Am J Epidemiol 2002; 156:1070-1077.
Copyright © 2002 by Johns
Hopkins Bloomberg School of Public Health
PRACTICE OF EPIDEMIOLOGY |
Metabolic Syndrome and Development of Diabetes Mellitus: Application and Validation of Recently Suggested Definitions of the Metabolic Syndrome in a Prospective Cohort Study
1 Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
2 Department of Physiology, University of Kuopio, Kuopio, Finland.
3 Research Institute of Public Health, University of Kuopio, Kuopio, Finland.
4 Department of Public Health and General Practice, University of Kuopio, Kuopio, Finland.
5 Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI.
6 Inner Savo Health Centre, Suonenjoki, Finland.
7 Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
Received for publication January 23, 2002; accepted for publication June 18, 2002.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The World Health Organization (WHO) and the National Cholesterol Education Program (NCEP) recently proposed definitions for the metabolic syndrome. Little is known of their validity, however. The authors assessed the sensitivity and specificity of the definitions of the metabolic syndrome for prevalent and incident diabetes mellitus in a Finnish population-based cohort of middle-aged men (n = 1,005) followed for 4 years since the late 1980s. Four definitions based on the WHO and NCEP recommendations were compared. All definitions identified persons at high risk for developing diabetes during the 4-year follow-up (odds ratios = 5.0–8.8). The WHO definition including waist-hip ratio > 0.90 or body mass index
30 kg/m2 was the most sensitive (0.83 and 0.67) and least specific (0.78 and 0.80) in detecting the 47 prevalent and 51 incident cases of diabetes. The NCEP definition in which adiposity was defined as waist girth > 102 cm detected only 61% of prevalent and 41% of incident diabetes, although it was the most specific (0.89 and 0.90). The WHO definition seems valid as judged by its relatively high sensitivity and specificity in predicting diabetes. The NCEP definition including waist > 102 cm also identifies persons at high risk for diabetes, but it is relatively insensitive in predicting diabetes.
diabetes mellitus; hyperinsulinism; hyperlipidemia; hypertension; insulin resistance; obesity
Abbreviations: Abbreviations: EGIR, European Group for the Study of Insulin Resistance; HDL, high density lipoprotein; NCEP, National Cholesterol Education Program; QUICKI, quantitative insulin sensitivity check index; WHO, World Health Organization.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension and its association with subsequent development of type 2 diabetes mellitus and cardiovascular disease has given rise to the concept of the metabolic syndrome, also known as the insulin resistance syndrome (1, 2). Insulin resistance is considered the underlying abnormality in this syndrome. The pathogenesis of this syndrome is still unclear, although environmental factors such as diet and physical activity, coupled with still largely unknown genetic factors, clearly interact to produce the syndrome (1–3).
Despite abundant epidemiologic and experimental research that has been published on the metabolic syndrome, definitions of this syndrome and the various cutoffs for its components have varied widely (2). The World Health Organization (WHO) consultation for the classification of diabetes and its complications (4) and the National Cholesterol Education Program (NCEP) Expert Panel (5) recently published definitions of the metabolic syndrome.
The WHO published a working definition meant to facilitate research on the metabolic syndrome and aid comparability between studies rather than serve as a strict definition (4). For men, the metabolic syndrome was defined (without assumptions of causality) as insulin resistance in the top 25 percent of the population as measured by the euglycemic hyperinsulinemic clamp or the presence of impaired glucose tolerance or type 2 diabetes and the presence of at least two of the following: abdominal obesity (waist-hip ratio > 0.90 or body mass index 30 kg/m2), dyslipidemia (serum tri-glycerides 1.70 mmol/liter or high density lipoprotein (HDL) cholesterol < 0.9 mmol/liter), hypertension (160/90 mmHg), or microalbuminuria. These core components were considered most suitable for a general definition, although many other disturbances—for example, disorders of coagulation and endothelial function, hyperuricemia, and elevated leptin levels—have been associated with the metabolic syndrome (2).
This working definition has not been without criticism. Inclusion of microalbuminuria as a core component is controversial, and microalbuminuria in nondiabetic persons is uncommon (6–9). The most appropriate measure of abdominal obesity is also in dispute. Although the waist-hip ratio may carry information relevant to disease endpoints independently of waist girth or body mass index (10), waist circumference correlates better with visceral fat deposits as measured by computerized tomography (11). Defining adiposity as waist girth 94 cm has been proposed by experts in the European Group for the Study of Insulin Resistance (EGIR) (9). Furthermore, the euglycemic hyperinsulinemic clamp is not practical for epidemiologic research. The EGIR recommended use of fasting insulin levels to estimate insulin resistance and impaired fasting glycemia as a substitute for impaired glucose tolerance in epidemiologic studies (9). The EGIR also proposed lower cutoffs for hypertension (140/90 mmHg) that are in accordance with current WHO–International Society of Hypertension and Sixth Joint National Committee recommendations (9, 12, 13).
The NCEP Expert Panel also recently published a definition of the metabolic syndrome for clinical use (5). The metabolic syndrome was defined as three or more of the following: fasting plasma glucose levels 6.1 mmol/liter, serum triglycerides 1.7 mmol/liter, serum HDL cholesterol < 1.0 mmol/liter, blood pressure 130/85 mmHg, and waist girth > 102 cm. Use of waist circumference > 94 cm was suggested for some men who might be genetically susceptible to insulin resistance (5).
Knowledge of the risk of developing type 2 diabetes associated with the metabolic syndrome as defined by the WHO or NCEP is scanty. Although type 2 diabetes is a heterogeneous disease, most type 2 diabetes patients are insulin resistant and also have the metabolic syndrome before onset of type 2 diabetes (1, 2, 14). Application of definitions to predicting diabetes in prospective cohort studies can serve to validate definitions of the metabolic syndrome. We compared the sensitivity, specificity, and prevalent and incident diabetes risk of definitions of the metabolic syndrome based on the WHO consultation (4) and NCEP (5) recommendations in a cohort of middle-aged nondiabetic men who were followed for 4 years. The two modified WHO definitions (waist vs. waist-hip ratio) and the two NCEP definitions (waist > 102 cm vs. waist > 94 cm) differed only with regard to adiposity.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The study population for the prospective, population-based Kuopio Ischemic Heart Disease Risk Factor Study (15) was a random, age-stratified sample of men living in eastern Finland aged 42, 48, 54, or 60 years at baseline. The University of Kuopio Research Ethics Committee approved the study. All subjects gave their written informed consent.
The Kuopio Ischemic Heart Disease Risk Factor Study 4-year follow-up study included 1,038 subjects who had undergone carotid ultrasound examination during the original study. Baseline visits were conducted between 1988 and 1989 and follow-up visits between 1992 and 1993. Both the baseline and the 4-year follow-up studies have been described in detail previously (15, 16).
For the present study, analyses were limited to the 1,005 men participating in the 4-year follow-up for whom complete data for assessment of the metabolic syndrome were available. Men who had diabetes at baseline (n = 47) were excluded from prospective analyses. Diabetes at baseline and at the 4-year follow-up was defined as fasting blood glucose 6.1 mmol/liter or a clinical diagnosis of diabetes with either dietary, oral, or insulin treatment (4, 17); impaired fasting glycemia was defined as fasting blood glucose of 5.6–6.0 mmol/liter (4).
Measurements of adiposity
Body mass index was computed as the ratio of weight (kg) to the square of height (m) (kg/m2). Waist circumference was defined as the average of two measurements taken after subject inspiration and after expiration (mean difference between the two measurements, 
1.5 cm) at the midpoint between the lowest rib and the iliac crest. Waist-hip ratio was defined as the ratio of waist girth to the circumference of the hips measured at the trochanter major.
