There are several current trials investigating the effect of resveratrol supplementation on biomarkers of inflammation and oxidative stress among patients with metabolic syndrome (MetS); however, their findings are controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to summarize the existing evidence and collectively determine the effects of resveratrol supplementation on biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. Two authors independently searched electronic databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science databases, until May 2018 in order to find relevant RCTs. The quality of the selected RCTs was evaluated using the Cochrane Collaboration risk of bias tool. Cochran's Q test and I-square (I2) statistic were used to determine whether heterogeneity exists across included trials. Standardized mean difference (SMD) and 95% CI between two intervention groups were used to determine pooled effect sizes. Out of 317 potential citations selected based on keywords, 24 RCTs met the inclusion criteria and were eligible for the current meta-analysis. The pooled results obtained by using the random-effects model showed that resveratrol supplementation significantly decreased C-reactive protein (CRP) (SMD = -0.55; 95% CI, -0.84, -0.26; P < 0.001; I2: 84.0) and tumor necrosis factor-α (TNF-α) (SMD = -0.68; 95% CI, -1.08, -0.28; P = 0.001; I2: 81.3) concentrations among patients with MetS and related disorders. Interleukin 6 (IL-6) (SMD = 0.05; 95% CI, -0.31, 0.41; P = 0.79; I2: 85.0) and superoxide dismutase (SOD) (SMD = 0.21; 95% CI, -3.16, 3.59; P = 0.90; I2: 97.7) concentrations did not significantly change following resveratrol supplementation. Resveratrol supplementation showed a promising lowering effect on some of the inflammatory markers among patients with MetS and related disorders. Additional prospective studies regarding the effect of resveratrol supplementation on biomarkers of inflammation and oxidative stress by using higher doses of resveratrol and longer duration of supplementation are necessary.
In 1996, adiponectin was reported to be the most abundant transcript in adipose tissue. Animal studies revealed that administering adiponectin improves insulin resistance and blood glucose levels and inhibits atherosclerosis. In the present article, we review the significance of measuring serum high-molecular-weight (HMW) adiponectin levels in human subjects. Our cross-sectional studies revealed that the serum HMW adiponectin concentration was 1.9 times higher in healthy Japanese females than males and had a strong positive correlation with HDL-cholesterol but a negative correlation with BMI and the homeostasis model assessment insulin resistance index (HOMA-IR). They also indicated that the serum HMW adiponectin concentration had a stronger association with HOMA-IR and metabolic syndrome than the total adiponectin concentration. Our longitudinal study, a 6-year follow-up of Japanese men, suggested that a decreased level of HMW adiponectin is a predictor of progression to metabolic syndrome. In another intervention study, lifestyle modification for 3 months induced a decrease in BMI and waist circumference and an increase in serum HMW adiponectin but not the total adiponectin level in 16 Japanese males with metabolic syndrome. Administering thiazolidinediones to diabetic patients increased the serum HMW adiponectin concentration 3 fold and improved glucose and lipid profiles and blood pressure. Some people may inherit a lower serum concentration of adiponectin, and have a higher risk of developing cardiovascular diseases.It is suggested that HMW adiponectin is a useful marker for the evaluation and care of subjects with metabolic syndrome and related disorders.
Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta-analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%-34.4%; N = 198; n = 52,678). Relative risk meta-analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta-analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = -3.6, p = 0.0003, r(2) = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic-naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35-1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.
Individuals with schizophrenia have high levels of medical comorbidity and cardiovascular risk factors. The presence of 3 or more specific factors is indicative of metabolic syndrome, which is a significant influence upon future morbidity and mortality. We aimed to clarify the prevalence and predictors of metabolic syndrome (MetS) in adults with schizophrenia and related disorders, accounting for subgroup differences. A PRISMA systematic search, appraisal, and meta-analysis were conducted of 126 analyses in 77 publications (n = 25,692). The overall rate of MetS was 32.5% (95% CI = 30.1%-35.0%), and there were only minor differences according to the different definitions of MetS, treatment setting (inpatient vs outpatient), by country of origin and no appreciable difference between males and females. Older age had a modest influence on the rate of MetS (adjusted R(2) = .20; P < .0001), but the strongest influence was of illness duration (adjusted R(2) = .35; P < .0001). At a study level, waist size was most useful in predicting high rate of MetS with a sensitivity of 79.4% and a specificity of 78.8%. Sensitivity and specificity of high blood pressure, high triglycerides, high glucose and low high-density lipoprotein, and age (>38 y) are shown in supplementary appendix 2 online. Regarding prescribed antipsychotic medication, highest rates were seen in those prescribed clozapine (51.9%) and lowest rates of MetS in those who were unmedicated (20.2%). Present findings strongly support the notion that patients with schizophrenia should be considered a high-risk group. Patients with schizophrenia should receive regular monitoring and adequate treatment of cardio-metabolic risk factors.
