Directly responsible for an estimated 1.6 million deaths in 2015, diabetes is predicted by the World Health Organization to become the seventh leading cause of death in 2030. Rates of people living with the disease are also rapidly rising, more than doubling in the UK since 1996.
A chronic disease characterized by a lack of blood glucose control, diabetes is associated with the development of a range of health conditions, including heart disease, stroke, eye problems and kidney disease. Diagnosing diabetes early is crucial in seeking appropriate treatment and minimizing the risk of complications developing. Yet estimates suggest that almost one in four people in the UK don’t know they have the disease.
EKF Diagnostics has recently published a guide to ‘Diabetes and HbA1c testing’, which provides an overview of the global diabetes ‘epidemic’, symptoms and complications, and discusses both glucose and HbA1c testing.
We spoke to EKF’s Gavin Jones to learn more about the current methods of diabetes diagnosis and monitoring, the advantages of HbA1C testing, and how testing may change in the future.
How can diabetes be diagnosed?
There are multiple options for the diagnosis of diabetes, most of which involve measuring the level of glycemic control a person exhibits i.e. how much glucose is present in their blood.
Measuring blood sugar levels
Currently, the two main methods used in the UK are:
Fasting plasma glucose concentration ≥ 7.0 mmol/l (whole blood ≥ 6.1 mmol/l) or
Two hour plasma glucose concentration ≥ 11.1 mmol/l two hours after 75g anhydrous glucose administered in an oral glucose tolerance test (OGTT).
When using either fasting plasma glucose or the OGTT to diagnose diabetes it’s important to consider the accuracy of the device being used to make the measurements. Most people with diabetes use handheld blood glucose analysers to monitor their glucose concentration throughout the day. However, although this is ok for monitoring, it’s not appropriate for initial diagnosis. This is because the current 2013 ISO criteria for handheld monitoring systems requires that 95% of blood glucose results should be:
• Within ± 15 mg/dl of laboratory results at concentrations of under 100 mg/dL
• Within ± 20% of laboratory results at concentrations of 100 mg/dL (5.6 mmol/L) or more
Whilst this may be ok for monitoring, 20% accuracy against lab results is quite wide and certainly not appropriate for diagnosis, which should only be carried out using a suitably accurate lab test. In fact the FDA has gone one step further and determined that glucose measurement within a clinical setting should meet the below criteria:
• 95% of meter values should be within 12% of the reference value for blood sugars over 75 mg/dL, and within 12 mg/dL for blood sugars below 75 mg/dL; and
• 98% of meter values should be within 15% of the reference value for blood sugars over 75 mg/dL, and within 15 mg/dL for blood sugars below 75 mg/dL.
Moving forward this criteria is only likely to get tighter. This means that handheld glucose analysers will have to significantly improve their accuracy, or clinical glucose measurement should only be handled by lab-based systems with more control over accuracy, precision and quality control.
Measuring HbA1c levels
That said, another diagnostic option is to use glycated hemoglobin (HbA1c). For some time now it’s been accepted that HbA1c can be used to not only manage glycemic control, but also to diagnose diabetes.
In 2011 the World Health Organization (WHO) reviewed their previous decision to recommend HbA1c as a diagnostic marker for diabetes. Their conclusion was 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 criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement. An HbA1c of 6.5% is recommended as the cut-off point for diagnosing diabetes. A value of less than 6.5% does not exclude diabetes diagnosed using glucose tests.”
WHO have also approved HbA1c for the diagnosis of diabetes with a Point-of-Care-Testing (POCT) device. This is as long as the test is carried out by a trained professional adhering to an appropriate External Quality Assurance (EQA) scheme and using a methodology that is traceable to the IFCC reference method.
This decision by WHO has significantly impacted the diabetes diagnostic landscape; previously lab-based HbA1c tests did not offer much of an advantage over fasting glucose or OGTT diagnosis techniques in terms of time and added-value. However, now POCT HbA1c tests can give a strong indication of not only diabetes, but also pre-diabetes in a timeframe where intervention can be made immediately.