Blood pressure
Study subjects’ blood pressure was measured with a random zero mercury sphygmomanometer (Hawksley & Sons, Ltd.; Lancing, United Kingdom). The measurement protocol included, after a supine rest of 5 minutes, three measurements in the supine position, one in the standing position, and two in the sitting position at 5-minute intervals. The mean of all six measurements was used as the systolic and diastolic blood pressures.
Biochemical determinations
Subjects were asked to fast for 12 hours before blood sampling. They were also asked to refrain from smoking for 12 hours and from consuming alcohol for 3 days before blood draws.
Blood glucose was measured at baseline and 4-year follow-up by using a glucose dehydrogenase method after precipitation of proteins by trichloroacetic acid. The serum samples for insulin determination were stored at –80°C. Serum insulin was determined by using a Novo Biolabs radioimmunoassay kit (Novo Nordisk, Bagsvaerd, Denmark).
Fractions of low density lipoprotein and HDL cholesterol were separated from fresh serum by combined ultracentrifugation and precipitation. The cholesterol contents of lipoprotein fractions and serum triglycerides were measured enzymatically.
Metabolic syndrome
For men, the metabolic syndrome according to the WHO definition was modified for epidemiologic studies in part as proposed by the EGIR (9) and was defined as hyperinsulinemia (fasting insulin levels in the top 25 percent of the nondiabetic population), impaired fasting glycemia or diabetes, and the presence of at least two of the following: abdominal obesity, dyslipidemia (triglycerides 1.70 or HDL cholesterol < 0.9 mmol/liter), or hypertension (blood pressure 140/90 mmHg or blood pressure medication use) (4). Insulin resistance was estimated as hyperinsulinemia based on fasting insulin concentrations in the upper 25 percent (9). Insulin resistance was also estimated as the bottom 25 percent of insulin sensitivity as measured by a recently validated index (quantitative insulin sensitivity check index (QUICKI)) based on fasting insulin and glucose concentrations ([log (insulin) + log (glucose)]–1) (18). Hypertension was defined according to the EGIR recommendations at a lower level than specified by the original WHO definition for consistency with current WHO–International Society of Hypertension and Sixth Joint National Committee recommendations (9, 12, 13). Microalbuminuria was not included in the definition (9). Abdominal obesity was defined on the basis of two definitions—1) according to the original WHO definition: waist-hip ratio > 0.90 or body mass index 30 kg/m2 (4), and 2) modified according to the EGIR recommendation: waist circumference 94 cm (9).
The metabolic syndrome as defined by the NCEP included three or more of the following: fasting plasma glucose levels 6.1 mmol/liter (blood glucose levels 5.6 mmol/liter), serum triglycerides 1.7 mmol/liter, serum HDL cholesterol < 1.0 mmol/liter, blood pressure 130/85 mmHg, and waist girth > 102 cm (5). Use of waist girth > 94 cm was suggested for men genetically susceptible to insulin resistance (5).
Inclusion of a measure of hyperglycemia in the definitions of the metabolic syndrome will obviously affect the prediction of diabetes. Therefore, we also repeated the analyses by excluding impaired fasting glycemia from the definitions.
Statistical analysis
Differences in baseline clinical and biochemical characteristics among men who had diabetes at baseline, who developed diabetes during follow-up, and who remained nondiabetic were tested for statistical significance with one-way analysis of variance and, where indicated, the chi-square test. The association of the metabolic syndrome with the risk of developing diabetes was estimated by using logistic regression analysis, adjusting for age. Sensitivity and specificity of the definitions of the metabolic syndrome for prevalent and incident diabetes were calculated and then compared by using McNemar’s test. Receiver operating characteristic analysis was performed by using continuous variables to derive cutoffs for waist circumference corresponding to body mass index 25 kg/m2 and 30 kg/m2. In this paper, data are presented as means and standard deviations, medians (interquartile ranges), or simple percentages. Triglyceride and insulin concentrations were corrected for skewing by log transformation but are presented here as medians (interquartile ranges) by using untransformed values. Significance was considered to be p < 0.05. All statistical analyses were performed with SPSS 10.0 software for Windows (SPSS, Inc., Chicago, Illinois).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Baseline
Compared with men who were nondiabetic throughout the study, men who had diabetes at baseline and men who developed diabetes during the 4-year follow-up were heavier and more dyslipidemic, hypertensive, and insulin resistant at baseline (table 1). The overwhelming majority who developed diabetes (88 percent) had a body mass index of
25 kg/m2 (overweight or obese as defined by the National Institutes of Health and WHO (19, 20)), although most men who remained nondiabetic were also overweight. Most men who subsequently developed diabetes had a body mass index of <30 kg/m2, although more men who developed diabetes were obese.
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Similarly, almost all men who developed diabetes had a waist-hip ratio of >0.90, although the majority of men who did not develop diabetes also had a waist-hip ratio of >0.90 (table 1). Only 59 percent of men who developed diabetes had a waist circumference of
94 cm at baseline. Less than a third of the men who developed diabetes had a waist girth of >102 cm.
Because the 94-cm and 102-cm waist circumference cutoffs were derived at least in part from a cross-sectional population study from the Netherlands in which those cutoffs corresponded to a body mass index of 25 kg/m2 and 30 kg/m2 (21), respectively, we repeated receiver operating characteristic analyses to derive cutoffs for this population. In this cohort, the body mass index cutoffs of 25 kg/m2 and 30 kg/m2 corresponded to a waist girth of 87 cm (sensitivity, 0.84; specificity, 0.84) and 96 cm (sensitivity, 0.86; specificity, 0.88), respectively. The cutoff of 87 cm was as sensitive as a body mass index of 25 kg/m2 (0.90 vs. 0.88) in identifying men who developed diabetes during follow-up.
Association of the metabolic syndrome with development of diabetes
Men who met the WHO definition of the metabolic syndrome in which adiposity was defined as waist-hip ratio > 0.90 or body mass index 30 kg/m2 had a nearly ninefold greater likelihood of developing diabetes than men without the metabolic syndrome (figure 1). Furthermore, sensitivity (0.83 and 0.67) and specificity (0.78–0.80) for detecting prevalent and incident diabetes, respectively, was quite high (table 2). Use of the insulin sensitivity index (QUICKI) to estimate insulin resistance resulted in a slightly higher sensitivity (0.69), specificity (0.82), and odds ratio (10.4) of the WHO definition for incident diabetes (not shown).
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Men fulfilling the WHO definition of the metabolic syndrome in which adiposity was defined as waist girth
94 cm were 7.0 times more likely to develop diabetes during follow-up (figure 1). The metabolic syndrome definition of waist girth as 94 cm had a clearly lower sensitivity (0.68 and 0.57) for prevalent and incident diabetes, respectively, and was only slightly more specific (0.81–0.83) (table 2). We repeated the analyses by using the waist girth cutoff corresponding to a body mass index of 25 kg/m2 in this population, 87 cm. The sensitivity, specificity, and odds ratio for the prediction of diabetes were virtually identical to the WHO definition based on waist-hip ratio > 0.90 or body mass index 30 kg/m2 (not shown). Even when adiposity was defined as body mass index 25 kg/m2 or waist 102 cm, a definition proposed by the National Institutes of Health for screening in the presence of other risk factors (20), results were nearly identical (not shown). Use of the NCEP definition of the metabolic syndrome detected only 61 percent of prevalent and 41 percent of incident diabetes, although specificity was quite high (0.89–0.90) (table 2). The likelihood of men with the metabolic syndrome, as defined by the NCEP, to develop diabetes was high (figure 1).
