Epidemiology of metabolic syndrome

Japanese

1) Diagnostic criteria for metabolic syndrome (Table 1)

During the last several years, a number of diagnostic criteria for metabolic syndrome have been advocated by different organizations. The World Health Organization (WHO) first advocated its criteria in 1998 ¹⁾ and subsequently the National Cholesterol Education Program's Adults Treatment Panel III (NCEP-ATP III) in USA advocated its criteria in 2001 ²⁾. Also, the International Diabetes Federation (IDF) and the Japanese Society of Internal Medicine advocated their criteria at almost identical timing in 2005.

Table 1 Comparison of definition of the metabolic syndrome

	WHO (1999)	NCEP-ATP III (2001)	Revised NCEP-ATP III (2004)	IDF (2005)	The Japanese Society of Internal Medicine (2005)
Definition	Diabetes or impaired fasting glycaemia or impaired glucose tolerance or insulin resistance plus 2 or more of the following:	At least 3 of the following:	At least 3 of the following:	Central obesity with ethnicity specific values plus any two of the following	Central obesity (waist-circumference with gender specific values) and two or more of the following:
Obesity	Waist-to-hip ratio >0.90 (male) >0.85 (female) or BMI>30kg/m^2	Waist-circumference ≥102cm (male) ≥88cm (female)	Waist-circumference ≥102cm (male) ≥88cm (female)	«Essential requirement» Waist-circumference (ex. Europids) ≥94cm (male) ≥80cm (female)	«Essential requirement» Waist-circumference (Japanese) ≥85cm (male) ≥90cm (female) or area of central adiposity ≥100cm^2
Serum triglycerides	≥150mg/dl	≥150mg/dl	≥150mg/dl or medication	≥150mg/dl or medication	≥150mg/dl or medication
Serum HDL Cholesterol	<35mg/dl (male) <39mg/dl (female)	<40mg/dl (male) <50mg/dl (female)	<40mg/dl (male) <50mg/dl (female) or medication	<40mg/dl (male) <50mg/dl (female) or medication	<40mg/dl or medication
Blood Pressure	≥140/90mmHg	≥130/85mmHg or medication	≥130/85mmHg or medication	≥130/85mmHg or medication	≥130/85mmHg or medication
Fasting plasma glucose	«Essential requirement» Assessment of plasma glucose levels 2 hours after glucose tolerance test and insulin resistance	≥110mg/dl	≥100mg/dl	≥100mg/dl or previously diagnosed type 2 diabetes	≥110mg/dl or medication
Micro- albuminuria	Urinary albumin excretion rate≥20μg/min or albumin/creatinine ratio ≥30mg/g

In the WHO's criteria, the metabolic syndrome was considered to be a special categorization for people possessing increased risk of type 2 diabetes. That is, they necessitate the presence of abnormal plasma glucose levels and/or insulin resistance, where the other cardiovascular risk factors can frequently cluster. In terms of clinical application, the WHO's criteria were not always practical because they adopted some parameters not routinely measured, such as plasma glucose levels at 2 hours after glucose tolerance test, HOMA (homeostasis model assessment insulin resistance) index and micro-albuminuria. In the NCEP-ATP III's criteria, on the other hand, any three conditions were required among the following five parameters of metabolic abnormalities: waist circumference, triglyceride, HDL cholesterol, blood pressure and fasting plasma glucose. Here, it has to be noted: 1) that the risk of visceral fat accumulation was emphasized in obesity or overweight; 2) that a criterion of insulin resistance was omitted; 3) that micro-albuminuria, which could not be routinely measured in the clinic, was omitted; and 4) that individual risk factors were evaluated equally without assigning any priority.

Following these two types of criteria, the IDF has recently presented a new version of criteria for metabolic syndrome, which necessitate the presence of central obesity (large waist circumference) in 2005 ³⁾. At the same timing, a Japanese version of criteria has been presented, on the basis of clinical evidence for the Japanese subjects, from the combined working committee which comprises 8 academic societies including the Japanese Society of Internal Medicine ⁴⁾. Similar to the IDF's criteria, the Japanese ones also necessitate the presence of central obesity which is evaluated by the waist circumference of ≥85 cm in males and ≥90 cm in females, and additionally require any two conditions among the three metabolic abnormalities-‑lipoprotein abnormality (triglyceride ≥150 mg/dl and or HDL cholesterol ≤40 mg/dl), high blood pressure (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg) and IGT (fasting plasma glucose ≥110 mg/dl). This new version of criteria is presumed to be advocated in face of the recent international trend for researchers to regard the metabolic syndrome as a constellation of risk factors, where lipid profile abnormality, hypertension and IGT are secondarily caused by central obesity via insulin resistance.

