In an Editorial accompanying PLOS Medicine's Special Issue on Diabetes Prevention, Guest Editors Nicholas Wareham and William Herman discuss some of the challenges for researchers and policy makers in developing effective and equitable solutions to the worldwide problem of type 2 diabetes

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The Clinical and Public Health Challenges of Diabetes Prevention: A Search for Sustainable Solutions.

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EDITORIALThe Clinical and Public Health Challenges ofDiabetes Prevention: A Search for SustainableSolutionsNicholas J. Wareham1*, William H. Herman21 MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom, 2 Departments of InternalMedicine and Epidemiology, University of Michigan, Ann Arbor, Michigan, United States of America* nick.wareham@mrc-epid.cam.ac.ukThe well-documented rise in the prevalence of type 2 diabetes (T2D) is a major global clinicaland public health challenge, as described by Juliana Chan and Andrea Luk in their accompa-nying Perspective article [1]. Somewhat less attention has been paid to the potential for the ris-ing global diabetes problem to widen health inequalities, and for the solutions that are put inplace to tackle the problem to worsen or improve those inequalities. Inequity is at the heart ofthe diabetes problem, since 75% of cases occur in low- and middle-income countries [2]. Theimpact of diabetes on emerging countries will be particularly severe as the disease is chronic,expensive to treat, and tends to affect economically active people. The economic cost of dealingwith the consequences of diabetes is not only a threat to health systems but is a far broader eco-nomic and social problem and thus a threat to future long-term sustainable development.Research aimed at diabetes prevention is therefore the focus of this special issue of PLOSMedicine.The pattern of the incidence and prevalence of T2D between countries suggests that the dis-order originates from a complex interaction between lifestyles, obesity, and innate susceptibil-ity, driven by both genetic factors and developmental programming by maternal and postnatalnutrition. The major driving force behind the contemporary rise in prevalence is a rising inci-dence of disease driven by major secular changes in dietary and physical activity behavior. TheT2D epidemic can be viewed at several different levels. At the individual level, the interplaybetween susceptibility factors and lifestyles is understood in broad terms, but our understand-ing at the molecular level is still limited. At the level of specific populations, more is understoodabout how changes in societal influences on diet and physical activity are driving the epidemic,but much of this understanding is restricted to developed countries. Finally, at the global level,there is a strong interconnection between the emergence of T2D and changes in the food sup-ply and patterns of consumption, changes in transportation use, and related issues such as airpollution and climate change [3]. At this level, T2D can be seen as a clinical manifestation of awider societal problem created by the undesirable consequences of rapid economicdevelopment.Randomized controlled trials in people at high risk of diabetes clearly demonstrate that life-style interventions can result in an approximate halving of the risk of developing the disease,exceeding the apparent benefit of oral diabetes drugs [4]; this impact of behavior-change pro-grams can be sustained over the long term [5]. These studies prove that T2D is preventable butdo not directly provide information about how it should be prevented in real-world settings.Even in developed countries, efforts to translate such research interventions into practicalPLOSMedicine | DOI:10.1371/journal.pmed.1002097 July 26, 2016 1 / 3a11111OPEN ACCESSCitation:Wareham NJ, Herman WH (2016) TheClinical and Public Health Challenges of DiabetesPrevention: A Search for Sustainable Solutions. PLoSMed 13(7): e1002097. doi:10.1371/journal.pmed.1002097Published: July 26, 2016Copyright: © 2016 Wareham, Herman. This is anopen access article distributed under the terms of theCreative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in anymedium, provided the original author and source arecredited.Funding: The authors received no specific fundingfor this work.Competing Interests: The authors have read thejournal's policy and have the following conflicts: WHHserves on Data and Safety Monitoring Boards forMerck and Lexicon. NJW and WHH served as guesteditors on PLOS Medicine’s Diabetes PreventionSpecial Issue.Abbreviations: T2D, type 2 diabetesProvenance: Commissioned; not externally peer-reviewedprograms have met challenges, with a large gulf persisting between efficacy and effectiveness,the gap between the health benefits that are achievable in a clinical trial as opposed to thosethat are realized in the real world [6]. As an illustration, in a research article in this issue, LauraGray and colleagues report on a diabetes prevention trial carried out in the United Kingdom,and their findings indicate the importance of engaging and retaining people in such preventionprograms [7].Diabetes prevention programs that target high-risk individuals require an integration ofefforts to test for prevalent undiagnosed diabetes, as well as so-called prediabetes, and are inessence large scale screening programs for hyperglycemia and diabetes. In the short term, inte-grated screening programs will increase costs as patients with newly diagnosed diabetes areidentified alongside people with prediabetes who require monitoring and follow-up. In the lon-ger term, this type of integrated program may be cost-effective, but this still remains to be dem-onstrated. Such approaches to prevention need to be focused on a relatively small group ofpeople at high absolute risk. Attempts to provide individual-level prevention interventions tolarge groups of people at moderately elevated risk are not likely to be cost-effective [8]. There isalso a concern that inequalities in health could be widened by individual-level interventionsbecause, in general, more affluent people tend to be more