Because the NCEP also pointed out that some genetically susceptible men with only mild increases in abdominal obesity (waist circumference, 94–102 cm) can develop multiple metabolic risk factors and should similarly benefit from intervention, we repeated the analyses by using waist circumference > 94 cm. Prevalence increased from 11 percent to 18 percent, with an odds ratio of 5.0 for developing diabetes during follow-up (figure 1). Sensitivity for prevalent (0.72) and incident (0.49) diabetes improved (table 2). Again, because a waist circumference of 87 cm corresponds to a body mass index of 25 kg/m2 in this population, we repeated the analyses by using a waist girth of 87 cm. Prevalence increased to 23 percent, and, with waist as 87 cm, the sensitivity, specificity, and odds ratio for predicting diabetes were 0.59, 0.79, and 5.1, respectively (not shown).
In corresponding analyses in which impaired fasting glycemia was excluded from the definitions, sensitivity, especially for the NCEP definitions, decreased (WHO definition with waist-hip ratio > 0.90 or body mass index 30 kg/m2, and sensitivity, 0.55; WHO definition with waist 94 cm and sensitivity, 0.49; NCEP definition with waist > 102 cm and sensitivity, 0.31; and NCEP definition with waist > 94 cm and sensitivity, 0.37), with almost no effect of specificity (not shown)).
Clustering of insulin resistance and components of the metabolic syndrome
Over 95 percent of men with the metabolic syndrome as defined by the WHO had hyperinsulinemia. Conversely, over 80 percent of the men with insulin resistance had the metabolic syndrome with adiposity as defined by the WHO, emphasizing the clustering of insulin resistance and other components of the metabolic syndrome. At baseline, 11 percent of men had the metabolic syndrome according to both the NCEP definition using the lower 94-cm cutoff for waist circumference and the WHO definition based on waist-hip ratio > 0.90, of whom 23 (21 percent) developed diabetes.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The WHO definition of the metabolic syndrome that included waist-hip ratio > 0.90 or body mass index
30 kg/m2 was the most sensitive of the definitions for diabetes, detecting over four fifths of prevalent and two thirds of incident cases of diabetes with good specificity (0.78–0.80). The NCEP definition in which adiposity was defined as waist girth > 102 cm missed most incident cases of diabetes, although it was the most specific. All four definitions identified subjects at high risk for developing diabetes during follow-up in this population-based cohort of middle-aged men.
The WHO definition of the metabolic syndrome used in this study was modified largely according to the EGIR recommendations (9). The original WHO definition included insulin resistance as measured by the euglycemic hyperinsulinemic clamp and impaired glucose tolerance (4). At the same time, the WHO consultation acknowledged the need for internationally agreed-upon criteria for insulin resistance and hyperinsulinemia. Clamp studies are not well suited to most epidemiologic research, and, for many studies, glucose tolerance tests are not possible. Our study suggests that the EGIR recommendation to estimate insulin resistance by using hyperinsulinemia instead of clamp studies and to use impaired fasting glycemia instead of impaired glucose tolerance to define the metabolic syndrome is valid for epidemiologic studies. The recently validated insulin sensitivity index QUICKI, closely related to homeostasis model assessment (HOMA) (18), slightly increased the sensitivity and specificity for prevalent and incident diabetes. Hypertension was defined according to the EGIR recommendations at a lower level (140/90 mmHg) than the original WHO definition (160/90 mmHg) for consistency with current WHO–International Society of Hypertension and Sixth Joint National Committee recommendations (9, 12, 13). In addition, as recommended by the EGIR (9), microalbuminuria was not included in the definition. The EGIR also recommended that triglycerides 2.0 or HDL cholesterol < 1.0 mmol/liter be used to define dyslipidemia (9). A triglyceride cutoff of 1.70 mmol/liter has been recommended by both the WHO and NCEP. Definitions of the metabolic syndrome using this cutoff are slightly more sensitive for predicting diabetes than those using triglycerides 2.0. HDL cholesterol cutoffs of 0.9 mmol/liter versus 1.0 mmol/liter have little effect on the prevalence of the metabolic syndrome or its sensitivity or specificity for diabetes. We therefore used the original WHO definition of dyslipidemia.
One of the most controversial aspects of the metabolic syndrome is the definition of adiposity. The WHO definition in which adiposity was defined by waist-hip ratio > 0.90 or body mass index 30 kg/m2 detected diabetes well, identifying 83 percent of prevalent and 67 percent of incident cases of diabetes, with a specificity of 0.78–0.80. The WHO definition in which adiposity was modified according to the EGIR recommendation as waist circumference 94 cm performed less well, present at baseline in only 68 percent of prevalent and 57 percent of incident cases of diabetes. The NCEP definition in which adiposity was defined as waist circumference > 102 cm was quite specific but insensitive, detecting only 61 percent of prevalent and 41 percent of incident diabetes. The NCEP recommendations suggest that some men may be genetically predisposed to the metabolic syndrome even at lower levels of abdominal obesity, with waist circumferences of 94–102 cm (5). Using a cutoff of 94 cm for waist girth improved sensitivity of the definition to 0.72 for prevalent and 0.49 for incident diabetes with decreased, but still good specificity (0.82–0.84). This finding suggests that the genetic susceptibility for the metabolic syndrome associated with waist circumferences of 94–102 cm could be generalized to all middle-aged men, at least in the Finnish population.
The 94-cm and 102-cm cutoffs for waist circumference are influenced by a Netherlands cross-sectional study in which these cutoffs corresponded to body mass indexes of 25 kg/m2 and 30 kg/m2, respectively (21). A waist girth cutoff of 87 cm corresponded to a body mass index of 25 kg/m2 in the nondiabetic Kuopio Ischemic Heart Disease Risk Factor Study cohort, underscoring the well-described (19) variable and population-specific relation of waist circumference to body mass index, even in northern European populations. Substituting a waist girth cutoff of 87 cm improved sensitivity of the NCEP definition to 0.59 for new-onset diabetes, with decreased, but still quite high specificity (0.79). Similarly, defining adiposity as waist girth 87 cm or even as body mass index 25 kg/m2 or waist girth 102 cm (action level in the presence of other risk factors, as recommended by the National Institutes of Health) for the modified WHO definition of the metabolic syndrome was more sensitive than defining adiposity as waist 94 cm and as sensitive as defining adiposity as waist-hip ratio > 0.90 or body mass index 30 kg/m2 in detecting prevalent and incident diabetes.
Even mild overweight, especially in the presence of insulin resistance, increases the risk of diabetes (19, 22). Both the WHO and NCEP definitions of the metabolic syndrome are based on insulin resistance, the WHO definition directly and the NCEP definition indirectly through markers or correlates of insulin resistance. Failure to consider even mild overweight or abdominal obesity in the presence of insulin resistance or markers of insulin resistance as a significant risk factor could be a major shortcoming from both a clinical and public health perspective, missing most persons at risk for developing an increasingly common disease such as diabetes, which is associated with high morbidity and mortality.
Even though mild disturbances in glucose metabolism are a central feature of the metabolic syndrome, including a measure of hyperglycemia in the definitions is problematic when diabetes is used as an endpoint. Even when impaired fasting glycemia was excluded from the definitions, the sensitivity of the WHO definitions was still fairly high (0.49–0.55), whereas the sensitivity of the NCEP definitions was only 0.31–0.37. The relatively greater effect of removing hyperglycemia from the NCEP definitions is mainly due to the absence of a measure of insulin resistance (e.g., hyperinsulinemia). Excluding hyperglycemia from the definitions did not affect specificity.