Abstract Background There are current trials investigating the effect of resveratrol supplementation on lipid profiles and liver enzymes among patients with metabolic syndrome (MetS) and related disorders; however, their findings are controversial. This systematic review and meta-analysis were aimed to determine the effects of resveratrol supplementation on lipid profiles and liver enzymes among patients with MetS and related disorders. Methods We performed a comprehensive search of the following online databases up to November 2018: Cochrane Library, PubMed, Embase, and Web of Science. The relevant articles were assessed for quality of studies using the Cochrane risk of bias tool. Results Out of 2459 citations, 31 articles were appropriate for including to the current meta-analysis. The pooled results indicated that resveratrol use significantly decreased total cholesterol [weighted mean difference (WMD) = − 7.65 mg/dL; 95% CI, − 12.93, − 2.37; P < 0.01; I 2 : 83.4%] and increased gamma-glutamyl transferase (GGT) concentrations (WMD = 1.76 U/l; 95% CI, 0.58, 2.94; P < 0.01; I 2 : 20.1%). We found no significant effect of resveratrol supplementation on triglycerides (WMD = − 5.84 mg/dL; 95% CI, − 12.68, 1.00; P = 0.09; I 2 : 66.8%), LDL- (WMD = -2.90 mg/dL; 95% CI, − 10.88, 5.09; P = 0.47; I 2 : 96.0%), HDL-cholesterol (WMD = 0.49 mg/dL; 95% CI, − 0.80, 1.78; P = 0.45; I 2 : 74.0%), alanine aminotransferase (ALT) (WMD = -0.14 U/l; 95% CI, − 3.69, 3.41; P = 0.93; I 2 : 79.6%), and aspartate aminotransferase (AST) (WMD = -0.34 U/l; 95% CI, − 2.94, 2.27; P = 0.80; I 2 : 88.0%) concentrations. Conclusions This meta-analysis demonstrated that resveratrol supplementation among patients with MetS and related disorders significantly reduced total cholesterol and increased GGT concentrations, but did not affect triglycerides, LDL-, HDL-cholesterol, ALT, and AST concentrations. This data suggests that resveratrol may have a potential cardio-protective effect in patients with MetS and related disorders.
Background and objective: The current systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to assess the influence of curcumin intake on weight among patients with metabolic syndrome and related disorders. Methods: We searched the following databases up until January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and evaluated for quality of the studies in accordance with the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (MDs) with 95% confidence intervals (95% CI). Results: Eighteen studies that comprised a total of 1645 individuals were finally included in the meta-analysis. Curcumin intake significantly reduced body mass index (BMI) (SMD -0.45; 95% CI, -0.78, -0.13; P=0.006), weight (SMD -0.33; 95% CI, -0.52, -0.14; P=0.001), waist-to-hip ratio (WHR) (SMD -0.35; 95% CI, -0.64, -0.06; P=0.01) and leptin levels (SMD -2.57; 95% CI, -2.93, -2.21; P<0.0001). We found no significant effect of curcumin intake on hip ratio (HR) (SMD -0.27; 95% CI, -0.63, 0.08; P=0.13) and adiponectin levels (SMD 1.96; 95% CI, -0.13, 4.05; P=0.06). Conclusions: Overall, we have found that curcumin intake among patients with metabolic syndrome and related disorders may be correlated with a decline in BMI, weight, WHR and leptin.
BACKGROUND: This systematic review and meta-analysis of randomized controlled trials (RCTs), were performed to determine the effects of curcumin intake on glycemic control and lipid profiles among patients with metabolic syndrome (MetS) and related disorders. METHODS: We searched the following databases up until January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and evaluated for quality of the studies in accordance with the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (MDs) with 95% confidence intervals (95% CI). RESULTS: Twenty-six trials with 1890 participants were included in the current meta-analysis. The findings demonstrated the significant association between curcumin intake and reduced fasting glucose levels (SMD -0.78; 95% CI, -1.20, -0.37; P<0.001), homeostasis model of assessment-estimated insulin resistance (SMD -0.91; 95% CI, -1.52, -0.31; P=0.003) and HbA1c (SMD -0.92; 95% CI, -1.37, -0.47; P<0.001). In addition, curcumin supplementation was significantly associated with triglyceride (SMD -1.21; 95 % CI, -1.78, -0.65; P<0.001) and total cholesterol reduction (SMD -0.73; 95 % CI, -1.32, -0.13; P= 0.01). However, curcumin intake significantly increased insulin levels (SMD 0.92; 95% CI, 0.06, 1.78; P=0.036). We found no significant effect of curcumin supplementation on LDL- (SMD -0.52; 95% CI, -1.14, 0.11; P=0.10) and HDL-cholesterol levels (SMD 0.28; 95% CI, -0.22, 0.77; P=0.27). CONCLUSION: Overall, curcumin consumption was associated with a significant reduction in fasting glucose, HOMA-IR, HbA1c, triglycerides and total cholesterol levels among patients with MetS and related disorders, but did not affect LDL- and HDL-cholesterol levels.
