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| 3 | 2008
Klinisk Biokemi i Norden
Background
The HbA1c value reflects the
degree of non-enzymatic, irrever-
sible glycation of hemoglobin. In
parallel with this process hund-
reds of other plasma and mem-
brane proteins are glycated. The
process of glycation starts with
the formation of a labile Schiff ’s
base followed by an Amadori
rearrangement to a deoxyfruc-
tosyl derivate of the protein in
a Maillard reaction. The degree
of glycation of hemoglobin is
determined by the balance bet-
ween the life span of erythrocytes
(approximately 120 days) and the
glucose concentration and the
time length of hyperglycemia. At
the start of intensive therapy of diabetes the HbA1c
level decreases rapidly during the initial 8 weeks fol-
lowed by a gradual decrease to a steady-state level
after another 8 weeks (1).
The rate of microvascular complications in diabe-
tes (retinopathy, nephropathy and neuropathy) has
been shown to be related to the HbA1c value and
HbA1c has therefore become the established standard
to assess the metabolic control in diabetes and predict
long term complications (2,3). An increasing risk also
of macrovascular diseases (cardiovascular disease,
stroke and peripheral vascular disease) with increa-
sing HbA1c has been shown in the non-diabetic part
of the population (4).
The risk for complication in diabetes is exponen-
tially related to HbA1c. To visualize this effect the
theoretical amount of individuals with retinopathy at
a certain HbA1c concentration have been calculated
(Fig. 1). High HbA1c values mean much higher risk
than medium values. A reduction of HbA1c from
10% to 9% contributes to the same reduction of com-
plications, as does a reduction from HbA1c 9% to
5%. However there is no threshold under which the
complications are absent. The lack of standardization
of HbA1c methods has resulted in several regional
and national harmonization programs.
A National Diabetes Register (NDR) was establis-
hed in Sweden 1996 for quality assessment of the
diabetes care. HbA1c values, blood pressure, other
risk parameters and treatment are now registered for
about 50% of the patients with diabetes. Results are
presented once a year where the degree of fulfilment
of actual treatment goals is compared among diffe-
rent parts of Sweden (5). A similar register exists for
diabetic children, The Swedish Childhood Diabetes
Registry (6).
National and international clinical diabetes orga-
nisations recommend target values for HbA1c below
where the risk to develop late complications is mini-
mal. It is therefore important that laboratory assays
HbA1c – new standardization and new unit
Gunnar Nordin
1
and Jan-Olof Jeppsson
2
1
EQUALIS, Uppsala, Sweden. E-mail gunnar.nordin@equalis.se,
2
Department of Clinical Chemistry, Malmö, Sweden. E-mail jan-olof.jeppsson@med.lu.se
Fig 1. There is an exponential relation between HbA1c and
risk for retinopathy. This graph represents theoretical number
of retinopathy patients per year in Sweden if all patients (400
000) have a certain HbA1c concentration. Calculated from the
DCCT study (Reproduced from reference 23.).
