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Triglyceride-increasing alleles may lower risk for type 2 diabetes
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Genetic variants associated with higher levels of triglycerides also are associated with a lower risk for developing type 2 diabetes, according to research in PLOS Genetics.
In three prospective cohort studies composed of black and white participants, researchers found that triglyceride-increasing alleles were correlated with decreased type 2 diabetes incidence across racial groups and statistical models.
“This is a seemingly paradoxical finding since triglyceride levels are considered a major risk factor for developing type 2 diabetes,” Yann Klimentidis, PhD, MS, of the Mel and Enid Zuckerman College of Public Health at the University of Arizona, told Endocrine Today. “These findings suggest that there are some physiological mechanisms [that] involve these genes, whereby triglycerides are produced and/or stored and glucose and/or insulin resistance levels are reduced.”
Yann Klimentidis
Klimentidis and colleagues analyzed data from 16,485 adults from three prospective cohort studies. These included 9,957 adults (7,868 white) from the Atherosclerosis Risk in Communities (ARIC) study, a multicenter prospective study of men and women aged 45 to 64 years designed to investigate risk factors with atherosclerosis; 3,430 white adults from the Framingham Heart Study (FHS), a prospective cohort study to examine the causes of heart disease; and 3,098 adults (1,949 white) from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of men and women aged 45 to 85 years on risk factors for atherosclerosis.
Researchers calculated a genetic risk score based on 31 validated single nucleotide polymorphisms (SNPs) and found the triglycerides genetic risk score to be negatively associated with type 2 diabetes (HR = 0.997; 95% CI, 0.994-0.999) after adjusting for race. After also adjusting for age, sex, BMI, HDL cholesterol and triglycerides, the triglyceride genetic risk score was significantly and negatively associated with type 2 diabetes among both races (HR = 0.993; 95% CI, 0.99-0.995).
“Our findings suggest that the risk conferred by triglycerides is greatest among individuals with low genetic predisposition for triglycerides,” the researchers wrote.
Researchers found similar patterns in both white and black participants, although triglyceride SNPs were mainly identified in white participants and the association of the triglyceride genetic risk score with triglycerides among black participants is relatively weak when compared with white participants.
Researchers found no single SNP driving the association between genetically elevated triglycerides and type 2 diabetes, Klimentidis said.
“There are no immediate clinical implications, as further work is needed to understand the physiological mechanisms that underlie these findings,” he said. “Once we identify and better understand the underlying mechanisms, it may be possible to develop targeted prevention or therapeutic strategies.”
More research is needed to determine the function of any triglyceride-associated genetic variants and how they may decrease type 2 diabetes risk, Klimentidis said.
“This will require a multifaceted approach that integrates genetic variation, molecular pathway analysis and highly refined phenotype measures.” he said. - by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
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