Metabolic Syndrome X A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS.

The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556) Year introduced: 2002

Obesity A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY). Premenopause The period before MENOPAUSE. In premenopausal women, the climacteric transition from full sexual maturity to cessation of ovarian cycle takes place between the age of late thirty and early fifty. Year introduced: 1994 Associations between sex hormone binding globulin and metabolic syndrome parameters in premenopausal obese women. Indian J Med Sci. 2008 Oct;62(10):407-15. Akin F, Bastemir M, Alkis E, Kaptanoglu B. Source Department of Endocrinology and Metabolism, Pamukkale Universitesi Endokrinoloji ve Metabolizma Hastaliklari, Kinikli Kampusu 20070 Denizli, Turkey. fulyaendo@yahoo.com.tr Abstract BACKGROUND AND AIMS: The aim of this study was to determine sex hormone binding globulin (SHBG) concentrations in premenopausal obese women and to evaluate the relationships between sex hormones and features of the metabolic syndrome (MetS).

SETTINGS AND DESIGN: Retrospective cross-sectional analysis was carried out on 350 obese patients aged 25 to 69 years referred to the Department of Endocrinology, Pamukkale University in 20022003. MATERIALS AND METHODS: 125 premenopausal euthyroid patients were eligible for this study. Subjects were divided into two groups according to the body mass index (BMI): Group I, women with BMI 2 (n = 17) and Group II,, women with BMI > or = 30 kg/m 2 (n = 108). Median SHBG concentration of Group I was 50.1 nmol/L. Group II was divided into two subgroups according to the median SHBG concentration of Group I: subjects with high SHBG levels (SHBG concentration > or = median level of the control group, i.e > or = 50.1 nmol/L) and subjects with low SHBG levels ( RESULTS: No significant difference was found in mean age between the low and high SHBG groups. The low SHBG group was significantly heavier, and with higher waist circumference than the high SHBG group. In the low SHBG group, fasting glucose, postprandial glucose and gamma glutamyl transferase (GGT) and free androgen index (FAI) were significantly higher. Lipid profile, blood pressure, uric acid, insulin and HOMA were found similar between two groups. Linear regression analyses revealed that body mass index and FAI were significant, being independent predictors of SHBG concentrations in premenopausal women. (r = 0.365, r square = 0.134). CONCLUSIONS: It is concluded that low SHBG concentrations may indicate visceral obesity and glucose intolerance in premenopausal women. PMID: 19008614 [PubMed - indexed for MEDLINE]

Comparison of risk variables associated with the metabolic syndrome in pre- and postmenopausal Bengalee women. Cardiovasc J Afr. 2008 Jul-Aug;19(4):183-7. Ghosh A. Source Department of Anthropology, Palli Charcha Kendra, Visva Bharati University, Santiniketan, West Bengal, India. arnab_cu@rediffmail.com Abstract BACKGROUND: Clustering of risk variables associated with the metabolic syndrome (MS) begins before

the onset of menopause. However, studies of the factors underlying this clustering have focused on only postmenopausal women. AIM: The present community-based, cross-sectional investigation was aimed at identifying the principal components of risk variables associated with the metabolic syndrome in preand postmenopausal Bengalee women. METHODS: A total of 200 (100 premenopausal women; mean age = 40.2 +/- 6.5 years and 100 postmenopausal women; mean age = 55.4 +/- 5.2 years) healthy adult (30 years and older) Bengalee women took part in the study. Obesity measures, metabolic profiles and blood pressures were taken. Principal components factor analysis (PCFA) was used to identify the principal components of the MS. RESULTS: There were significant differences between the two groups for obesity measures, metabolic profiles and blood pressure, even after adjusting for age. PCFA revealed three uncorrelated factors with a 67.1% explanation in the premenopausal women. Four factors, with overlapping between the first three factors, and a 73% explanation were evident for the postmenopausal women. CONCLUSION: Since more than one factor was identified, more than one physiological mechanism could have accounted for clustering of the risk variables associated with the MS and this would warrant early intervention, well before the menopause. PMID: 18776958 [PubMed - indexed for MEDLINE] Free full text Peak growth hormone-releasing hormone-arginine-stimulated growth hormone is inversely associated with intramyocellular and intrahepatic lipid content in premenopausal women with obesity. Bredella MA, Torriani M, Thomas BJ, Ghomi RH, Brick DJ, Gerweck AV, Miller KK. Source Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mbredella@partners.org Abstract CONTEXT: Visceral adiposity is a strong determinant of GH secretion, and low endogenous GH secretion is associated with increased insulin resistance, a key component of the metabolic syndrome. Increased fat accumulation in skeletal muscle and liver may play an

