medwireNews: A Mendelian randomization analysis suggests that having a lower bodyweight will protect people against type 2 diabetes regardless of whether they have a high genetic risk or a family history of the condition.
This suggests, firstly, that lower weight equals a lower risk even for people without other risk factors, say Manuel Rivas (Stanford University, California, USA) and study co-authors.
And secondly, the findings indicate “that despite some degree of genetic and environmental predisposition, all individuals can still take charge of their diabetes risk through lifestyle modifications.”
The researchers say the results “support the broad deployment of weight loss interventions to individuals at all levels of diabetes risk as a public health measure.”
But they caution: “[A] key limitation to keep in mind is that genetic mutations, because they act across an individual’s entire lifespan, are not a perfect proxy for weight loss interventions that happen only later in life.”
The findings come from an analysis of 287,394 White British people from the UK Biobank, 4.9% of whom had type 2 diabetes. The team stratified these people by their current BMI, whether they had a family history of type 2 diabetes, and by a polygenic risk score for diabetes, based on 136,795 polymorphisms identified in a recent genome-wide association study.
Rivas and colleagues also identified 57 polymorphisms with “individually measurable effects on BMI,” allowing them to show that the effect of a genetically determined kg/m2 increase in bodyweight on diabetes risk was very similar across all subgroups. It conferred relative risk increases of 31%, 36%, and 25% among healthy-weight, overweight, and obese people, respectively, with family history and polygenic risk score appearing to have “minimal influence” on the odds ratios.
“While overweight and obese individuals are predicted to have similar relative risk reduction with weight loss, it is also worth considering how this translates into absolute risk reduction (i.e., reduction in population prevalence), which is arguably more important from a public health perspective,” write the researchers in PLOS Medicine.
Based on current estimates of diabetes prevalence in England and the weight loss effects calculated in this study, a 1 kg/m2 loss would result in a 0.6 percentage point reduction (from 2.4 to 1.8%) in diabetes rates among healthy-weight people, and 1.4 and 2.5 percentage point reductions among overweight and obese people, respectively.
“The larger absolute risk reduction from weight loss among obese individuals suggests that existing public health efforts focused on this high-risk group have not been misplaced,” says the research team.
But they add: “We note, however, that there is still substantial interindividual variation in treatment adherence, and personalized adherence strategies remain a fruitful area for further research.”
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