Scientists in Australia found that when they studied insulin resistance in people with Hepatitis C little or none of it was in the liver and nearly all the insulin resistance occured in muscle, which surprised them because Hepatitis C is a liver disease that not only leads to cirrhosis and cancer, but also makes people three to four times more likely to develop Type 2 diabetes.

You can read about the study that led to these findings in the March 2010 issue of the journal Gastroenterology, which is also available online.

Among the researchers were Dr Kerry Lee Milner and Professor Don Chisholm from Sydney’s Garvan Institute of Medical Research and Professor Jacob George from the Storr Liver Unit, University of Sydney at Westmead Hospital.

Hepatitis C is a virus that lives in the blood and can be passed from one drug user to another by sharing needles: in Australia this is the main route of transmission. However, unsterile tattooing or body piercing is another way the virus can spread.

Unlike Hepatitis A and B, there is no vaccine for Hepatitis C, of which there are 6 strains, the two most common in Australia being Genotype 1 and Genotype 3, which causes significant amounts of fat to deposit in the liver.

Insulin, a hormone that helps the body convert glucose into energy, is made in the pancreas, but the two most important organs that respond to it are the liver and muscle, each responding differently. When it detects insulin, the liver stops making glucose, while healthy muscle responds by using glucose.

A liver that has become insulin resistant overproduces glucose, while muscle that has become insulin resistant does not absorb glucose so well from the bloodstream. In both cases the result is too much circulating glucose.

When they studied the insulin resistance of 29 people with Hepatitis C (14 with Genotype 1 and 15 with Genotype 3) and confirmed they had high insulin resistance, they found to their surprise that nearly all the insulin resistance was in the muscle and hardly any in the liver.

Chisholm also told the media that contrary to expectations, not only did they find no significant insulin resistance in the liver of the study participants: “The fifteen people with very high levels of fat in the liver [the participants with Genotype 3] had the same degree of insulin resistance as the fourteen that didn’t have fatty livers.”

Chisolm said experts around the world have been arguing that fat in the liver is an important factor in the development of insulin resistance, perhaps the most important. But this study shows this may not be the case, he said.

“Before you get Type 2 diabetes, you must become insulin resistant and your insulin producing cells must also fail to compensate. Insulin resistance alone will not give you diabetes,” he explained.

For this study, Chisolm and colleagues gave intravenous glucose, which specifically stimulates insulin secretion, and showed that it was not impaired in the Hepatitis C patients compared to controls.

“This finding tells us that people with Hepatitis C who develop diabetes probably have susceptible insulin-producing cells, and would probably get it anyway — but much later in life,” said Chisolm.

The extra insulin resistance caused by Hepatitis C apparently brings on diabetes at 35 or 40, instead of 65 or 70,” he added.

The researchers suggest further research should now be done to find out why Hepatitis C causes insulin resistance in muscle.

“That will give us better insight into the behaviour of the disease,” said Chisolm.

For people with Hepatitis C, the message from this study is a deeper understanding of insulin resistance, and perhaps, if they have family members with Type 2 diabetes, they would be advised to manage their diets very carefully and take plenty of exercise, as this delays onset.

Estimates suggest there are currently around 212,000 Australians infected with Hepatitis C, with 10,000 new infections a year.

“Chronic Hepatitis C Is Associated With Peripheral Rather Than Hepatic Insulin Resistance.”
Kerry-Lee Milner, David van der Poorten, Michael Trenell, Arthur B. Jenkins, Aimin Xu, George Smythe, Gregory J. Dore, Amany Zekry, Martin Weltman, Vincent Fragomeli, Jacob George, Donald J. Chisholm.
Gastroenterology, March 2010 (Vol. 138, Issue 3, Pages 932-941.e3)

Source: GAVAN Institute.

Written by: Catharine Paddock, PhD