etiological role in the development of insulin resistance and other complications of the metabolic syndrome. Little is known about the role of decreased endogenous GH secretion in the pathogenesis of insulin resistance in obesity. OBJECTIVE: To investigate the relationship between intramyocellular lipids (IMCL), intrahepatic lipids, and peak-stimulated GH in premenopausal women with obesity. DESIGN AND SETTING: We conducted a cross-sectional study at a clinical translational research center. PATIENTS: Patients included 21 premenopausal women with obesity (mean body mass index, 34.0 +/- 4.5 kg/m(2)) and 17 normal-weight controls (mean body mass index, 21.9 +/- 2.0 kg/m(2)) of comparable mean age. MAIN OUTCOMES MEASURES: IMCL and intrahepatic lipids were measured with proton magnetic resonance spectroscopy ((1)H-MRS). Body composition was measured with magnetic resonance imaging. Peak GH was measured after stimulation with GHRH-arginine. RESULTS: Obese subjects had higher IMCL, intrahepatic lipids, abdominal and thigh fat, and thigh muscle mass compared with normal-weight controls. There were strong inverse associations between peak GH and both IMCL and intrahepatic lipids independent of age and visceral adiposity. There were positive associations between IMCL and intrahepatic lipids with measures of insulin resistance and serum triglycerides. CONCLUSION: In premenopausal women with obesity, peak GH is inversely associated with IMCL and intrahepatic lipids independent of age and visceral adiposity. This suggests that low GH may contribute to insulin resistance in obesity through effects on muscle and intrahepatic lipids. Changes in metabolic profile and adipoinsular axis in morbidly obese premenopausal females treated with restrictive bariatric surgery. Marantos G, Daskalakis M, Karkavitsas N, Matalliotakis I, Papadakis JA, Melissas J. Source Bariatric Unit, Department of Surgical Oncology, P.O. Box 1352, Heraklion, 71110, Crete, Greece. Abstract BACKGROUND: The aim of the present study was to evaluate the effects of surgically induced weight loss on the metabolic profile and adipocytokine levels in premenopausal morbidly obese

females. METHODS: Twenty premenopausal morbidly obese (MO) women with a median age of 34 years (range: 24-48 years) and a median body mass index (BMI) of 41.47 kg/m(2) (range: 38.056.73 kg/m(2)) were studied (13 women underwent gastric banding and 7 women underwent sleeve gastrectomy). In addition, 20 lean premenopausal women with a median age of 32 years (range: 22-44 years) and a median BMI of 20.0 kg/m(2) (range: 18.5-24.7 kg/m(2)) were also studied. Anthropometric measurements and metabolic parameters were analyzed in each patient, along with changes in leptin, adiponectin, resistin, and interleukin-6 (IL-6) before surgery, 6 months after surgery, and 12 months after surgery. Comparisons with the reference normal-weight subjects were also performed. RESULTS: Both weight and BMI were found to be significantly decreased postoperatively. A 54.5% loss of excess BMI was observed 12 months after surgery, and was associated with significant improvement in all anthropometric and metabolic parameters. Twelve months after surgery we also observed decreased levels of serum leptin, resistin, and IL-6; increased levels of serum adiponectin; and a remarkable improvement in metabolic syndrome markers. Furthermore, postoperative serum resistin and IL-6 levels were found to reach those of normal-weight volunteers. CONCLUSIONS: The results of this study suggest that weight loss through restrictive bariatric surgery results in a significant reduction in leptin, resistin, and IL-6 levels, and an increase in adiponectin levels, in addition to improving insulin sensitivity and glucose and lipid homeostasis in young morbidly obese female patients. These changes were significantly correlated with the magnitude of weight loss.