The WHO definition of the metabolic syndrome based on waist-hip ratio > 0.90 or body mass index 30 kg/m2 was common, present in slightly more than one fifth of all nondiabetic men at baseline. Over 95 percent of men who had the metabolic syndrome had hyperinsulinemia. Conversely, over 80 percent of the men with insulin resistance had the metabolic syndrome with adiposity as defined by the WHO, emphasizing the clustering of insulin resistance and other components of the metabolic syndrome. The metabolic syndrome that included the EGIR definition of adiposity (waist 94 cm) was less prevalent, affecting about 19 percent of the men at baseline. The NCEP definition in which adiposity was defined as waist > 102 cm was much less common, present in about 11 percent of the men at baseline. Using a cutoff of 94 cm for waist girth increased prevalence to 18 percent.
At baseline, 11 percent of the men had the metabolic syndrome according to both the NCEP definition in which the lower 94-cm cutoff for waist circumference was used and the WHO definition based on waist-hip ratio > 0.90; 23 (21 percent) of these men developed diabetes. This concurrence occurred even though the WHO and NCEP used rather different approaches to define the metabolic syndrome (the former based strongly on insulin resistance and the latter on only the numbers of features related to insulin resistance), again emphasizing clustering of components of the metabolic syndrome. Despite the concurrence of the WHO and NCEP definitions, the absence of a measure of insulin resistance (e.g., hyperinsulinemia) in the definition may also partly explain the lower sensitivity of the NCEP definitions in detecting prevalent and incident diabetes.
An obvious shortcoming of using type 2 diabetes as an endpoint for evaluating the sensitivity of the metabolic syndrome is that few data are available on the proportion of type 2 diabetes cases expected to have the metabolic syndrome prior to developing diabetes. Even so, type 2 diabetes is closely related to the metabolic syndrome and can in large part be considered an end-stage manifestation of this syndrome. Therefore, definitions of the metabolic syndrome can be compared according to their sensitivity and specificity for detecting new cases of incident diabetes in a prospective cohort study design. Roughly 5–10 percent of middle-aged diabetic patients have latent autoimmune diabetes of the adult (23), in which insulin secretion is the primary defect, and the overall proportion of diabetic patients thought to have insulin resistance before onset of diabetes has been estimated to be 75–85 percent (14, 24). If this information were taken into account, the sensitivity of the WHO and NCEP definitions in detecting prevalent and incident diabetes in which the metabolic syndrome may be expected to precede diagnosis would be even higher.
The WHO and NCEP definitions of the metabolic syndrome appear valid, identifying those with a five- to ninefold increased likelihood of developing diabetes during follow-up in this population-based cohort of middle-aged men. The modified WHO definition based on waist-hip ratio > 0.90 was the most sensitive in detecting prevalent and incident diabetes and had good specificity. The NCEP definition in which adiposity was defined as waist girth > 102 cm was the most specific, but it did not detect most cases of incident diabetes. Defining adiposity as waist circumference > 94 cm improves the sensitivity of the NCEP definition.
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ACKNOWLEDGMENTS |
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The Kuopio Ischemic Heart Disease Risk Factor Study was supported by the Academy of Finland (grants for projects 41471, 1041086, and 2041022 to Dr. Jukka T. Salonen); the Ministry of Education of Finland; and the National Heart, Lung and Blood Institute (grant HL44199 to Dr. George A. Kaplan).
Timo Lakka was a postdoctoral researcher of the Academy of Finland.
The authors are indebted to Dr. Kristiina Nyyssönen and Kari Seppänen for supervising chemical analyses and to Dr. Riitta Salonen for participation in the management of data collection.
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NOTES |
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Correspondence to Dr. Jukka T. Salonen, Research Institute of Public Health, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland (e-mail: jukka.salonen{at}uku.fi).
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REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
- Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595–607.[Abstract]
- Liese AD, Mayer-Davis EJ, Haffner SM. Development of the multiple metabolic syndrome: an epidemiologic perspective. Epidemiol Rev 1998;20:157–72.
[Free Full Text] - Bouchard C. Genetics and the metabolic syndrome. Int J Obes Relat Metab Disord 1995;19(suppl 1):S52–9.
- Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15:539–53.[Web of Science][Medline]
- Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486–97.
[Free Full Text] - Hodge AM, Dowse GK, Zimmet PZ. Microalbuminuria, cardiovascular risk factors, and insulin resistance in two populations with a high risk of type 2 diabetes mellitus. Diabet Med 1996;13:441–9.[Web of Science][Medline]
- Zavaroni I, Bonini L, Gasparini P, et al. Dissociation between urinary albumin excretion and variables associated with insulin resistance in a healthy population. J Intern Med 1996;240:151–6.[Web of Science][Medline]
- Jager A, Kostense PJ, Nijpels G, et al. Microalbuminuria is strongly associated with NIDDM and hypertension, but not with the insulin resistance syndrome: the Hoorn Study. Diabetologia 1998;41:694–700.[Web of Science][Medline]
- Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999;16:442–3.[Web of Science][Medline]
- Folsom AR, Kushi LH, Anderson KE, et al. Associations of general and abdominal obesity with multiple health outcomes in older women: the Iowa Women’s Health Study. Arch Intern Med 2000;160:2117–28.
[Abstract/Free Full Text] - Seidell JC, Oosterlee A, Deurenberg P, et al. Abdominal fat depots measured with computed tomography: effects of degree of obesity, sex, and age. Eur J Clin Nutr 1988;42:805–15.[Web of Science][Medline]
- The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997;157:2413–46.
[Abstract/Free Full Text] - 1999 World Health Organization–International Society of Hypertension guidelines for the management of hypertension. Guidelines Subcommittee. J Hypertens 1999;17:151–83.[Web of Science][Medline]
- Ferrannini E. Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: problems and prospects. Endocr Rev 1998;19:477–90.
[Abstract/Free Full Text] - Salonen JT. Is there a continuing need for longitudinal epidemiologic research? The Kuopio Ischaemic Heart Disease Risk Factor Study. Ann Clin Res 1988;20:46–50.[Web of Science][Medline]
- Salonen JT, Lakka TA, Lakka HM, et al. Hyperinsulinemia is associated with the incidence of hypertension and dyslipidemia in middle-aged men. Diabetes 1998;47:270–5.[Abstract]
- Salonen JT, Tuomainen TP, Kontula K. Role of C282Y mutation in haemochromatosis gene in development of type 2 diabetes in healthy men: prospective cohort study. BMJ 2000;320:1706–7.
[Free Full Text] - Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000;85:2402–10.
[Abstract/Free Full Text] - World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. Geneva, Switzerland: World Health Organization, 2000. (WHO technical report series, 894).
- National Heart, Lung, and Blood Institute. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Bethesda, MD: Department of Health and Human Services, National Institutes of Health, 1998. (NIH publication no. 98-4083).
- Han TS, van Leer EM, Seidell JC, et al. Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample. BMJ 1995;311:1401–5.
[Abstract/Free Full Text] - Chan JM, Rimm EB, Colditz GA, et al. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994;17:961–9.[Abstract]
- Niskanen LK, Tuomi T, Karjalainen J, et al. GAD antibodies in NIDDM. Ten-year follow-up from the diagnosis. Diabetes Care 1995;18:1557–65.[Abstract]
- Lebovitz HE. Type 2 diabetes: an overview. Clin Chem 1999;45:1339–45.
