Genetic Study Points to Abdominal Fat as Cause of Diabetes, CHD

Marlene Busko

February 14, 2017

People with a genetic predisposition to put on weight around their middle were more likely to have elevated triglycerides, serum glucose, and blood pressure and develop type 2 diabetes or coronary heart disease (CHD), in a new study.

It suggested that a genetic predisposition to a higher waist-to-hip ratio, adjusted for body mass index (BMI) as a surrogate for visceral adiposity, was associated with increased risk of type 2 diabetes and CHD, write Connor A Emdin, DPhil, from Harvard Medical School, Boston, Massachusetts, and colleagues in an article published February 14 in the Journal of the American Medical Association.

"These results provide evidence supportive of a causal association between abdominal adiposity and these outcomes," they conclude.

Genomewide Associations

Studies looking at the link between abdominal fat and subsequent type 2 diabetes or CHD may be muddied by unknown confounders (such as lifestyle factors) or reverse causality, Dr Emdin and colleagues note. Investigating how genetic predisposition to abdominal fat affects these outcomes would avoid these problems.

Thus, the researchers examined data from 322,154 participants in four genomewide-association studies from 2007 to 2015 and from 111,986 individuals who had data in collected from 2007 to 2011 in the UK Biobank. The individuals in the UK Biobank had a mean age of 57, and 53% were women. They had a mean waist-to-hip ratio of 0.875.

Researchers developed a genetic risk score based on the presence of 48 single nucleotide polymorphisms (SNPs) that are associated with abdominal fat.

In a Mendelian randomization analysis, having a polygenetic predisposition for abdominal fat was tied to having increased levels of cardiometabolic risk factors and a greater risk of developing type 2 diabetes and CHD.

Specifically, each one-standard-deviation increase in waist-to-hip ratio based on the polygenic risk score and adjusted for BMI was associated with 27-mg/dL higher triglyceride levels, 4.1-mg/dL higher 2-hour glucose levels, and 2.1–mm Hg higher systolic blood-pressure levels (P < .001 for each).

Also, the group writes, the same waist-to-hip ratio parameter was associated with a higher risk of type 2 diabetes (odds ratio [OR], 1.77; 95% CI, 1.57–2.00) and CHD (OR, 1.46; 95% CI, 1.32–1.62).

According to Emdin and colleagues, three main conclusions can be drawn from this study. "First, these findings lend human genetic support to previous observations associating abdominal adiposity with cardiometabolic disease," such as those seen in the INTERHEART acute MI case-control study.

"Second, these results suggest that body-fat distribution, beyond simple measurement of BMI, could explain part of the variation in risk of type 2 diabetes and CHD noted across individuals and subpopulations." For example, increased abdominal adiposity for a given BMI may explain the excess risk of CHD in South Asians vs other populations or in men vs women, they write.

"Third, [waist-to-hip ratio] adjusted for BMI might prove useful as a biomarker for the development of therapies to prevent type 2 diabetes and CHD," since so far there has been little effort to develop therapies to change how fat is distributed in the body.

The authors have no relevant financial relationships.

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JAMA. Published online February 14, 2017. Abstract

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