Study shows causal link between obesity and multiple diseases

A new study published in The Lancet Digital Health presents the strongest evidence yet of a causal relationship between obesity and a wide range of serious conditions, including cardiovascular disease, diabetes, cancer, and neurological, musculoskeletal, and respiratory afflictions.

Led by Elina Hyppönen, PhD, from the Australian Centre for Precision Health, the research draws data from the UK Biobank, a research database holding health and genetic information from half a million volunteers, to analyze associations between body mass index (BMI) and a range of disease outcomes in 337,536 people.

Previous research has suggested that high BMI is associated with increased risk of chronic diseases such as type 2 diabetes, cardiovascular disease and cancer, but due to the difficulty of conducting clinical trials related to obesity, it has been hard to prove causation.

Hyppönen and her team developed a multi-dimensional analysis in which genetic data was subjected to a suite of stringent examinations in order to deliver high confidence of causality. They compared evidence from five different statistical approaches to establish how strong the evidence for causal effect is. Fully consistent evidence across all approaches was seen for 14 different diseases, and for 26 different diseases evidence was obtained by at least for four of the five methods used, she said.

"What increases the confidence that these associations are largely reflective of real effects is the fact that those effects which came across with consistent evidence are also ones for which we have previous clinical evidence,” said Hyppönen.

One key finding from the study was the extent to which it confirms existing concerns over the link between obesity and diabetes, with many of the diseases identified as related to high BMI known to be commonly associated with poorly controlled diabetes.

"For example, we saw evidence for effects on peripheral nerve disorders, chronic leg and foot ulcers, and even gangrene and kidney failure, which are all known to be diabetic complications,” said Hyppönen. “This suggests a key aspect to reduce comorbidity risk in obesity is careful monitoring of blood sugar and effective control of diabetes and its complications.”

The study also highlights the importance of genetic research to further our understanding of the role genes play in obesity, and the insights it can provide for the future management and treatment of obesity.

“There is an urgent need to find new approaches to manage and prevent obesity,” said Hyppönen. “We know that obesity has a strong genetic basis, which can make weight management very difficult to some of us and the same strategies for prevention may also not work for all. Genetic studies are giving us deeper insights into the biological pathways which drive obesity, and hopefully these types of studies will also provide us with new strategies for prevention."