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UA Researchers Find Genetically High Triglyceride Levels Associated With Protection Against Type 2 Diabetes

Yann Klimentidis, PhD, MS

Yann Klimentidis, PhD, MS

Researchers at the University of Arizona Mel and Enid Zuckerman College of Public Health, found high levels of genetically-elevated triglycerides are associated with a decreased risk of type 2 diabetes. The study was published recently in PLOS Genetics.

Triglycerides are a type of fat found in your blood. When you eat, your body converts any calories it doesn’t need to use right away into triglycerides. The triglycerides are stored in fat cells. Too much of this type of fat may raise the risk of many diseases, including heart disease, diabetes, and high blood pressure.

An elevated triglyceride level is generally considered a risk factor for the development of type-2 diabetes. Lead researcher Yann Klimentidis, PhD, an assistant professor who studies genetic epidemiology at the UA Zuckerman College of Public Health, said he decided to study the association between triglyceride-associated genes and type 2 diabetes because his team and another group found evidence suggesting that triglyceride-associated genes could paradoxically be associated with protection against T2D.

“In our group, we discovered this hint somewhat serendipitously in a separate large-scale examination of genetic risk for many cardio-metabolic traits. In general, we are using genetics as a tool to gain insight into the etiology of metabolic syndrome and type 2 diabetes.”

Building on previous studies that suggest the same association, Klimentidis and colleagues tested the relationship of triglyceride-associated genetic variants, collectively and individually, with type 2 diabetes incidence across three prospective cohort studies comprised of 13,247 European-Americans and 3,238 African-Americans.

Their findings across studies, racial groups, and statistical models consistently demonstrate that triglyceride-increasing alleles are associated with decreased type 2 diabetes incidence. The studied genes therefore appear to both increase triglyceride levels and decrease type 2 diabetes risk. Although no single gene appeared to be driving this trend, several, including a variant near the APOA1 gene, stood out as potentially interesting to this finding.

“Our study does not suggest that high triglycerides are OK,” said Dr. Klimentidis. “Perhaps they are simply a little bit ‘less bad’ if you have them because of genetic reasons. In other words, one possible interpretation of our study is that if you have a high triglyceride level, it’s better for your type 2 diabetes risk if you have that high triglyceride level because of your genetic predisposition than because of some other non-genetic risk factors.”

Dr. Klimentidis said that more work is needed to fully understand the physiological mechanisms that underlie these genetic associations and to further tease apart the causal relationship between triglycerides and type 2 diabetes.

“With this research, we can gain insight into how and why type 2 diabetes and other related diseases develop. We can also begin to identify the specific physiological mechanisms and pathways that these genes are involved in – thus potentially leading to targeted prevention and therapeutic strategies,” said Dr.

“By studying genetics, we hope that we can understand how and why disease develops, and thereby determine how we might best prevent and treat it, eventually on a ‘personalized’ basis. However, the genome is a very big place, and our biology is complex!”

Triglyceride-Increasing Alleles Associated with Protection against Type-2 Diabetes
PLOS Genetics, May 28, 2015

The University of Arizona