The analysis, led by Claudia Langenberg from the MRC Epidemiology Unit at the University of Cambridge, UK, suggests that the contribution of genetics to the risk of developing type 2 diabetes is greatest in those who are younger and leaner. However, in this group, the absolute risk of developing type 2 diabetes is low and the number of people who would have to be screened in order to guide targeted prevention would be impractically large.
Type 2 diabetes is thought to be caused by a combination of genetic and lifestyle factors, such as overweight and physical inactivity. While progress has been made in understanding the genetic basis of type 2 diabetes, the details of how adverse lifestyles combine with genetic risk to determine risk of developing type 2 diabetes are uncertain.
The authors quantified the association of genetic and lifestyle factors with the risk of developing type 2 diabetes in a large cohort of 340,234 people in 8 European countries followed for 11.7 years. In this EPIC-InterAct study, 12,403 people developed type 2 diabetes. The researchers identified an individual's genetic risk by determining how many of a list of 49 known type 2 diabetes genetic variants each study participant carried. They then assessed how this genetic risk contributed to each individual's overall risk of developing type 2 diabetes after several risk factors (such as age, waist circumference, physical activity and Mediterranean diet) were taken into account.
They found that the relative increase in risk of type 2 diabetes for each additional adverse gene carried was greatest in participants who were younger and thinner at baseline. The 10-year cumulative incidence of type 2 diabetes was substantially greater for those with the lowest genetic risk who were overweight (1.29%) or obese (4.22%) compared to normal weight individuals with the highest genetic risk (0.89%).
Professor Nick Wareham, who led the EPIC-InterAct study said, "This is the largest study to date examining the impact of genetic susceptibility and lifestyle factors on the risk of developing type 2 diabetes." He added that, "The high absolute risk associated with obesity at any level of genetic risk highlights the importance of population-wide, rather than genetically targeted, approaches to promoting healthy lifestyles that minimize excess weight."
- The contribution of genetics to the risk of developing type 2 diabetes is greatest in those who are younger and leaner
- Relative increase in risk of type 2 diabetes for each additional adverse gene carried was greatest in participants who were younger and thinner at baseline
- Risk of developing type 2 diabetes was highest in people who were obese, whatever their level of genetic risk for diabetes
Gene-Lifestyle Interaction and Type 2 Diabetes: The EPIC InterAct Case-Cohort Study, Langenberg C, Sharp SJ, Franks PW, Scott RA, Deloukas P, et al. PLoS Med, DOI:10.1371/journal.pmed.1001647, published 20 May 2014.