The present review provides an update of the biological actions of Pycnogenol® in the treatment of metabolic syndrome and related disorders such as obesity, dyslipidaemia, diabetes and hypertension. Pycnogenol® is a French maritime pine bark extract produced from the outer bark of Pinus pinaster Ait. Subsp. atlantica. Its strong antioxidant, antiinflammatory, endothelium-dependent vasodilator activity, and also its anti-thrombotic effects make it appropriate for targeting the multifaceted pathophysiology of metabolic syndrome. Clinical studies have shown that it can reduce blood glucose levels in people with diabetes, blood pressure in mild to moderate hypertensive patients, and waist circumference, and improve lipid profile, renal and endothelial functions in metabolic syndrome. This review highlights the pathophysiology of metabolic syndrome and related clinical research findings on the safety and efficacy of Pycnogenol®. The results of clinical research studies performed with Pycnogenol® are discussed using an evidence-based, target-oriented approach following the pathophysiology of individual components as well as in metabolic syndrome overall.
BACKGROUND: Disturbances in leptin and insulin signaling pathways are related to obesity and metabolic syndrome (MS) with increased risk of diabetes and cardiovascular disease. Janus kinase 2 (JAK2) is a tyrosine kinase involved in the activation of mechanisms that mediate leptin and insulin actions. We conducted a population cross-sectional study to explore the association between two common variants in JAK2 gene and MS related traits in 724 Argentinean healthy male subjects. METHODS: A total of 724 unrelated men aged 37.11 ± 10.91 yr were included in a cross-sectional study. Physical examination, anthropometric measurements and biochemical analysis were determined by a standardized protocol. rs7849191 and rs3780378 were genotyped. Analyses were done separately for each SNP and followed up by haplotype analysis. RESULTS: rs7849191 and rs3780378 were both associated with reduced risk of MS [p = 0.005; OR (95%CI) = 0.52 (0.33-0.80) and p = 0.006; OR (95% CI) = 0.59 (0.40-0.86) respectively, assuming a dominant model]. rs3780378 T allele was associated with triglyceridemia values under 150 mg/dl [p = 0.007; OR (95%CI) = 0.610 (0.429-0.868)] and TT carriers showed lower triglycerides (p = 0.017), triglycerides/HDL-C ratio (p = 0.022) and lipid accumulation product (p = 0.007) compared to allele C carriers. The two-SNPs-haplotype analysis was consistent with single locus analysis. CONCLUSIONS: It was found for the first time, significant associations of JAK2 common variants and related haplotypes with reduced risk of MS. These findings could be explained by the role of JAK2 in insulin and/or leptin signaling.
Aims: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to determine the effect of quercetin administration on lipid profiles and inflammatory markers among patients with metabolic syndrome (MetS) and related disorders.Methods: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until November 2018. Q-test and I2 statistics were applied to assess heterogeneity among included studies. Data were combined using fixed- or random-effects model and presented as standardized mean difference (SMD) with 95% confidence interval (CI).Results: Out of 591 citations, 16 RCTs were included in the meta-analysis. The pooled findings showed that quercetin consumption significantly decreased total-cholesterol (SMD = −0.98; 95% CI, −1.48, −0.49; p < 0.001; I2: 94.0), LDL-cholesterol (SMD = −0.88; 95% CI, −1.35, −0.41; p < 0.001; I2: 92.7) and C-reactive protein (CRP) levels (−0.64; 95% CI, −1.03, −0.25; p = 0.001; I2: 90.2). While, quercetin supplementation did not significantly affect triglycerides (TG) (SMD = −0.32; 95% CI, −0.68, 0.04; p = 0.08; I2: 84.8), HDL-cholesterol (SMD = 0.20; 95% CI, −0.20, 0.24; p = 0.84; I2: 70.6), interleukin 6 (IL-6) (SMD = −0.69; 95% CI, −1.69, 0.31; p = 0.17; I2: 94.5) and tumor necrosis factor-alpha (TNF-α) levels (SMD = −0.06; 95% CI, −0.25, 0.14; p = 0.58; I2: 35.6)Conclusions: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced total-cholesterol, LDL-cholesterol, and CRP levels, yet did not affect triglycerides, HDL-cholesterol, IL-6 and TNF-α among patients with MetS and related disorders.
This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of alpha-lipoic acid (ALA) supplementation on the inflammatory markers among patients with metabolic syndrome (MetS) and related disorders. We searched the following databases until November 2017: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran’s Q test and I-square (I2) statistic. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as the summary effect size. Eighteen trials out of 912 potential citations were found to be eligible for our meta-analysis. The findings indicated that ALA supplementation significantly decreased C-reactive protein (CRP) (SMD = − 1.52; 95% CI, − 2.25, − 0.80; P < 0.001), interlokin-6 (IL-6) (SMD = − 1.96; 95% CI, − 2.60, − 1.32; P < 0.001), and tumor necrosis factor alpha levels (TNF-α) (SMD = − 2.62; 95% CI, − 3.70, − 1.55; P < 0.001) in patients diagnosed with metabolic diseases. In summary, the current meta-analysis demonstrated the promising impact of ALA administration on decreasing inflammatory markers such as CRP, IL-6 and TNF-α among patients with MetS and related disorders.
There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1) thrifty phenotype; (2) postnatal accelerated or catch-up growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.
