BMJ  2005;331:1153-1154 (19 November), doi:10.1136/bmj.331.7526.1153

Editorial

Metabolic syndrome

Independently raises cardiovascular risk and should be picked up in primary care

Metabolic syndrome is characterised by hyper-insulinaemia, low glucose tolerance, dyslipidaemia, hypertension, and obesity. This cluster of factors has been recognised for many years, but the syndrome was not formally labelled until Reaven did so in 1988 and suggested that insulin resistance was its central characteristic.¹ Insulin resistance seems to be the main underlying factor leading to the increased risk of mortality from coronary heart disease among people with the syndrome.² Strategies to combat the forecast epidemic of type 2 diabetes and its vascular complications should focus on preventing and intervening early in metabolic syndrome.

Established macrovascular pathology is common when diabetes is diagnosed,³ implying either delayed diagnosis or an atherogenic prediabetic state. The UK prospective diabetes study showed that, once diabetes is diagnosed glycaemia is only modestly related to cardiovascular disease.⁴ Insulin resistance may be the common antecedent of metabolic syndrome, type 2 diabetes, and cardiovascular disease. Any strategy aimed at preventing the principal cause of death in type 2 diabetes should, therefore, encompass treatment of the metabolic syndrome.

The clinical identification of metabolic syndrome is based on measures of abdominal obesity, atherogenic dyslipidaemia, hypertension, and glucose intolerance. The World Health Organization's definition of metabolic syndrome requires evidence of insulin resistance and measurement of fasting insulin or its surrogates as essential criteria.^w1 However, the Adult Treatment Panel III of the US National Cholesterol Education Program (NCEP) proposed a simpler definition, developed for clinical use and not including any estimation of insulin resistance.^w2 People meeting three of the following criteria qualify as having the metabolic syndrome: raised blood pressure (> 130/85 mm Hg), a low serum concentration of HDL cholesterol (< 1.04 mmol/l in men and < 1.29 mmol/l in women), a high serum triglyceride concentration (> 1.69 mmol/l), a high fasting plasma glucose concentration (> 6.1 mmol/l), and abdominal obesity (waist circumference > 102 cm in men and > 88 cm in women). A new definition, proposed recently by the International Diabetes Federation, has central obesity as an essential criterion, with a range of cut-offs for waist circumference for people from different ethnic groups.⁵

In a recent joint statement, the American Diabetes Association and European Association for the Study of Diabetes questioned the diagnosis of metabolic syndrome.^w3 The debate will, no doubt, continue. Yet the concept of metabolic syndrome provides a practical and useful way to identify patients with multiple factors that place them at high risk of developing diabetes and cardiovascular disease.⁵

The prevalence of metabolic syndrome in the adult population in developed countries is 22-39% and varies depending on the definition used and on ethnicity.^{2 6 7} As defined by both WHO and NCEP metabolic syndrome is associated with future coronary heart disease events and type 2 diabetes.^w4 Both definitions also predict cardiovascular mortality,^w5 although only the NCEP definition has also been shown to predict all cause mortality.^w6 Metabolic syndrome seems to evolve gradually. Having even one or two features of the syndrome was associated in one study with increased risk of mortality from coronary heart disease and cardiovascular disease.^w7

People with metabolic syndrome and a Framingham risk score greater than 20% have an increased risk of major coronary events over the next 10 years compared with people without metabolic syndrome and with the same risk score.⁸ Furthermore, the Framingham risk score—based on age, serum concentrations of both LDL and HDL cholesterol, blood pressure, cigarette smoking, and diabetes mellitus—predicts full development only of cardiovascular disease whereas the presence of metabolic syndrome predicts both diabetes and cardiovascular disease.

