People with a genetic predisposition to high waist-to-hip ratio (WHR) adjusted for body mass index (BMI), a marker of abdominal obesity, had significantly increased risk for type 2 diabetes and coronary heart disease, according to the results of a study published in JAMA.
“We observed that individuals who had high waist-to-hip ratio, or those who were more likely to have fat around their abdomen, had a 46% higher rate of coronary heart disease and had a 77% higher risk of type 2 diabetes, in addition to higher rates of systolic blood pressure, triglyceride levels and glucose levels in their blood,” Connor A. Emdin, DPhil, of the Center for Genomic Medicine and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, told Medical Economics.
According to Emdin, a number of observational studies have proposed that high WHR causes heart disease and diabetes.
“This relationship could potentially explain why women have lower rates of heart disease then men, and why there are different rates of heart disease and diabetes in different populations,” Emdin said.
However, it was not clear whether or not the association between WHR and diabetes and heart disease was causal. In this Mendelian randomization study, the researchers wanted to determine whether a genetic predisposition to increased WHR adjusted for BMI was associated with increased cardiometabolic traits, type 2 diabetes, and heart disease.
Next: Genetic predisposition findings
They measured genetic predisposition to abdominal adiposity using 48 single-nucleotide polymorphisms and constructed a polygenic risk score. The association of this score with cardiometabolic traits, type 2 diabetes and coronary heart disease was tested in a analysis that combined case-control and cross-sectional data sets. Estimates for cardiometabolic traits were taken from four genome-wide association studies that included 322,154 participants, as well as data from the UK Biobank from 111,986 individuals. Estimates for type 2 diabetes and heart disease were taken from two genome-wide association studies, as well as data from the UK Biobank.
Emdin and colleagues found that one standard deviation genetic increase in WHR adjusted for BMI was associated with a 77% increased risk for type 2 diabetes (odds ratio [OR]=1.77; 95% CI, 1.57-2.00), and a 46% increased risk for coronary heart disease (OR=1.46; 95% CI, 1.32-1.62). In addition, each standard deviation increase in WHR adjusted for BMI was associated with increased in several cardiometabolic factors: 27-mg/dL higher triglyceride levels, 4.1-mg/dL higher 2-hour glucose levels, and 2.1-mm Hg higher systolic blood pressure (P<.0001 for all).
According to Emdin, based on these results, it is important for clinicians to recognize that not all body fat is created equally.
“Individuals who store fat in the abdomen are at a higher risk to develop complications of heart disease and type 2 diabetes,” he said.
The researchers concluded that WHR adjusted for BMI might be useful in the development of therapies for type 2 diabetes, which frequently focus on reduction of overall adiposity instead of abdominal adiposity.