Targeted interventions based on genetic risk may not be the best approach for preventing type 2 diabetes and instead universal strategies to prevent obesity should be prioritized, according to new research published in this week's PLOS Medicine. This 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.
Diabetes is currently estimated to affect more than 380 million people and the epidemic is likely to increase to 592 million by 2035. Type 2 diabetes is thought to be caused by a combination of genetic and lifestyle factors, such as overweight and physically 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. However, risk of developing type 2 diabetes was highest in people who were obese, whatever their level of genetic risk for diabetes. 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 minimise excess weight".
Funding: No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; PD: Work was supported by the Wellcome Trust; LCG: Swedish Research Council; MJT: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (Nu 6236); LA: EJD: The Spanish Ministry of Health – ISCII RETICC RD06/0020; RK: German Cancer Aid, German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: Medical Research Council UK, Cancer Research UK; APM: Wellcome Trust grant numbers WT098017 and WT090532; CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (Nu 6236); PMN: Swedish Research Council; KO: Danish Cancer Society; SP: Compagnia di San Paolo; JRQ: Asturias Regional Government; OR: The Va¨sterboten County Council; AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; YTvdS: Verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; IB: Wellcome Trust grant 098051 and United Kingdom NIHR Cambridge Biomedical Research Centre; MIM: InterAct, Wellcome Trust (083270/Z/07/Z), MRC (G0601261); ER: Imperial College Biomedical Research Centre.
Competing Interests: IB and her spouse own stock in the companies GlaxoSmithKline (GSK) and Incyte (INCY). LCG and MIM are members of the Editorial Board of PLOS Medicine.
Citation: Langenberg C, Sharp SJ, Franks PW, Scott RA, Deloukas P, et al. (2014) Gene-Lifestyle Interaction and Type 2 Diabetes: The EPIC InterAct Case-Cohort Study. PLoS Med 11(5): e1001647. doi:10.1371/journal.pmed.1001647
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