What does the diagnosis of metabolic syndrome mean for screening for and preventing chronic disease, particularly in primary care? All components of the NCEP and the International Diabetes Federation criteria for metabolic syndrome—hypertension, dyslipidaemia, abdominal obesity, and fasting glucose concentration—can readily be measured in primary care. Unlike the WHO criteria, these criteria do not include a glucose tolerance test, which would increase workload in primary care. Patients and primary care teams should focus on preventing all components of metabolic syndrome, bearing in mind that the risk of developing the metabolic syndrome increases with weight gain⁹ and insulin insensitivity is improved by weight loss,¹⁰ and eating less saturated fat.¹¹ Earlier this month in its report Preventing chronic diseases: a vital investment, WHO published its latest projections on increased premature deaths from chronic diseases, including diabetes, and called for urgent action on modifiable risk factors such as unhealthy diets and physical inactivity.^w8

It is becoming increasingly clear that a proinflammatory state is a common feature of the syndrome and of atheromatous disease. A recent randomised controlled trial showed that insulin resistance and measurements of C reactive protein were significantly lower at two year follow-up in patients with metabolic syndrome who had been allocated to a Mediterranean diet than in those who continued their normal diets.¹² Although large intervention studies have shown that intensive modification of lifestyle delays the onset of diabetes in patients with impaired glucose tolerance,^w9 no similar trials have aimed at reducing all the cardiovascular disease risk factors among people with metabolic syndrome.

(kk22{at}le.ac.uk)
Department of Health Sciences, University of Leicester, Leicester General Hospital, Leicester LE5 4PW

University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, Leicester LE1 5WW

---

Additional references w1-w9 are on bmj.com

Competing interests: None declared.

References

1. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37: 1595-607.[Abstract]
2. Meigs JB, Wilson PWF, Nathan DM, D'Agostino Sr RB, Williams K, Haffner SM. Prevalence and characteristics of the metabolic syndrome in the San Antonio heart and Framingham offspring studies. Diabetes 2003;52: 2160-7.[Abstract/Free Full Text]
3. UK Prospective Diabetes Study 6. Complications in newly diagnosed type 2 diabetic patients and their association with different clinical and biochemical risk factors. Diabetes Res 1990;13: 1-11.[Medline]
4. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321: 405-12.[Abstract/Free Full Text]
5. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome—a new worldwide definition. Lancet 2005;366: 1059-60.[CrossRef][ISI][Medline]
6. Ilanne-Parikka P, Eriksson JG, Lindstrom J, Hamalainen H, Keinanen-Kiukaanniemi S, Laakso M, et al. Prevalence of the metabolic syndrome and its components: Findings from a Finnish general population sample and the diabetes prevention study cohort. Diabetes Care 2004;27: 2135-40.[Abstract/Free Full Text]
7. Park Y-W, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: Prevalence and associated risk factor findings in the US population from the third national health and nutrition examination survey, 1988-1994. Arch Intern Med 2003;163: 427-36.[Abstract/Free Full Text]
8. Girman CJ, Rhodes T, Mercuri M, Pyorala K, Kjekshus J, Pedersen TR, et al. The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas coronary atherosclerosis prevention study (AFCAPS/TexCAPS). Am J Cardiol 2004;93: 136-41.[CrossRef][ISI][Medline]
9. Carnethon MR, Loria CM, Hill JO, Sidney S, Savage PJ, Liu K. Risk factors for metabolic syndrome: The Coronary Artery Risk Development in Young Adults (CARDIA) study, 1985-2001. Diabetes Care 2004;27: 2707-15.[Abstract/Free Full Text]
10. Calle-Pascual AL, Saavedra A, Benedi A, Martin-Alvarez PJ, Garcia-Honduvilla J, Calle JR, et al. Changes in nutritional pattern, insulin sensitivity and glucose tolerance during weight loss in obese patients from a Mediterranean area. Hormone Metabol Res 1995;27: 499-502.[ISI][Medline]
11. Hu FB, Van Dam RM, Liu S. Diet and risk of type II diabetes: The role of types of fat and carbohydrate. Diabetologia 2001;44: 805-17.[CrossRef][ISI][Medline]
12. Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: A randomized trial. JAMA 2004;292: 1440-6.[Abstract/Free Full Text]

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