For the International Diabetes Federation, the metabolic syndrome is driving the twin global epidemics of type 2 diabetes and cardiovascular disease. Consequently, there is an overwhelming moral, medical, and economic imperative to identify those individuals with metabolic syndrome early. However, the existence of multiple definitions for the metabolic syndrome has created confusion. In an effort to clarify the situation, the IDF proposes a new definition addressing both clinical and research needs and providing an accessible diagnostic tool suitable for worldwide use.

One of the most significant events of the first International Congress on Prediabetes and the Metabolic Syndrome held in Berlin from April 13 to April 16, 2005, was the presentation by Professor Sir George Alberti of the recent International Diabetes Federation (IDF) consensus on definition of the metabolic syndrome. Compared with the widely known NCEP-ATP III definition, the IDF definition insists on the presence of intra-abdominal obesity, which becomes a mandatory diagnostic criterion, recommends using ethnic-specific waist circumference cutoffs, and proposes a lower threshold for fasting blood glucose.

More than yet another definition

In 1999, the WHO published a definition of the metabolic syndrome with a sine qua non of glucose intolerance (documented by OGTT) or insulin resistance. The more clinically oriented NCEP-ATP III definition proposed two years later gave less primacy to glucose intolerance and acknowledged the importance of central obesity by including the presence of an enlarged waist circumference in the set of diagnostic criteria for metabolic syndrome. Other expert groups, such as the European Study Group for Insulin Resistance, proposed their own definitions.

In order to clarify the situation, the IDF held a Consensus meeting in 2004 to see whether a single common clinically and epidemiologically useful definition could be agreed for use worldwide. In the new definition (Table 1), central obesity, which is independently associated with each of the other metabolic syndrome components, including insulin resistance, is a prerequisite risk factor for the diagnosis of the syndrome. Insulin resistance, which is difficult to measure in day to-day clinical practice, is not an essential requirement.

Table 1: The new International Diabetes Federation (IDF) definition of the metabolic syndrome

According to the new IDF definition, for a person to be defined as having the metabolic syndrome they must have: Central obesity (defined as waist circumference ≥ 94cm for Europid men and ≥ 80cm for Europid women, with ethnicity specific values for other groups) plus any two of the following four factors: raised TG level: ≥150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality reduced HDL cholesterol: < 40 mg/dL (1.03 mmol/L) in males and < 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality raised blood pressure: systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg, or treatment of previously diagnosed hypertension raised fasting plasma glucose (FPG) ≥ 100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes. If above 5.6 mmol/L or 100 mg/dL, OGTT is strongly recommended but is not necessary to define presence of the syndrome.

A significant difference between the IDF and NCEP-ATP III definitions is the recommendation to use waist circumference thresholds that are ethnic-group specific (Table 2). The IDF strongly recommends that for epidemiological studies and, wherever possible, for case detection, specific cut-points should be used for people of the same ethnic group whatever their country of residence. The new definition will be useful to compare the prevalence of the metabolic syndrome between different nations.

“The criteria we are using for Asians are substantially lower than those recommended in European populations, but they imply the same risk of heart disease and diabetes,” explained Professor Paul Zimmet, Director of the International Diabetes Institute, who developed with Professor Sir George Alberti the idea for the consensus workshop.

Table 2: Ethnic specific values for waist circumference proposed by the IDF

Country/Ethnic group		Waist circumference*
Europids In the USA, the ATP III values (102 cm male; 88 cm female) are likely to continue to be used for clinical purposes	Male	≥ 94 cm
	Female	≥ 80 cm
South Asians Based on a Chinese, Malay and Asian-Indian population	Male	≥ 90 cm
	Female	≥ 80 cm
Chinese	Male	≥ 90 cm
	Female	≥ 80 cm
Japanese	Male	≥ 85 cm
	Female	≥ 90 cm
Ethnic South and Central Americans	Use South Asian recommendations until more specific data are available
Sub-Saharan Africans	Use European data until more specific data are available
Eastern Mediterranean and Middle East (Arab) populations	Use European data until more specific data are available

Another specificity of the new definition is the fasting blood glucose threshold recommended. The ATP III definition includes a 110 mg/dl cutoff for fasting blood glucose, but the American Diabetes Association recently decided to lower the plasma glucose level defining impaired fasting glucose to 100 mg/dL (5.6 mmol/L)./p>

The other components of the new IDF definition are low HDL-cholesterol (gender specific), raised triglycerides, and hypertension, with cutpoints similar to those used in the NCEP-ATP III definition.

“With a single, universally accepted diagnostic tool, clinicians can now more quickly identify patients with the metabolic syndrome in the practice setting,” said Professor Sir George Alberti past President of IDF and consensus group co-chairman.

“We hope that ATP III will come in line with this new definition very soon,” added Professor Paul Zimmet. It should be noted that Doctor Scott Grundy, President of the IAS and chairman of the NCEP-ATP III panel, was consultant to the writing committee in charge of developing the results of the IDF consensus meeting.

The IDF acknowledges that some refinements will be needed to have a “platinum standard” definition of the metabolic syndrome. The new IDF consensus statement enumerates a number of parameters which appear to be related to the syndrome and should be included in research studies to help determine their predictive power for cardiovascular disease and/or diabetes (Table 3).

Table 3: Additional metabolic criteria for research identified by the IDF consensus

Abnormal body fat distribution	General body fat distribution (DXA) Central fat distribution (CT/MRI) Adipose tissue biomarkers: leptin, adiponectin Liver fat content (MRS)
Atherogenic dyslipidaemia (beyond elevated triglyceride and low HDL)	ApoB (or non-HDL-c) Small LDL particles
Dysglycaemia	OGTT
Insulin resistance (other than elevated fasting glucose)	Fasting insulin/proinsulin levels HOMA-IR Insulin resistance by Bergman Minimal Model Elevated free fatty acids (fasting and during OGTT) M value from clamp
Vascular dysregulation (beyond elevated blood pressure)	Measurement of endothelial dysfunction Microalbuminuria
Proinflammatory state	Elevated high sensitivity C-reactive protein (SAA) Elevated inflammatory cytokines (eg TNF-alpha, IL-6) Decrease in adiponectin plasma levels
Prothrombotic state	Fibrinolytic factors (PAI-1 etc) Clotting factors (fibrinogen etc)
Hormonal factors	Pituitary-adrenal axis