PHILADELPHIA — Using new genetic evidence, an international team of scientists led by experts at the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia has found that an increased body mass index (BMI) raised the risk for both type 2 diabetes and higher blood pressure. The results add to mounting evidence about the risks of obesity and are of major importance for the obesity pandemic that is affecting the United States – where two-thirds of adults are overweight or obese – and other countries. According to the findings, published online in The American Journal of Human Genetics, for every 1 kg/m2 increase in BMI – equivalent to a 196-pound, 40-year old man of average height gaining seven pounds – the risk of developing type 2 diabetes increases by 27 percent. The same rise in BMI also increases blood pressure by 0.7 mmHg.
“Our findings provide solid genetic support indicating that a higher body mass index causes a raised risk of type 2 diabetes and high blood pressure,” said the study’s lead author, Michael V. Holmes, MD, PhD, research assistant professor of Surgery in the division of Transplant at Penn Medicine.
In the new study, the research team used a recently developed statistical tool called Mendelian randomization (MR), which helps researchers identify genes responsible for particular diseases or conditions (such as obesity), independent of potentially confounding factors such as differences in behavior and lifestyle, which can lead to false-positive associations. In this case, the use of MR virtually rules out the possibility that both a high BMI and type 2 diabetes are caused by a third, unidentified factor.
“Whether high BMI raises the risk of adverse outcomes is of critical importance given that BMI is modifiable,” said Holmes. “Now that we know high BMI is indeed a direct cause of type 2 diabetes, we can reinforce to patients the importance of maintaining body mass within established benchmarks.”
Results of the new study were based on the assessment of the genotypes for over 34,500 patients from previous studies. In addition to the results on diabetes and blood pressure, Holmes and his colleagues found that an elevated BMI has potentially harmful effects on several blood markers of inflammation. While this could be tied to increased risk for coronary heart disease, the researchers suggest it requires further study.
“While this study has strong foundations and implications, there are many more BMI signals emerging,” said senior author Brendan Keating, PhD, research assistant professor of Pediatrics and Surgery at Penn Medicine and lead clinical data analyst in the Center for Applied Genomics at The Children’s Hospital of Philadelphia. “Future research will likely generate even more useful information about genetics and the associated risks for disease for both physicians and patients.”
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
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