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Role of Genomic Variance to Belly Fat in Diabetes

Mar 25, 2017

Genetic predisposition to a higher waist-to-hip ratio may lead to diabetes.

Distribution of body fat varies from one individual to another. Some may put on more belly fat, whereas, others may get more fat on their hips and thighs. However, the link between belly fat and diabetes has been confirmed. Researchers have found that a person’s genetic makeup plays a pivotal role in his health issues. Thus, those who are genetically predisposed to an apple-shaped body may have an increased the risk of type 2 diabetes (T2D) and heart disease.

Several observational studies have reported higher incidence of T2D and coronary heart disease (CHD) among individuals with abdominal adiposity, but poor lifestyle choices, such as diet, smoking, and a lack of exercise also pose a threat in disease risk. Limited ability to perform physical activity may lead to abdominal adiposity that could result in early stages of heart disease. Previously, observational studies uncovered an association between belly fat, T2D, and heart disease, but were unable to prove the cause and effect. The study was conducted at Massachusetts General Hospital (MGH) to find whether inherited gene variants actually cause outcomes such as the development of a disease by applying a genetic approach called mendelian randomization.

The objective was to test the association of a polygenic risk score for waist-to-hip ratio (WHR) adjusted for body mass index (BMI), a measure of abdominal adiposity, with type 2 diabetes and CHD through the potential intermediates of blood lipids, blood pressure, and glycemic phenotypes. The main outcome and measures were T2D and CHD and they found a pattern of gene variants associated with a body type, in which weight accumulated around the abdomen versus hips and thighs, which increased the risk for T2D, CHD, and the incidence of several cardiovascular risk factors. Data from a previous study with 48 variant genes were identified that predisposed patients to a higher waist-to-hip ratio resulting in a genetic risk score for T2D.

The scores were applied to data from six major genome-wide association studies and to individual data from the U.K. Biobank in about 400,000 patients by analyzing any association between their genetic predisposition to abdominal adiposity and CHD and its role in diabetes. Among 111,986 individuals in the UK Biobank with a mean age of 57 years old, 58,845 participants were women, and mean WHR was 0.875. Analysis of genome-wide association study results at a summary-level and individual-level U.K. Biobank data demonstrated a 1 SD increase in WHR adjusted for BMI mediated by the polygenic risk score was associated with 27 mg/dL higher triglyceride levels, 4.1 mg/dL higher 2 hr glucose levels, and 2.1 mmHg higher systolic blood pressure (each P < 0.001). A 1 SD genetic increase in WHR adjusted for BMI was also associated with a higher risk of T2D with odds ratio, 1.77 at 95% CI and CHD with odds ratio, 1.46 at 95% CI.

The results suggested that genetic predisposition to abdominal adiposity is associated with significant increase in the incidence of T2D and CHD, along with increases in blood lipids, blood glucose and systolic blood pressure. There was no correlation between the genetic risk score and lifestyle factors, but it confirmed that the belly fat effects of the identified gene variants associated with cardiometabolic risk. However, the lack of association between the body type, genetic risk score, and confounding factors such as diet, sedentary lifestyle, and smoking provides strong evidence that abdominal adiposity itself contributes to causing T2D and CHD. The result proved that body shape is a marker for increased cardiometabolic risk.

Another study by the University of Florida are challenging that T2D is a disease of the overweight and obese. Prof. Arch Mainous, the lead author reported that people over 45 years of age at a healthy weight might be at prediabetic conditions. According to him, “Being at a healthy weight may not necessarily mean being healthy” and therefore, medical fraternity should consider looking for diabetes in patients not just overweight and obese. Future research could identify individual genes that could be targeted to improve body fat distribution to reduce these risks. Also, development of drugs to modify fat distribution may actually prevent these diseases.

In conclusion, a genetic predisposition to higher WHR adjusted for BMI was associated with increased risk of T2D and CHD. Moreover, the results provided evidence that supports the association between abdominal adiposity and these outcomes.

Practice Pearls:

  • Genetic predisposition to abdominal adiposity associates with the risk for type 2 diabetes and coronary heart disease.
  • The study illustrated using genetics to determine the effects of abdominal adiposity on cardiometabolic outcomes.
  • Development of drugs designed to target belly fat may lower the risk of diabetes and heart disease.


“Apple-shaped’ Body Could Raise Risk of Diabetes.” Www.newvision.co.ug. Chatter Box Daily, 15 Feb. 2017. Web. 01 Mar. 2017. <http://www.newvision.co.ug/new_vision/news/1446302/apple-shaped-body-raise-risk-diabetes>.

Emdin CA, Khera AV, Natarajan P, Klarin D, Zekavat SM, Hsiao AJ, et. al. Genetic Association of Waist-to-Hip Ratio With Cardiometabolic Traits, Type 2 Diabetes, and Coronary Heart Disease. JAMA. Feb 14, 2017;317(6):626-634. doi:10.1001/jama.2016.21042

Massachusetts General Hospital. “Gene variants associated with body shape increase risk of heart disease, type 2 diabetes.” ScienceDaily. ScienceDaily, 14 February 2017. <www.sciencedaily.com/releases/2017/02/170214162852.htm>.