The metabolic syndrome (visceral obesity, dyslipidaemia, hyperglycaemia, and hypertension), has become one of the major public-health challenges worldwide.1There has been growing interest in this constellation of cloly related cardiovascular risk factors. Although the association of veral of the risk factors has been known for more than 80years,2the clustering received scant attention until 1988 when Reaven described syndrome X: insulin resistance, hyperglycaemia, hypertension, low HDL-cholesterol, and raid VLDL-triglycerides.3Surpris-ingly, he omitted obesity, now en by many as an esntial component, especially visceral obesity.1Various names were subquently propod, the most popular being metabolic syndrome.1
The cau of the syndrome remains obscure. Reaven propod that insulin resistance played a causative role,3 but this remains uncertain. Lemieux et al suggested visceral obesity and the hypertriglyceridaemic waist phenotype as a central component,4but this too has been contested. Several different factors are probably involved, many related to changes in lifestyle.1
The ultimate importance of metabolic syndrome is that it helps identify individuals at high risk of both type 2 diabetes and cardiovascular dia (CVD). Several expert groups have therefore attempted to produce diagnostic criteria. The first attempt was by a WHO diabetes group in 1999, which propod a definition that could be modified as more information became available.5The criteria had insulin resista
nce or its surrogates, impaired gluco tolerance or diabetes, as esntial components, together with at least two of: raid blood pressure, hyper-triglyceridaemia and/or low HDL-cholesterol, obesity (as measured by waist/hip ratio or body-mass index), and microalbuminuria. The European Group for the Study of Insulin Resistance6then produced a modification of the WHO criteria excluding people with diabetes and requiring hyperinsulinaemia to be prent. Waist circumference was the measure of obesity, with different cutoffs for the other variables.
A fresh approach came from the US National Cholesterol Education Program: Adult Treatment Panel III in 2001, with a focus on cardiovascular dia risk.7The specific remit was to facilitate clinical diagnosis of high-risk individuals. It was less glucocentric than the definition from WHO and the European Group for the Study of Insulin Resistance, requiring the prence of any three of five components: central obesity, raid blood pressure, raid triglycerides, low HDL-cholesterol, and fasting hyperglycaemia.
The different definitions inevitably led to substantial confusion and abnce of comparability between studies. One difficulty has been that the conceptual framework ud to underpin the metabolic syndrome (and hence drive definitions) has not been agreed on. Opinions have varied as to whether the metabolic syndrome should be defined to mainly indicate insulin resistance, the metabolic con
quences of obesity, risk for CVD, or simply a collection of statistically related factors. Prevalence figures for the syndrome have been similar in any given population regardless of which definition is ud, but different individuals are identified.8What matters, of cour, is which produces the best prediction of subquent diabetes and CVD. Thus Adult Treatment Panel III was superior to WHO in the San Antonio Study, but WHO gave better prediction of CVD in Finnish men.9,10 Another problem with the WHO and the Adult Treatment Panel definitions has been their applicability to different ethnic groups, especially as relates to obesity cutoffs.11For example, the risk of type 2 diabetes is apparent at much lower levels of adiposity in Asian populations than in European populations.12With current metabolic syndrome definitions, particularly Adult Treatment Panel III, suspiciously low prevalence figures in Asian populations resulted,12 suggesting the need for ethnic-specific cutoffs, at least for obesity.
The International Diabetes Federation (IDF) felt there was a strong need for one practical definition that would be uful in any country for the identification of people at high risk of CVD, but also diabetes. This definition would also allow comparative long-term studies, which could then be ud, if necessary, to refine the definition on the basis of solid endpoints. As a result, an IDF connsus group met in 2004, with reprentatives from the organisations that had generated the previous definitions and members from all IDF regions. Their recommenda-tions are now available.13
There was connsus that the components identified by Adult Treatment Panel III were a nsible starting point. It was also agreed that diabetes and insulin resistance had been overemphasid as core measurements in the earlier
The metabolic syndrome—a new worldwide definition
definitions. Measurement of insulin resistance was deemed impractical, although it is clear that veral metabolic syndrome components, especially waist circumference and triglycerides, are highly correlated with insulin nsitivity.4
Central obesity, as assd by waist circumference, was agreed as esntial (panel), becau of the strength of the evidence linking waist circumference with cardiovascular dia and the other metabolic syndrome components,and the likelihood that central obesity is an early step in the aetiological cascade leading to full metabolic syndrome. The waist circumference cutoff lected was the same as that ud by European Group for the Study of Insulin Resistance, and lower than the main Adult Treatment Panel III recommendations, becau most available data suggest an increa in other cardiovascular dia risk factors in Europids (white people of European origin, regardless of where they live in the world) when the waist circumference ris above 94 cm in men a
nd 80cm in women.1Ethnic-specific waist circumference cutoffs have been incorporated into the definition (table),and have been bad on available data linking waist circumference to other components of the metabolic syndrome in different populations.12,14,15The levels of the other variables were as described by Adult Treatment Panel III, except that the most recent diagnostic level from the American Diabetes Association for impaired fasting gluco (5·6 mmol/L [100 mg/dL]) was ud.16Although this new definition will still miss substantial numbers of people with impaired gluco tolerance (becau an oral gluco-tolerance test is not required), it retains the simplicity of the instrument.