Endocr J. 2011;58(2):87-93. Association between bone mineral density and metabolic syndrome in pre- and postmenopausal women. Jeon YK, Lee JG, Kim SS, Kim BH, Kim SJ, Kim YK, Kim IJ. Source Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea. Abstract Metabolic syndrome (MS) has 2 conflicting factors: obesity known to be protective against osteoporosis and an inflammation that activates bone resorption. The aim of this study was to evaluate the difference of bone mineral density(BMD) in women with or

without MS according to menopausal state. This is a cross-sectional study of 2,265 women(1,234-premenopausal, 931-postmenopausal) aged over 20 years who visited the Health Promotion Center from January 2006 to December 2009. We measured BMD at the lumbar spine and femoral neck. MS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria. The prevalence of MS was 5.5% in the premenopausal group and 13.5% in the postmenopausal group. In the postmenopausal group, C-reactive protein (CRP) was significantly higher in subjects with MS than those without MS, but it was not in the premenopausal group. In the postmenopausal group, women with MS had a lower BMD at the lumbar spine and femoral neck before or after adjustment. In the premenopausal group, women with MS had a lower BMD at the lumbar spine, but not at the femoral neck. In stepwise linear regression analysis, predictive variables for BMD of the lumbar spine were systolic blood pressure in the premenopausal group and HDL-cholesterol and diastolic blood pressure (DBP) in the postmenopausal group. The predictive variables for BMD of the femoral neck were DBP and waist circumference in the premenopausal group and CRP and DBP in the postmenopausal group. Inflammation might have a more important role in BMD than obesity in the postmenopausal women. Evaluation of metabolic syndrome risk in Korean premenopausal women: not waist circumference but visceral fat. - Hyun YJ - Circ J - 01-AUG-2008; 72(8): 1308-15 (MEDLINE is the source for the citation and abstract of this record ) DOI: 10.1253/circj.72.1308 Abstract: BACKGROUND: In clinical practice, using the patient's waist circumference (WC) to evaluate visceral obesity may underestimate disorders with a metabolic origin. This study examined whether or not the WC derived from the cut-off point of the visceral fat area (VFA) can reflect the features of metabolic syndrome (MetS) in premenopausal women. METHODS AND RESULTS: Computed tomography-scanned VFA, MetS components and the concentrations of high-sensitivity C-reactive protein (CRP) and adiponectin were measured in a total of 349 premenopausal women. The VFA at the L1 and the L4 sites was a significant index (p<0.001) of incremental MetS risk. Receiver-operating characteristic curve analysis showed that 75 cm2 of VFA at L4 and 87.5 cm2 at L1 were the optimal thresholds for discrimination of MetS risk. Significant differences in all MetS components, as well as CRP (p<0.05) and adiponectin levels (p<0.005), were observed when subjects were subdivided by the L4 VFA cut-off point (<75/>or=75 cm2), whereas there was a significant difference only in the triglycerides level in the groups divided by WC (WC<88/>or=88 cm). Moreover, subjects with a lower WC-higher VFA showed a similar pattern in MetS components and lower adiponectin than those with a higher WChigher VFA. CONCLUSIONS: This study clarified that VFA rather than WC is a major determinant of MetS risk in premenopausal women.

Short-term effects of a non-dieting lifestyle intervention program on weight management, fitness, metabolic risk, and psychological well-being in obese premenopausal females with the metabolic syndrome. - Carroll S - Appl Physiol Nutr Metab - 01-FEB-2007; 32(1): 125-42 (MEDLINE is the source for the citation and abstract of this record ) DOI: 10.1139/H06-093 Abstract: Lifestyle modification has been widely acknowledged as the primary treatment for the metabolic syndrome (MetS). We examined the short-term effects of a non-dieting lifestyle intervention program, within the theoretical psychological framework of selfdetermination theory (SDT), on metabolic fitness and psychological well-being among premenopausal, clinically obese women. A secondary analysis of a randomized, controlled, 3 month, intensive, community-based lifestyle intervention study was performed on 31 pre-menopausal obese women with the MetS (56.4% of original study sample). These participants had been randomly allocated to a non-dieting lifestyle intervention group (n = 17) or waiting list control (n = 14). Among participants who completed repeat anthropometric and cardiorespiratory fitness measurements after 3 months intervention, the lifestyle intervention group showed a significant improvement in VO2 (mL.kg(-1).min(-1)) compared with control (test for interaction, p = 0.003). No significant difference was found for body mass. Metabolic improvements were evident for diastolic blood pressure and high-density lipoprotein cholesterol in both groups. The lifestyle intervention group also showed significantly improved general psychological well-being compared with the control group (test for interaction, p = 0.0005). All of the psychological well-being subscales showed significant favourable changes in the intervention group as compared with controls. This short-term, non-dieting lifestyle intervention, consistent with the "Health at Every Size" (HAES) obesity treatment paradigm, significantly improved cardiorespiratory fitness and psychological well-being. Metabolic risk tended to improve after 3 months intervention with no significant difference in the resolution of the MetS between intervention and control participants. Metabolic syndrome: do clinical criteria identify similar individuals among overweight premenopausal women? - Alhassan S - Metabolism - 01-JAN-2008; 57(1): 49-56 (MEDLINE is the source for the citation and abstract of this record ) Abstract: The purpose of this analysis was to determine to what extent the clinical criteria for metabolic syndrome (MetSyn) proposed by the World Health Organization (WHO), the European Group for Study of Insulin Resistance (EGIR), the National Cholesterol Education Program Adult Treatment Panel III (ATP III), and the International Diabetes Foundation (IDF); triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio >/=3.0; and enlarged waist circumference (>/=88 cm) and elevated TG (>/=129 mg/dL)

