The Diabetes Epidemic and the role of HbA1c

The significance of HbA1c for the diagnosis and follow-up of diabetes has increased with the continuing rise in the number of patients. This represents a significant workload challenge to many laboratories.

 

How to measure HbA1c?

One of the reference methods for HbA1c measurement is “High Performance Liquid Chromatography”, better known as “HPLC” (this method was also used in the DCCT and UKPDS trials). With this technique the different haemoglobin fractions are separated based on charge.

 

When using the Tosoh Automated Glycohemoglobin Analyzer HLC-723GX (GX) separation of the haemoglobin fractions is obtained by use of a negatively charged column and positively charged buffers that compete with the different haemoglobins to bind to the column (= cation exchange). Tosoh offers you over 35 years of world leading HPLC experience.

 

Why use HPLC?

Besides being the method used during the DCCT and UKPDS trials different arguments are raised in literature.

 

“The method of choice should measure HbA1c highly precisely; should be economical, automatable and simple to perform; and should yield results that are comparable between different laboratories, …one should use a method that meets the following conditions: The Hb variant should be recognised; and HbA1c, HbA0 and Hb variants should be separated and quantified reliably.” (2)

 

“The advantage of HPLC lies in its ability to separate variant haemoglobins and, in doing so, allowing better interpretation of the result!” (3)

 

The Importance of low CV%

HbA1c can be used for three specific applications*:

1. For identifying risk. HbA1c could be used as a tool, among other parameters, to identify individuals at risk for developing diabetes. The American Diabetes Association (ADA) suggested 5.7 – 6.4 % (39 – 47 mmol/mol) as the high risk range. (4,5)
2. For Diagnosis. An international expert committee assembled by the American Diabetes Association (ADA), International Diabetes Federation (IDF), and European Association for the Study of Diabetes (EASD) has recommended the HbA1c assay as the new test for the diagnosis of diabetes. An HbA1c value greater than or equal to 6.5 %, or 48 mmol/mol, is used as cut-off for the diagnosis of diabetes. Diagnosis should be confirmed with a repeat HbA1c test. (4,5)
3. For treatment follow-up. Lowering HbA1c to below or around 7 %, or 53 mmol/mol, has been shown to reduce micro-vascular and neuropathic complications of type 1 and type 2 diabetes. HbA1c of ≥ 7 %, or 53 mmol/mol, should initiate or change therapy to reach an HbA1c level of < 7 %, or 53 mmol/mol. Relevant changes in serial measurements of HbA1c testing serve as the guide to changes in therapeutic regimes. (6,7)

 

The Coefficient of Variation (CV) determines the difference between two serial HbA1c measurements. At a medical decision point of 7 %, or 53 mmol/mol, a healthcare provider should be able to conclude that a significant difference of 0.5 %, or 5 mmol/mol, is caused by a change in glycaemic control of a patient and not by the analytical imprecision. For that reason the CV% of the method should be ≤ 2.4 %. (8)

 

“…95 % of the laboratories using a method from Tosoh were able to meet the criteria of having an analytical CV% of ≤ 2.4 %!” (8)

 

* Official guidelines on the use of HbA1c may vary from country to country.

 

Stable HbA1c result with variant detection in 2.2 minutes,

 

The GX will deliver:

• Precision - Direct determination of stable HbA1c with less than 1 % CV.
• Speed - Stable HbA1c result with variant detection in 2.2 minutes. Time to first result is 6.6 minutes.
• Operational Simplicity - With cap piercing, positive sample identification, automated maintenance, the GX is simplicity itself.
• Absence of Interference  - In the presence of the most common haemoglobin variants, HbF or haemoglobin derivatives such as labile and carbamylated haemoglobin, HbA1c results are unaffected.

 

with less than 1 % CV. Time to first result is 6.6 minutes.

 

The GX provides you exceptional Operational Simplicity…

• Cap piercing capability minimises manual handling.
• Positive sample identification via barcode reader (optional).
• Up to 10 samples per batch.
• Automated daily maintenance.
• A user friendly touch screen enables easy instrument operation.
• Simple finger tight connectors permit quick, convenient and easy replacement of columns and pre-filters.
• Constant visual monitoring of buffer consumption with customisable alarm.
• Integration to Tosoh’s data management software (optional) for full data management capabilities including:

                      - Patient linked result validation 

                     - Chromatogram review with overlay and library facility

                     - Full QC-package including Levey-Jennings charts

                     - Reagent logging and audit trail

                     - Data storage and full result archiving

 

…and an unparalleled level of patient safety.

• Highly developed function for programming user-selectable flags to ensure easy interpretation of results.
• Unique TSKgel column and optimal column temperature control guarantee stable results.

 

The GX: the perfect solution for reliable diabetic patient monitoring!

•  HbA1c results directly determined with less than 1 % CV and reportable to 2 decimal places.
• Results unaffected by the presence of the most common haemoglobin variants or haemoglobin derivatives such as labile HbA1c and carbamylated - or acetylated haemoglobin.
• HbA1c results traceable to the NGSP / DCCT and IFCC.

 

Best-in-class chromatographic separation!

•  Separation of labile A1c from stable A1c is achieved without loss of precision or resolution and without manipulating the sample or using mathematical algorithms.

 

Traceability to International Standards

HbA1c results obtained with the G8 are traceable to the “National Glycohemoglobin Standardization Program (NGSP; DCCT-aligned)” and the “International Federation of Clinical Chemistry (IFCC)”.

Tosoh GX HbA1C Analyzers