Thus, although there is substantial overlapping between the diagnostic conditions and cut-off points used for the three types of criteria above-mentioned, these do not define the metabolic syndrome from the identical viewpoint. We should bear in mind that the temporary goal of diagnosing the metabolic syndrome is, at least for the moment, to find out high-risk people for efficient prevention of cardiovascular diseases and not to strictly determine clinical entity with unique (or uniform) etiology.

Reference / URL

1) http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf

2) National Cholesterol Education Program: JAMA, 285: 2486, 2001

3) http://www.idf.org/home/index

4) Committee to evaluate diagnostic standards for metabolic syndrome: The Journal of the Japanese Society of Internal Medicine, 94: 749, 2005

2) Prevalence of metabolic syndrome (Table 2)

The prevalence of metabolic syndrome is varied among a number of epidemiological studies conducted to date, mostly dependent on the diagnostic criteria adopted, gender and ethnic origin of study population.

Table 2 Prevalence of metabolic syndrome in epidemiological study

Study or ethnic group	Country / Area	Year	Number of	Average	Male/Female	Diagnostic	Prevalence
		(year published)	subject	Age	(%)	criteria	(%)
Western countries
NHANES III	USA	1988-1994	12,363	64.3	48 / 52	NCEP	Male: 22.8
							Female: 22.6
San Antonio Heart Study	USA	1979-1988	1,081	52	44 / 56	NCEP	Male: 24.7
			(Caucasian)				Female: 21.3
						WHO	Male: 24.7
							Female: 17.2
			1,656	50	42 / 58	NCEP	Male: 29.0
			(Mexican -American)				Female: 32.8
						WHO	Male: 32.0
							Female: 28.3
Framingham Offspring Study	USA	1991-1995	3,224	54	47 / 53	NCEP	Male: 26.9
							Female: 21.4
						WHO	Male: 30.3
							Female: 18.1
DECODE study	Europe	1971-1994	11,507	57(median)	54 / 46	WHO*	Male: 15.7
							Female: 14.2
The Kuopio Ischemic Heart Disease Risk Factor Study	Finland	1984-1989	1,209	51.5 ± 5.9	(male only)	NCEP WHO	Male: 8.8 Male: 14.2
Asia
Indian population	India	(2003)	1,091		49 / 51	NCEP	Male: 9.8
							Female: 20.4
Korean population	South Korea	2001	40,698	41.2 ± 9.2	65 / 35	NCEP	Male: 5.2
							Female: 9.0
Hisayama study	Japan	1988	2,366			NCEP	Male: 16.6
							Female: 22.0
Tanno-Sobetsu study	Japan	1993	808	60.3 ± 11.9	(male only)	Japanese Society	Male: 25.3
						of Internal Medicine

In USA, by using the NCEP's criteria, the prevalence of metabolic syndrome in the general population has been reported to range from 21 to 27 % (22.8-26.9 % in males and 21.3-22.6 % in females), which could be estimated in three population-based studies, i.e., the Third National Health and Nutrition Examination Survey (NHANES III), the Framingham Offspring Study and the San Antonio Heart Study ^1-3). In particular, the latter two studies did compare the prevalence of metabolic syndrome based on the NCEP's criteria with that based on the WHO's criteria and they demonstrated that the higher prevalence was observed for the WHO's criteria in males and for the NCEP's criteria in females, respectively.

In Europe, by using the WHO's criteria, the prevalence of metabolic syndrome in the general population has been reported to be lower than that in USA, i.e., 15.7 % in males and 14.2 % in females, which could be estimated in the DECODE (Diabetes Epidemiology: Collaborative analysis of Diagnostic criteria in Europe) study integrating 11 cohort studies conducted in Europe ³⁾.

