Researchers working with Pima volunteers have discovered that the baby of a mother who has diabetes during pregnancy has a very high risk of becoming overweight and developing diabetes as a young adult. This added risk is separate from any genetic tendency for diabetes the child may have inherited.

Earlier research has given doctors important information about how a mother's diabetes affects her unborn child, and how to prevent complications in babies whose mothers have diabetes. Scientists know that babies exposed in the womb to high levels of blood sugar (glucose) often have problems at birth. The more uncontrolled a mother's blood sugar is, the bigger the problems:

• Babies of diabetic women are more than three times more likely to have birth defects.
• Overfed through the placenta by high levels of blood sugar, the babies of diabetic mothers may grow too large for safe delivery through the birth canal, and often require delivery by C-section.
• Babies of diabetic women are more often born prematurely, and as a result, have more brain and nerve problems than those born to mothers with normal blood sugar.
• Babies of diabetic women often have changes in the insulin-producing cells of the pancreas, which may place them at risk for problems with glucose metabolism later in life.
• Their mothers are more likely to suffer from toxemia, a life-threatening condition that endangers both mother and infant.

Sonia Antone measures a patient's height at the NIH clinic at Hu Hu Kam Memorial Hospital in Sacaton.

By taking insulin and paying attention to diet and exercise, a woman with diabetes can help keep blood sugar levels as normal as possible during pregnancy. By doing this, she can usually avoid the short-term complications for herself and her baby. For this reason, it is important for a woman to have a glucose tolerance test before and during pregnancy. This test is now routine for pregnant woman all over America because of what NIH doctors have learned from Pima Indian volunteers.

Because of the long-term studies being conducted among the Pima Indians, doctors also now know that a mother's diabetes can affect her child's health many years later. This long-term research has a special place in science. It can give insights and answer questions when other research approaches fall short. Because some of the children born to Pima mothers after the study began are now 28 to 30 years old, researchers are able to understand how a mother's diabetes can influence a child's health in adulthood.

A 19^th Century Pima woman.

By observing these children over the years, NIH scientists discovered that the children of women with diabetes during pregnancy have a higher risk of becoming obese and getting diabetes earlier in life than those born to mothers who had normal blood sugar during pregnancy but developed diabetes later. Apart from any genetic tendency the children may have inherited, those exposed to high blood sugar in the uterus had an added risk for unhealthy weight and diabetes at a younger age.

"We now know there is a non-genetic cause of diabetes, the diabetic intrauterine environment, which poses problems for the child that extend well beyond those apparent at birth," says Dr. David Pettitt of NIH.

Animal studies also show that exposure to a high level of blood sugar in the uterus has long-lasting effects on offspring. Abnormal changes in pancreatic tissue were seen in rats whose mothers had chemically induced diabetes but no genetic tendency to the disease. As adults, both second and third generation offspring of these rats had abnormal glucose tolerance and gestational diabetes.

"It's a vicious cycle," says Dr. Pettitt. "Children whose mothers had diabetes during pregnancy have a higher risk of becoming obese and getting diabetes at a young age. Many will already have diabetes or abnormal glucose tolerance by the time they reach their child-bearing years, thus perpetuating the cycle."

Devil's claw (Ihuk) is cultivated by the Pima to make baskets. The claw provides the fiber splint for weaving. The use of the devil's claw can be dated as far back as 300 A.D. to late prehistoric times.

Can the cycle be broken? Researchers hope that recent discoveries will pave the way to preventing obesity and diabetes later in the child's life. Tight control of blood sugar reduces complications for mother and baby at birth. Today, many more babies born to mothers with diabetes survive than did 30 years ago, and doctors know a lot more about how to control diabetes. Strict control of blood sugar can only benefit mother and child. Whether it can also reduce the child's long-term risk of diabetes is a question no one can answer yet.

"The challenge for the future is to see if it's possible to achieve diabetes control good enough to prevent the developing fetus from recognizing that its mother has diabetes," says Dr. Pettitt. "If we can do that, the rate of diabetes in the next generation is likely to decline, an achievement that would benefit not only the immediate children but future generations."

In a joint quest spanning three decades, Pima Indians and NIDDK researchers have begun to unravel some of the mysteries surrounding the causes of diabetes. Each new insight adds to a growing body of knowledge that promises to benefit generations of Pima Indians and millions of others around the world who share a high risk of developing diabetes and its devastating complications.
— Joan Chamberlain