The aim of this systematic review and meta-analysis was to evaluate the effects of resistant starch (RS) on glycemic status, serum lipoproteins and inflammatory markers in patients with metabolic syndrome (MetS) and related disorders. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until 30 April 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane’s Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. Nineteen trials were included in this meta-analysis. Administration of RS resulted in significant reduction in fasting plasma glucose (FPG) (14 studies) (WMD: −4.28; 95% CI: −7.01, −1.55), insulin (12 studies) (WMD: −1.95; 95% CI: −3.22, −0.68), and HbA1C (8 studies) (WMD: −0.60; 95% CI: −0.95, −0.24). When pooling data from 13 studies, a significant reduction in total cholesterol levels (WMD: −8.19; 95% CI: −15.38, −1.00) and LDL-cholesterol (WMD: −8.57; 95% CI: −13.48, −3.66) were found as well. Finally, RS administration was associated with a significant decrease in tumor necrosis factor alpha (TNF-α) (WMD: −2.02; 95% CI: −3.14, −0.90). This meta-analysis showed beneficial effects of RS on improving FPG, insulin, HbA1c, total cholesterol, LDL-cholesterol and TNF-α levels in patients with MetS and related disorders, but it did not affect HOMA-IR, triglycerides, HDL-cholesterol, CRP and IL-6 levels.
BACKGROUND: This systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to determine the effect of quercetin administration on blood pressures and endothelial function among patients with metabolic syndrome (MetS) and related disorders. METHODS: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until December 2018. Q-test and I2 statistics were applied to assess heterogeneity among the included studies. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. RESULTS: Out of 284 citations, 8 RCTs were included in the meta-analysis. We found a significant reduction in systolic blood pressure (SBP) (WMD: -1.69; 95% CI: -3.22, -0.17) following the intake of quercetin supplements. However, quercetin supplementation did not significantly affect diastolic blood pressure (DBP) (WMD: -3.14; 95% CI: -8.24, 1.95), vascular cell adhesion molecule 1 (VCAM-1) (WMD: -24.49; 95% CI: -53.74, 4.77) and intercellular adhesion molecule 1 (ICAM-1) (WMD: -5.78; 95% CI: -12.93, 1.38). CONCLUSION: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced SBP, yet did not affect DBP, VCAM-1 and ICAM-1 among patients with MetS and related disorders.
We systematically reviewed randomized clinical trials (RCTs) to elucidate the overall effects of flaxseed oil consumption on blood pressure (BP) in patients with metabolic syndrome and related disorders. PubMed, Scopus, Cochrane Library, and ISI Web of Science databases were systematically searched until March 31, 2020, to find RCTs that examined the effect of flaxseed oil consumption on BP. Weighed mean difference (WMD) was pooled using a random-effects model. Standard methods were used for the assessment of heterogeneity, sensitivity analysis, and publication bias. Meta-analysis of five trials (6 arms) showed significant reductions in systolic (WMD: -3.86 mmHg, 95% CI: -7.59 to -0.13, p = .04) BP (SBP) after flaxseed oil consumption. However, the overall effect illustrated no significant change in diastolic (WMD: -1.71 mmHg, 95% CI: -3.67 to 0.26, p = .09) BP (DBP) in the intervention group compared with the control group. Our findings revealed that flaxseed oil consumption has favorable effects on SBP in patients with metabolic syndrome and related disorders. However, further investigations are needed to provide more reliable evidence.
The growing worldwide prevalence of type 2 diabetes mellitus in the young, as underlined by an earlier International Diabetes Federation (IDF) Consensus Statement 1, has highlighted a significant shortfall of data on the epidemiology of the disorder and the identification and treatment of children and adolescents at risk of progression to this disease. Urbanization, unhealthy diets, and increasingly sedentary lifestyles have contributed to increase the prevalence of childhood obesity, particularly in developing countries 2. Current treatment initiatives include school-based programs addressing physical activity and diet, which have been conducted with mixed success in reducing adiposity. There are limited safety data supporting the use of drugs for the treatment of obesity and related conditions such as type 2 diabetes in children and adolescents, and non-compliance in this population suggests that pharmacotherapy is unlikely to be effective long term 1. Although criteria have now been developed for bariatric surgery in teenagers 3, there are few evidence-based data available to support the increasing use of this modality in adolescents. Governments and society in general must be made more aware of the problems associated with obesity and the likelihood of progression to the metabolic syndrome in children and adolescents. Obesity, particularly in the central (abdominal) region, has been determined as a key factor in the etiology of type 2 diabetes 2. The prediction of health risks associated with obesity in youth is improved by the additional inclusion of waist circumference (WC) measure to the body mass index (BMI) percentile 4, 5. Such observations reinforce the importance of including WC in the assessment of childhood obesity to identify those at increased metabolic risk as a result of excess abdominal fat 5. The role of obesity can clearly be demonstrated in Japan, where a parallel increase in type 2 diabetes and obesity in children has occurred over the past few decades 6. Central (abdominal) obesity is also a key component in the IDF definition of metabolic syndrome in adults 2. The link between obesity, metabolic syndrome, and type 2 diabetes has already been characterized in adult populations 2. At present, 50–80% of almost 250 million adults worldwide with diabetes 7 are at risk of death from cardiovascular disease. Those with the metabolic syndrome