[Abstract/Free Full Text]
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 P. Cirillo, M. S. Gersch, W. Mu, P. M. Scherer, K. M. Kim, L. Gesualdo, G. N. Henderson, R. J. Johnson, and Y. Y. Sautin Ketohexokinase-Dependent Metabolism of Fructose Induces Proinflammatory Mediators in Proximal Tubular Cells J. Am. Soc. Nephrol., March 1, 2009; 20(3): 545 - 553. [Abstract] [Full Text] [PDF]
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 S.-H. Park and B. Lindholm DEFINITION OF METABOLIC SYNDROME IN PERITONEAL DIALYSIS Perit. Dial. Int., February 1, 2009; 29(Supplement_2): S137 - S144. [Abstract] [Full Text] [PDF]
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 J. B Lindsey, F. Cipollone, S. M Abdullah, and D. K Mcguire Receptor for advanced glycation end-products (RAGE) and soluble RAGE (sRAGE): cardiovascular implications Diabetes and Vascular Disease Research, January 1, 2009; 6(1): 7 - 14. [Abstract] [PDF]
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M. Hanefeld, A. Karasik, C. Koehler, T. Westermeier, and J.-L. Chiasson Metabolic syndrome and its single traits as risk factors for diabetes in people with impaired glucose tolerance: the STOP-NIDDM trial Diabetes and Vascular Disease Research, January 1, 2009; 6(1): 32 - 37. [Abstract] [PDF]
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 M.-A. Cornier, D. Dabelea, T. L. Hernandez, R. C. Lindstrom, A. J. Steig, N. R. Stob, R. E. Van Pelt, H. Wang, and R. H. Eckel The Metabolic Syndrome Endocr. Rev., December 1, 2008; 29(7): 777 - 822. [Abstract] [Full Text] [PDF]
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 M. Valtonen, D. E. Laaksonen, T. Tolmunen, K. Nyyssonen, H. Viinamaki, J. Kauhanen, and L. Niskanen Hopelessness -- novel facet of the metabolic syndrome in men Scand J Public Health, November 1, 2008; 36(8): 795 - 802. [Abstract] [PDF]
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 K. L. Chichlowska, K. M. Rose, A. V. Diez-Roux, S. H. Golden, A. M. McNeill, and G. Heiss Individual and Neighborhood Socioeconomic Status Characteristics and Prevalence of Metabolic Syndrome: The Atherosclerosis Risk in Communities (ARIC) Study Psychosom Med, November 1, 2008; 70(9): 986 - 992. [Abstract] [Full Text] [PDF]
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Studies to Treat or Prevent Pediatric Type 2 Diabe Prevalence of the Metabolic Syndrome Among a Racially/Ethnically Diverse Group of U.S. Eighth-Grade Adolescents and Associations With Fasting Insulin and Homeostasis Model Assessment of Insulin Resistance Levels Diabetes Care, October 1, 2008; 31(10): 2020 - 2025. [Abstract] [Full Text] [PDF]
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 M. Chinali, G. de Simone, M. J. Roman, L. G. Best, E. T. Lee, M. Russell, B. V. Howard, and R. B. Devereux Cardiac Markers of Pre-Clinical Disease in Adolescents With the Metabolic Syndrome: The Strong Heart Study J. Am. Coll. Cardiol., September 9, 2008; 52(11): 932 - 938. [Abstract] [Full Text] [PDF]
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A. M. Wassink, Y. Van Der Graaf, S. S Soedamah-Muthu, W. Spiering, and F. L. Visseren Metabolic syndrome and incidence of type 2 diabetes in patients with manifest vascular disease Diabetes and Vascular Disease Research, June 1, 2008; 5(2): 114 - 122. [Abstract] [PDF]
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 R Olufadi and C D Byrne Clinical and laboratory diagnosis of the metabolic syndrome J. Clin. Pathol., June 1, 2008; 61(6): 697 - 706. [Abstract] [Full Text] [PDF]
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 H. Kyrolainen, K. Hakkinen, H. Kautiainen, M. Santtila, K. Pihlainen, and A. Hakkinen Physical fitness, BMI and sickness absence in male military personnel Occup. Med., June 1, 2008; 58(4): 251 - 256. [Abstract] [Full Text] [PDF]
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M. Hassinen, T. A. Lakka, K. Savonen, H. Litmanen, L. Kiviaho, D. E. Laaksonen, P. Komulainen, and R. Rauramaa Cardiorespiratory Fitness as a Feature of Metabolic Syndrome in Older Men and Women: The Dose-Responses to Exercise Training Study (DR's EXTRA) Diabetes Care, June 1, 2008; 31(6): 1242 - 1247. [Abstract] [Full Text] [PDF]
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 J.-P. Despres, I. Lemieux, J. Bergeron, P. Pibarot, P. Mathieu, E. Larose, J. Rodes-Cabau, O. F. Bertrand, and P. Poirier Abdominal Obesity and the Metabolic Syndrome: Contribution to Global Cardiometabolic Risk Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1039 - 1049. [Abstract] [Full Text] [PDF]
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L.-Y. Lin, H.-K. Kuo, L.-P. Lai, J.-L. Lin, C.-D. Tseng, and J.-J. Hwang Inverse Correlation Between Heart Rate Recovery and Metabolic Risks in Healthy Children and Adolescents: Insight from the National Health and Nutrition Examination Survey 1999-2002 Diabetes Care, May 1, 2008; 31(5): 1015 - 1020. [Abstract] [Full Text] [PDF]
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 N. Mattsson, T. Ronnemaa, M. Juonala, J. S.A. Viikari, E. Jokinen, N. Hutri-Kahonen, M. Kahonen, T. Laitinen, and O. T. Raitakari Arterial structure and function in young adults with the metabolic syndrome: the Cardiovascular Risk in Young Finns Study Eur. Heart J., March 2, 2008; 29(6): 784 - 791. [Abstract] [Full Text] [PDF]
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D. D Morales, F. E. R Punzalan, E. Paz-Pacheco, R. G Sy, and C. A Duante Metabolic syndrome in the Philippine general population: prevalence and risk for atherosclerotic cardiovascular disease and diabetes mellitus Diabetes and Vascular Disease Research, March 1, 2008; 5(1): 36 - 43. [Abstract] [PDF]
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 R. J Kaaja Metabolic syndrome and the menopause Menopause Int, March 1, 2008; 14(1): 21 - 25. [Abstract] [Full Text] [PDF]
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 F. Lopez-Jimenez, F. H. Sert Kuniyoshi, A. Gami, and V. K. Somers Obstructive Sleep Apnea: Implications for Cardiac and Vascular Disease Chest, March 1, 2008; 133(3): 793 - 804. [Full Text] [PDF]
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 G. Hu, J. Lindstrom, P. Jousilahti, M. Peltonen, L. Sjoberg, R. Kaaja, J. Sundvall, and J. Tuomilehto The Increasing Prevalence of Metabolic Syndrome among Finnish Men and Women over a Decade J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 832 - 836. [Abstract] [Full Text] [PDF]
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A. M.J. Wassink, Y. van der Graaf, J. K. Olijhoek, F. L.J. Visseren, and for the SMART Study Group Metabolic syndrome and the risk of new vascular events and all-cause mortality in patients with coronary artery disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm Eur. Heart J., January 2, 2008; 29(2): 213 - 223. [Abstract] [Full Text] [PDF]
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Q. Qi, Z. Yu, X. Ye, F. Zhao, P. Huang, F. B. Hu, O. H. Franco, J. Wang, H. Li, Y. Liu, et al. Elevated Retinol-Binding Protein 4 Levels Are Associated with Metabolic Syndrome in Chinese People J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4827 - 4834. [Abstract] [Full Text] [PDF]
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 A. Rashidi, A. Ghanbarian, and F. Azizi Are Patients Who Have Metabolic Syndrome without Diabetes at Risk for Developing Chronic Kidney Disease? Evidence Based on Data from a Large Cohort Screening Population Clin. J. Am. Soc. Nephrol., September 1, 2007; 2(5): 976 - 983. [Abstract] [Full Text] [PDF]
