Exercise links genetic regions to prediabetes

Our bodies respond to exercise in different ways, and our genetic makeup is partly responsible.

People differ in how exercise alters their blood sugar equilibrium, an effect demonstrated in a study by researchers at the School of Medicine and other institutions.

The study is part of the HERITAGE (Health, Risk Factors, Exercise Training and Genetics Family Study), a multicenter study of human genetic variation and its influence on cardiovascular and metabolic responses to aerobic exercise training.

The divergence in exercise response allowed the researchers to identify regions on chromosomes 6, 7 and 19 that are linked to prediabetes.

The researchers’ report appeared in the June issue of Diabetologia.

Prediabetes is characterized by the body’s elevated resistance to insulin, the hormone that regulates blood glucose levels and energy storage. The condition generally advances to type 2 diabetes as the pancreas works to secrete insulin to compensate for increased insulin resistance in the body’s liver, muscle and fat cells.

When the pancreas can no longer make enough insulin to keep blood sugar levels in the normal range, clinically overt type 2 diabetes results.

“There’s no question that prediabetes and type 2 diabetes have a genetic basis,” said lead author Ping An, M.D., research assistant professor of genetics and of biostatistics. “The rising incidence of type 2 diabetes makes it more and more important to locate the genes so they can lead to effective intervention and treatments.”

The study examined 441 nondiabetic, sedentary parents and offspring in 98 white and 90 African-American families. Each participant traded an inactive lifestyle for a 20-week, supervised aerobic exercise program.

Researchers made sophisticated measurements of insulin action and glucose metabolism at the start of the program and then again after it was completed.

“At the end of the exercise program, the insulin sensitivity of the participants had improved overall — they needed to produce less insulin to handle the same amount of glucose intake,” An said. “But the amount of improvement varied across families and family members. This variation allowed us to locate sites on the chromosomes associated with dynamic prediabetes traits.”

An area on chromosome 19 showed the strongest link to training response among African-American participants.

That link was revealed by the effect of exercise on a measurement of glucose metabolism and indicates the chromosomal location is likely to contain gene variants that influence the propensity for prediabetes.

Very close to the area identified is a gene vital for storing glucose in the form of glycogen within skeletal muscles. Patients with type 2 diabetes often have impaired glycogen storage.

Although not as strong, other links to prediabetes traits were found on chromosomes 6 and 7 among white participants in the study. These locations have been shown to contain several genes related to fat and glucose metabolism, insulin sensitivity and glucose-induced insulin secretion.

“Genetic dissection of type 2 diabetes is challenging because the disease is affected by many genes and environmental factors like eating habits or amount of exercise,” An said. “We need to employ insightful study designs and analysis strategies.

“By selecting nondiabetic, sedentary people and then looking at their exercise response in this study, we were able to analyze a unique sample and directly measure insulin secretion and action.”

An explained that his team’s findings are consistent with other kinds of studies of type 2 diabetes traits.

“The replication of findings from independent studies and samples, although difficult, is important for establishing genetic links,” he said.