A revealing peek into the diabetes puzzle

Faulty mitochondrias appears to cause fat to pile up in muscle and spur type II diabetes even in lean kids whose parents have the disease

By Samuel Munson

Decreased activity of muscle mitochondria may be a major factor in the development of type II diabetes in children of diabetic parents. An inherited defect that causes these cellular powerhouses to pump out less energy may even put offspring who are lean and fit at risk.

Transfer of glucose into muscle cells -- a process that is aided by the pancreatic hormone insulin -- delivers fuel to the mitochondria, which 'burn' the glucose to provide energy. Now, the findings of a study published in the February 12 issue of the New England Journal of Medicine indicate that the improper functioning of the mitochondria may cause fat to pile up inside muscle cells. The fat buildup may lead to the development of insulin resistance according to the researchers.

"There is a strong relationship between lipid content in the muscle and insulin resistance," said Dr Gerald Schulman, lead author of the paper and a professor of internal medicine and cellular and molecular physiology at the Yale University School of Medicine. "Insulin resistance is the best predictor of whether someone will eventually develop type II diabetes."

The study compared 14 insulin-resistant, non-diabetic offspring of parents who both had type II diabetes with a control group of 12 offspring who had normal insulin sensitivity. Participants averaged 27 years of age and were matched for weight, height and level of physical activity.

Proton magnetic resonance spectroscopy, a harmless, nondestructive way of peeking inside living cells, was used to examine whether liver and muscle cells in the insulin-resistant participants had increased amounts of fat stockpiled inside them, and how efficiently this fuel was burned.

Insulin-resistant offspring accumulated 80% more lipid in muscle cells than did the controls. Also, this stockpiled fuel was used a whopping 30% less than that of the controls.

No other factors appeared to contribute to the insulin resistance. "What we hypothesize is that these insulin-resistant offspring inherit genes that result in a reduction of mitochondrial activity," said Dr Schulman. "This predisposes them to accumulate fat inside the muscle cells, resulting in insulin resistance, which in turn will lead them to develop diabetes later in life."

The researchers are now investigating whether the wimpy mitochondrial activity is due to a lower number of mitochondria and/or their reduced function.

Dr Shulman foresees the development of medications that would supplement diet and exercise by further ratcheting up the activity of the defective mitochondria. This could lessen or perhaps even prevent type II diabetes.