are also at increased risk being twice as likely to die from, and three times as likely to have, cardiovascular complications as compared with those without the syndrome 8, 9. In addition, adults with the metabolic syndrome have a fivefold greater risk of developing type 2 diabetes 10. Already, one-quarter of the world’s adult population have metabolic syndrome 11, 12, and this condition is appearing with increasing frequency in children and adolescents, driven by the growing obesity epidemic in this young population 13-15. In 2004, the World Health Organization (WHO) reported that an estimated 22 million children younger than 5 yr of age and 10% of school-aged children, between 5 and 17 yr, were overweight or obese 16. WHO predicts that the prevalence of childhood obesity in developed and developing countries will continue to increase as has been seen in recent years. For example, from 1985 to 1997, in young Australians, the prevalence of overweight and obesity combined doubled and that of obesity trebled 17. In Thailand, the prevalence of obesity in those aged 5–12 yr increased from 12.2 to 15.6% in just 2 yr 18. In 2003–2004, 17.1% of children aged 2–19 yr in the USA were obese 19. Obesity is associated with an increase in cardiovascular risk factors (also indicators of metabolic syndrome) 20, and the persistence of these indicators from childhood and adolescence to young adulthood has been shown in several studies, including the Quebec Family Study 21, 22. Recently, the IDF released its guidelines for defining and diagnosing the metabolic syndrome in adults 2. The intention was to rationalize the existing multiple definitions of the syndrome and to avoid the confusion that arose as a result of conflicting opinions on the value of each set of criteria. The use of a single unified definition makes it possible to estimate the global prevalence of metabolic syndrome and make valid comparisons between nations. However, to date, there has not been a unified definition that can be used to assess risk in children and adolescents, and existing adult-based definitions of the metabolic syndrome may not be appropriate to address the problem in this age group. A study of adolescents using modified National Cholesterol Education Program (NCEP) [Adult Treatment Panel III (ATP III)] criteria 23 identified that 12% of the study group had the metabolic syndrome 24. When the ≥95th percentile of BMI was used as a cutoff point in the same study group, 31.3% were identified as having the syndrome, more than double of those previously found to be at risk. Duncan et al. 25 studied 991 adolescents (aged 12–19 yr) from National Health and Nutrition Examination Study (NHANES) 1999–2000 and used the ATP III definition modified for age. The overall prevalence of a metabolic syndrome phenotype among US adolescents increased from 4.2% in NHANES III (1988–1992) to 6.4% in NHANES 1999–2000. Based on population-weighted estimates, they estimated that more than 2 million US adolescents currently have a metabolic syndrome phenotype. In a population-based study of a Canadian Qji-Cree community involving 236 children aged 10–19 yr, Retnakaran et al. reported that 18.6% of the children met the criteria for the metabolic syndrome based on a pediatric metabolic syndrome definition based on the ATP III definition, and they used the ATP III definition modified for age and gender 26. Goodman et al. reported on a school-based, cross-sectional study of 1513 black, white, and Hispanic teenagers 27. Overall, the prevalence of ATP III-defined metabolic syndrome was 4.2% and that of the WHO-defined metabolic syndrome was 8.4%. The metabolic syndrome was found almost exclusively among obese teenagers in whom prevalence of the ATP III-defined metabolic syndrome was 19.5% and prevalence of WHO-defined metabolic syndrome 28 was 38.9%. No race or sex differences were present for ATP III definition. However, non-white teenagers were more likely to have metabolic syndrome by WHO criteria, and it was more common among girls if the WHO definition was used. Chi et al. have recently undertaken a literature review on definitions of the metabolic syndrome in children and adolescents published in the past decade 29. They noted that the prevalence of metabolic syndrome in pre-adolescent girls varies widely because of disagreement among proposed definitions of metabolic syndrome in pediatrics. They called for a consensus definition for the metabolic syndrome in children, which would allow researchers to make better temporal, biological, environmental, and social comparisons between data sets. The American College of Endocrinology definition 30 is not ideal in pediatric subjects as WC is rarely measured in children, and nomograms have only recently become available 31 for some ethnic groups but are not available for all. A recent paper has suggested yet another set of criteria with age- and gender-specific cutoff points 32. The variety of cutoff points used for the different components in this paper underlines the need for a single consistent definition with easily measurable components. Therefore, to date, no formal definition for the diagnosis of the metabolic syndrome in children and adolescents has been developed. The rapid increase in obesity highlights the urgency for a definition that could be used to further understand who is at high risk and to distinguish them from those with ‘simple’ uncomplicated obesity. The metabolic syndrome in adults is defined as a cluster of cardiovascular and diabetes risk factors including abdominal obesity, dyslipidemia, glucose intolerance, and hypertension 2. While the danger associated with clustering of components of the metabolic syndrome has been demonstrated in adults, where the presence of three or more components significantly increases the risk for coronary heart disease death/non-fatal myocardial infarction and the onset of new diabetes 33, few, if any, outcome data in children exist. While one definition, although with