Issue 46 / 8 December 2014

GLYCATED haemoglobin, specifically HbA1c, long used to monitor control of diabetes, has also recently been approved as a diagnostic test for diabetes in asymptomatic patients at high risk.

HbA1c usually works well in monitoring the management of diabetes since HbA1c levels in the plasma reflect the average blood glucose levels over the past several months in most patients. However, practitioners need to be aware that HbA1c levels do not always reflect average blood glucose levels in some patients and this can be a trap.

While guidelines such as those produced by the RACGP give a good description of the potential problems with HbA1c, it is very easy to forget this when confronted with a patient who seems completely well except for possibly elevated blood glucose levels.

Two examples of patients where HbA1c measurements gave misleading results illustrate the need to sometimes consider uncommon problems. In one of these cases none of the doctors involved detected the problem over a period of more than 20 years!
    
Case 1

In a case we recently reported in Pathology, a middle-aged man was given a diagnosis of diabetes after he experienced symptoms and had several elevated blood glucose levels measured in the laboratory.

He was started on dietary management and medication. HbA1c measurements were commenced and were always in the normal range, so his medications were ceased. However, the patient continued home blood glucose monitoring and these measurements usually showed elevated levels. These home blood glucose results over a period of many years were dismissed by a series of doctors, both GPs and specialists, because of his “good” HbA1c results and otherwise normal pathology test results.

Eventually, one doctor became suspicious and investigated further, demonstrating that the patient had a low-grade haemolytic anaemia that was lowering his HbA1c levels because of the shortened red cell lifespan. Serum fructosamine levels were elevated and HbA1c testing was abandoned as inappropriate for this particular patient.

Case 2

The second patient* was again a middle-aged male with repeatedly elevated blood glucose levels but with a normal HbA1c. Other routine biochemistry tests were normal. Because his blood glucose results were consistently high he was referred to a diabetes educator and dietitian.

Home blood glucose monitoring was started and this showed lower but still elevated blood glucose levels. A repeat HbA1c 3 months after the initial test was again normal.

In this case the discrepancy was investigated earlier than in Case 1. Haematological investigations showed the presence of haemoglobin C disease, which is associated with shortened red cell survival and thus falsely low HbA1c levels.

Again, HbA1c testing was abandoned as being not suitable for this particular patient.

As with many other things in medicine, it pays to have a high index of suspicion where there are discrepancies in the expected pattern of results or clinical findings. The section on glycaemic monitoring and control in the 2014–2015 RACGP clinical guidelines describes these and other potential problems with HbA1c measurements.

There are a variety of methods in use to measure HbA1c in pathology laboratories. They do not all respond in the same manner to different haemoglobinopathies.

Depending on the type of abnormal haemoglobin present in the patient sample, some may show falsely low or high HbA1c levels. However, if the red blood cell (RBC) survival is shortened for any reason, HbA1c levels will be lower than expected because in vivo glycosylation is a slow process and haemoglobin in young RBCs is always less glycosylated than in older RBCs.

There is also potential for pathology laboratories to do more to assist doctors. For example, by calculating and reporting an estimated average glucose (eAG) as a comparator with measured blood glucose, or by detecting and flagging discrepancies between concurrent serum glucose and HbA1c levels, and even scanning other available results for clues as to the cause.

Laboratories may be reluctant to do this because it is an uncommon problem and doctors are already burdened with the volume of data from investigations.

For best patient care, we would advise doctors to not rely blindly on the HbA1c test result being “always” correct. If the “pattern” of results does not look right, be alert to the possibility of shortened RBC lifespan as a possible explanation for discrepancies between glucose and HbA1c levels.

 

Dr Bruce Campbell is the Editor-in-Chief of Lab Tests Online Australasia and a retired chemical pathologist.
Professor Leslie Burnett is past chair of the board of directors of Lab Tests Online Australasia, and clinical professor in pathology and genetic medicine, University of Sydney.