(EWET) identified similar or different overweight women and, secondarily, to examine the effect of 7% weight reduction on MetSyn status. Metabolic syndrome was determined among 256 premenopausal women (age = 41 +/- 6 years, body mass index [BMI] = 32 +/- 4 kg/m(2)) participating in a dietary weight loss clinical trial based on the clinical criteria proposed by WHO, EGIR, ATP III, and IDF. The prevalence of TG/HDL-C ratio >/=3.0 and EWET was determined and compared with MetSyn status. Based on the clinical criteria, 16.1% (EGIR), 20.7% (WHO), 31.0% (ATP III), and 31.8% (IDF) of participants met the criteria for MetSyn; 30.3% and 31.8% had TG/HDL-C >/=3.0 and EWET, respectively. Between 77% and 99% of participants were similarly classified across the clinical criteria. The highest and lowest agreements were between ATP III and IDF (kappa = 0.98; 95% confidence interval, 0.96-1.0) and WHO and IDF (kappa = 0.39; 95% confidence interval, 0.26-0.51), respectively. The TG/HDL-C ratio >/=3.0 and EWET moderately agreed with all 4 clinical criteria for MetSyn (kappa range, 0.36-0.59). Among those diagnosed with MetSyn at baseline, 64.0% to 75.0% of the participants who lost >/=7% and 25.8% to 55.6% of participants who lost <7% of their baseline body weight in 6 months no longer met the various clinical criteria for MetSyn, TG/HDL-C >/=3.0, or EWET. Our findings indicate that MetSyn varies substantially between clinical criteria, which raise questions about the clinical utility of these criteria. Regardless of MetSyn clinical criteria, >/=7% reduction in body weight has a beneficial impact on variables used to define MetSyn. J Am Coll Nutr. 2005 Dec;24(6):486-93. Weight loss favorably modifies anthropometrics and reverses the metabolic syndrome in premenopausal women. Lofgren IE, Herron KL, West KL, Zern TL, Brownbill RA, Ilich JZ, Koo SI, Fernandez ML. Source University of Connecticut, Department of Nutritional Sciences 3624 Horsebarn Road Extension, U 4017, Storrs, CT 06269, USA. Abstract OBJECTIVE: To determine the effects of a weight loss program, including dietary modifications, increased physical activity and dietary supplement (L-carnitine or placebo) on anthropometrics, leptin, insulin, the metabolic syndrome (MS) and insulin resistance in overweight /obese premenopausal women. METHODS: Participants consumed a hypocaloric diet; 30% protein, 30% fat and 40% carbohydrate in addition to increasing number of steps/day. Carnitine supplementation followed a randomized double blind protocol. Protocol lasted for 10 weeks. Seventy subjects (35 in the control and 35 in the carnitine group) completed the intervention. Anthropometrics, plasma insulin and leptin concentrations and body composition were measured. The number of subjects with the MetSyn and insulin resistance, were assessed at baseline and

