diabetes is a leading cause of morbidity and mortality prevalence of diabetes in terms of the number who need would not develop diabetes despite their …
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Predictive genetic testing for type 2 diabetes
A Cecile J W Janssens, Marta Gwinn, Rodolfo Valdez, K M Venkat Narayan and Muin J Khoury BMJ 2006;333;509-510 doi:101136/bmj3895359894780
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References
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Editorials
greater benefit for older people by virtue of their higher absolute risk for future stroke8 Stroke specialists have a responsibility to disseminate these principles of good practice actively in their local healthcare communities One way is to redesign stroke
services and to integrate specialist and primary care responses to the management of transient ischaemic attacks in a similar manner to the approaches developed for coronary heart disease, which have led to a welcome reduction in the degree of related ageism9 Ageism will always prosper when resources are inadequate for the target population The UK government has recently been embarrassed into action by a damning report from the National Audit Office that highlighted deficiencies in specialist stroke services nationally, including the underprovision of clinics for patients with transient ischaemic attacks10 Tackling institutionalised age discrimination more broadly in health services will require national leadership, with governments and health services openly acknowledging the presence of ageism In England some early progress has been made, almost certainly due in part to a policy initiative delivered through the National Service Framework for Older People since 200111 Mortality from coronary heart disease and cancer declined between 1993 and 2003, and access to elective surgery increased between 2000 and 200312 Some will argue, however, that ageism is so deeply embedded in our
health service that policy initiatives will never represent more than a tinkering round the edges Dont be surprised if older people lose trust in their health service and lobby for protection through anti-discrimination legislation The result would indeed be a patient led health service John Young Head of academic unit of elderly care and rehabilitation
johnyoung@bradfordhospitalsnhsuk Academic Unit of Elderly Care and Rehabilitation, St Lukes Hospital, Bradford BD5 0NA
Competing interests: None declared
1 2 Roberts E, Robinson J, Seymour L Old habits die hard London: Kings Fund, 2002 Turner NJ, Haward RA, Mulley GP, Selby PJ Cancer in older age–is it adequately investigated and treated? BMJ 1999;319:309-12 3 Dudley N, Burns E The influence of age on policies for admission and thrombolysis in coronary care units in the UK Age Ageing 1992;21:95-8 4 DeWilde S, Carey IM, Bremner SA, Richards N, Hilton SR, Cook DG Evolution of statin prescribing 1994-2001: a case of ageism but not sexism? Heart 2003;89:417-21 5 Burns A, Dening T, Baldwin R Care of older people: mental health problems BMJ 2001;322:789-91 6 Fairhead JF, Rothwell PM Underinvestigation and undertreatment of carotid
disease in elderly patients with transient ischaemic attack and stroke: comparative population based study BMJ 2006 doi: 101136/ bmj3889564689855 7 Fuat A, Hungin AP, Murphy JJ Barriers to accurate diagnosis and effective management of heart failure in primary care BMJ 2003;326:196-201 8 Endarterectomy Trialists Collaboration Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery Lancet 2004;363:915-24 9 Ramsay SE, Whincup PH, Lawlor DA, Papacosta O, Lennon LT, Thomas MC, et al Secondary prevention of coronary heart disease in older people after the National Service Framework: population based study BMJ 2006;332:144-5 10 National Audit Office Reducing brain damage: faster access to better stroke care London: Department of Health, 2005 wwwnaoorguk/publications/ nao_reports/05-06/0506452pdf last accessed 4 September 11 Department of Health National Service Framework for older people London: DoH, 2001 wwwdhgovuk/assetRoot/04/07/12/83/ 04071283pdf last accessed 4 September 12 Department of Health Better health in old age London: DoH, 2004 wwwassoc-optometristsorg/uploaded_files/ better_health_in_old_age_philp_021104pdf last accessed 4
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Predictive genetic testing for type 2 diabetes
May raise unrealistic expectations
he discovery earlier this year that a variant of the TCF7L2 transcription factor 7-like 2 gene is associated with type 2 diabetes was reported in a front page story in the New York Times1 2 The principal investigator, Kari Stefansson, told the newspaper that the discovery could lead to a diagnostic test to identify people who carry the variant gene People who knew of their extra risk, he said, would be motivated to avoid the lifestyle habits that lead to diabetes A Scottish scientist headed the research team, which led the Glasgow Herald to report, Discovery of holy grail will help scientists treat diabetes3 Undeniably this discovery is noteworthy Type 2 diabetes is a leading cause of morbidity and mortality in the developed world and is increasing in prevalence worldwide The association is robust–the finding has been replicated in three large independent study populations and offers potential new insight into the pathobiology of diabetes Yet the claim that this knowledge will lead to a diagnostic test and hence to disease prevention–now routine for such
genetic discoveries– may not be true We believe that this syllogism a logical argument in which one proposition the conclusion is inferred from two others the premises
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oversimplifies the research findings and the challenge of translation and, above all, misleads the public The investigators estimated a 21 population attributable risk for the risk genotypes This means that 21 of cases of the disease can be prevented when the negative effects of the genetic exposure are eliminated However, by itself, a large population attributable risk does not indicate what efforts are needed to reduce the prevalence of diabetes in terms of the number who need intervention or the effectiveness of the preventive strategy If this discovery led to a 100 effective intervention that specifically targeted the effects of the genetic variant, 45 of the general population would need to receive this intervention to prevent 21 of diabetes cases If we assume an overall lifetime risk of diabetes of 33,4 88 of heterozygous carriers and 63 of homozygotes might not benefit from this intervention because they would not develop diabetes despite their TCF7L2 carrier
