Body Type Can Increase Risk of Heart Disease and Diabetes

Researchers have identified a pattern of gene variants associated with an “apple-shaped” body type, in which weight is deposited around the abdomen rather than in the hips and thighs, increases risk for type 2 diabetes and coronary heart disease, as well as the incidence of several cardiovascular risk factors.

“People vary in their distribution of body fat – some put fat in their belly, which we call abdominal adiposity,” said study leader Prof. Sekar Kathiresan, MD, of Massachusetts General Hospital (MA, USA) and Harvard Medical School (MA, USA), “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 coronary heart disease and found that the answer was a firm yes.”

While several observational studies have reported greater incidence of type 2 diabetes and heart disease among individuals with abdominal adiposity, they could not rule out the possibility that lifestyle factors – such as diet, smoking and a lack of exercise – were the actual causes of increased disease risk. It also could have been possible that individuals in the early stages of heart disease might develop abdominal adiposity because of a limited ability to exercise.

The current study was designed to determine whether body type really could increase cardiometabolic risk. The research team applied the genetic approach of mendelian randomization, which measures whether inherited gene variants actually cause outcomes, such as the development of a disease. Using data from a previous study that identified 48 gene variants associated with waist-to-hip ratio (WHR) adjusted for body mass index (BMI), they developed a genetic risk score. They then applied that score to data from 6 major genome-wide association studies and to individual data from the UK Biobank to determine if there is an association between a genetic predisposition to abdominal adiposity and cardiometabolic disease and its risk factors.

The results clearly indicated that genetic predisposition to abdominal adiposity is associated with significant increases in the incidence of type 2 diabetes and coronary heart disease, along with increases in blood lipids, blood glucose, and systolic blood pressure. No association was found between the genetic risk score and lifestyle factors, and testing confirmed that only the abdominal adiposity effects of the identified gene variants were associated with cardiometabolic risk.

“These results illustrate the power of using genetics as a method of determining the effects of a characteristic like abdominal adiposity on cardiometabolic outcomes,” said lead author Connor Emdin, DPhil, at MGH, “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.” Dr. Emdin continued, “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.”

The study, by Emdin CA et al, was published in the February 14, 2017, issue of the journal JAMA.