October 2, 2018

A research team at the University of North Carolina at Chapel Hill’s Gillings School of Global Public Health found that a well-known gene variant linked to Type 2 diabetes, called transcription Factor 7-like 2 (TCF7L2) gene, also may predispose a person to being leaner or having a lower body weight.

The findings are striking, as many individuals with Type 2 diabetes are obese. However, individuals with this gene variant may be at risk for Type 2 diabetes even while maintaining a low body weight. As researchers uncover genes, they are finding distinct pathways through which individuals develop Type 2 diabetes. This information ultimately may be used to tailor treatments to populations and individuals and to help prevent diabetes or better control blood glucose levels once diabetes has developed.

Dr. Kari North

Dr. Kari North

Kari North, PhD, professor of epidemiology at the UNC Gillings School and the study’s senior author, describes the study, published Oct. 2 in the journal BMC Obesity,  as one of the first examinations of the TCF7L2 gene in a very large, representative sample of diverse Hispanic Latinos.

“The counterintuitive discovery that some people are predisposed both to being thin and developing Type 2 diabetes refocuses our attention on the need to collect data in diverse populations and across time,” said North. “Hispanic/Latinos are a diverse and understudied population, so this study is an important step forward for understanding their health risks. Also, a clinician’s radar [for diabetes] typically will be triggered when an individual is obese, but perhaps not so much when seeing someone who is lean. In reality, based upon our findings, the lean person, depending on his or her genetic composition, may still be at risk for Type 2 diabetes.”

The research team used population-based study data from more than 9,000 Hispanic Latino adults, ages 21 to 76 years, with complete weight history and genetic data from the Hispanic Community Health Study/Study of Latinos. Using complex modeling, researchers looked at the impact of a specific complex gene variant on changes in body mass index and then estimated the odds of Type 2 diabetes across time.

In the United States, according to the Centers for Disease Control and Prevention, Hispanics/Latinos face a striking disparity in Type 2 diabetes, with one in two developing the condition. This population is also 50 percent more likely than are whites to die of Type 2 diabetes.

“The other important takeaway from this study, which is especially timely now during National Hispanic Heritage Month, is that diverse populations, such as Hispanics, are heterogeneous and have distinct genetics, meaning that they may have ancestry from the Americas, Europe and Africa,” says North. “As we continue to develop initiatives around personalized medicine, we need to ensure that we are addressing the needs of all populations.”

North said the Factor 7-like 2 gene is the most widely accepted in its association with diabetes and there is reason to believe that it might apply to other populations.

The study notes that clinicians do not routinely screen for the transcription Factor 7-like 2 gene. In coming years, this research will help scientists use genetic information to understand the causes and interrelationships of diabetes and obesity, potentially leading to personalization in medication and to clinicians’ being better able to offer advice on treatments or the preventive adoption of healthy lifestyles.

The study used cohort data with detailed medical histories, allowing the research team to demonstrate that leanness and Type 2 diabetes co-occur at a high rate in this diverse Hispanic/Latino population. Future studies will incorporate longitudinal data.

North’s research collaborators at the UNC Gillings School included Lindsay Fernández-Rhodes, PhD, now assistant professor of biobehavioral health at Pennsylvania State University; Annie Green Howard, PhD, assistant professor of biostatistics; Mariaelisa Graff, PhD, assistant professor of epidemiology; Heather Highland, PhD, postdoctoral trainee in epidemiology, and Kristin Young, PhD, assistant professor of epidemiology.

Other collaborators and co-authors are Carmen Isasi, MD, PhD, associate professor, Qibin Qi, PhD, associate professor, and Robert Kaplan, PhD, professor, all in Albert Einstein College of Medicine’s Department of Epidemiology and Population Health; Esteban Parra, PhD, professor of anthropology at the University of Toronto at Mississauga; Jennifer Below, PhD, assistant professor of medicine at Vanderbilt University Medical Center; Anne Justice, PhD, formerly a postdoctoral trainee at the Gillings School, now assistant professor at the Geisinger Health System, in Danville, Pa.; George Papanicolauo, PhD, of the National Heart, Lung and Blood Institute; Cathy Laurie, senior principal research scientist in the University of Washington School of Public Health’s Department of Biostatistics; Struan Grant, PhD, of Children’s Hospital of Philadelphia Research Institute; Christopher Haiman, ScD, professor of medicine at the University of Southern California; and Ruth Loos, PhD, professor of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai.


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