSS) provides subsidised blood glucose monitoring strips for SMBG for a six-month period after an initial diagnosis of diabetes. Ongoing access, in six-monthly increments, is available when assessed as clinically necessary and authorised by a general practitioner, credentialled diabetes educator, endocrinologist, nurse practitioner or other registered medical practitioner in the following categories: intercurrent illness; medications affecting blood glucose; critical need for self-monitoring; diabetes management change; and diabetes management not stable. Refer to the NDSS website for further information. 

For adults with type 2 diabetes who are self-monitoring their capillary blood glucose levels, a structured assessment at least annually should include:³ 

• the person’s self-monitoring skills 
• the quality and frequency of testing 
• checking that the person knows how to interpret the blood glucose results and what action to take 
• the impact on the person’s quality of life 
• the continued benefit to the individual 
• the equipment used. 

There is an emerging role for CGM and flash glucose monitoring in people with type 2 diabetes on complex insulin regimens who have not achieved their glycaemic targets; however, this technology is not available through the NDSS for people with type 2 diabetes. For more information, refer to ‘Use of technology in type 2 diabetes management’. 

Glycaemic variability represents the degree of stability of the glucose profile and refers to swings in blood glucose levels. Glycaemic variability can be measured as within-day, between-days or, most commonly, as the mean (and standard deviation) glucose level over two weeks. 

Emerging evidence in randomised controlled trials of people using multiple daily insulin shows an association between within-day or between-days glycaemic variability or ‘time spent in range’ observations and diabetes-related complications, especially microvascular complication.^26–28 Additional observational studies have linked same-day or between-days glycaemic variability to higher rates of both hypo- and hyperglycaemia for a given HbA1c, as well as peripheral neuropathy and retinopathy.²⁹ Lower levels of HbA1c are not directly linked to increased hypoglycaemia risk.³⁰ 

In adults with type 2 diabetes using basal bolus insulin therapy who have not achieved their HbA1c target, and who are willing to use CGM, real-time CGM maybe used to reduce HbA1c and the duration of hypoglycaemia. If using CGM to assess glycaemia, targets for non-pregnant adults are as follows:^2,31 

• time in range >70%, with time below range <4% and time <3 mmol/L being <1% 
• for those with frailty or at high risk of hypoglycaemia, a target of >50% time in range, with <1% time below range, is recommended.