gender- and ethnicity-specific cutoff points, is suitable for use in the at-risk adult population 2, transposing a single definition to children and adolescents is problematic. Blood pressure, lipid levels, and anthropometric variables change with age and pubertal development. Puberty impacts on fat distribution and is known to cause a decrease both in insulin sensitivity, of approximately 30% with a complementary increase in insulin secretion 34, and in adiponectin levels 35. Therefore, single cutoff points cannot be used to define abnormalities in children. Instead, values above the 90th, 95th, or 97th percentile for gender and age are used. However, there has not been universal agreement as to which level to use for the criteria for the metabolic syndrome. The importance of the early identification of children at risk of developing the metabolic syndrome and subsequently progressing to type 2 diabetes and cardiovascular disease in later life must not be underestimated. From birth and before, circumstances can predispose a child to conditions such as obesity or dysglycemia. The presence of maternal gestational diabetes 36, low birth weight 37, infant feeding practices 38, early adiposity rebound 39, and genetic factors may all contribute to a child’s future level of risk. Being raised in an ‘obesogenic’ environment can also have a strong impact, as can the influence of socioeconomic factors 40, with weight gain often being observed as a positive correlate to affluence in developing countries. Longitudinal outcome studies and further research on the progression and etiology of the metabolic syndrome are urgently required to ascertain the long-term outcomes of abdominal obesity and clustering of the components of metabolic syndrome in at-risk children and to help improve future definitions of the syndrome. This new IDF definition of metabolic syndrome in children and adolescents was developed during a consensus workshop that brought together experts in the field of the metabolic syndrome and pediatrics. The purpose of the new definition of metabolic syndrome in children and adolescents is to expand on the IDF recommendations for managing type 2 diabetes in the young 1 and to provide a useful and unified tool for identifying those at risk. A clinically accessible diagnostic tool, avoiding measurements that may only be available in research settings, is needed to identify the metabolic syndrome in children and adolescents globally. This need has prompted the IDF to develop a definition that has used the limited data available from existing studies in youth. As with the adult criteria, we look on these new criteria as a starting point. As new information emerges, they can be modified. Inspired, in part, by the IDF worldwide definition of metabolic syndrome in adults 2, this new definition builds on previous studies investigating the prevalence of metabolic syndrome in children and adolescents, which have used modified adult criteria with varying cutoff points 12-14, 41, 42 (Table 1). The wide variety of cutoff points used has emphasized the need for a single consistent set of criteria, which is easily measurable and can be used as the basis for future work 29. Because of the developmental challenges presented by the age-related differences in children and adolescents, the new IDF definition of metabolic syndrome has been divided according to the following age groups: 6 to <10, 10 to <16, and ≥16 yr (Table 2). In all the three age groups, abdominal obesity is the ‘sine qua non’. We suggest that below the age of 10 yr, the metabolic syndrome as an entity is not diagnosed, although a strong message for weight reduction will be made for these children. At the age of 10 yr and more, a diagnosis of metabolic syndrome can be made. It requires the presence of abdominal obesity plus the presence of two or more of the other components (elevated triglycerides, low high-density lipoprotein (HDL)-cholesterol, high blood pressure, and elevated plasma glucose). The IDF adult criteria 2 can be used for adolescents aged ≥16 yr, while a modified version of these criteria will be applied to those aged 10 to <16 yr (use 90th percentile cutoff point for waist and <40 mg/dL of HDL for both sexes). On the basis of emerging new data, these criteria may change in the future. In adults, insulin resistance and abdominal obesity are considered to be significant causative factors in the development of the metabolic syndrome 9, 43, 44. The link between obesity, insulin resistance, and the risk of developing the metabolic syndrome has also been described in children 22, 27. With measurement of insulin resistance considered to be impractical for clinical use, abdominal adiposity was positioned as the ‘sine qua non’ in the IDF definition of metabolic syndrome in adults 2 and is recognized to be an independent risk factor for the development of cardiovascular disease in adults 45. Abdominal obesity can be easily assessed using the simple measure of WC, which is known to correlate more strongly with visceral adipose tissue (VAT) than BMI in adults 46 and is a strong predictor of cardiovascular disease risk factors in children 47. The correlation between WC and VAT has also been more recently demonstrated in children 48, further strengthening the existing evidence that WC is an effective measure of abdominal obesity 49 in the youth population. In children and adolescents, a number of studies have demonstrated a similar link between childhood obesity and elevated cardiovascular risk in later life. The Bogalusa Heart study showed that childhood overweight is related to the development of adverse risk factors (BMI, lipids, insulin, diabetes mellitus, and blood pressure) in adulthood and is attributable to the strong persistence of weight status from childhood to adulthood 50. Of the overweight children in the Bogalusa Heart study (BMI ≥95th percentile), 77% remained obese in adulthood. Furthermore, the Muscatine study demonstrated that in young adults, excess