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Review
HbA1c in pregnancy
Dalia Rafat a, Jamal Ahmad b,*
a
b
Department of Obstetrics and Gynecology, Faculty of Medicine, J.N. Medical College, Aligarh Muslim University, Aligarh 202002, India
Rajiv Gandhi Centre for Diabetes and Endocrinology, Faculty of Medicine, J.N. Medical College, Aligarh Muslim University, Aligarh 202002, India
A R T I C L E I N F O
A B S T R A C T
Keywords:
Pregnancy
HbA1c
Glycemia
During pregnancy, the glucose levels vary according to the hormonal changes and the metabolic needs
necessary to maintain fetal nutrition but strict glycemic control is essential to minimize the maternal and
fetal morbidity and mortality of pregnancies complicated by diabetes. Although considered the gold
standard for diagnosis, measurement of glucose in the blood is subject to several limitations, many of
which are not widely appreciated. Measurement of A1c for diagnosis is appealing as with one number, a
total, integrated view of glycemia over time is derived though it has some inherent limitations. Thus,
supplementation with HbA1c, as is common outside pregnancy, seems appropriate. Before pregnancy,
the target for metabolic control in women with diabetes is HbA1c values near the normal range. However,
the upper normal range of HbA1c during normal pregnancy is only sparsely investigated with different
methods though recently a number of papers have been published regarding the determination of
reference ranges for HbA1c in pregnancy. These changes may have clinical implications for the
assessment and management of glycemic control in diabetic pregnancy and calls for establishment of
separate reference limits of HbA1c levels in different trimesters as compared to general population.
2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Contents
1.
2.
3.
4.
5.
6.
7.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Use of hemoglobin A1c as a reection of glycemia . . .
Confounders of HbA1c . . . . . . . . . . . . . . . . . . . . . . . . . .
Factors contributing to variations in results of HbA1c.
HbA1c in normal pregnancy . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction
Strict glycemic control is important in pregnancy as two
generations are at risk the fetus and the mother. Before 2010
virtually all diabetes societies recommended blood glucose
analysis as the exclusive method to diagnose diabetes but over
the last few years Physicians have been using hemoglobin A1c to
screen for and diagnose diabetes [1]. Although considered the
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1871-4021/$ see front matter 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.dsx.2012.05.010
60
D. Rafat, J. Ahmad / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 6 (2012) 5964
2. Chemistry
The glycosylation of hemoglobin takes place under physiologic
conditions, at a specic site on the protein. Normally, about 5
percent of hemoglobin in a population of normal human red cells is
covalently linked to glucose, resulting in the formation of a
chromatographically distinct minor component designated by
Allen et al. [4] as hemoglobin A1c. Interest in HbA1c was
considerably enhanced by the discovery that there is a two- to
three-fold increase in this glycoprotein in patients with diabetes
mellitus [5]. In adults and children above the age of 6 months,
about 90 percent of their hemoglobin is Hb A (a2b2), a tetramer
composed of two pairs of unlike polypeptide chains, each attached
to the prosthetic heme group. Hemoglobin A2 (a2b2) and Hb F (a2
g2) comprise about 2.5 percent and 0.2 percent of the total. The
other minor hemoglobin components found in human red cell are
posttranslational modications of Hb A. Four minor hemoglobin
components which have been designated A1a1, A1a2, A1b and A1c
[6]. Hemoglobin chemistry soon demonstrated the relevant
features of HbA1c that made it such a useful tool [79]. Glycation
of the N-terminal valine residues of hemoglobin gradually occurs
as the erythrocyte circulates, changing the electrophoretic
mobility into the A1c region. This post-translational, postsecretory glycation proceeds through a relatively unstable
aldamine, Schiff base that then slowly undergoes an Amadori
rearrangement to form a stable, essentially irreversible ketoamine
linkage. Since erythrocytes gradually lose their ability to metabolize glucose as they age, but remain permeable to glucose, the
intracellular glucose concentration reects the extracellular
(plasma) glucose.
Key features of HbA1c formation include the following
Hemoglobin becomes progressively glycated over its 120 day
life span as it circulates in the erythrocyte.
Therefore, older, senescent red blood cells have more glycated
hemoglobin than do reticulocytes.
The rate of the reaction reects the ambient plasma glucose.
The reaction is essentially irreversible, such that a given
molecule of hemoglobin that is glycated remains so until the
end of its lifespan.
The clinical assay of HbA1c measures total glycation of
hemoglobin, thus measuring the young, less glycated erythrocytes as well as the older, moreglycated red blood cells.
D. Rafat, J. Ahmad / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 6 (2012) 5964
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D. Rafat, J. Ahmad / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 6 (2012) 5964
D. Rafat, J. Ahmad / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 6 (2012) 5964
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