post-intervention. RESULTS: Because there were no significant differences between the carnitine and the placebo groups for all measured parameters, participants were grouped together for all analysis. Subjects decreased total energy (-26.6%, p < 0.01) and energy from carbohydrate (17.3%, p < 0.01) and increased energy from protein by 67% (p < 0.01) and number of steps/day (42.6%, p < 0.01). Body weight (-4.6%, p < 0.001), body mass index (-4.5%, p < 0.01), waist circumference (-6.5%, p < 0.01), total fat mass (-1.7%, p < 0.01), trunk fat mass (-2.0%, p < 0.01), insulin (- 17.9%, p < 0.01) and leptin (-5.9%, p < 0.05) decreased after the intervention. Ten of 19 participants with insulin resistance became insulin sensitive and 7 of 8 participants with the MetSyn no longer had the syndrome after the intervention. CONCLUSION: Moderate increases in physical activity and a hypocaloric/high protein diet resulted in multiple beneficial effects on body anthropometrics and insulin sensitivity. Realistic dietary and physical activity goals must be the focus of intervention strategies for overweight and obese individuals. Insulin resistance but not visceral adipose tissue is associated with plasminogen activator inhibitor type 1 levels in overweight and obese premenopausal AfricanAmerican women. Int J Obes Relat Metab Disord. 2003 Jan;27(1):82-7. Solano MP, Perry AC, Wang X, Ross R, Goldberg RB. Source Department of Medicine, University of Miami School of Medicine, Miami, Florida 33136, USA. msolano@med.miami.edu Abstract OBJECTIVE: To compare plasma plasminogen activator inhibitor type 1 (PAI-1) levels and to examine the association of PAI-1 with visceral adiposity and other components of the metabolic syndrome in overweight and obese premenopausal African-American (AA) and Caucasian (CC) women. DESIGN: Cross-sectional study. SUBJECTS: 33 CC and 23 AA healthy, overweight and obese, premenopausal women (age 19-53 y, body mass index 28.1-48.9 kg/m(2)). MEASUREMENTS: Body mass index, sagittal diameter, waist circumference, percentage body fat, visceral and subcutaneous adipose tissue (by anthropometry, magnetic resonance imaging (MRI),

and bioelectric impedance techniques), PAI-1, leptin, lipids, glucose, insulin, and insulin resistance (by HOMA IR). RESULTS: AA women had lower triglyceride levels and less visceral adipose tissue (VAT) volume than CC despite similar BMI. PAI-1 levels were not significantly different in the two groups. Insulin resistance was associated with PAI-1 in both groups but only in CC women were VAT, triglyceride, HDL cholesterol and blood pressure related to plasma PAI-1 levels. Multiple regression analysis showed that VAT in CC and insulin resistance in AA were independent predictors of PAI-1. CONCLUSION: VAT is significantly associated with circulating PAI-1 levels in overweight and obese CC but not AA premenopausal women. PMID: 12532158 [PubMed - indexed for MEDLINE] The androgenic sex hormone profile is an essential feature of metabolic syndrome in premenopausal women: a controlled community-based study. Korhonen S, Hippelinen M, Vanhala M, Heinonen S, Niskanen L. Source Department of Obstetrics and Gynecology, Mikkeli Central Hospital, Mikkeli, Finland. Abstract OBJECTIVE: To evaluate sex hormones in premenopausal white women with metabolic syndrome (MBS). DESIGN: Cross-sectional controlled community-based study. SETTING: Pieksmki District Health Center, Pieksmki, Finland. PATIENT(S): Five hundred forty-three women, aged 34 to 54 years, were screened according to National Cholesterol Education Program criteria: waist >88 cm, hypertension >/=130/>/=85 mm Hg, hypertriglyceridemia >/=1.7 mmol/L, high-density lipoprotein (HDL)-cholesterol <1.3 mmol/L, and fasting glucose >/=6.1 mmol/L. Sixty-three women fulfilled at least three of the above-mentioned criteria and were enrolled. Eighty-eight age-matched women without MBS served as controls. INTERVENTION(S): None.

MAIN OUTCOME MEASURES: Sex steroid levels in relation to insulin sensitivity and body composition. RESULT(S): A markedly lower insulin sensitivity index and higher free androgen index were detected in the women with MBS than in the controls. Abdominal obesity and increased diastolic blood pressure were significantly associated with high free androgen index in multiple regression analysis. CONCLUSION(S): A hyperandrogenic hormone profile appeared to be a typical feature of premenopausal female MBS even without polycystic ovary syndrome (PCOS).