Kenneth Cusi, MD, FACP, FACE
Kenneth Cusi, MD, FACP, FACE
Chief of the Division of Endocrinology, Diabetes, and Metabolism, University of Florida College of Medicine
|ADA Research Funding|
Clinical Translational Award
Nonalcoholic fatty liver disease—NAFLD, for short—is the most common chronic liver disease in America. Because of the liver’s central role in so many body processes, fat in the liver can have a ripple effect, increasing the risks of developing both cardiovascular disease and type 2 diabetes.
The links between NAFLD and type 2 are particularly well documented. Eighty percent of people with diabetes have fat in the liver, says Kenneth Cusi, MD, FACP, FACE, an endocrinologist at the University of Florida in Gainesville.
Increasingly, researchers are realizing that the connection is no coincidence. “When I was in medical school, people thought obesity-related fat in the liver was an innocent bystander,” Cusi says. “Now endocrinologists are starting to realize this is a problem that hits home.”
Research indicates that NAFLD may contribute to prediabetes and type 2 diabetes. Because the liver plays such an important role in regulating the body’s blood sugar, the buildup of fat in the vital organ makes it harder to control fasting glucose levels. It also makes the body more resistant to insulin, straining the pancreas and its beta cells and speeding up the arrival of type 2 diabetes. “When you get fatty liver, diabetes is harder to control,” Cusi says.
Yet even though the majority of people with type 2 diabetes may have fatty livers, Cusi says the condition is typically undiagnosed, because of a lack of awareness among some doctors and the hidden nature of the disease.
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Obesity is one indicator that the liver may be fatty, but NAFLD is very hard to detect, often eluding blood tests and physical exams. The most reliable way to diagnose it is a liver biopsy, an invasive and expensive procedure. Other options include MRI scans and ultrasound, a less precise but more economical method. Physical exams and blood tests might not yield any results at all: “A minority of patients have discomfort or tenderness, but for the vast majority it gives no symptoms,” Cusi says. “That’s why it’s so hard for clinicians. Even [patients’] liver enzymes can be normal.”
So who gets fatty liver, and why? Studies have shown that Latinos are more likely to have type 2 diabetes than most other ethnic or racial groups, a finding that made Cusi wonder if there was a link to NAFLD. “Because Hispanics get more type 2 diabetes, there was a thought that they get more fatty liver disease,” Cusi says. “Our hypothesis was that Hispanics would have worse insulin resistance and worse liver disease.”
To test his theory, Cusi enrolled 152 overweight or obese patients in a study funded by the American Diabetes Association. Ninety-six of them were Latinos and 56 of them non-Hispanic whites. There were also 10 normal-weight participants in the study, to act as a “control” group. Cusi expected a higher proportion of the overweight or obese Latinos in the study to have fatty liver disease, defined as having more than 5.5 percent of the liver occupied by fat.
The study involved a range of tests, including scans of the liver and glucose tolerance tests. “We measured tolerance—how they were making insulin, insulin sensitivity in the muscle and liver—and took measurements of the adipose [fat] tissues,” Cusi explains.
As the results came in, though, it turned out that ethnicity had little to do with fat in the liver. “When we did studies, we found [Latinos] weren’t really that different,” Cusi says. The most important single factor seemed to be obesity, and Latinos tend to have more problems with obesity than other groups. “It’s not that Hispanics are doomed by genetics; they just tend to have more obesity,” Cusi says.
Was the experiment a failure? Certainly not, says Cusi: “Our hypothesis was wrong, but we learned that the main factor is obesity. That’s important, because we can do something about it,” Cusi says. “If there’s fat in your liver, think very seriously about lifestyle changes, and talk with your doctor about whether vitamin E supplements or pioglitazone [Actos] is right for you,” he adds, noting that pioglitazone is approved only for patients with type 2 diabetes.
The key to reversing the course of fatty liver disease is weight loss. “Reduce carbohydrates, and that reduces fat in the liver very quickly,” Cusi says. A loss of 5 percent of body weight is enough to start reducing liver fat, and just a few percentage points more begin reducing the inflammation that is so closely connected to insulin resistance. “If you start losing weight,” Cusi says, “a lot of things get better.”