News & Research

The University of Texas Health Science Center at San Antonio San Antonio, Texas

Role of early screening and intervention for fatty liver disease (NAFLD) in a predominantly hispanic population with type 2 diabetes mellitus

General Research Subject: Type 2 Diabetes

Focus: Integrated Physiology\Insulin Resistance, Integrated Physiology\Liver

Type of Grant: Clinical Translational Research

Project Start Date: January 1, 2008

Project End Date: June 30, 2012

Research Description

Non-alcoholic fatty liver disease (NAFLD) is a liver disease of epidemic proportions in the United States, associated with hepatic fat accumulation, insulin resistance and type 2 diabetes (T2DM). Diabetics typically have more severe disease and progression to inflammation and scarring (known as nonalcoholic steatohepatitis or NASH). About 40% of patients with NAFLD develop NASH and up to 1/3 may develop cirrhosis over time. NAFLD is much more common in adolescents and adult Hispanics compared to other ethnic groups. Surprisingly, no large studies have been conducted in this population to understand its pathogenesis/natural history, with diagnostic and treatment limitations making NAFLD to be largely overlooked by physicians taking care of Hispanic patients. Without such knowledge, our ability to intervene early and prevent complications is highly unlikely. Weight loss is the standard of care as there are no other treatments. However, we recently showed that pioglitazone treatment for 6 months led to significant benefit in T2DM with NASH patients.

My long-term goal is to understand the host of factors that regulate the development of NAFLD/NASH in Hispanics, and find interventions that can alter its natural history and improve our management strategies. The first step towards this goal is to determine the magnitude of the NAFLD epidemic in Hispanics with T2DM and its associated metabolic/molecular abnormalities (Aim #1). Second, assess the long-term impact of pioglitazone to reverse these defects (Aim #2). This work will address a major public health problem in South Texas and nationally and yield key information for longer-term, multi-center studies.

Reseacher Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

This research targets a public health problem of increasing concern in the United States, being closely linked to the epidemic of obesity. It is a condition believed to affect ~1/3 of all adults and perhaps as many as ~2/3 of patients with type 2 diabetes mellitus (T2DM). Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic fat accumulation. It is frequently associated with insulin resistance, a poor response of the body to insulin. Liver fat accumulation is commonly associated with inflammation (known as nonalcoholic steatohepatitis or NASH). About 40% of patients with NAFLD develop NASH, which may cause cirrhosis over time in many patients. Patients with diabetes more frequently develop NASH, typically having more rapid progression to cirrhosis and end-stage liver disease. NASH is considered to be one of the most common causes of liver failure, after alcohol and viral hepatitis. For unclear reasons, NAFLD/NASH is also much more common in adolescents and adult Hispanics compared to other ethnic groups. Weight loss is the standard of care as there are no proven long-term pharmacological treatments. This project will play an important role in finding a cure for this common complication of patients with diabetes.

However, because the disease gives no symptoms and is difficult to diagnose, most physicians taking care of patients are unaware of the condition and NAFLD is frequently overlooked. Surprisingly, no large studies have been conducted in Hispanic patients with T2DM and fatty liver disease, nor in any other ethnic groups. This is essential to understand its causes and natural history, as well as to improve current diagnostic and treatment approaches. Without such knowledge, our ability to intervene early and prevent complications will remain limited. However, we are optimistic because we plan to apply a novel magnetic resonance imaging and spectroscopy (MRS) technique to screen a large number of subjects with T2DM. We are also encouraged because recently we have shown that pioglitazone treatment for 6 months led to significant benefit in T2DM with NASH patients (Belfort et al, NEJM 11/30/2006). Taken together, we have the possibility for the first time to make significant advances in the prevention and treatment of the NAFLD in T2DM, with a focus in those at the greatest risk, the Hispanic community.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

This project will fill an important gap in our knowledge because its goal is to understand the host of factors that lead to the development of fatty liver (NAFLD/NASH) in Hispanics. This will lead to implementation of strategies for its early diagnosis and for finding interventions that can prevent long-term complications (i.e., end-stage liver damage). We believe that fatty liver disease will be incorporated into the list of complications that patients with T2DM will be screened and monitored for, such as we currently do for eye, kidney, nerve and heart disease. The first step towards this goal is to determine the magnitude of the NAFLD epidemic in Hispanics with T2DM and its associated metabolic/molecular abnormalities (Aim #1). Second, assess the long-term impact of an FDA-approved medication used for the treatment of T2DM called pioglitazone (Actos ) to reverse these defects (Aim #2). This work will address a major public health problem in Hispanics and yield key information for large, longer-term, multi-ethnic studies.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

Personally, doing research in diabetes allows me to work in something beyond the ordinary, to be part of an effort to tackle one of the greatest public health problems of our time. Every family has someone with diabetes. I feel honored of being part of such an effort to prevent, and eventually cure diabetes. It is important to me because it gives me the opportunity to focus many years of training and use the talents that God gives to each one of us to serve a worthwhile cause with so many in need. In research we build upon those that have preceded us and carry the flame to the next generation, hoping that they will continue our effort with the same or greater passion. I feel that what we discover can have real practical implications for millions one day. Although we may or may not see the tangible impact of our research, our findings may be the essential stepping stone for the breakthrough of the next generation.

In what direction do you see the future of diabetes research going?

I see that there will be increasing interaction among disciplines, and between basic and clinical research, as knowledge grows exponentially demolishing previous views of diseases belonging to just a specific area. Public health problems such as obesity, diabetes, cardiovascular disease and their associated complications will require the efforts and talents of many. As fields learn more from each other, it is likely that this will accelerate understanding of diseases and enrich each discipline. Breakthroughs will accelerate and the possibilities will go beyond anything we can currently imagine.p>