At
one time, biomedical researchers routinely used radioactive isotopes such
as Carbon 14 and tritium-labeled compounds/molecules as “tracers” to help
them follow molecules as they made their way through the human body. The isotopes
would be chemically attached to molecules such as glucose, for example, to
study how the human body processes these as fuel.
But as scientists learned more about the hazards of exposure to even minute levels of radiation, an uncertainty arose: What were the long-term effects of purposely introducing radioactive isotopes into humans, especially during growth and development such as newborn babies and pregnant women involved in diabetes research?
In 1972, Satish Kalhan, MD, was among the first to use nonradioactive, or stable, isotopes to monitor human metabolism – a practice that is now the standard for metabolic research.
Today, Dr. Kalhan is a renowned neonatologist in the Institute's Department of Pathobiology who has a particular interest in understanding and managing changes in metabolism of mothers during pregnancy and as a result of diabetes in pregnancy, as well as its consequences to the growing fetus and newborn infant. He also is known for developing nutritional intervention strategies for the care of premature infants.
“It's a little harder using [the stable isotope] Carbon 13, but it's safe. About 1.1% of total carbon in our bodies is Carbon 13,” he said. Carbon 13 and a number of other stable isotopes help researchers to unlock human metabolic processes.
Studying how glucose is metabolized is key to understanding the fuel metabolism of organ systems. Glucose is most commonly associated with diabetes, or the body's inability to process sugar.
“Why does blood sugar increase in diabetes? Why does the body not metabolize the sugar? By studying it metabolism, we can study its actions, the rate it's produced by the liver and utilized by muscles, and target how to treat people,” Dr. Kalhan said.
Glucose is a major metabolic fuel in our body. Maintenance of normal glucose metabolism in the mother is critical for the growth of the fetus in utero.
“All pregnant women develop some level of insulin resistance. That insulin resistance in part helps fetal growth and development. In fact, mothers who don't develop insulin resistance give birth to babies that are smaller,” Dr. Kalhan said. “In the puberty-associated growth spurt, all children develop insulin resistance.”
Glucose also is the primary fuel for the brain. The brain greatly suffers when blood glucose levels are low. This state can cause seizures.
How glucose is metabolized also plays a role in obesity, hypertension and fatty liver disease, to name several. “We cannot take the liver out to study it, but by using various labeled tracers we can study the metabolism of the liver itself in the patient,” he said.
“All of us need energy to live and for the body to function. Whether it's glucose or fat as the fuel, a balanced metabolism is essential to providing the fuel needed for health,” Dr. Kalhan said. “Understanding metabolism leads to an understanding of a variety of diseases, and helps develop management or treatment strategies.”