UNMC researchers have received a $1.6 million grant from the National
Institutes of Health to study the effect of diabetes on the developing
embryo. The grant, to be funded over five years, was awarded to Claudia
Kappen, Ph.D., associate professor of genetics, cell biology and anatomy
in UNMCs Munroe-Meyer Institute.
Diabetes of the mother is a significant risk factor for birth defects,
Dr. Kappen said. The risk for birth defects in these pregnancies is four
to 10 times higher than in the general population. We want to understand
how maternal diabetes affects the developing embryo.
Heart defects, neural tube defects and caudal defects are most commonly
associated with maternal diabetes, although they are not exclusive to the
disease. Diabetes is a disease in which the body does not produce or properly
use insulin. Insulin is a hormone that is needed to convert sugar, starches
and other food into energy needed for daily life.
Glucose and insulin levels vary widely in diabetes, making it difficult
to study the origins of such birth defects and understand how they develop.
To do so, Dr. Kappens team has created mouse models for two of the most
common characteristic defects in diabetic embryopathy, neural tube defects
and caudal regression. Caudal defects, which encompass severe growth defects
of sacral (lower) vertebrae, the anorectal region and, in some cases, the
kidney, are most highly correlated to diabetes, Dr. Kappen said.
Dr. Kappens team is using transgenic mice to better understand the
pathogenesis of the disorders at a molecular level. In transgenic mice,
researchers add a gene. The team has found that several embryonic genes
important for normal development are changed when the mother has diabetes.
Dr. Kappens team also has found that the Wnt3A gene, which is known to
play a role with caudal growth defects, is changed when the mother has
diabetes.
There is increased cell death in these embryos which is why the caudal
area doesnt develop properly, Dr. Kappen said. We dont know why these
cells died. One of the areas were looking at is the role of cell death
in these defects.
According to the American Diabetes Association, 18.2 million people
in the United States, or 6.3 percent of the population, have diabetes.
While an estimated 13 million have been diagnosed, unfortunately, 5.2 million
people (or nearly one-third) are unaware that they have the disease. Gestational
diabetes affects about 4 percent of all pregnant women – about 135,000
cases in the United States each year.
Michael Salbaum, Ph.D., assistant professor of genetics, cell biology
and anatomy at UNMC, is co-investigator on the project. Dr. Kappens team
also is studying the regulation of genes affected by diabetes and the underlying
molecular mechanisms of skeletal development.