The connsus group also recommended additional criteria that should be part of further rearch into metabolic syndrome, including: tomographic asssment of visceral adiposity and liver fat, biomarkers of adipo tissue (adiponectin, leptin), apolipoprotein B, LDL particle size, formal measurement of insulin resistance and an oral gluco-tolerance test, endothelial dysfunction, urinary albumin, inflammatory markers (C-reactive protein,tumour necrosis factor ␣, interleukin 6), and thrombotic markers (plasminogen activator inhibitor type 1,fibrinogen). The factors should be combined with asssment of CVD outcome and development of diabetes so better predictors can be developed.
Rearchers and clinicians should u the new criteria for the identification of high-risk individuals and for rearch studies. Preventive measures are obviously needed in the people identified. Mounting evidence suggests that lifestyle modification with weight loss and incread physical activity will be beneficial, although specific studies in metabolic syndrome are needed. There
thinkquest
Panel:International Diabetes Federation: metabolic syndrome definition
Central obesity
考研英语复习资料Waist circumference*—ethnicity specific (e table 1)Plus any two:Raid triglycerides
anaerobicϾ150 mg/dL (1·7 mmol/L)
Specific treatment for this lipid abnormality Reduced HDL-cholesterol
Ͻ40 mg/dL (1·03 mmol/L) in men Ͻ50 mg/dL (1·29 mmol/L) in women
Specific treatment for this lipid abnormality Raid blood pressure Systolic у130 mm Hg Diastolic у85 mm Hg
Treatment of previously diagnod hypertension Raid fasting plasma gluco†
Fasting plasma gluco у100 mg/dL (5·6 mmol/L)Previously diagnod type 2 diabetes
If above 5·6 mmol/L or 100 mg/dL, oral gluco tolerance test is strongly recommended,but is not necessary to define prence of syndrome
*If body-mass index is over 30 kg/m 2, central obesity can be assumed and waist circumference does not need to be measured. †In clinical practice, impaired gluco tolerance is also acceptable, but all reports of prevalence of metabolic syndrome should u only fasting plasma gluco and prence of previously diagnod diabetes to define hyperglycaemia. Prevalences also incorporating 2-h gluco results can be added as supplementary findings.
are suggestions from the Finnish Diabetes Prevention Study that individuals with metabolic syndrome show less development of diabetes with lifestyle advice.17In many people, however, pharmacological intervention will be needed. There is no specific treatment for the metabolic syndrome so individual abnormalities will have to be attended to.Again, long-term studies will help establish whether existing or newer agents, such as agonists for the peroxisome-proliferator-activated ␣/␥receptors or cannabinoid-1 receptor blockers,18could be of specific benefit.
Recently, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have published a provocative discussion paper on the syndrome.19They rai veral interesting questions, bad on a critique of the earlier WHO and Adult Treatment Panel III criteria: 1) is it indeed a syndrome, particularly as the preci cau is unknown, 2) does it rve a uful purpo, and 3) is it labelling (and medicalising) people unnecessarily? Additionally, it has bee
n suggested in an editorial that recognition of the metabolic syndrome has been largely driven by industry to create new markets.20
A major part of the ADA/EASD19stance is bad on pure mantics, but the IDF (and the cardiovascular community) feel strongly that this clustering of cloly related risk factors for CVD and type 2 diabetes is indeed a very good basis for calling this a syndrome. Many examples exist of conditions being given a name even when the preci underlying cau or caus, are unknown (eg, type 2 diabetes). The IDF feels that it rves a uful purpo to focus on people, in both the community and clinical ttings, who are at high risk of developing CVD and type 2 diabetes, particularly using the new IDF criteria propod above.