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J. A Kim, S. M. Kim, J. S. Lee, H. J. Oh, J. H. Han, Y. Song, H. Joung, and H. S. Park Dietary Patterns and the Metabolic Syndrome in Korean Adolescents: 2001 Korean National Health and Nutrition Survey Diabetes Care, July 1, 2007; 30(7): 1904 - 1905. [Full Text] [PDF]
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B. M.Y. Cheung, N. M.S. Wat, Y. B. Man, S. Tam, G. N. Thomas, G. M. Leung, C. H. Cheng, J. Woo, E. D. Janus, C. P. Lau, et al. Development of Diabetes in Chinese With the Metabolic Syndrome: A 6-year prospective study Diabetes Care, June 1, 2007; 30(6): 1430 - 1436. [Abstract] [Full Text] [PDF]
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 G. Vazquez, S. Duval, D. R. Jacobs Jr., and K. Silventoinen Comparison of Body Mass Index, Waist Circumference, and Waist/Hip Ratio in Predicting Incident Diabetes: A Meta-Analysis Epidemiol. Rev., May 10, 2007; (2007) mxm008v1. [Abstract] [Full Text] [PDF]
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 P. Kallio, M. Kolehmainen, D. E Laaksonen, J. Kekalainen, T. Salopuro, K. Sivenius, L. Pulkkinen, H. M Mykkanen, L. Niskanen, M. Uusitupa, et al. Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study Am. J. Clinical Nutrition, May 1, 2007; 85(5): 1417 - 1427. [Abstract] [Full Text] [PDF]
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G. Q. Shaibi, M. L. Cruz, M. J. Weigensberg, C. M. Toledo-Corral, C. J. Lane, L. A. Kelly, J. N. Davis, C. Koebnick, E. E. Ventura, C. K. Roberts, et al. Adiponectin Independently Predicts Metabolic Syndrome in Overweight Latino Youth J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1809 - 1813. [Abstract] [Full Text] [PDF]
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G. Pambianco, T. Costacou, and T. J. Orchard The Prediction of Major Outcomes of Type 1 Diabetes: a 12-Year Prospective Evaluation of Three Separate Definitions of the Metabolic Syndrome and Their Components and Estimated Glucose Disposal Rate: The Pittsburgh Epidemiology of Diabetes Complications Study experience Diabetes Care, May 1, 2007; 30(5): 1248 - 1254. [Abstract] [Full Text] [PDF]
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 A. I. Kakafika, D. P. Mikhailidis, A. Karagiannis, and V. G. Athyros The Role of Endocannabinoid System Blockade in the Treatment of the Metabolic Syndrome J. Clin. Pharmacol., May 1, 2007; 47(5): 642 - 652. [Abstract] [Full Text] [PDF]
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K. Raikkonen, K. A. Matthews, and L. H. Kuller Depressive Symptoms and Stressful Life Events Predict Metabolic Syndrome Among Middle-Aged Women: A comparison of World Health Organization, Adult Treatment Panel III, and International Diabetes Foundation definitions Diabetes Care, April 1, 2007; 30(4): 872 - 877. [Abstract] [Full Text] [PDF]
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 E. Nisoli, E. Clementi, M. O. Carruba, and S. Moncada Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome? Circ. Res., March 30, 2007; 100(6): 795 - 806. [Abstract] [Full Text] [PDF]
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 A. H. Auchincloss, A. V. Diez Roux, D. G. Brown, E. S. O'Meara, and T. E. Raghunathan Association of Insulin Resistance with Distance to Wealthy Areas: The Multi-Ethnic Study of Atherosclerosis Am. J. Epidemiol., February 15, 2007; 165(4): 389 - 397. [Abstract] [Full Text] [PDF]
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 A. H. Friedlander, J. Weinreb, I. Friedlander, and J. A. Yagiela Metabolic syndrome: Pathogenesis, medical care and dental implications J Am Dent Assoc, February 1, 2007; 138(2): 179 - 187. [Abstract] [Full Text] [PDF]
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G. A. Nichols, T. A. Hillier, and J. B. Brown Progression From Newly Acquired Impaired Fasting Glusose to Type 2 Diabetes Diabetes Care, February 1, 2007; 30(2): 228 - 233. [Abstract] [Full Text] [PDF]
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U. Ekelund, S. J. Griffin, N. J. Wareham, and on behalf of the ProActive Research Group Physical Activity and Metabolic Risk in Individuals With a Family History of Type 2 Diabetes Diabetes Care, February 1, 2007; 30(2): 337 - 342. [Abstract] [Full Text] [PDF]
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J. Lee, S. Ma, D. Heng, C.-E. Tan, S.-K. Chew, K. Hughes, and E-S. Tai Should Central Obesity Be an Optional or Essential Component of the Metabolic Syndrome?: Ischemic heart disease risk in the Singapore Cardiovascular Cohort Study Diabetes Care, February 1, 2007; 30(2): 343 - 347. [Abstract] [Full Text] [PDF]
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 G. R Hajer, Y. van der Graaf, J. K Olijhoek, M. C Verhaar, F. L J Visseren, and for the SMART Study Group Levels of homocysteine are increased in metabolic syndrome patients but are not associated with an increased cardiovascular risk, in contrast to patients without the metabolic syndrome Heart, February 1, 2007; 93(2): 216 - 220. [Abstract] [Full Text] [PDF]
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 C. P Chung, I. Avalos, A. Oeser, T. Gebretsadik, A. Shintani, P. Raggi, and C Michael Stein High prevalence of the metabolic syndrome in patients with systemic lupus erythematosus: association with disease characteristics and cardiovascular risk factors Ann Rheum Dis, February 1, 2007; 66(2): 208 - 214. [Abstract] [Full Text] [PDF]
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 C. Li, E. S Ford, L. C McGuire, and A. H Mokdad Association of metabolic syndrome and insulin resistance with congestive heart failure: findings from the Third National Health and Nutrition Examination Survey J Epidemiol Community Health, January 1, 2007; 61(1): 67 - 73. [Abstract] [Full Text] [PDF]
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B. Richelsen, S. Tonstad, S. Rossner, S. Toubro, L. Niskanen, S. Madsbad, P. Mustajoki, and A. Rissanen Effect of Orlistat on Weight Regain and Cardiovascular Risk Factors Following a Very-Low-Energy Diet in Abdominally Obese Patients: A 3-year randomized, placebo-controlled study Diabetes Care, January 1, 2007; 30(1): 27 - 32. [Abstract] [Full Text] [PDF]
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P. Cirillo, W. Sato, S. Reungjui, M. Heinig, M. Gersch, Y. Sautin, T. Nakagawa, and R. J. Johnson Uric Acid, the Metabolic Syndrome, and Renal Disease J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S165 - S168. [Abstract] [Full Text] [PDF]
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 M. Buresova, V. Zidek, A. Musilova, M. Simakova, A. Fucikova, V. Bila, V. Kren, L. Kazdova, R. Di Nicolantonio, and M. Pravenec Genetic relationship between placental and fetal weights and markers of the metabolic syndrome in rat recombinant inbred strains Physiol Genomics, September 14, 2006; 26(3): 226 - 231. [Abstract] [Full Text] [PDF]
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 N. Unwin The metabolic syndrome J R Soc Med, September 1, 2006; 99(9): 457 - 462. [Full Text] [PDF]
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|
 B. Ovbiagele, J. L. Saver, M. J. Lynn, M. Chimowitz, and for the WASID Study Group Impact of metabolic syndrome on prognosis of symptomatic intracranial atherostenosis Neurology, May 9, 2006; 66(9): 1344 - 1349. [Abstract] [Full Text] [PDF]