* Thanks to Dr Mona Botros, chemical pathology registrar, for identifying the second case.

6 thoughts on “Bruce Campbell

  1. Jan Sheringham says:

    Very pertinent advice. However, if FBG AND HbA1c are BOTH elevated I think we can be confident in diagnosing diabetes, thus avoiding that HORRIBLE glucose drink test! AND, with a correctly written request form, both tests can be collected at the same time.

     

  2. Ramachandra Pararajasegaram MD says:

     A very timely reminder of an important pitfall in the management of persons with and without Diabetes mellitus using only the HbA1C as the sole biomarker of successful diabetes mellitus control.

  3. Steve Kelly says:

    “For best patient care, we would advise doctors to not rely blindly on the HbA1c test result being “always” correct. If the “pattern” of results does not look right, ….”

    How is this story different to all of our job? We should never assume any result is correct in the face of other evidence – almost whatever disease we would be discussing. Of course, it may in the end be correct even when it is not confluent with everything else, but we should always observe the whole scene to arrive at the best understanding of the situation.

    Treating DIABETES is not the same as treating HbA1c and it never was.

    However, knowing that the RBC life is shortened and the HbA1c result is therefore a reflection of (perhaps) 30 days rather than 120 days, is more accurate than ignoring the result. Does the low HbA1c (30 day version) remain unreliable? Does it still reflect the current DM control? The story seems to suggest the test is in fact WRONG rather than just relating to shortened time!

  4. angus mc phail says:

    Seems this is an edited version of my case

    I was diagnosed in 1986 – hospitalised with HHS spent 7 days in hospital put on diamicron

    Went for 20 yrs of my 28 yrs with T2 diabetes with GPs and Path reports showing A1c ranged from 3-8 to max 5

    Was always told “great control”. Finally demanded referral to endocrinologist who took 10 secs to “diagnose” suspected haemoglobinopathy

    s a retired QA engineer, decided to investigate and found the following systemic errors:

    a) Path Labs presented 12 fasting a1c in 2 pages P1:A1c; P2: blood chemistry – done in 2 separate labs.

    b) Path reports went to GPs computer but did not sight both pages – A1c 4.0 /FGlucose 15.5mmols!!!

    c) These type of discordant results not picked up for 20 yrs of tests!

    d) Found that haemoglobinopathies are “more common in Australia in several ethnic heritage groups, eg, southern Mediterranean(Greek, Italia Spanish, etc) Middle Eastern; Chinese; SE Asian; Indian Sub continent;Latin American; Maori nd Pacific Islanders; some Aboriginal communities

    Is this not the populations with the highest incidence of T2 diabetes, most hospitalised withb diabetic complications;and with the highest morbidity rates in Australia? Are they “falling through the net”

    e) Received a position statement from UK Advisory Group – Women with iron deficiency, VitB12 def folatate defs, heavy menstrual bleeding ALL throw A1c falsley High –if GP misses this in diabetic women, they get overmedicated!!! with hypos becoming more likely

    Remedy – path labs pit A1c/Fg on the same page

     

  5. Ramachandra Pararajasegaram FRCP says:

    Moral of the story:

     Treat the patient; not the path. lab report (whether on the same page or not.)

  6. angus mc phail says:

    Addendum to aka 1

    GPs receive a PIP (performance incentive payment)  under Medicare for diabetes Patients.Under RACGP Std 3.2.3.2.1 “they must update the diabetes knowledge—-this is not audited and so

    becomes a “Std in Name Only”. a common problem in QA accreditation systems

    RACGP have udated their “Guidelines” 2014 sect 8.1 covering the “confounders”of Hba1c

    Suggestion

    AGPAL the Accreditation arm of RACGP MUST include Auditing an attendance record sightings

    to 2014 Guidelines–if not updated to current date– PIP  is stopped until presentation of Attendance

    certification  updated to .2014.

     

Leave a Reply

Your email address will not be published.