The quest to develop a one-size-fits-all therapy to combat obesity is “highly unlikely” to be effective due to the sheer number of rare genetic variants involved, according to the results of a 25-year study into type 2 diabetes.

The research, conducted by Australian diabetes researchers Dr Arthur Jenkins and Dr Marijka Batterham from the University of Wollongong in conjunction with Professor Lesley Campbell, Director of Diabetes Services at St Vincent’s Hospital in Sydney and researcher at the Garyan Institute of Medical Research, was published in open-access academic journal PLOS ONE 7 August 2013.

25 years of data analysed

Over the last 25 years, Professor Campbell has gathered detailed information of more than 300 healthy people with a family history of type 2 diabetes, including their body shape, size and composition (using Dual-energy X-ray absorptiometry to obtain accurate measurements). Her research looked specifically at people who were genetically at risk of developing type 2 diabetes and were overweight or obese before they got the disease.

Many ‘genetic stories’

The data gathered by Professor Campbell was analysed by Dr Jenkins using a specially constructed mathematical model. Dr Jenkins concluded that many genes are responsible for obesity, with each affected family likely to tell a slightly different genetic story.

“We can see that there are many, many different ways in which the system can go wrong, with more variety than commonality,” Dr Jenkins said.

“In my opinion, the current quest to develop a single anti-obesity drug is misguided – because there are too many potential problems to be targeted by a single drug, or indeed any small number of drugs,” Dr Jenkins said.

Researchers said it was likely that the same is true of type 2 diabetes.

“The underlying cause is genetic and the genetic causes are very rare, but there are many differences between people,” Dr Jenkins said. “Rare genetic defects account for something like 95 per cent of the total problem. That is a very unwelcome fact for most people, who would like to think an easy solution is close at hand,” he said.

Interaction between genes and environment

Researchers said that while genes bring out “underlying predispositions”, there are also “fairly predictable” interactions between genes and environment. According to the researchers, this means that if people are predisposed to a strong appetite, large amounts of easily available, highly palatable foods are likely to make them fat.

“The reason we see so many people getting fat is that they carry strong hunger genes,” Professor Campbell said. “It’s an obesogenic environment that rewards eating,” she said.

“People no longer have to go fishing, or hunting and gathering in order to eat. They just go to McDonald’s or KFC or the freezer. The point is that people don’t have to expend any energy to get an abundance of food, often high in fat or sugar,” Professor Campbell said.

Professor Campbell said previous studies had shown that people with diabetes in the family tended to be hungry more often, were more able to eat more in a sitting, and would generally opt to eat high calorie foods.

“This does not mean they are ‘greedy’, it just means that their bodies are genetically driven to eat more,” Professor Campbell said. “The same genes would serve these people well in times of food scarcity or famine. They would survive, while their leaner neighbours would perish,” she said.

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