weight was the earliest predictor of coronary artery calcification 51. The ATP III definition, applied to a cohort of individuals aged 12–19 yr (NHANES III), identified that 4% of those studied were found to have the metabolic syndrome, with 80% of those meeting the criteria of being overweight 13. Using a modified version of the ATP III definition, metabolic syndrome in adolescents has also been linked to high levels of C-reactive protein, a pro-inflammatory marker. Of the five components of metabolic syndrome, C-reactive protein was higher only among those with abdominal obesity 41. Waist circumference in children is an independent predictor of insulin resistance, lipid levels, and blood pressure 4, 52-54– all components of metabolic syndrome. Moreover, in obese youth with similar BMI, insulin sensitivity is lower in those with high VAT and high waist/hip ratio 53, 54. Furthermore, insulin sensitivity decreases and insulin levels increase with increasing WC percentiles 3. These data, combined with the unequivocal evidence of the dangers of abdominal obesity in adulthood, support the use of abdominal obesity as the ‘sine qua non’ for the diagnosis of metabolic syndrome in children and adolescents. Percentiles rather than absolute values of WC have been used in the new criteria to compensate for varying degrees of development and ethnicity in the youth population. WC percentile data are becoming increasingly available worldwide 31, 55-58. Children with a WC >90th percentile are more likely to have multiple risk factors than those with a WC below this level 59. Several studies attempting to estimate the prevalence of metabolic syndrome in children and adolescents have already used the 90th percentile as a cutoff point for WC 13, 14, 41. We have also chosen to use the 90th percentile as a cutoff point for WC based on this existing evidence and aim to reassess criteria and cutoff points in 5 yr and modify the guidelines, if necessary, based on the new outcome data. Previous studies investigating the metabolic syndrome in children and adolescents have used a range of cutoff points primarily based on ATP III criteria for categorizing additional components of the syndrome, i.e., triglycerides, HDL-cholesterol, blood pressure, and fasting glucose (Table 1) 12-14, 41, 42. Other definitive sources include the National High Blood Pressure Education Program, which recommends blood pressure cutoff points of >90th or >95th percentile adjusted for height, age, and gender to identify ‘high normal’ blood pressure or prehypertension and high blood pressure or hypertension in children and adolescents 60. Cutoff points for impaired fasting glucose have previously followed recommendations by the American Diabetes Association (ADA) [100–125 mg/dL (≥5.6–6.9 mmol/L)] 61 and the NCEP/ATP III in adults [≥110 mg/dL (6.1 mmol/L)] 23, although the latter has recently changed to the lower ADA recommended levels 62. Criteria for defining lipid (triglyceride and HDL-cholesterol) imbalances are even less consistent in the youth population, with recommendations by the NCEP/ATP III (age specific), NHANES III (age and gender specific), and the National Growth and Health Study (age, gender, and ethnic specific), employing either absolute value or percentile cutoff points. In view of this lack of consistency, we believe that use of the adult levels for the present is wise until further information is available. We recommend the following topics as priorities for future research: Develop a better understanding of the relationship between body fat and its distribution in children and adolescents, e.g., dual energy X-ray absorptiometry (DEXA), WC, BMI, and height and weight percentiles; a) Explore whether early growth patterns predict future adiposity and features of the metabolic syndrome, diabetes, and cardiovascular disease and b) explore whether low birth weight predicts future metabolic syndrome, diabetes, and cardiovascular disease; Perform factor analysis in children and adolescents to establish grouping of metabolic characteristics – adiposity, dyslipidemia, hyperinsulinemia, hypoadiponectinemia, and insulin resistance; Investigate how should obesity in children could be better defined, e.g., weight/height, WC etc.; Develop ethnic-specific normal ranges for WC, ideally based on healthy values; Perform ethnic-specific studies of WC etc. vs. abdominal (truncal) fat based on magnetic resonance imaging and DEXA; Support studies of adiponectin, leptin, etc. in children and adolescents to determine if they may be predictors of metabolic syndrome in adulthood; Initiate long-term studies of multi-ethnic cohorts followed into adulthood to determine the natural history and effectiveness of intervention strategies, particularly lifestyle. In conclusion, to combat any conflict that could arise from these multiple interpretations of the metabolic syndrome in children and adolescents, the IDF consensus group has aimed primarily at developing a simple, easy-to-apply definition to begin using in the clinical setting. In the absence of definitive research findings at this time, the proposed IDF definition of the metabolic syndrome in children and adolescents (Table 2) adheres to the absolute values presented in the adult definition 2, with the exception of WC. As described previously, until such time that outcome data from studies in children and adolescents indicate otherwise, WC percentiles are recommended for use. Early detection, followed by treatment in the form of lifestyle intervention and possibly pharmacotherapy, if its safety has been clearly demonstrated, is vital in halting the progression of this syndrome pathway in the adolescent population. It is likely that this will reduce morbidity and mortality in adulthood, as well as minimize the global socioeconomic burden of cardiovascular disease and type 2 diabetes. The workshop was sponsored by an unrestricted educational grant to the IDF Task Force on Epidemiology and Prevention from sanofi-aventis.
