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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 
Nature Medicine.

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 
press statement.

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/