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Genetic predisposition to abdominal adiposity increases type 2 diabetes, CHD risks
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The risks for type 2 diabetes and coronary heart disease were increased among adults with a genetic predisposition to higher waist-to-hip ratio adjusted for BMI, an indicator of abdominal fat, study data show.
“People vary in their body fat — some put fat in their belly, which we call abdominal obesity, and some in their hips and thighs,” Sekar Kathiresan, MD, director of the Massachusetts General Hospital Center for Genomic Medicine and associate professor of medicine at Harvard Medical School, said in a press release. “Abdominal adiposity has been correlated with cardiometabolic disease, but whether it actually has a role in causing those conditions was unknown. We tested whether genetic predisposition to abdominal adiposity was associated with the risk for type 2 diabetes and CHD and found that the answer was a firm ‘yes.’”
Kathiresan and colleagues evaluated data from the U.K. Biobank on 111,986 adults (mean age, 57 years; 52.5% women; mean waist-to-hip ratio, 0.875) to determine the association of a polygenic risk score for waist-to-hip ratio adjusted for BMI with type 2 diabetes and CHD. Forty-eight single nucleotide polymorphisms were used to construct a polygenic risk score for waist-to-hip ratio adjusted for BMI.
Overall, 5% of participants had CHD and 5.1% had type 2 diabetes.
A 1-point decrease in BMI, a 2-cm increase in waist circumference, a 4.1-cm decrease in hip circumference and an increase of 0.068 in waist-to-hip ratio were associated with a 1-standard deviation (SD) increase in waist-to-hip ratio adjusted for BMI due to polygenic risk score. Higher total cholesterol level (5.6 mg/dL), higher LDL cholesterol level (5.7 mg/dL), higher triglyceride level (27 mg/dL) and lower HDL cholesterol level (6 mg/dL), higher log-transformed fasting insulin levels (0.07 log pmol/L), higher 2-hour glucose levels (4.1 mg/dL) and higher systolic blood pressure (2.1 mm Hg) were also associated with a 1-SD increase in waist-to-hip ratio after adjustment.
The risks for type 2 diabetes (OR = 1.77; 95% CI, 1.57-2) and CHD (OR = 1.46; 95% CI, 1.32-1.62) were also higher with a 1-SD increase in waist-to-hip ratio after adjustment.
“These results illustrate the power of using genetics as a method of determining the effects of a characteristic like abdominal obesity on cardiometabolic outcomes,” Connor Emdin, DPhil, of the Massachusetts General Hospital Center for Genomic Medicine and the cardiology division, said in the release. “The lack of association between the body type genetic risk score and confounding factors, such as diet and smoking, provides strong evidence that abdominal adiposity itself contributes to causing type 2 diabetes and heart disease. Not only do these results allow us to use body shape as a marker for increased cardiometabolic risk, they also suggest that developing drugs that modify fat distribution may help prevent these diseases. Future research also could identify individual genes that could be targeted to improve body fat distribution to reduce these risks.” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.
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