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 UNMC’s 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. Kappen’s 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. Kappen’s 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. Kappen’s 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 doesn’t develop properly,” Dr. Kappen said. “We don’t know why these cells died. One of the areas we’re 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. Kappen’s team also is studying the regulation of genes affected by diabetes and the underlying molecular mechanisms of skeletal development.