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 L. E. Bernstein, J. Berry, S. Kim, B. Canavan, and S. K. Grinspoon Effects of Etanercept in Patients With the Metabolic Syndrome. Arch Intern Med, April 24, 2006; 166(8): 902 - 908. [Abstract] [Full Text] [PDF]
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 B. Desvergne, L. Michalik, and W. Wahli Transcriptional Regulation of Metabolism Physiol Rev, April 1, 2006; 86(2): 465 - 514. [Abstract] [Full Text] [PDF]
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 |
|
 D. I Brixner, Q. Said, P. K Corey-Lisle, A V. Tuomari, G. J L'Italien, W. Stockdale, and G. M Oderda Naturalistic Impact of Second-Generation Antipsychotics on Weight Gain Ann. Pharmacother., April 1, 2006; 40(4): 626 - 632. [Abstract] [Full Text] [PDF]
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S. M. Grundy Metabolic Syndrome: Connecting and Reconciling Cardiovascular and Diabetes Worlds J. Am. Coll. Cardiol., March 21, 2006; 47(6): 1093 - 1100. [Abstract] [Full Text] [PDF]
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J. Dallongeville, M.-C. Grupposo, D. Cottel, J. Ferrieres, D. Arveiler, A. Bingham, J.-B. Ruidavets, B. Haas, P. Ducimetiere, and P. Amouyel Association between the metabolic syndrome and parental history of premature cardiovascular disease Eur. Heart J., March 2, 2006; 27(6): 722 - 728. [Abstract] [Full Text] [PDF]
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 P. C Deedwania and R. Schmieder Angiotensin Receptor Blockers: Cardiovascular Protection in the Metabolic Syndrome Journal of Renin-Angiotensin-Aldosterone System, March 1, 2006; 7(1_suppl): S12 - S18. [Abstract] [PDF]
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P. T. Katzmarzyk, I. Janssen, R. Ross, T. S. Church, and S. N. Blair The Importance of Waist Circumference in the Definition of Metabolic Syndrome: Prospective analyses of mortality in men Diabetes Care, February 1, 2006; 29(2): 404 - 409. [Abstract] [Full Text] [PDF]
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F. Fallo, F. Veglio, C. Bertello, N. Sonino, P. Della Mea, M. Ermani, F. Rabbia, G. Federspil, and P. Mulatero Prevalence and Characteristics of the Metabolic Syndrome in Primary Aldosteronism J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 454 - 459. [Abstract] [Full Text] [PDF]
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R. M. Najarian, L. M. Sullivan, W. B. Kannel, P. W. F. Wilson, R. B. D'Agostino, and P. A. Wolf Metabolic Syndrome Compared With Type 2 Diabetes Mellitus as a Risk Factor for Stroke: The Framingham Offspring Study Arch Intern Med, January 9, 2006; 166(1): 106 - 111. [Abstract] [Full Text] [PDF]
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M. Pladevall, B. Singal, L. K. Williams, C. Brotons, H. Guyer, J. Sadurni, C. Falces, M. Serrano-Rios, R. Gabriel, J. E. Shaw, et al. A Single Factor Underlies the Metabolic Syndrome: A confirmatory factor analysis Diabetes Care, January 1, 2006; 29(1): 113 - 122. [Abstract] [Full Text] [PDF]
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L. E. Eberly, R. Prineas, J. D. Cohen, G. Vazquez, X. Zhi, J. D. Neaton, L. H. Kuller, and for the Multiple Risk Factor Intervention Trial Re Metabolic Syndrome: Risk factor distribution and 18-year mortality in the Multiple Risk Factor Intervention Trial Diabetes Care, January 1, 2006; 29(1): 123 - 130. [Abstract] [Full Text] [PDF]
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 A. J.G. Hanley, A. J. Karter, K. Williams, A. Festa, R. B. D'Agostino Jr, L. E. Wagenknecht, and S. M. Haffner Prediction of Type 2 Diabetes Mellitus With Alternative Definitions of the Metabolic Syndrome: The Insulin Resistance Atherosclerosis Study Circulation, December 13, 2005; 112(24): 3713 - 3721. [Abstract] [Full Text] [PDF]
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S. G. Wannamethee, A. G. Shaper, L. Lennon, and R. W. Morris Metabolic Syndrome vs Framingham Risk Score for Prediction of Coronary Heart Disease, Stroke, and Type 2 Diabetes Mellitus Arch Intern Med, December 12, 2005; 165(22): 2644 - 2650. [Abstract] [Full Text] [PDF]
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D. E Laaksonen, L. K Toppinen, K. S Juntunen, K. Autio, K.-H. Liukkonen, K. S Poutanen, L. Niskanen, and H. M Mykkanen Dietary carbohydrate modification enhances insulin secretion in persons with the metabolic syndrome Am. J. Clinical Nutrition, December 1, 2005; 82(6): 1218 - 1227. [Abstract] [Full Text] [PDF]
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P. C. Y. Tong, C.-S. Ho, V. T. F. Yeung, M. C. Y. Ng, W.-Y. So, R. Ozaki, G. T. C. Ko, R. C. W. Ma, E. Poon, N. N. Chan, et al. Association of Testosterone, Insulin-Like Growth Factor-I, and C-Reactive Protein with Metabolic Syndrome in Chinese Middle-Aged Men with a Family History of Type 2 Diabetes J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6418 - 6423. [Abstract] [Full Text] [PDF]
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Prepared by: British Cardiac Society, British Hype JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice Heart, December 1, 2005; 91(suppl_5): v1 - v52. [Full Text] [PDF]
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|
|
|
P. W.F. Wilson, R. B. D'Agostino, H. Parise, L. Sullivan, and J. B. Meigs Metabolic Syndrome as a Precursor of Cardiovascular Disease and Type 2 Diabetes Mellitus Circulation, November 15, 2005; 112(20): 3066 - 3072. [Abstract] [Full Text] [PDF]
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 I. Eskurza, L. A Myerburgh, Z. D Kahn, and D. R Seals Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults J. Physiol., November 1, 2005; 568(3): 1057 - 1065. [Abstract] [Full Text] [PDF]
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S. M. Grundy, J. I. Cleeman, S. R. Daniels, K. A. Donato, R. H. Eckel, B. A. Franklin, D. J. Gordon, R. M. Krauss, P. J. Savage, S. C. Smith Jr, et al. Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement Circulation, October 25, 2005; 112(17): 2735 - 2752. [Full Text] [PDF]
|
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|
|
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C. Lorenzo, K. Williams, C. Gonzalez-Villalpando, and S. M. Haffner The Prevalence of the Metabolic Syndrome Did Not Increase in Mexico City Between 1990-1992 and 1997-1999 Despite More Central Obesity Diabetes Care, October 1, 2005; 28(10): 2480 - 2485. [Abstract] [Full Text] [PDF]
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 A. T. Kraja, D. C. Rao, A. B. Weder, R. Cooper, J. D. Curb, C. L. Hanis, S. T. Turner, M. de Andrade, C. A. Hsiung, T. Quertermous, et al. Two Major QTLs and Several Others Relate to Factors of Metabolic Syndrome in the Family Blood Pressure Program Hypertension, October 1, 2005; 46(4): 751 - 757. [Abstract] [Full Text] [PDF]
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C. J. Girman, J. M. Dekker, T. Rhodes, G. Nijpels, C. D. A. Stehouwer, L. M. Bouter, and R. J. Heine An Exploratory Analysis of Criteria for the Metabolic Syndrome and Its Prediction of Long-term Cardiovascular Outcomes: The Hoorn Study Am. J. Epidemiol., September 1, 2005; 162(5): 438 - 447. [Abstract] [Full Text] [PDF]
