Upper trunk fat –– deposits of fat on the chest and back –– is associated with an increased risk of insulin resistance, a condition that is a precursor of type 2 diabetes, according to a study led by researchers at the San Francisco VA Medical Center (SFVAMC).

It is the first time such an association has been demonstrated, say the researchers.

The association was equally strong in both HIV infected subjects and HIV negative control subjects in the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM), a national long-term longitudinal study of HIV infected people taking modern antiretroviral therapy and HIV negative controls.

The presence of visceral fat, which is located between and around the internal organs, was also associated with an increased risk of insulin resistance in both populations. The researchers found that each type of fat contributes independently to insulin resistance whether or not the other type is present.

The study appears in online Publish Ahead of Print section (http://www.jaids.com/pt/re/jaids/paptoc.htm) of the Journal of Acquired Immune Deficiency Syndromes.

“We knew about the insulin resistance risk associated with visceral fat, which has been shown in previous studies, but no one had ever looked at the contribution of upper trunk fat,” says lead author and FRAM principal investigator Carl Grunfeld, MD, PhD, chief of the metabolism and endocrine sections at SFVAMC. “Strikingly, there was very little difference between HIV infected people and controls. If you have fat up top, it’s bad for you.”

In insulin resistance, cells in the body become increasingly resistant to the action of insulin, a hormone that regulates blood glucose levels. The result is chronically high blood glucose, which has many adverse health effects.

The researchers measured visceral and subcutaneous fat deposits in the legs, arms, upper trunk, and lower trunk of 926 HIV infected subjects and 258 HIV negative controls. They divided each population into tertiles, or thirds, based on the amount of fat in each location. Among the HIV infected subjects in the highest tertile of upper trunk fat, 57 percent showed insulin resistance; of those, half lacked high visceral fat. Among the highest tertile of controls with upper trunk fat, 61 percent were insulin resistant. A third of that group did not have high visceral fat.

“So, basically, there are people who have a lot of fat in their upper trunk and not so much inside their belly, yet they are at risk for insulin resistance,” observes Grunfeld, who is also a professor of medicine at the University of California, San Francisco (UCSF). “And there are people with a lot of visceral fat but not upper trunk fat who are in the same boat. But if you’ve got both, it’s a double whammy. Your risk of insulin resistance is quite high.”

Grunfeld says that the researchers looked at all regions of the body where fat is usually deposited in order to investigate abnormalities in fat distribution that have been reported in HIV infection, particularly the presence of so-called “buffalo hump,” a prominent fat deposit in the middle of the upper back. “But we found that fat in that area was present, and associated with the same risk for insulin resistance, in both HIV infected and control subjects,” he says.

Grunfeld explains the lack of difference in risk between HIV infected and HIV negative subjects by noting that two thirds of all Americans are overweight and one third are obese. “With the new, highly effective antiretroviral medications, Americans with HIV now have the same weight problems as everybody else,” he says. “No matter who you are, if you eat too much and you don’t exercise, you’re going to be at risk for insulin resistance, cardiovascular disease, and every other problem associated with being overweight.”

Coauthors of the paper were David Rimland, MD, of the Atlanta Veterans Affairs Medical Center; Cynthia L. Gilbert, MD, of the Washington, DC, Veterans Affairs Medical Center; William G. Powderly, MD, formerly of Washington University, St. Louis, Mo., and now of University College, Dublin, Ireland; Stephen Sidney, MD, of Kaiser Permanente, Oakland, Calif.; Michael G. Shlipak, MD, MPH, of SFVAMC and UCSF; Peter Bacchetti, PhD, of UCSF; Rebecca Scherzer, MS, of the Northern California Institute for Research and Education (NCIRE) and SFVAMC; Steven M. Haffner, MD, of the University of Texas Health Sciences Center, San Antonio, Tex., and Steven B. Heymsfield, MD, formerly of Columbia University School of Medicine and now at Merck, Inc.

The research was funded by grants from the National Institutes of Health that were administered in part by NCIRE.

NCIRE - the Veterans Health Research Institute - is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.

SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.