H
b
A1
c
levels
in
individuals
heterozygous
for
hemoglobin
variants
R
ev
A
ssoc
M
ed
B
ras
2017; 63(4):341-346
343
Data were tabulated using statistical software, Mi-
crosoft Excel
®
and GraphPad Software, Inc., version
Prisma 6. Comparison of HbA1c levels between individu-
als heterozygous for hemoglobin variants and controls
with no change in hemoglobin structure was performed
based on standard deviation, mean and G-Test.
R
esults
We analyzed 50 patients heterozygous for hemoglobin
variants with normal blood glucose levels, of which 23
were male, representing 46% of the study population, and
27 were female, totaling 54%. Of the total 50, 16% are AC
and the remaining 84% are AS.
Dividing the group by age, we found 39 adults with
a mean age of 34.6 years (21 ± 38 years) and 11 children
and adolescents with a mean age of 5.9 years, ranging
from 1 to 13 years. In this group, no interferer was ob-
served, as described in Table 1.
TABLE 1
Assessment of interferers in a heterozygous
population.
Tests
Mean Minimum
value
Maximum
value
Reference
value
Urea
27 mg/dL 17 mg/dL 39 mg/dL 15-40 mg/dL
Triglycerides 113 mg/dL 80 mg/dL 143 mg/dL < 150 mg/dL
Total bilirubin 0.9 mg/dL 0.6 mg/dL 1.2 mg/dL ≤ 1.2 mg/dL
Source: Clinical Laboratory at PUC Goiás.
The mean values of HbA1c in heterozygous children were
at 5.11%, with a minimum of 3.9% and maximum of 5.97%.
The mean fasting glucose in this group was 89.56 mg/dL,
ranging from a minimum of 75 mg/dL to a maximum of
97 mg/dL, while mean hemoglobin was 12.9 g/dL, rang-
ing from 12.1 g/dL and 14 g/dL.
The mean A1c of heterozygous adults was close to the
values found for children, at 5.0%, ranging from a mini-
mum of 3.1% to a maximum of 6.9%. As for mean fasting
blood glucose, the adult population presented 84 mg/dL,
ranging from a minimum of 69 mg/dL to a maximum of
97 mg/dL. Mean hemoglobin was at 13.8 g/dL, ranging
from 12.3 g/dL to 15.8 g/dL.
In order to compare the data, we analyzed the same
tests in 50 patients without heterozygosity for hemoglo-
binopathies, with normal glycemic levels, of which 71.4%
were female. This group included 11 children and adoles-
cents, with a mean age of 10 years (6 ± 14 years). The fol-
lowing results were found in this class: HbA1c 5.78%, fast-
ing blood glucose 78.8 mg/dL and hemoglobin 14 g/dL.
With regard to the adult control population, 39 people
withmean age of 45 years (22 ± 37 years) were analyzed. We
found in this group the following mean test results: HbA1c
5.84%, ranging from 4.1% to a maximum of 6.9%, fasting
blood glucose at 89.3 mg/dL, ranging from 60 mg/dL to
99 mg/dL, and mean hemoglobin at 13.6 g/dL, ranging
from a minimum of 12 g/dL to a maximum of 15.7 g/dL.
HbA1c standard deviation of the children was then
calculated, reaching the result of 0.40 in the control group
and 0.75 in the test group. The standard deviation from
the adult test population was also calculated, which was
1.09 and the control was 0.57.
The value of the G-test was also determined, repre-
senting the result of HbA1c in the normal group compared
to the altered group, reaching p=0.93 for children and
p=0.89 for adults (Figures 1 and 2).
Of the 50 heterozygous individuals, ten had results
below the lower limit of 4%. Of these, eight were adults
and two were children, of whom nine were female. The
electrophoretic pattern of this group was verified and
eight fit the AS profile, while two were AC.
D
iscussion
This study showed significant similarity with the findings
of Menezes et al.,
19
whose comparative inferential analy-
sis of HbA1c was: AA, AS, AC and SS obtained from blood
samples from 150 participants, including diabetics, was
not significant, the same being observed in our study with
100 subjects who had normal glycemic levels.
Yedla, Kuchay and Mithal
20
evaluated the levels of
fasting blood glucose, postprandial blood glucose, fruc
tosamine and HbA1c (immunoassay technique) of a dia
betic patient, resulting in higher levels of fasting blood
glucose, postprandial blood glucose and fructosamine,
but not HbA1c, which remained normal. They concluded
that the result was underestimated, and a different tech
nique should be performed for this type of examination.
According to the study, ion exchange chromatography
(HPLC) as a method used to measure HbA1c is not influ-
enced by heterozygous hemoglobinopathies, as Copeland
et al.
21
report that some methodologies may have interfer-
ence from heterozygous hemoglobins.
In a study by Camargo and Gross,
22
the authors ana-
lyzed more than 25,000 samples and found patients het-
erozygous for HbS, HbC or HbD, noting that the presence
of a hemoglobin variant may yield lower (false) results.
However, anemia is also a source of negative interference.
The hematological status should be considered for the
correct interpretation of GHb results.
Despite cation exchange, HPLC is the reference meth
od, and the presence of hemoglobin variants may inter-
fere with levels of HbA1c, yielding false high or low levels