Indeed, the ADA has just reinvented and redefined the condition of “prediabetes” for people who only have a 50% chance of developing diabetes.20We also emphasi most strongly in our longer article13that treatment must be focud on lifestyle change—and on the individual components if the former fails. This is a far cry from a condition claimed to be invented by industry.21The metabolic syndrome concept has been around for over 80years.1The burgeoning epidemic of type 2 diabetes and CVD worldwide, particularly in the developing world em adequate reasons for identifying and treating people with the syndrome.
We would stress that the new IDF criteria are not the final word, but hopefully will help identify people at incread risk, and through further rearch will lead to more accurate predictive indices.
*K George M M Alberti, Paul Zimmet, Jonathan Shaw, for the IDF Epidemiology Task Force Connsus Group Department of Endocrinology and Metabolism, St Marys Hospital, London W2 1NY, UK (KGMMA); and International Diabetes Institute, Melbourne, Victoria, Australia (PZ, JS)suede
George.Alberti@newcastle.ac.uk
The International Diabetes Federation Connsus Group was supported by an unrestricted educational grant from AstraZeneca. KGMMA receives consultancy fees from AstraZeneca, GlaxoSmithKline, Novartis, and Servier. PZ has received consultancy fees from Novartis, GlaxoSmithKline, Bristol Myer Squibb, Bayer AG, Abbott, and Merck, and has received payment for speaking from E Merck, Sanofi-Aventis, AstraZeneca, Kisi, and Fournier. JS has received consultant fees from Merck, Eli Lilly, and Novo Nordisk.
1Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet2005;
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miesyndrom. Zentralblatt fuer Innere Medizin1923; 44: 105–27.
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4Lemieux I, Pascot A, Couillard C, et al. Hypertriglyceridemic waist: a marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, den LDL) in men? Circulation2000; 102: 179–84.
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Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III).
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18
Van Gaal LF, Rissanen AM, Scheen AJ, for the RIO-Europe Study Group.Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005; 365: 1389–97.19
Kahn R, Bu J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care
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Gale EAM. Editorial: the myth of the metabolic syndrome. Diabetologia 2005; 10: 1873–75.
Last year I joined the rearch advisory board of the drug company GlaxoSmithKline and get paid for that work. I was asked to write this article by The Lancet and my fee for writing will be diverted to a charity. You need to know the things before you read on.
A ward round can reveal that many patients are taking ten or more drugs. A scan of a newspaper identified no fewer than six stories suggesting therapeutic breakthroughs. Therapeutic interventions, central to the practice of medicine, have spilled over into daily news—ranging from the adoption of fluoxetine as a drug for well-being in the 1990s to the pursuit of cardiovascular dia prevention resulting in 2003 for calls for a “polypill” for the entire population.1Yet despite this enthusiasm for drugs from doctors and patients,paradoxically the reputation of the drug industry is at an all time low—the industry is often portrayed as aiming for profit above all el. And it is not just the moral highgrounders who are voicing concern. Read this, from
the business ction of a major newspaper: “most drug failures are a by-product of the way the industry is structured: it develops drugs as fast as possible and employs an army of salesmen to ll like crazy before the patent expires. It ignores the fact that the side-effects of a drug are often not known until it has been taken by hundreds of thousands of patients.”2If this picture is correct, is industry alone to blame or are the medical profession and academia complicit in helping industry pursue profit above all el? This question is the theme of a report by Carl Elliott.3
Let us get one thing straight: the drug industry works within a system that demands it makes a profit to satisfy shareholders. Indeed it has a fiduciary duty to do so. The best way to make a lot of money is to invent a drug that produces a dramatically beneficial clinical effect, is far more effective than any existing options, and has few unwanted effects. Unfortunately most drugs fall short of this ideal. Does this stop doctors from prescribing them,or patients’ groups from demanding availability for all?
Clearly not. Even if we consider novel drugs rather than me-too products, recent examples provide some insights:the interferons for multiple sclerosis, drugs for dementia,and the inhibitors of cyclo-oxygena 2 (COX-2).
Interferon was potentially an exciting scientific advance and emed to produce detectable biological effects in patients with multiple sclerosis. However, you needed an MRI to detect the change and the extent to which structural changes translated into clinical benefit,and improvement in quality of life, was unclear. In 2000,the UK National Institute for Clinical Excellence 4relead an early statement that “on the basis of a very careful consideration of the evidence their [the interferons]modest clinical benefit appears to be outweighed by their very high cost”. The outcry was immediate, loud, and successful. Doctors, nurs, carers, and a patients’ group lobbied Government and the drug was made available within the UK National Health Service (NHS), albeit with
Developing an open relationship with the drug industry
Published online July 7, 2005DOI:10.1016/S0140-6736(05)shameonyou
66835-3
See Correspondence
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