In Asian countries (other than Japan), the prevalence of metabolic syndrome has been also reported to be particularly lower in males than that in USA and Europe; e.g., based on the NCEP's criteria, the prevalence is estimated to be 9.7 % in males and 20.4 % in females in India ⁴⁾, and 5.2 % in males and 9.0 % in females in Korea ⁵⁾, respectively.

In Japan, the prevalence of metabolic syndrome has been reported by two population-based cohort studies--the Hisayama study ⁶⁾ and the Tanno-Sobetsu study ⁷⁾. The prevalence in the Hisayama study (16.6 % in males and 22.0 % in females) appeared to be comparable to that reported in USA at least in females, whereas the prevalence in the Tanno-Sobetsu study (26.4 % in males and 8.8 % in females) became much higher in males and lower in females. Here, the former adopted the NCEP's criteria and the latter did the latest Japanese version. Consequently, marked differences in cut-off levels of the waist circumference between the two criteria did affect the estimated prevalence of central obesity. As shown in Figure 1, when the NCEP's criteria (≥102 cm in males and ≥88 cm in females) was applied similarly to Caucasians, only 0.8% of males and 24.2 % of females turned out to satisfy them in the Japanese people. This may lead us to hastily conclude that the prevalence of central obesity and the resultant metabolic syndrome is much lower in the Japanese (as well as people in the other Asian countries) than that in USA and Europe particularly in males.

Thus, although setting the identical threshold for each of diagnostic criteria seems to be useful for inter-regional (or inter-ethnicity) comparison, the current consensus is the need of setting ethnicity- and gender-specific threshold at least for a criterion of central obesity. Accordingly, this point has been deliberately considered in the latest IDF's criteria of metabolic syndrome.

Reference

1) Park YW, et al.: Arch Intern Med, 163: 427, 2003

2) Meigs JB, et al.: Diabetes, 52: 2160, 2003

3) Hu G, et al.: Arch Intern Med, 164: 1066,2004

4) Gupta A, et al.: Diabetes Res Clin Pract, 61: 69, 2003

5) Lee WY, et al.: Diabetes Res Clin Pract, 65: 143,2004

6) Ohkubo K, et al.: The Japanese journal of clinical and experimental medicine, 81: 1736, 2004

7) Takeuchi H, et al.: Hypertens Res, 28: 203, 2005

3) Significance of diagnosing metabolic syndrome

Diagnosing metabolic syndrome is closely related preventing cardiovascular diseases. In this line, several epidemiological studies have reported positive association between metabolic syndrome and the risk for cardiovascular diseases. For example, it has been shown that metabolic syndrome can increase by 3-4 times the risk of death due to ischemic heart disease by the Kuopio Ischemic Disease Risk Factor Study in Finland, where metabolic syndrome was diagnosed among 1.209 male participants based on the NCEP's criteria and an 11-year follow-up investigation performed for the mortality of cardiovascular events and total causes ¹⁾. Also, it has been shown that metabolic syndrome can considerably increase the risk of developing coronary artery disease (with a relative risk of 2.96), myocardial infarction (with a relative risk of 2.63) and brain infarction (with a relative risk of 2.27) independently of risk factors including obesity, lipid profile abnormality, hypertension, micro-albuminuria and insulin resistance by the Botnia study, where metabolic syndrome was diagnosed among 3,606 participants based on the WHO's criteria and an average of 6.9-year follow-up investigation performed ²⁾. These two studies have highlighted a concept of metabolic syndrome that the clustering of risk factors multiplicatively increases the risk of developing cardiovascular diseases even if the disease status of individual risk factors are still at the mild to modest level.

In summary, diagnosing metabolic syndrome in a particular group of high-risk patients allows for early and comprehensive control of risk factors, and it eventually enables us to decrease the incident of cardiovascular diseases efficiently and effectively. This is a topic of health care which is currently most noted around the world.

1) Lakka HM, et al.: JAMA, 288: 2709, 2002

2) Issomaa B, et al.: Diabetes Care, 24: 683, 2001

Written by Miyuki Makaya and Norihiro Kato

Department of Gene Diagnostics and Therapeutics, Research Institute, International Medical Center of Japan

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