likely to accept invitations for screen-ing and treatment [9].There is no universal recommendation on whether a country should or should not adoptsuch a clinical approach to diabetes prevention, as investment would need to be considered incompetition with other clinical priorities. It is difficult to see how under-resourced health caresystems could switch clinical investment to individual-level prevention when they are failing tomeet the demands to provide systematic care and treatment to people with diabetes or its com-plications. In such settings, calls to screen for hyperglycemia run the risk of swamping healthcare systems that are already struggling to provide care. In the face of ageing populations,health care systems globally will struggle to cope with treating the estimated 642 million peoplewith diagnosed diabetes anticipated by 2040 [2]. To countenance trying to provide individual-ized preventive interventions to a further half a billion people who by then will have prediabe-tes would put those health systems under unbearable pressure and would be an unsustainableproposition.Thus, as a complement to individualized approaches to prevention, there needs to be a con-siderable scaling up of research into the societal determinants of diabetes, and evaluation ofsolutions that tackle the root causes of the problem, which are fundamental shifts in popula-tion-level dietary and physical activity behavior. As discussed by Martin White in a Perspectivein this issue of PLOS Medicine [10], the nature of the evidence base supporting these popula-tion-level solutions will be fundamentally different from that which underpins clinical inter-ventions, because randomized controlled trials are unlikely to be undertaken and most studieswill be quasiexperimental or observational. This evidence base is beginning to emerge—as anexample, the research article from Lindsey Smith Taillie and colleagues in this special issuepresents an analysis of the effects of a tax on nonessential energy-dense foods enacted inMexico [11].At present, the evidence base for public health approaches to diabetes prevention is domi-nated by research from developed countries. However, it is likely that population-basedapproaches will be even more important in relatively resource-poor countries because healthcare systems will not be able to afford prevention programs targeting high-risk individuals. Yetthe evidence base for population-based approaches to diabetes prevention in developing coun-tries is limited and needs to be generated specifically in those contexts, as solutions cannot beexported from developed countries. Given the economic circumstances of the countries inwhich the diabetes epidemic is most pressing, there needs to be much greater investment inPLOSMedicine | DOI:10.1371/journal.pmed.1002097 July 26, 2016 2 / 3development of the evidence base for sustainable solutions that narrow inequalities, are eco-nomically affordable, support rather than hinder economic development, and can bring aboutthe long-term changes in public health outcomes that are so urgently required.Author ContributionsWrote the first draft of the manuscript: NJWWHH. Contributed to the writing of the manu-script: NJWWHH. Agree with the manuscript’s results and conclusions: NJWWHH. Theauthors have read, and confirm that they meet, ICMJE criteria for authorship.References1. Chan JCN, Luk AOY. Diabetes: A Cinderella Subject We Can’t Afford to Ignore. PLoS Med 2016; 13:e1002068. doi: 10.1371/journal.pmed.1002068 PMID: 273799252. International Diabetes Federation. Diabetes Atlas 7th edn. Brussels, Belgium: International DiabetesFederation; 2015.3. Monsivais P, Scarborough P, Lloyd T, Mizdrak A, Luben R, Mulligan AA, et al. Greater accordance withthe Dietary Approaches to Stop Hypertension dietary pattern is associated with lower diet-relatedgreenhouse gas production but higher dietary costs in the United Kingdom. Am J Clin Nutr 2015;102:138–145. doi: 10.3945/ajcn.114.090639 PMID: 259265054. Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and life-style interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: sys-tematic review and meta-analysis. BMJ 2007; 334:299. PMID: 172372995. Li G, Zhang P, Wang J, Gregg EW, YangW, Gong Q, et al. The long-term effect of lifestyle interventionsto prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet2008; 371:1783–1789. doi: 10.1016/S0140-6736(08)60766-7 PMID: 185023036. Wareham NJ. Mind the gap: efficacy versus effectiveness of lifestyle interventions to prevent diabetes.Lancet Diabetes Endocrinol 2015; 3:160–161. doi: 10.1016/S2213-8587(15)70015-X PMID: 256521287. Gray LJ, Yates T, Troughton J, Khunti K, Davies MJ. Engagement, Retention, and Progression to Type2 Diabetes: A Retrospective Analysis of the Cluster-Randomized "Let's Prevent Diabetes" Trial. PLoSMed 2016; 13:e1002078. doi: 10.1371/journal.pmed.10020788. Zhuo X, Zhang P, Kahn HS, Gregg EW. Cost-effectiveness of alternative thresholds of the fastingplasma glucose test to identify the target population for type 2 diabetes prevention in adults aged >/ =45 years. Diabetes Care 2013; 36:3992–3998. doi: 10.2337/dc13-0497 PMID: 241353869. Adams J, Mytton O, White M, Monsivais P. Why Are Some Population Interventions for Diet and Obe-sity More Equitable and Effective Than Others? The Role of Individual Agency. PLoS Med 2016; 13:e1001990. doi: 10.1371/journal.pmed.1001990 PMID: 2704623410. White M. Population Approaches to Prevention of Type 2 Diabetes. PLoS Med 2016; 13;e1002080.doi: 10.1371/journal.pmed.100208011. Batis C, Rivera JA, Popkin BM, Taillie LS. First-Year Evaluation of Mexico’s Tax on NonessentialEnergy-Dense Foods: An Observational Study. PLoS Med 2016; 13:e1002057. doi: 10.1371/journal.pmed.1002057 PMID: 27379797PLOSMedicine | DOI:10.1371/journal.pmed.1002097 July 26, 2016 3 / 3

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The Clinical and Public Health Challenges of Diabetes Prevention: A Search for Sustainable Solutions

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The Clinical and Public Health Challenges of Diabetes Prevention: A Search for Sustainable Solutions.

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