status or they would develop diabetes from other causes An intervention that specifically targets the effects of TCF7L2 variants would need to be cheap, harmless, and burdenless to warrant such substantial overtreatment
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Alternatively, as Kari Stefansson suggested, the genetic test could identify people at high risk who would benefit from appropriate advice on diet and physical activity although this advice is applicable to all The risk of diabetes is increased from 33 to 63 in homozygous TCF7L2 carriers 7 of the population, but the risk is increased from 33 to only 38 in heterozygous carriers 38 of the population Would these figures provide enough incentive for carriers to change their lifestyles?5 Only a month before online publication of the discovery of TCF7L2, another study evaluated the simultaneous testing of PPARG peroxisome proliferative activated receptor and CAPN10 calpain 10 SNP43/44 single nuclear protein 43/44 genotypes and claimed that genetic testing might become a future approach to identify people at risk of developing type 2 diabetes6 This conclusion was based on the finding that
carriers of the PPARG PP and CAPN10 SNP43/44 GG/TT genotypes who were obese and had raised fasting plasma glucose values, had a 212-fold increased risk for type 2 diabetes compared with non-obese noncarriers with normal fasting plasma glucose We showed that testing for these genetic variants would not improve the prediction of type 2 diabetes over body mass index and fasting plasma glucose concentration7 Inferences about the public health applications of genetic testing are often based on single measures of association or indicators of test performance, such as the risk ratio or population attributable risk Predictive genetic testing is useful when the value it adds to existing interventions outweighs the additional personal and social costs This requires a complete evaluation of the tests performance characteristics, including sensitivity and specificity; its positive and negative predictive value in the population to be tested; the likelihood ratio of positive and negative test results; and the rates of false positive and false negative test results These data are only part of the evidence base needed to recommend a test, which also includes information about effectiveness
relative to existing alternatives, side effects, and costs8 A risk ratio or population attributable risk alone cannot predict the potential usefulness of genetic testing News about genetic associations with type 2 diabetes and the potential for predictive testing was quickly picked up by patient organisations912 Ultimately, genetic discoveries may lead to better understanding of the disease process and to better therapeutic and preventive interventions In the meantime, scientists and the media are responsible for accurately and carefully interpreting the implications of studies of genetic associations for the benefit of the general public Raising unrealistic expectations–even inadvertently–could distract attention from what can be done by applying what we already know to prevent diabetes and its complications13 A Cecile J W Janssens epidemiologist
ajanssens@erasmusmcnl Department of Public Health, Erasmus MC University Medical Centre Rotterdam, 3000 CA Rotterdam, Netherlands
Marta Gwinn epidemiologist Rodolfo Valdez epidemiologist K M Venkat Narayan chief Muin J Khoury director
Centers for Disease Control and Prevention, Atlanta, GA 30341, USA
Competing interests: None
declared
1 Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, et al Variant of transcription factor 7-like 2 TCF7L2 gene confers risk of type 2 diabetes Nat Genet 2006;38:320-3 Wade N Gene increases diabetes risk, scientists find New York Times 16 Jan 2006:1 Morgan J Scot raises diabetes hopes Discovery of holy grail will help scientists treat diabetes Herald 17 Jan 2006:1; 4 Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF Lifetime risk for diabetes mellitus in the United States JAMA 2003;290:188490 Marteau TM, Weinman J Self-regulation and the behavioural response to DNA risk information: a theoretical analysis and framework for future research Soc Sci Med 2006;62:1360-8 Lyssenko V, Almgren P, Anevski D, Orho-Melander M, Sjogren M, Saloranta C, et al Genetic prediction of future type 2 diabetes PLOS Med 2005;2:e345 Janssens ACJW, Gwinn M, Subramonia-Iyer S, Khoury MJ Does genetic testing really improve the prediction of future type 2 diabetes? PLOS Med 2006;3:e114 Haddow JE, Palomaki GE ACCE: a model process for evaluating data on emerging genetic tests In: Khoury MJ, Little J, Burke W, eds Human genome epidemiology: a scientific
foundation for using genetic information to improve health and prevent disease Oxford: Oxford University Press, 2003:217-33 Diabetesincontrolcom Two diabetes genes predict the risk of type 2 diabetes wwwdiabetesincontrolcom/modulesphp?name Newsfile article sid 3242 last accessed 11 May 2006 Diabetescouk Important genetic discovery could treat diabetics wwwdiabetescouk/news/2006/Jan/important-genetic-discovery-couldtreat-diabeticshtml last accessed 11 May 2006 Diabetesheadlinescom Gene variation linked to one-fifth of type 2 diabetes cases wwwdiabetesheadlinescom/archive/01-17-2006 last accessed 11 May 2006 Diabetesincontrolcom Gene for diabetes found in 40 of population wwwdiabetesincontrolcom/modulesphp?name Newsfile article sid 3436 last accessed 11 May 2006 Narayan KM, Benjamin E, Gregg EW, Norris SL, Engelgau MM Diabetes translation research: where are we and where do we want to be? Ann Intern Med 2004;140:958-63
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Tackling alcohol misuse at the front line
Training staff where patients usually present should improve detection and advice
he UK government announced at the end of last year that 32m 48m; 6m was
to be made available for new initiatives which will help identify and intervene early with people who may be damaging themselves with alcohol1 In 2004 in England 38 of men and 16 of women aged 16-64 had an alcohol use disorder 26 overall, equivalent to around 82 million people2 About 217m is currently spent on specialist alcohol treatment, but compare that with the 20bn
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estimated cost of alcohol misuse We hope that some of the new money will be used to support those clinical settings in which alcohol misuse is common and detection and intervention are most likely to be rewarding– for example, in hospital emergency departments, general practices, and hospital wards Most conurbations in England have one or more specialist alcohol units, which are usually headed by psychiatrists and largely deal with complex problems such as dependence, psychiatric comorbidity, and
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