Deformations and disruptions Teratogenic agents Chromosomal syndromes I: common and/or well known syndromes Chromosomal syndromes II: unusual variants METABOLIC DISORDERS the mucopolysaccharidoses the oligosaccharidoses and related disorders metabolic disorders and dysmorphic features Syndromes affecting bone I: the osteogenesis imperfectas Syndromes affecting bone II: chondrodysplasias and chondrodystrophies Syndromes affecting bone III: craniotubular bone disorders Syndromes affecting bone IV: other skeletal disorders Proportionate short stature syndromes Overgrowth syndromes and postnatal onset obesity syndromes Hamartoneoplastic syndromes Syndromes affecting the skin and mucosa Syndromes with craniosynostosis I: general aspects and well known syndromes Syndromes with craniosynostosis II: miscellaneous syndromes Syndromes of abnormal craniofacial contour Syndromes affecting the central nervous system Syndromes with contractures BRANCHIAL ARCH AND ORO-ACRAL DISORDERS branchial arch syndromes oromandibular-limb hypogenesis syndromes oro-facial-digital syndromes otopalatal digital syndromes Orofacial clefting syndromes I: general aspects Orofacial clefting syndromes II: common and/or well known syndromes Orofacial clefting syndromes III: other syndromes Orofacial clefting syndromes IV: associations Syndromes with unusual facies I: well known syndromes Syndromes with hypertelorism Syndromes with unusual nasal anomalies Syndromes with unusual ocular anomalies Syndromes with facial fat atrophy Syndromes with unusual facies II: other syndromes Syndromes with gingival-periodontal components Syndromes with unusual dental findings Miscellaneous syndromes I: well known syndromes Miscellaneous syndromes II: other syndromes Appendix.
BACKGROUND: There are few existing large population studies on the epidemiology of metabolic syndrome-related disorders of Turkey. The purpose of this study was to assess the prevalence of metabolic syndrome-related disorders in the Turkish adult population, to address sex, age, educational and geographical differences, and to examine blood pressure, body mass index, fasting blood glucose and serum lipids in Turkey. METHODS: This study was executed under the population study "The Healthy Nutrition for Healthy Heart Study" conducted between December 2000 and December 2002 by the Health Ministry of Turkey. Overall, 15,468 Caucasian inhabitants aged over 30 were recruited in 14 centers in the seven main different regions of Turkey. The data were analyzed with the Students' t, ANOVA or Chi-Square tests. RESULTS: Overall, more than one-third (35.08 %) of the participants was obese. The hypertensive people ratio in the population was 13.66 %, while these ratios for DM and metabolic syndrome were 4.16 % and 17.91 %, respectively. The prevalence of hypertension, metabolic syndrome and obesity were higher in females than males, whereas diabetes mellitus was higher in males than females. The prevalence of metabolic syndrome and related disorders were found to be significantly different across educational attainments for both men and women. The prevalence of hypertension increased with age, while it was remarkable that in the age group of 60-69 years, prevalence of diabetes mellitus and metabolic syndrome reached a peak value and than decreased. For obesity, the peak prevalence occurred in the 50-59 year old group. The prevalence of metabolic syndrome and related disorders were found to be significantly different according to geographical region. CONCLUSION: In conclusion, high prevalence of obesity and metabolic syndrome, particularly among women, is one of the major public health problems in Turkey. Interestingly, obesity prevalence is relatively high, but the prevalence of hypertension and hypercholesterolemia is relatively low in Turkish people. Future studies may focus on elucidating the reasons behind this controversy. Our findings may be helpful in formulating public health policy and prevention strategies on future health in Turkey.
OBJECTIVE: Patients with bipolar disorder have high levels of cardiovascular disease risk factors. The presence of metabolic syndrome significantly influences future cardiovascular disease morbidity and mortality. The authors sought to clarify the prevalence and moderators of metabolic syndrome in bipolar patients, accounting for subgroup differences. METHOD: The authors searched MEDLINE, PsycINFO, EMBASE, and CINAHL through April 2012 for research reporting metabolic syndrome prevalence rates in bipolar patients. Medical subject headings "metabolic syndrome" and "bipolar" were used in the title, abstract, or index term fields. Manual searches were conducted using the reference lists from identified articles. RESULTS: The search yielded 81 articles in 37 publications (N=6,983). The overall metabolic syndrome rate was 37.3% (95% confidence interval [CI]=36.1-39.0) using any standardized metabolic syndrome criteria. Compared with general population groups, bipolar patients had higher metabolic syndrome rates (odds ratio=1.98; 95% CI=1.74-2.25). In bipolar patients, older age had a modest effect on the metabolic syndrome rate. The strongest moderator was the region in which the study took place, with the highest rates observed in New Zealand and Australia (64.2% [95% CI=38.3-83.9]) and North America (49.3% [95% CI=29.7-69.3]). Metabolic syndrome was significantly more prevalent in patients currently treated with antipsychotics (45.3% [95% CI=39.6-50.9] than in patients who were antipsychotic free (32.4% [95% CI=27.5-37.4]; odds ratio=1.72 [95% CI=1.24-2.38]). CONCLUSIONS: These findings strongly support the claim that patients with bipolar disorder are at high risk for metabolic syndrome and related cardiovascular morbidity and mortality and require regular monitoring and adequate preventive efforts and treatment for cardio-metabolic risk factors. These findings further suggest that the risk of metabolic syndrome is greater in bipolar patients taking prescribed antipsychotic medication.
The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …