Sleep & the metabolic syndrome.
Abstract: Sleep is an essential part of our daily living, and sleep disturbances may intervene with the biological and physiological processes in human body leading to the development of metabolic dysfunction. Short sleep duration and poor sleep quality have adverse effects on metabolism and hormonal processes, contributing to increased cardiovascular risk. Obstructive sleep apnoea is a chronic condition characterized by repetitive upper airway collapse during sleep, causing intermittent hypoxaemia, recurrent arousals and sleep fragmentation. Sleep disturbances can increase sympathetic activity, provoke systemic inflammation and oxidative stress, and impair vascular endothelial function. Obstructive sleep apnoea is increasingly recognized to be an independent cardiovascular risk factor. There is intense research interest in the association between obstructive sleep apnoea and the metabolic syndrome--the constellation of inter-related metabolic derangements including central obesity, hypertension, insulin resistance and dyslipidaemia, which appears to directly promote the development of atherosclerosis. The underlying pathophysiologic pathways or mechanistic links between obstructive sleep apnoea and metabolic syndrome have not been well delineated. This article reviews the current knowledge of the relationship between sleep disturbances, sleep-disordered breathing and the metabolic syndrome in adults.

Key words Diabetes mellitus--hypertension--metabolic syndrome--obesity--obstructive sleep apnoea--sleep-disordered breathing--sleep disturbances
Article Type: Report
Subject: Sleep apnea syndromes (Complications and side effects)
Sleep deprivation (Complications and side effects)
Metabolic syndrome X (Risk factors)
Metabolic syndrome X (Development and progression)
Metabolic syndrome X (Research)
Authors: Lam, Jamie C.M.
Ip, Mary S.M.
Pub Date: 02/01/2010
Publication: Name: Indian Journal of Medical Research Publisher: Indian Council of Medical Research Audience: Academic Format: Magazine/Journal Subject: Biological sciences; Health Copyright: COPYRIGHT 2010 Indian Council of Medical Research ISSN: 0971-5916
Issue: Date: Feb, 2010 Source Volume: 131 Source Issue: 2
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: China Geographic Code: 9CHIN China
Accession Number: 229718090
Full Text: Introduction

Short sleep duration and poor quality of sleep, increasingly common in our modern society, have many effects on our endocrine and metabolic function. Sleep is a major buffer for hormonal release, glucose regulation and cardiovascular function (1). The quality of sleep declines with age, with predominant light and fragmented sleep in the elderly (2). Deep or slow wave sleep occurs during stages 3 and 4 of non rapid eye movement (NREM) sleep and is considered to be the most restorative of all sleep stages. Chronic sleep insufficiency or deprivation not only leads to frequent mental and physical distress, physical incapability and anxiety (3) but also contributes to the ageing process, and may increase the risk for diabetes and obesity (4).

Sleep-disordered breathing (SDB) disrupts sleep pattern and quality. Obstructive sleep apnoea (OSA) is the most common sleep disorder being diagnosed. It is a chronic condition characterized by repetitive episodes of the upper airway collapse during sleep. The effects of intermittent hypoxia and re-oxygenation may provoke a number of pathological cascades which involve sympathetic overactivity, systemic inflammation, oxidative stress and endothelial dysfunction. These are believed to be the underlying mechanisms of OSA contributing independently to increased cardiometabolic risk (5). Untreated OSA subjects have been shown to suffer a significantly increased risk of both fatal and non fatal cardiovascular events by 3-fold, when compared to healthy subjects (6).

The metabolic syndrome is a constellation of inter-related risk factors of metabolic origin and its prevalence is increasing due to the obesity epidemic. Metabolic syndrome is associated with cardiovascular mortality because it comprises established risk factors for cardiometabolic diseases (7). Recent data show a strong association between OSA and the metabolic syndrome, which is indicative of adverse cardiovascular outcomes (8). This article reviews the current knowledge of the relationship between sleep disturbances, sleep-disordered breathing and the metabolic syndrome in adults.

The metabolic syndrome

Metabolic syndrome was first described as a cluster of metabolic abnormalities, with insulin resistance as the central pathophysiological feature, and it was labelled as "Syndrome X" (9). There are different accepted criteria for its definitions, and the most widely used criteria have been proposed by the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR), the National Cholesterol Education Program--Third Adult Treatment Panel (NCEP ATP III) and International Diabetes Federation (Table). All these organizations have suggested that the core features of metabolic syndrome are central/visceral obesity, hypertension, insulin resistance and dyslipidaemia but they have applied the criteria differently in identifying the cluster of syndrome components (10). Therefore, there have been cases that could be classified as metabolic syndrome by one definition but not by the others. Today, insulin resistance and central obesity have been acknowledged as key driving forces for metabolic syndrome, and these are, independently, also well known cardiovascular risk factors. Patients with metabolic syndrome are at increased risk for the development of type II diabetes mellitus and cardiovascular disease (11).

Different definitions for the metabolic syndrome inevitably led to limited comparability between studies. Besides, there are problems of applicability of these definitions to different ethnic groups, especially in relation to obesity cut-offs. With the current metabolic syndrome definitions, particularly NCEP ATP III, low prevalence figures in Asian population resulted. In a study of over 2800 Chinese subjects, the prevalence of the metabolic syndrome was at 16.7 per cent, however, if using WHO recommendations for waist circumference for Asians (12), the age and gender-adjusted prevalence significantly increased to 21.2 per cent (13). Knowing the recent evidence and with the spreading obesity epidemic, the prevalence of metabolic syndrome and its associated complications is definitely on the rising trend regardless of the exact criteria used for the syndrome.

Obstructive sleep apnoea and metabolic syndrome

A number of neural, humoral, metabolic, vascular and inflammatory abnormalities are evident in subjects with OSA, and it is increasingly recognized to be an independent cardiovascular risk factor (14). Current data suggest that OSA increases cardiovascular morbidity and mortality, and continuous positive airway pressure (CPAP) treatment has the potential to diminish such risk (15). Different mechanisms have been proposed for these derangements to better understand the pathophysiologic core features and hence to formulate treatment strategies (16).

Many studies have investigated the relationship of OSA and different cardiometabolic parameters (17-21), and CPAP treatment has produced some beneficial effects on individual metabolic components (22,23). There is also recent focus on the relationship between sleep apnoea and the metabolic syndrome as a single entity (24). OSA or snoring is shown to be independently associated with an increased prevalence of metabolic syndrome, and this is consistent across different ethnic origins (25-30).

In a cross-sectional clinic-based study (31) of 184 patients with co-morbidities, those who suffered from OSA and the metabolic syndrome had higher brachial-ankle pulse wave velocity (a measure of endothelial dysfunction) and plasma levels of C-reactive protein (an inflammatory marker) compared to those without metabolic syndrome. Therefore, the concurrent presence of metabolic syndrome in OSA patients may have an additive effect on cardiovascular risk (31). In another observational study of 195 patients with cardiovascular diseases, the metabolic syndrome was a better predictor of nocturnal desaturation than apnoea-hypoapnoea index (AHI) in those patients with sleep apnoea, with the odds ratio of 2.63 (32). However, in an interventional study of 89 OSA patients, the presence of metabolic syndrome did not increase the risk of cardiovascular events in OSA patients who had good CPAP compliance after 22 [+ or -] 10 months of follow up (33).

The co-existence of OSA and metabolic syndrome may increase the risk for the development of cardiovascular diseases either additively or synergistically. The underlying mechanisms are as yet poorly defined, but intermittent hypoxia and sleep fragmentation in OSA are thought to be the main triggers of various pathogenetic mediating pathways leading to metabolic dysfunction with multi-directional interactions and feedback (Fig. 1).

Sleep and metabolic dysfunction

Sleep is closely related to the regulation of physical and emotional well being (34). Hormonal events during sleep are dependent upon sleep duration and sleep quality, and the multiple peripheral effects of sleep suggest that sleep loss might be associated with deleterious health consequences (35). Sleep duration plays a role in the regulation of leptin and ghrelin levels in humans. Both of these hormones integrate control of feeding, wakefulness and energy expenditure in the body although the mechanisms are unclear, and may act in parallel as metabolic counterparts for body weight control (36).

[FIGURE 1 OMITTED]

The Wisconsin sleep cohort study has provided important data on sleep duration, showing that a loss of 3 h of sleep from a baseline of approximately 8 h was associated with an average 4-5 per cent higher body weight (37). A recent systemic review of both cross-sectional and longitudinal studies revealed that short sleep duration is independently associated with weight gain, particularly in young age groups (38). In a retrospective study of 1000 patients from four different primary care practices, women were found to sleep more than men, and overweight [body mass index (BMI) 25 - 29.9 kg/[m.sup.2]] and obese (BMI 30-39.9 kg/ [m.sup.2]) patients slept less than patients with a normal BMI (<25 kg/[m.sup.2]) (39). Interestingly, in a cross-sectional study of 500 Chinese adolescent twins who were relatively lean, short sleep duration was significantly associated with higher adiposity measures in terms of total and central adiposity rather than lean body mass (40).

Short sleep duration is associated with an upregulation of appetite and has an adverse impact on glucose homeostasis (41). A limited number of prospective studies have examined the association between sleep duration and the development of diabetes mellitus. The Sleep Heart Health Study of 1500 subjects shows that a sleep duration of 6 h or less or 9 h or more is associated with increased prevalence of diabetes and glucose intolerance, compared to those sleeping 7 to 8 h per night, after adjustment for age, sex, BMI and AHI (42). In the Massachusetts Male Aging Study, 1139 men participated, those who had sleep duration < 5 h or > 8 h were found to be two to three times more likely to develop incident diabetes respectively (43). For over 70,000 middle-aged women in the United States Nurses Health Study, who were not diabetic at baseline, an increased risk of incident symptomatic diabetes was found among those reporting sleep durations of < 5 h and > 9 h over 10 yr, but the risk became insignificant after adjustment for BMI and other confounders (44). Similarly, in another Finnish study of 1336 men and 1434 women, sleep duration of < 6 h or > 8 h was independently associated with type II diabetes in women only after adjustment for confounders (45). For the First National Health and Nutrition Examination Survey (NHANES) in the United States, with a large population size of 8992 subjects, also concluded that subjects with sleep durations of < 5 h or [greater than or equal to] 9 h were significantly more likely to have incident diabetes over 10 yr after controlling for covariates, with odds ratios of 1.47 and 1.52 respectively (46). Therefore, both short and long sleep durations may play a role in the aetiology of diabetes in some individuals.

The influence of sleep quality on glucose metabolism has also been investigated in some longitudinal studies (47-50). Some reported that sleep disturbances, such as difficulty initiating sleep, difficulty maintaining sleep and regular use of hypnotics, were associated with an increased risk for incident diabetes (47-49). However, in a prospective population study of female participants, there was no association between sleep problems at baseline and diabetic risk in a 32 yr follow-up (50). In addition, poor sleep quality was also reported by those who had diabetes compared to those did not (51), and sleep duration and quality were shown to be significant predictors of glycaemic control in a cross-sectional study of volunteers with type II diabetes (52). It is possible that both the quantity and quality of sleep are equally important in glucose regulation that involves P-cell responsiveness and insulin sensitivity, and the underlying mechanisms are likely to be multifactorial (53) (Fig. 2).

Hypertension is another component of the metabolic syndrome. It was reported that short sleep duration of < 5 h was associated with increased risk of hypertension in the NHANES (54). Further, the combination of short sleep duration and higher nighttime, relative to daytime and systolic blood pressure are strongly predictive of future cardiovascular disease (55).

There have been studies evaluating the relationship between sleep duration and the metabolic syndrome. In a community--based cross-sectional study of 1214 subjects, the odds for having metabolic syndrome was increased by 45 per cent in both short and long sleepers after adjustment of co-variates, compared to those sleeping 7 to 8 h per night, and sleep duration was also associated with visceral obesity, elevated fasting glucose and hypertriglyceridaemia (56). In the Korean National Health and Nutrition Survey, of the 4222 participants, those who slept < 5 h and > 9 h had increased risk of developing metabolic syndrome with odds ratios of 1.74 (95% CI 1.33-2.26) and 1.69 (95% CI 1.17-2.45) respectively (57).

[FIGURE 2 OMITTED]

Obstructive sleep apnoea and hypertension

There is strong evidence that OSA is an independent risk factor for hypertension independent of obesity (58). The putative mediating pathways involved are sympathetic activation, arterial chemoreceptor response, baroreceptor sensitivity and vasoactive mediators affecting endothelial function (59). The Wisconsin study with longitudinal follow-up of over 700 subjects is considered as a landmark study in the independent association of OSA and hypertension (60). For an AHI > 15 versus AHI=0 at baseline, the odds of developing hypertension over 4-8 yr was 2.89, independent of confounding factors. This association was present throughout the whole spectrum of OSA, from mild to severe degree, but those with moderate to severe OSA had almost three times greater risk for developing hypertension than controls without OSA (60).

Several randomized trials have assessed the effect of CPAP on ambulatory blood pressure in patients with OSA, and both positive (61-64) and negative findings have been reported (65-67). In a study of 118 normotensive and sleepy patients, 1-month of CPAP treatment reduced 24 h mean blood pressure by 2.5mmHg. Further subgroup analyses showed that mean blood pressure reduced by 5mm Hg in those with severe OSA, and by 8 mmHg in those with hypertension on treatment (62). In another randomized controlled study of 60 sleepy subjects, mostly hypertensive on medications, both systolic and diastolic blood pressures were reduced by 10 mm Hg after 2 months of CPAP treatment (63). However, in a 6 wk randomized controlled trial of CPAP treatment group (n=29) versus sham CPAP group (n=25), there was no improvement of arterial blood pressure in subjects with severe OSA but no daytime sleepiness after treatment (65). Further, in a study of 35 OSA patients without sleepiness, most of whom had elevated blood pressure at the entry point, 1- month therapeutic CPAP treatment did not reduce blood pressure (66). In another trial of 68 hypertensive patients, 1 month of CPAP treatment had no effect on blood pressure (67), but the lack of effect may be related to the good baseline control of blood pressure by medications in these subjects.

All of these trials were of short treatment periods, and ambulatory blood pressure was measured with different ambulatory devices. Besides, blood pressure was on the rising trend in the sham CPAP groups in two of these trials (62,64), indicating that sham CPAP might not be the best placebo and tended to give more stress to subjects with OSA during sleep. In two recent meta-analyses of 12 and 16 placebo-controlled randomized trials respectively, comprising both normotensive and hypertensive subjects, an average reduction of 2 mm Hg in mean arterial blood pressure was reported (68,69), while a third meta-analysis did not show any therapeutic effect of CPAP on blood pressure (70). Taken together, these findings suggest that CPAP treatment of OSA can lower blood pressure, but the effect is not uniform in all, and a bigger blood pressure lowering effect is more likely seen in those with severe OSA, greater degree of sleepiness and higher baseline blood pressure.

The association of OSA and hypertension has additive effects on the development of atherosclerosis. In a recent study of 94 middle-aged patients, the intima-media thickness of carotid artery was positively related to systolic blood pressure and AHI (71). So, the rate of progression of carotid atherosclerosis not only predicts future cardiovascular events but also contributes to the increased risk of cerebrovascular accidents.

Obstructive sleep apnoea and obesity

Obesity is becoming a global epidemic in both children and adults, and it is associated with a number of co-morbidities such as cardiovascular diseases, type II diabetes, hypertension and obstructive sleep apnoea (72). The most important risk factor for OSA is obesity. The prevalence of OSA among obese patients has been reported to exceed 30 per cent, and 60-90 per cent of adults with OSA are overweight, and the relative risk of sleep apnoea from obesity with a BMI >30 kg/ [m.sup.2] may be as great as 10 (73). Previous studies revealed that a 10 per cent increase in body weight in 4 yr was associated with a six-fold higher risk of developing OSA (74), and a 6 kg/[m.sup.2] increase in BMI was associated with a four-fold increased risk for the development of OSA (75).

Obesity affects upper airway anatomy because of increased fat deposition in the neck region which in turn predisposes to upper airway collapsibility during sleep. In addition to anatomical factors, collapsibility can be increased by upper airway structural / functional control, disturbances in neuromuscular balance and genetic predisposition (76). Hormonal status and metabolic activity of adipose tissue may impact on sleep apnoea susceptibility, particularly in women. In postmenopausal women fat redistribution to a more central pattern may be responsible for the increased risk of developing OSA (77).

Adipose tissue is metabolically active, it secretes humoral factors and adipokines that regulate the distribution of body fat (78). Leptin plays a key role in body weight regulation through the stimulation of satiety hypothalamic pathways. Human obesity is typically associated with increased leptin levels, thus suggesting a condition of leptin resistance which may contribute to the pathogenesis of sleep apnoea. On the other hand, adiponectin is closely related to visceral adiposity and insulin resistance (79). Recent data suggest that hypoadiponectinaemia is related to sympathetic activity and severity of OSA (80). Obesity and sleep apnoea are often associated with dysregulation of glucose and lipid metabolism, although the precise mechanisms are not clear. Visceral fat produces large amounts of proinflammatory cytokines which are thought to provoke inflammation, oxidative stress, cell adhesion and endothelial dysfunction, and hence, contributing to the development of atherosclersis as well as the sleep-disordered breathing in association with the metabolic syndrome (81).

Obstructive sleep apnoea and insulin resistance/ glucose intolerance/diabetes mellitus

There are accumulating data that obstructive sleep apnoea is independently associated with adverse glucose homeostasis. Previous studies have found increased insulin resistance/glucose intolerance/ diabetes in OSA patients, independent of obesity (82-85), particularly amongst those with excessive daytime sleepiness (86). Very recently, a study on in vivo kinetics of glucose and insulin confirmed that sleep-disordered breathing is associated not only with insulin sensitivity but also with the ability of glucose to mediate its own disposal and pancreatic beta-cell function (87). However, in the Winconsin Sleep Cohort, a four-year follow up of 1387 participants failed to find increased incidence of diabetes mellitus in those with OSA defined by AHI >15 (88).

Previous studies on the treatment effects of CPAP on insulin resistance or glycaemic control in OSA subjects showed conflicting results (89,90). Most did not show any improvement in glucose metabolism (91,92). It was reported that two nights of CPAP treatment improved insulin sensitivity as assessed by the hyperinsulinaemic euglycaemic clamp in a group of non-diabetic men with moderate OSA, and the effect was more prominent in non obese patients with a BMI <30 kg/[m.sup.2] compared to those who were obese with a BMI > 30 kg/[m.sup.2] (93). Recently, it was reported that the improvement in insulin sensitivity was well maintained at 3 yr in the same group of subjects (94). However, in a randomized controlled study with a cross-over design, otherwise healthy men with severe OSA showed no difference in insulin resistance, estimated by Homeostasis Model Assessment Method, after 6 wk of CPAP treatment versus 6 wk of sham CPAP (95).

Interventional studies on glucose metabolism in diabetic subjects with OSA are scanty. Three observational studies of small sample sizes showed improvement in glycaemic control with CPAP treatment (96-98). A randomized controlled study of diabetic patients treated with CPAP for 3 months demonstrated that there was no effect on insulin resistance or glycaemic control compared to sham CPAP (99).

Obesity is a risk factor for both OSA and insulin resistance. The strong association between OSA and obesity has long been recognized, and the severity of OSA is significantly correlated with visceral fat volume rather than subcutaneous fat in the body or in the neck (100). However, in the recent Sleep Heart Health Study of nondiabetic subjects in the community, those who suffered from sleep disordered breathing had higher prevalence of impaired glucose metabolism, in both non-overweight and overweight subjects (101). So, adiposity may play a role in some but not all individuals to account for the adverse glucose metabolism. The underlying pathophysiological pathways between sleep disordered breathing and altered glucose metabolism may involve adipose tissue as a source of sympathetic activation or inflammatory mediators (102). Indeed, sympathetic activation can affect glucose homeostatic state by increasing muscle glycogen breakdown, hepatic glucose output, and the release of free fatty acids via lipolysis.

OSA results in intermittent hypoxaemia with repetitive oxygen desaturation and re-oxygenation during sleep. In experimental animal models, leptin-deficient obese mice exposed to intermittent hypoxia for 12 wk had increased insulin levels and glucose intolerance (103). Another study showed that lean mice exposed to intermittent hypoxia had decreased glucose disposal as assessed with hyperinsulinaemic euglycaemic clamp, and the impairment of insulin sensitivity was independent of sympathetic activation as well as obesity (104).

Obstructive sleep apnoea and dyslipidaemia

Dyslipidaemia is a major cardiovascular risk factor and also part of the metabolic syndrome, characterized by elevated levels of triglycerides, decreased high -density lipoprotein cholesterol and normal or slightly elevated low-density lipoprotein cholesterol. There are a number of reports of abnormal lipid profiles in subjects with sleep-disordered breathing (17,19,20,21,25). In the Sleep Heart health study, there was an independent association between the severity of OSA and high-density lipoprotein cholesterol levels in females only; and in males, a minor but significant association with total cholesterol levels. These findings were evident in the age group < 65 yr after adjustment for co-variates (17). In contrast, in a recent case-control study of apnoeic obese, non apnoeic obese and non obese subjects, there was no significant difference in the lipid profile between obese apnoeic subjects and obese controls (18).

The effects of CPAP treatment of OSA on lipid parameters are inconsistent. In an analysis of 2 randomized placebo-controlled trials of one-month CPAP treatment, a significant fall of total cholesterol in OSA patients was observed but the difference between changes in the therapeutic CPAP and subtherapeutic CPAP groups failed to achieve statistical significance (105). In another randomized study with a cross-over design for 6 wk of CPAP treatment, there were no changes in the lipid profiles compared to sham CPAP (22). Nevertheless, there are positive studies with increase in high-density lipoprotein cholesterol by 5.8 per cent after CPAP treatment (106), and with good CPAP compliance, total cholesterol, triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels were all reduced (23).

Lipid metabolism involves a series of enzymatic interactions. Lipoprotein lipase may play a major role in lipid metabolism by hydrolyzing triglyceride-rich lipoproteins. Decreased lipoprotein lipase activity can trigger early inflammatory responses central to atheroslcerosis. In an interventional study, lipoprotein lipase was found to be decreased with the severity of OSA, and 3-month CPAP treatment significantly increased its concentrations (107). This may imply that CPAP treatment could be effective in reducing inflammatory responses and ameliorating lipid metabolism in OSA subjects. Interestingly, sleep apnoea may affect the function of lipids. In a Chinese study, high-density lipoprotein cholesterol was found to be less effective in preventing low-density lipoprotein oxidation in vivo (108). In addition to clinical data, animal experiments also support a role of intermittent hypoxia in the pathogenesis of dyslipidaemia in sleep-disordered breathing (109-111).

There is evidence that insulin resistance is the major underlying abnormality that drives the dyslipidaemia (112). There are convincing data showing that the effect on the assembly and secretion of very-low-density lipoprotein apolipoprotein B and triglycerides is central abnormality, especially in diabetic patients, and therefore, it appears that OSA, insulin resistance and dyslipidaemia are inter-related in a complex cascade of cardiovascular co-morbidities (14).

Conclusions

Both sleep disturbances and the metabolic syndrome are escalating throughout the world, in spite of, or perhaps due to modernization. Understanding the relationships between sleep disturbances, sleep-disordered breathing and metabolic syndrome will enable medical practitioners to approach the common problems, such as hypertension, diabetes, obesity and dyslipidaemia, in a rational and holistic manner.

Received March 13, 2009

References

(1.) Van Cauter E, Spiegel K, Tasali E, Leproult R. Metabolic consequences of sleep and sleep loss. Sleep Med 2008; 9 (Suppl) : S23-8.

(2.) Van Cauter E, Leproult R, Plat L. Age related changes in slow wave sleep and REM sleep relationship with growth hormone and cortisol levels in healthy men. JAMA 2000; 284 : 861-8.

(3.) Strine TW, Chapman DP. Associations of frequent sleep insufficiency with health-related quality of life and behaviors. Sleep Med 2005; 6 : 23-7.

(4.) Copinschi G. Metabolic and endocrine effects of sleep deprivation. Essent Psychopharmacol 2005; 6 : 341-7.

(5.) Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, et al. Sleep apnea and cardiovascular disease. An American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular nursing. J Am Coll Cardiol 2008; 52 : 686-717.

(6.) Marin JM, Carrizo SJ, Vicente L, Agusti AGN. Long term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005; 365 : 1046-53.

(7.) Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288 : 2709-16.

(8.) Kostoglou-Athanassiou I, Anthanassiou P. Metabolic syndrome and sleep apnea. Hippokratia 2008; 12 : 81-6.

(9.) Reaven G. Role of insulin resistance in human disease. Diabetes 1988; 37 : 1595-607.

(10.) Zimmet P, Magliano D, Matsuzama Y, Alberti G, Shaw J. The metabolic syndrome: a global public health problem and a new definition. J Atheroscler Thromb 2005; 12 : 295-300.

(11.) Wilson PW, D'Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 2005; 112 : 3066-72.

(12.) WHO expert consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004; 363 : 2709-16.

(13.) Thomas GN, Ho SY, Janus ED, Lam KSL. The US National Cholesterol Education Programme Adult Treatment Panel III, prevalence of the metabolic syndrome in a Chinese population. Hong Kong Cardiovascular Risk Factor Prevalence Study Steering Committee. Diabetes Res Clin Pract 2005; 67 : 251-7.

(14.) McNicholas WT, Bonsignore MR, and the Management Committee of EU COST ACTION B26. Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J 2007; 29 : 156-78.

(15.) Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular cnsequences. Lancet 2009; 373 : 82-93.

(16.) McNicholas WT. Cardiovascular outcomes of CPAP therapy in obstructive sleep apnea syndrome. Am J Physiol Regul Integr Comp Physiol 2007; 293 : 1666-70.

(17.) Newman AB, Nieto FJ, Guidry U, Lind BK, Redline S, Pickering TG, et al. Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study. Am J Epidemiol 2001; 154 : 50-9.

(18.) Sharma SK, Kumpawat S, Goel A, Banga A, Ramakrishnan L, Chaturvedi P. Obesity, and not obstructive sleep apnea, is responsible for metabolic abnormalities in a cohort with sleep-disordered breathing. Sleep Med 2007; 8 : 12-7.

(19.) Ip MSM, Lam KSL, Ho CM, Tsang KWT, Lam WK. Serum leptin and vascular risk factors in obstructive sleep apnea. Chest 2000; 118 : 580-6.

(20.) McArdle N, Hillman D, Beilin L, Watts G. Metabolic risk factors for vascular disease in obstructive sleep apnea--a matched controlled study. Am J Respir Crit Care Med 2007; 175 : 190-5.

(21.) Can M, Acikgoz S, Mungan G, Bayraktaroglu T, Kocak E, Giiven B, et al. Serum cardiovascular risk factors in obstructive sleep apnea. Chest 2006; 129 : 233-7.

(22.) Coughlin SR, Mawdsley L, Mugarza JA, Wilding JPH, Calverley PMA. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J 2007; 29 : 7207.

(23.) Dorkova Z, Petrasova D, Molcanyiova A, Popovnakova M, Tkacova R. Effects of CPAP on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome. Chest2008; 134 : 686-92.

(24.) Wolk R, Somers VK. Sleep and the metabolic syndrome. Exp Physiol 2007; 92 : 67-78.

(25.) Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP. Obstructive sleep apnea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J 2004; 25 : 735-41.

(26.) Sasanabe R, Banno K, Otake K, Hasegawa, Usui K, Morita M, et al. Metabolic syndrome in Japanese patients with obstructive sleep apnea syndrome. Hypertens Res 2006; 29 : 315-22.

(27.) Lam JCM, Lam B, Lam CL, Wang JKL, Tse HF, Lam KSL, et al. Obstructive sleep apnea and the metabolic syndrome in community-based Chinese subjects in Hong Kong. Resp Med 2006; 100 : 980-7.

(28.) Gruber A, Horwood F, Sithole J, Ali NJ, Idris I. Obstructive sleep apnoea is independently associated with metabolic syndrome but not the insulin resistance state. Cardiovasc Diabetol 2006; 5 : 1-7.

(29.) Parish JM, Adam T, Facchiano L. Relationship of metabolic syndrome and obstructive sleep apnea. J Clin Sleep Med 2007; 3 : 467-72.

(30.) Cho NH, Joo SJ, Kim JK, Abbott RD, Kim JH, Kimm K, et al. Relation of habitual snoring with components of metabolic syndrome in Korean adults. Diab Res Clin Prac 2006; 71 : 256-63.

(31.) Shiina K, Tomiyama H, Takata Y, Usui Y, Asano K, Hirayama Y, et al. Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk. A Sleep clinic cohort study. Hypertens Res 2006; 29 : 433-41.

(32.) Takama N, Kurabayashi M. Relationship between metabolic syndrome and sleep-disordered breathing in patients with cardiovascular disease--metabolic syndrome as a strong factor of nocturnal desaturation. Intern Med 2008; 47 : 70915.

(33.) Ambrosetti M, Lucioni AM, Conti S, Pedretti RFE, Neri M. Metabolic syndrome in obstructive sleep apnea and related cardiovascular risk. J CardiovascMed 2006; 7 : 826-9.

(34.) Haack M, Mullington JM. Sustained sleep restriction reduces emotional and physical well being. Pain 2005; 119 : 56-64.

(35.) Van Cauter E, Holmback U, Kuntson K, Leproult R, Miller A, Nedeltcheva A, et al. Impact of sleep and sleep loss on neuroendocrine and metabolic function. Horm Res 2007; 67 (Suppl 1) : 2-9.

(36.) Cummings DE, Foster KE. Ghrelin-leptin tango in bodyweight regulation. Gastroenterology 2003; 124 : 1532-5.

(37.) Taheri S, Lin L, Austin D, Young T, Mgnot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 2004; 1 : e62

(38.) Patel SR, Hu FB. Short sleep duration and weight gain: a systemic review. Obesity (Silver Spring) 2008; 16 : 643-53.

(39.) Vorona RD, Winn MP, Babineau TW, Eng BP, Feldman HR, Ware JC, et al. Overweight and obese patients in a primary care population report less sleep than patients with a normal body mass index. Arch Intern Med 2005; 165 : 25-30.

(40.) Yu Y, Lu BS, Wang B, Wang H, Yang J, Li Z, et al. Short sleep duration and adiposity in Chinese adolescents. Sleep 2007; 30 : 1688-97.

(41.) Knutson KL, Van Cuater E. Associations between sleep loss and increased risk of obesity and diabetes. Ann N Y Acad Sci 2008; 1129 : 287-304.

(42.) Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM, et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med 2005; 165 : 863-8.

(43.) Yaggi HK, Araujo AB, McKinlay JB. Sleep duration as a risk factor for the development of type 2 diabetes. Diabetes Care 2006; 29 : 657-61.

(44.) Ayas NT, White DP, Al-Delaimy WK, Manson JE, Stampfer MJ, Speizer FE, et al. A prospective study of self-reported sleep duration and incident diabetes in women. Diabetes Care 2003; 26 : 380-4.

(45.) Tuomilehto H, Peltonen M, Partinen M, Seppa J, Saaristo T, Korpihyovalti E, et al. Sleep duration is associated with an increased risk for the prevalence of type 2 diabetes in middle-aged women--The FIN D2D survey. Sleep Med 2008; 9 : 2217.

(46.) Gangwisch JE, Heymsfield B, Boden-Albala B, Buijs RM, Kreier F, Pickering TG, et al. Sleep duration as a risk factor for diabetes incidence in a large US sample. Sleep 2007; 30 : 1667-73.

(47.) Mallon L, Broman JE, Hetta J. High incidence of diabetes in men with sleep complaints or short sleep duration--a 12-year follow-up study of a middle-aged population. Diabetes Care 2005; 28 : 2762-7.

(48.) Nilsson PM, Roost M, Engstrom G, Hedblad B, Berglund G. Incidence of diabetes I middle-aged men is related to sleep disturbances. Diabetes Care 2004; 27 : 2464-9.

(49.) Meisinger C, Heier M, Loewel H; MONICA/KORA Augsburg Cohort Study. Sleep disturbance as a predictor of type 2 diabetes mellitus in men and women from the general population. Diabetologia 2005; 48 : 235-41.

(50.) Bjorkelund C, Bondyr-Carlsson D, Lapidus L, Lissner L, Mansson J, Skoog I, et al. Sleep disturbances in midlife unrelated to 32-year diabetes incidence: the prospective population study of women in Gothenburg. Diabetes Care 2005; 28 : 2739-44.

(51.) Lamond N, Tiggemann M, Dawson D. Factors predicting sleep disruption in type II diabetes. Sleep 2000; 23 : 415-6.

(52.) Knutson KL, Ryden AM, Mander BA, Van Cauter E. Role of sleep duration and quality in the risk and severity of type 2 diabetes mellitus. Arch Intern Med 2006; 166 : 1768-74.

(53.) Gonzalez-Ortiz M, Martinez-Abundis E. Impact of sleep deprivation on insulin secretion, insulin sensitivity, and other hormonal regulations. Metab Syndr Relat Disord 2005; 3 : 37.

(54.) Gangwisch JE, Heymsfield B, Boden-Albala B, Buijs RM, Kreier F, Pickering TG, et al. Short sleep duration as a risk factor for hypertension--analyses of the first National health and Nutrition Examination Survey. Hypertension 2006; 47 : 833-9.

(55.) Eguchi K, Pickering TG, Schwartz JE, Hoshide S, Ishikawa J, Ishikawa S, et al. Short sleep duration as an independent predictor of cardiovascular events in Japanese patients with hypertension. Arch Intern Med 2008; 168 : 2225-31.

(56.) Hall MH, Muldoon MF, Jennings JR, Buysse DJ, Flory JD, Manuck SB. Self-reported sleep duration is associated with the metabolic syndrome in midlife adults. Sleep 2008; 31 : 635-43.

(57.) Choi KM, Lee JS, Park HS, Baik SH, Choi DS, Kim SM. Relationship between sleep duration and the metabolic syndrome: Korean National Health and Nutritional Survey 2001. Int J Obes 2008; 32 : 1091-7.

(58.) Pepperell JC, Davies RJ, Stradling JR. Systemic hypertension and obstructive sleep apnoea. Sleep Med Rev 2002; 6 : 157-73.

(59.) Dopp JM, Reichmuth KJ, Morgan BJ. Obstructive sleep apnea and hypertension: mechanisms, evaluation, and management. Curr Hypertens Rep 2007; 9 : 529-34.

(60.) Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342 : 1378-84.

(61.) Faccenda JF, Mackay TW, Boon NA, Douglas NJ. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med 2001; 163 : 344-8.

(62.) Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet2002; 359 : 204-10.

(63.) Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, et al. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 2003; 107 : 68-73.

(64.) Norman D, Loredo JS, Nelesen RA, Ancoli-Israel S, Mills PJ, Ziegler MG, et al. Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure. Hypertension 2006; 47 : 840-5.

(65.) Barbe F, Mayoralas LR, Duran J, Masa JF, Maimo A, Montserrat JM, et al. Treatment with continuous positive airway pressure is not effective in patients with sleep apnea but no daytime sleepiness. A randomised controlled trial. Ann Intern Med 2001; 134 : 1015-23.

(66.) Robinson GV, Smith DM, Langford BA, Davis RJ. Stradling JR. Continuous positive airway pressure does not reduce blood pressure in non-sleepy hypertensive obstructive sleep apnoea patients. Eur Respir J 2006; 27 : 1229-35.

(67.) Campos-Rodriguez F, Grilo-Reina A, Perez-Ronchel J, Merino-Sanchez M, Gonzalez-Benitez MA, Beltran-Robies M. Effect of continuous positive airway pressure on ambulatory BP in patients with sleep apnea and hypertension: a placebo-controlled trial. Chest2006; 129 : 1459-67.

(68.) Bazzano LA, Khan Z, Reynolds K, He J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension 2007; 50 : 417-23.

(69.) Haentjens P, Van Meerhaeghe A, Moscariello A, De eerdt S, Poppe K, Dupont A, et al. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome--evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med 2007; 167 : 757-65.

(70.) Alajmi M, Mulgrew AT, Fox J, Davidson W, Schulzer M, Mak E, et al. Impact of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea hypopnea: a meta-analysis of randomized controlled trials. Lung 2007; 185 : 67-72.

(71.) Drager LF, Bortolotto LA, Krieger EM, Lorenzi-Filho G. Additive effects of obstructive sleep apnea and hypertension on early markers of carotid atherosclerosis. Hypertension 2009; 53 : 64-9.

(72.) Eckel RH, York DA, Rossner S, Hubbard V, Caterson I, St Jeor ST, et al. American Heart Association. Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease and stroke: executive summary. Circulation 2004; 110 : 2968-75.

(73.) Gami AS, Caples SM, Somers VK. Obesity and obstructive sleep apnea. Endocrinol Metab Clin North Am 2003; 32 : 869-94.

(74.) Peppard P, Young T, Malta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA 2000; 284 : 3015-21.

(75.) Young T, Shahar E, Nieto FJ, Redline S, Newman AB, Gottlieb DJ, et al. Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. Arch Intern Med 2002; 162 : 893-900.

(76.) Schwartz AR, Patil SP, Laffan AM, Polotsky V, Schneider H, Smith PL. Obesity and obstructive sleep apnea--pathogenic mechanisms and therapeutic approaches. Proc Am Thorac Soc 2008; 5 : 185-92.

(77.) Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328 : 1230-5.

(78.) de Sousa AGP, Cercato C, Mancini MC, Halpern A. Obesity and obstructive sleep apnea hypopnea syndrome. Obes Rev 2008; 9 : 340-54.

(79.) Vgontzas AN. Does obesity play a major role in the pathogenesis of sleep apnoea and its associated manifestations via inflammation, visceral adiposity, and insulin resistance? Arch Physiol Biochem 2008; 114 : 211-23.

(80.) Lam JC, Xu A, Tam S, Khong PL, Yao TJ, Lam DC, et al. Hypoadiponectinemia is related to the sympathetic activity and severity of obstructive sleep apnea. Sleep 2008; 31 : 1721-7.

(81.) Pillar G, Shehadeh N. Abdominal fat and sleep apnea. The chicken or the egg? Diabetes care 2008; 31 : S303-90.

(82.) Ip MSM, Lam B, Ng MMT, Lam WK, Tsang KWT, lam KSL. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 2002; 165 : 670-6.

(83.) Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL. Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med 2002; 165 : 677-82.

(84.) Tassone F, Lanfranco F, Gianotti L, Pivetti S, Navone F, Rossetto R, et al. Obstructive sleep apnoea syndrome impairs insulin sensitivity independently of anthropometric variables. Clin Endocrinol 2003; 59 : 374-379.

(85.) West SD, Nicoll DJ, Stradling JR. Prevalence of obstructive sleep apnoea in men with type 2 diabetes. Thorax 2006; 61 : 945-50.

(86.) Barcelo A, Barbe F, de la Pena M, Martinez P, Soriano JB, Pierola J, et al. Insulin resistance and daytime sleepiness in patients with sleep apnoea. Thorax 2008; 63 : 946-50.

(87.) Punjabi NM, Beamer BA. Alterations in glucose disposal in sleep-disordered breathing. Am J Respir Crit Care Med 2009; 179 : 235-40.

(88.) Reichmuth KJ, Austin D, Skatrud JB, Young T. Association of sleep apnea and type II diabetes: a population-based study. Am J Respire Crit Care Med 2005; 172 : 1590-5.

(89.) Ip MSM, Mokhlesi B. Sleep and glucose intolerance/diabetes mellitus. Sleep Med Clin 2007; 2 : 19-29.

(90.) Tasali E, Mokhlesi B, Van Cauter E. Obstructive sleep apnea and type 2 diabetes--interacting epidemics. Chest 2008; 133 : 496-506.

(91.) Tasali E, Ip MSM. Obstructive sleep apnea and metabolic syndrome--alterations in glucose metabolism and inflammation. Proc Am Thorac Soc 2008; 5 : 207-17.

(92.) Punjabi NM, Polotsky VY. Disorders of glucose metabolism in sleep apnea. J Appl Physiol 2005; 99 : 1998-2007.

(93.) Harsch IA, Schahin SP, Radespiel-Troger M, Weintz O, Jahrei B, Fuchs FS, et al. Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med 2004; 169 : 156-62.

(94.) Schahin SP, Nechanitzky T, Dittel C, Fuchs FS, Hahn EG, Konturek PC, et al. Long-term improvement of insulin sensitivity during CPAP therapy in the obstructive sleep apnoea syndrome. Med Sci Monit 2008: 14 : CR117-21.

(95.) Coughlin SR, Mawdsley L, Mugarza JA, Wilding JPH, Calverley PMA. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J 2007; 29 : 720-7.

(96.) Babu AR, Herdegen J, Fogelfeld L, Shott S, Mazzone T. Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive sleep apnea. Arch Intern Med 2005; 165 : 447-52.

(97.) Hassaballa HA, Tulaimat A, Herdegen JJ, Mokhllesi B. The effect of continuous positive airway pressure on glucose control in diabetic patients with severe obstructive sleep apnea. Sleep Breath 2005; 9 : 176-80.

(98.) Dawson A, Abel SL, Loving RT, Dailey G, Shadan FF, Cronin JW, et al. CPAP therapy of obstructive sleep apnea in type 2 diabetics improves glycemic control during sleep. J Clin Sleep Med 2008; 4 : 538-42.

(99.) West SD, Nicoll DJ, Wallace TM, Matthews DR, Stradling JR. The effect of CPAP on insulin resistance and HbA1C in men with obstructive sleep apnoea and type 2 diabetes. Thorax 2007; 62 : 969-74.

(100.) Schafer H, Pauleit D, Sudhop T, Gouni-Berthold I, Euig S, Berthold HK. Body fat distribution, serum leptin, and cardiovascular risk factors in men with obstructive sleep apnea. Chest 2002; 122 : 829-39.

(101.) Seicean S, Kirchner HL, Gottlieb DJ, Punjabi NM, Resnick H, Sanders M, et al. Sleep-disordered breathing and impaired glucose metabolism in normal-weight and overweight/obese individuals. Diabetes Care 2008; 1001-6.

(102.) Trakada G, Chrousos G, Pejovic S, Vgontzas A. Sleep apnea and its association with the stress system, inflammation, insulin resistance and visceral obesity. Sleep Med Clin 2007; 2 : 251-61.

(103.) Polotsky VY, Li J, Punjabi NM, Rubin AE, Smith PL, Schwartz AR, et al. Intermittent hypoxia increases insulin resistance in genetically obese mice. J Physiol 2003; 552 : 253-64.

(104.) Iiyori N, Alonso LC, Li J, Sanders NM, Garcia-Ocana A, O'Doherty RM, et al. Intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity. Am J Respir Crit Care Med 2007; 175 : 851-7.

(105.) Robinson GV, Pepperell JCT, Segal HC, Davies RJO, Stradling JR. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomized controlled trials. Thorax 2004; 59 : 777-82.

(106.) Borgel J, Sanner BM, Bittlinsky A, Keskin F, Barlets NK, Buechner N, et al. Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol serum levels. Eur Respir J 2006; 27 : 121-7.

(107.) Iesato K, Tatsumi K, Saibara T, Nakamura A, Terada J, Tada Y, et al. Decreased lipoprotein lipase in obstructive sleep apnea syndrome. Circ J 2007; 71 : 1293-8.

(108.) Tan KCB, Chow WS, Lam JC, Lam B, Wong WK, Tam S, et al. HDL dysfunction in obstructive sleep apnea. Atherosclerosis 2006; 184 : 377-82.

(109.) Li J, Grigoryev DN, Ye SQ, Thorne L, Schwartz AR, Smith PL, et al. Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol 2005; 99 : 1643-8.

(110.) Li J, Thorne LN, Punjabi NM, Sun CK, Schwartz AR, Smith PL, et al. Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 2005; 97 : 698-706.

(111.) Li J, Savransky V, Nanayakkara A, Smith PL. O'Donnell CP, Polotsky VT. Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia. J Appl Physiol 2007; 102 : 557-63.

(112.) Ginsberg HN, Zhang YL, Hernandez-Ono A. Metabolic syndrome: focus on dyslipidemia. Obesity 2006 (Suppl); 14 : S41-49.

Reprint requests: Dr M.S.M. Ip, University Department of Medicine, Queen Mary Hospital, 102 Pokfulam Road Hong Kong, SAR, China e-mail: msmip@hkucc.hku.hk

Jamie C.M. Lam & Mary S.M. Ip

Division of Respiratory Medicine, University Department of Medicine, Queen Mary Hospital The University of Hong Kong, SAR, China
Table. Different definitions of the metabolic syndrome

WHO (1999) (10)                   EGIR (1999) (10)

Diabetes or impaired              Insulin resistance or
glucose tolerance or              hyperinsulinaemia (only non-
insulin resistance, plus          diabetic subjects),
2 or more of the following,       plus 2 or more of the
                                  following,

BMI > 30 kg/[m.sup.2]             Waist circumference:
or waist to hip ratio > 0.9       > 94 cm in men , [greater
in men, > 0.85 in women           than or equal to] 80 cm in
                                  women

Triglycerides:                    Triglycerides:
[greater than or equal to]        > 2 mmol/l
1.7 mmol/l

HDL-C:                            HDL-C:
< 0.9 mmol/l in men               < 1.0 mmol/l
< 1.0 mmol/l in women

Blood pressure:                   Blood pressure:
>140/90 mmHg or medication        > 140/90 mm Hg or
                                  medication

Urine albumin excretion           Fasting plasma glucose:
[greater than or equal to] 20     > 6.1 mmol/l
[micro]g/min or albumin-
creatinine ratio > 30mg/g

WHO (1999) (10)                   NCEP ATP III (2001) (13)

Diabetes or impaired              Three or more of the
glucose tolerance or              following,
insulin resistance, plus
2 or more of the following,

BMI > 30 kg/[m.sup.2]             Waist circumference:
or waist to hip ratio > 0.9       >102 cm in men, >88 cm in
in men, > 0.85 in women           women

Triglycerides:                    Triglycerides:
[greater than or equal to]        > 1.7 mmol/l
1.7 mmol/l

HDL-C:                            HDL-C:
< 0.9 mmol/l in men               < 1.03 mmol /l in men
< 1.0 mmol/l in women             <1.29 mmol/l in women

Blood pressure:                   Blood pressure:
>140/90 mmHg or medication        > 130/85 mmHg or medication

Urine albumin excretion           Fasting plasma glucose:
[greater than or equal to] 20     > 6.1 mmol/l
[micro]g/min or albumin-
creatinine ratio > 30mg/g

WHO (1999) (10)                   IDF (2005) (10)

Diabetes or impaired              Waist circumference--
glucose tolerance or              ethnicity specific,
insulin resistance, plus          plus two or more of
2 or more of the following,       the following,

BMI > 30 kg/[m.sup.2]
or waist to hip ratio > 0.9
in men, > 0.85 in women

Triglycerides:                    Triglycerides:
[greater than or equal to]        > 1.7 mmol/l or
1.7 mmol/l                        medicaition

HDL-C:                            HDL-C:
< 0.9 mmol/l in men               <1.03 mmol/l in men
< 1.0 mmol/l in women             <1.29 mmol/l in women
                                  or medication

Blood pressure:                   Blood pressure:
>140/90 mmHg or medication        > 130/85 mmHg or medication

Urine albumin excretion           Fasting plasma glucose:
[greater than or equal to] 20     > 5.6 mmol/l or type II
[micro]g/min or albumin-          diabetes
creatinine ratio > 30mg/g

WHO, World Health Organization; EGIR, European Group for the Study
of Insulin Resistance; NCEP ATP III, National Cholesterol Education
Program--Third Adult Treatment Panel; IDF, International Diabetes
Federation; BMI, body mass index; HDL-C, high density lipoprotein
cholesterol
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