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 R. A. Hegele and R. L. Pollex Genetic and physiological insights into the metabolic syndrome Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2005; 289(3): R663 - R669. [Abstract] [Full Text] [PDF]
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W. S. Tzou, P. S. Douglas, S. R. Srinivasan, M. G. Bond, R. Tang, W. Chen, G. S. Berenson, and J. H. Stein Increased Subclinical Atherosclerosis in Young Adults With Metabolic Syndrome: The Bogalusa Heart Study J. Am. Coll. Cardiol., August 2, 2005; 46(3): 457 - 463. [Abstract] [Full Text] [PDF]
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M. I. Schmidt, B. B. Duncan, H. Bang, J. S. Pankow, C. M. Ballantyne, S. H. Golden, A. R. Folsom, L. E. Chambless, and for the Atherosclerosis Risk in Communities Invest Identifying Individuals at High Risk for Diabetes: The Atherosclerosis Risk in Communities study Diabetes Care, August 1, 2005; 28(8): 2013 - 2018. [Abstract] [Full Text] [PDF]
|
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|
|
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A S Wierzbicki, S Nishtar, P J Lumb, M Lambert-Hammill, C N Turner, M A Crook, M S Marber, and J Gill Metabolic syndrome and risk of coronary heart disease in a Pakistani cohort Heart, August 1, 2005; 91(8): 1003 - 1007. [Abstract] [Full Text] [PDF]
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M. J. LaMonte, C. E. Barlow, R. Jurca, J. B. Kampert, T. S. Church, and S. N. Blair Cardiorespiratory Fitness Is Inversely Associated With the Incidence of Metabolic Syndrome: A Prospective Study of Men and Women Circulation, July 26, 2005; 112(4): 505 - 512. [Abstract] [Full Text] [PDF]
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E. S. Ford Risks for All-Cause Mortality, Cardiovascular Disease, and Diabetes Associated With the Metabolic Syndrome: A summary of the evidence Diabetes Care, July 1, 2005; 28(7): 1769 - 1778. [Abstract] [Full Text] [PDF]
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M. Kurella, J. C. Lo, and G. M. Chertow Metabolic Syndrome and the Risk for Chronic Kidney Disease among Nondiabetic Adults J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2134 - 2140. [Abstract] [Full Text] [PDF]
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 C. C. Lee, S. G. Glickman, D. R. Dengel, M. D. Brown, and M. A. Supiano Abdominal Adiposity Assessed by Dual Energy X-Ray Absorptiometry Provides a Sex-Independent Predictor of Insulin Sensitivity in Older Adults J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2005; 60(7): 872 - 877. [Abstract] [Full Text] [PDF]
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J. Hung, B. M. McQuillan, C. M. L. Chapman, P. L. Thompson, and J. P. Beilby Elevated Interleukin-18 Levels Are Associated With the Metabolic Syndrome Independent of Obesity and Insulin Resistance Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1268 - 1273. [Abstract] [Full Text] [PDF]
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 THE DECODE STUDY GROUP and Q. Qiao Comparison of three different definitions for the metabolic syndrome in non-diabetic Europeans The British Journal of Diabetes & Vascular Disease, May 1, 2005; 5(3): 161 - 168. [Abstract] [PDF]
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U. Ekelund, S. Brage, P. W. Franks, S. Hennings, S. Emms, and N. J. Wareham Physical Activity Energy Expenditure Predicts Progression Toward the Metabolic Syndrome Independently of Aerobic Fitness in Middle-Aged Healthy Caucasians: The Medical Research Council Ely Study Diabetes Care, May 1, 2005; 28(5): 1195 - 1200. [Abstract] [Full Text] [PDF]
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N. R. Qi, J. Wang, V. Zidek, V. Landa, P. Mlejnek, L. Kazdova, M. Pravenec, and T. W. Kurtz A New Transgenic Rat Model of Hepatic Steatosis and the Metabolic Syndrome Hypertension, May 1, 2005; 45(5): 1004 - 1011. [Abstract] [Full Text] [PDF]
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M. E. Otiniano, X. L. Du, M. R. Maldonado, L. Ray, and K. Markides Effect of Metabolic Syndrome on Heart Attack and Mortality in Mexican-American Elderly Persons: Findings of 7-Year Follow-Up From the Hispanic Established Population for the Epidemiological Study of the Elderly J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2005; 60(4): 466 - 470. [Abstract] [Full Text] [PDF]
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A. Scuteri, S. S. Najjar, C. H. Morrell, and E. G. Lakatta The Metabolic Syndrome in Older Individuals: Prevalence and Prediction of Cardiovascular Events: The Cardiovascular Health Study Diabetes Care, April 1, 2005; 28(4): 882 - 887. [Abstract] [Full Text] [PDF]
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 K. Silventoinen, J. Pankow, P. Jousilahti, G. Hu, and J. Tuomilehto Educational inequalities in the metabolic syndrome and coronary heart disease among middle-aged men and women Int. J. Epidemiol., April 1, 2005; 34(2): 327 - 334. [Abstract] [Full Text] [PDF]
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R. J. Petrella, C. N. Lattanzio, A. Demeray, V. Varallo, and R. Blore Can Adoption of Regular Exercise Later in Life Prevent Metabolic Risk for Cardiovascular Disease? Diabetes Care, March 1, 2005; 28(3): 694 - 701. [Abstract] [Full Text] [PDF]
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A. M. McNeill, W. D. Rosamond, C. J. Girman, S. H. Golden, M. I. Schmidt, H. E. East, C. M. Ballantyne, and G. Heiss The Metabolic Syndrome and 11-Year Risk of Incident Cardiovascular Disease in the Atherosclerosis Risk in Communities Study Diabetes Care, February 1, 2005; 28(2): 385 - 390. [Abstract] [Full Text] [PDF]
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P. T. Katzmarzyk, T. S. Church, I. Janssen, R. Ross, and S. N. Blair Metabolic Syndrome, Obesity, and Mortality: Impact of cardiorespiratory fitness Diabetes Care, February 1, 2005; 28(2): 391 - 397. [Abstract] [Full Text] [PDF]
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J. Dallongeville, D. Cottel, J. Ferrieres, D. Arveiler, A. Bingham, J. B. Ruidavets, B. Haas, P. Ducimetiere, and P. Amouyel Household Income Is Associated With the Risk of Metabolic Syndrome in a Sex-Specific Manner Diabetes Care, February 1, 2005; 28(2): 409 - 415. [Abstract] [Full Text] [PDF]
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D. E. Laaksonen, L. Niskanen, K. Punnonen, K. Nyyssonen, T.-P. Tuomainen, V.-P. Valkonen, and J. T. Salonen The Metabolic Syndrome and Smoking in Relation to Hypogonadism in Middle-Aged Men: A Prospective Cohort Study J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 712 - 719. [Abstract] [Full Text] [PDF]
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 D. E. Laaksonen, J. Lindstrom, T. A. Lakka, J. G. Eriksson, L. Niskanen, K. Wikstrom, S. Aunola, S. Keinanen-Kiukaanniemi, M. Laakso, T. T. Valle, et al. Physical Activity in the Prevention of Type 2 Diabetes: The Finnish Diabetes Prevention Study Diabetes, January 1, 2005; 54(1): 158 - 165. [Abstract] [Full Text] [PDF]
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V. Lyssenko, P. Almgren, D. Anevski, R. Perfekt, K. Lahti, M. Nissen, B. Isomaa, B. Forsen, N. Homstrom, C. Saloranta, et al. Predictors of and Longitudinal Changes in Insulin Sensitivity and Secretion Preceding Onset of Type 2 Diabetes Diabetes, January 1, 2005; 54(1): 166 - 174. [Abstract] [Full Text] [PDF]
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