What are the advantages of the HbA1c test?Hemoglobin has the ability to bind with glucose in the bloodstream; this type of bonding is called glycation. The glycation process is irreversible so glycated hemoglobin (HbA1c) remains in its evolved state for the lifespan of the red blood cell - approximately 8-12 weeks. Therefore, by measuring the amount of HbA1c in the blood it is possible to determine average blood glucose control over an 8-12 week period. The more HbA1c in their blood, the less controlled a patient’s diabetes is and the more susceptible they are to developing long-term health complications.
Due to its ease of testing and reliability, currently the UK’s NICE preferred method of blood glucose monitoring for type II diabetes is through HbA1c measurement. This is because both fasting glucose and OGTT have always been reliant on two factors; patient compliance and appropriate administering of the test.
The fasting glucose test requires the patient to fast for a minimum of eight hours before the test is administered. This method is, therefore, problematic as it is easy for the patient to consume food or drink without giving thought to the impact this will have on their blood glucose level. The OGTT requires the patient to ingest a glucose concentration drink with a known value and then return two hours later for a plasma glucose test. The issues here centre around the patient returning to the clinician in the time frame allowed, or impacting the test by eating or drinking during this period.
Are there any situations when HbA1c testing would not be appropriate?Monitoring HbA1c is a measure of only the glucose that has bonded to the red blood cells over the previous 8-12 weeks. It is not impacted by the same issues as blood glucose monitoring. The ingestion of glucose before the test has no impact on the result, and there is no waiting time involved. As a result HbA1c testing is becoming the preferred technique for diabetes diagnosis.
However, there are situations where HbA1c is not appropriate for the diagnosis of diabetes:
• In children
• During pregnancy
• People showing symptoms of diabetes for less than two months
• Those suspected of having type 1 diabetes
• Patients with acute pancreatic damage, including pancreatic surgery
• Presence of genetic, hematologic and illness-related factors
Where do you see the future of diabetes diagnostics headed?
Stratified HbA1c levels
On top of proficiency and standardisation improvements, there is a fairly extensive amount of research looking into other variables that can impact upon HbA1c measurement such as ethnicity and age. It has often been thought that baseline HbA1c levels increase with age without a precise relationship to glucose tolerance. The exact mode of action for this increase is still being studied, but there is evidence to suggest this could have something to do with red blood cell lifespan.
The same is true for race considerations within HbA1c measurement, although some differences in HbA1c levels across ethnicities could potentially be attributed to sociodemographic or clinical factors, there is still considerable evidence to suggest there are other factors in play. More work still needs to be done in both of these areas of research, but in the long-term it could lead to a more stratified definition of clinical HbA1c cut-off levels based upon age and race.
Point-of-care testingAs POC HbA1c testing becomes more accepted, it will start to become a more viable option for the diagnosis of diabetes. There are already POC HbA1c methods that meet the same criteria for diagnosis as lab systems, and with the increased accuracy being imposed upon the industry, the argument for only allowing lab systems to be used for diagnosis is slipping away. The benefits of POC HbA1c measurement, both clinically and from a patient-engagement perspective, cannot be ignored. It is only a matter of time before this becomes the accepted method for diabetes diagnosis.
Gavin Jones was speaking to Anna MacDonald, Editor for Technology Networks.
EKF Diagnostics guide to ‘Diabetes and HbA1c testing’ can be found at EKF’s new Diabetes Portal (www.ekfdiagnostics.com/diabetes-portal.html). Or downloaded at: https://www.ekfdiagnostics.com/res/Diabetes%20Guide%20Digital%20EN%200.0-06.17.pdf
This new educational guide draws on EKF’s expertise in the diagnosis and monitoring of diabetes and associated conditions. It provides an overview of the global diabetes ‘epidemic’, symptoms and complications, through to discussion on methods for diagnosis and monitoring using both glucose and HbA1c testing, with consideration given to factors influencing their measurement.
Gavin Jones – Biography
Gavin Jones has overseen the marketing and development of EKF Diagnostics’ diabetes portfolio for the past four years. Gavin attended Liverpool John Moores University where he attained a Bachelor of Science in Forensic and Biomolecular Sciences. He has worked in multiple scientific fields from forensic toxicology for the Home Office, through to analytical chemistry in the pharmaceutical industry, and finally settling now in the life sciences focused on development of POCT medical devices.