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[IP] Diabetes linked to embryonic cell death
Monday November 30 6:45 PM ET
Diabetes linked to embryonic cell death
NEW YORK, Nov 30 (Reuters Health) -- Diabetic women with poor blood
sugar control are at increased risk for miscarriage and for delivering
children with birth defects because high blood sugar levels induce
embryonic cell death, according to a report in the December issue of
These findings suggest that diabetic women who are trying to become
pregnant should be particularly diligent about controlling their blood
sugar levels, according to Dr. Kelle H. Moley of Washington University
School of Medicine in St. Louis, Missouri, and colleagues.
``A lot of diabetic women figure they'll go to the doctor once they get
pregnant,'' Moley said in a statement to the press. ``But by that time,
the damage may be done. So, it's very important for them to tell their
doctor they want to get pregnant so they can be monitored very closely
from that point on.''
She added that the findings also have implications for women who do not
have diabetes, but are trying to conceive.
``Even if we are not insulin-dependent diabetics, many of us have blood
glucose fluctuations,'' Moley noted. ``And pregnancy itself causes a lot
of carbohydrate changes very early on. Perhaps even subtle metabolic
alterations during this early critical time in development have serious
effects on pregnancy outcomes. So, if you're thinking of getting
pregnant, you might want to pass up the soda and candy bars.''
Overall, diabetic women have about eight times as many infants with
malformations than do non-diabetic women. Even if a diabetic woman's
blood sugar levels are under control by the time her embryo's organs are
forming, deformity rates are still two to three times higher than in
other women, according to the Washington University School of Medicine
To determine whether increased risks of miscarriage and birth defects
might be due to the effects that elevated blood sugar levels -- or
``hyperglycemia'' -- have on embryonic cells soon after conception,
Moley and colleagues conducted several experiments using mouse models.
In one series of experiments, the researchers studied blastocysts from
hyperglycemic diabetic mice and from non-diabetic mice. After egg
fertilization and multiple cell divisions, a sphere of cells --
including what will become the embryo -- is formed. This structure is
called the blastocyst. Moley's team measured levels of a protein called
``Bax,'' in the blastocysts. Bax promotes cell death, or apoptosis.
``Apoptosis in the mammalian pre-implantation blastocyst is a normal
process, thought to protect the early embryo by eliminating abnormal
cells,'' the researchers explain.
Bax levels in blastocysts from diabetic mice with hyperglycemia were
roughly six times higher than those in blastocysts from non-diabetic
mice, the researchers found. But when diabetic mice were treated with
insulin before and immediately after they became pregnant -- resulting
in normal blood sugar levels -- their blastocysts had normal Bax levels,
the investigators report.
In an additional series of studies, Moley and colleagues found that
there was a greater degree of DNA fragmentation in embryos from
diabetic, hypoglycemic mice than in embryos from non-diabetic mice.
Together, these findings suggest that hyperglycemia increases Bax levels
in pre-implantation stage blastocysts, and these increased Bax levels
prompt the death of additional embryonic cells. If enough cells die,
deformity or miscarriage may be the result, the researchers suggest.
``These findings emphasize the importance of preconceptual strict
metabolic control in diabetic women,'' Moley and colleagues conclude.
SOURCE: Nature Medicine 1998;4:1421-1424.
Insulin-Pumpers website http://www.insulin-pumpers.org/