Metabolic Risk Indicators Research Articles

Dynamics of Traditional Metabolic Risk Factors Associate With Specific Causes of Death in Old Age

In contrast to middle age, higher body mass index (BMI), cholesterol levels, and blood pressures associate no longer with increased mortality in old age. With increasing age, these risk factors are prone to change over time. It is unclear whether dynamics of these traditional metabolic risk factors in late life associate with mortality and whether they occur in concert with each other. Within the Leiden 85-plus Study, a prospective population-based study of 599 participants aged 85 years, participants were annually assessed during a 5-year follow-up period and observed for mortality for 10 years. BMI, total cholesterol levels, glucose levels, and blood pressures declined and HDL cholesterol levels increased between ages 85 and 90 years (all p < .005). Participants who died at age 90 years had stronger annual declines in BMI, total cholesterol levels, and diastolic blood pressure and weaker increases in HDL cholesterol levels than participants who survived until the end of follow-up (all p < or = .001). In a principal component analysis, annual changes in total, LDL, and HDL cholesterol levels; blood pressures; and glucose, albumin, hemoglobin, leukocyte, and C-reactive protein levels grouped together in one component (all correlation r with component >.40), which associated with all-cause and cancer mortality. In old age, larger declines in BMI, total cholesterol levels, and blood pressures and weaker increases in HDL cholesterol levels associate with mortality. We identified distinct clustering in the dynamics of these traditional metabolic risk factors and indicators of health and disease in a profile that is suggestive of underlying wasting disease.

A multifaceted school-based intervention to reduce risk for type 2 diabetes in at-risk youth

Objective To evaluate the impact of a multifaceted, school-based intervention on inner city youth at high risk for type 2 diabetes mellitus (T2DM) and to determine whether the addition of coping skills training (CST) and health coaching improves outcomes. Method 198 students in New Haven, CT at risk for T2DM (BMI > 85th percentile and family history of diabetes) were randomized by school to an educational intervention with or without the addition of CST and health coaching. Students were enrolled from 2004 to 2007 and followed for 12 months. Results Students in both groups showed some improvement in anthropometric measures, lipids, and depressive symptoms over 12 months. BMI was not improved by the intervention. Students who received CST showed greater improvement on some indicators of metabolic risk than students who received education only. Conclusion A multifaceted, school-based intervention may hold promise for reducing metabolic risk in urban, minority youth.

Waist Circumference as a Cardiovascular and Metabolic Risk in Japanese Patients With Type 2 Diabetes

Excess waist circumference (WC) is a frequently used indicator of abdominal obesity and/or cardiovascular disease (CVD) risk. Nonetheless, search of the literature revealed no prospective studies on the association between WC and CVD events in diabetic patients. In this study, the clinical significance and implications of WC as a cardiovascular and metabolic risk indicator was prospectively investigated in Japanese patients with type 2 diabetes. For this purpose, baseline data on WC, hypertension, and dyslipidemia were collected and subsequent CVD (coronary heart disease and stroke) events during the following 8 years were studied in 1,424 Japanese type 2 diabetic patients, and the cross-sectional/longitudinal associations between WC and CVD risk factors/events were analyzed. Mean WC levels were significantly increased according to the number of coexisting risk factors. However, no significant difference in mean WC between subgroups with and without CVD events was noted, and excess WC alone was not predictive of subsequent CVD events either in male or female subjects even after adjustment for age, smoking, hypertension, and dyslipidemia. In female patients, excess WC (> or =80 cm) was predictive of CVD events only with the coexistence of hypertension. In Japanese diabetic patients, excess WC alone, although a good marker for clustering of CVD risk factors, did not raise the risk of CVD events unless accompanied by hypertension in female patients. Further investigations are necessary before WC as a risk factor can be utilized in clinical settings for the management of diabetes in this population.

Adiposity Measures as Indicators of Metabolic Risk Factors in Adolescents

Aim: To examine the relation between adiposity assessment methods (percentage body fat (%BF), BMI, and waist circumference (WC)) and individual metabolic risk factors (f-insulin, HDL cholesterol, triglycerides) and a combined measure of metabolic risk. Methods: Crosssectional study of 300 males (BMI 20.8 ± 3.0 kg/m²) and females (BMI 21.3 ± 2.9 kg/m²) 17 years of age. F-insulin and components of the metabolic syndrome defined by the International Diabetes Federation (IDF) were used as metabolic risk indicators, with samples stratified into BMI, %BF, and WC groups, respectively. Diagnostic accuracy was expressed as the area under the ROC curve (AUC). Results: In males, diagnostic accuracy for HDL and f-insulin was poor to fair for BMI (AUC 0.70, p = 0.001; 0.60, p = 0.22), WC (0.68, p = 0.003; 0.63, p = 0.11), and %BF (0.65, p = 0.009; 0.66, p = 0.04). The diagnostic accuracy for triglycerides was greater for all three measures (BMI 0.92, WC 0.95, %BF 0.87; all p < 0.001). For females, neither test performed better than chance for f-insulin and HDL, and only %BF performed better than chance for triglycerides (0.65, p = 0.08). All three measures exhibited higher accuracy for presence of ≥2 metabolic risk factors (AUCs 0.76–0.91, p < 0.001) in both sexes. Conclusion: %BF was not superior to BMI and WC for detecting metabolic risk in the general adolescent population.

Simple anthropometric measures correlate with metabolic risk indicators as strongly as magnetic resonance imaging–measured adipose tissue depots in both HIV-infected and control subjects

BackgroundStudies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects. ObjectiveWe compared anthropometric and magnetic resonance imaging (MRI)–based adiposity measures as correlates of metabolic complications of adiposity in HIV-infected and control subjects. DesignThe study was a cross-sectional analysis of 666 HIV-positive and 242 control subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study assessing body mass index (BMI), waist (WC) and hip (HC) circumferences, waist-to-hip ratio (WHR), %BF, and MRI-measured regional adipose tissue. Study outcomes were 3 metabolic risk variables [homeostatic model assessment (HOMA), triglycerides, and HDL cholesterol]. Analyses were stratified by sex and HIV status and adjusted for demographic, lifestyle, and HIV-related factors. ResultsIn HIV-infected and control subjects, univariate associations with HOMA, triglycerides, and HDL were strongest for WC, MRI-measured visceral adipose tissue, and WHR; in all cases, differences in correlation between the strongest measures for each outcome were small (r ≤ 0.07). Multivariate adjustment found no significant difference for optimally fitting models between the use of anthropometric and MRI measures, and the magnitudes of differences were small (adjusted R2 ≤ 0.06). For HOMA and HDL, WC appeared to be the best anthropometric correlate of metabolic complications, whereas, for triglycerides, the best was WHR. ConclusionRelations of simple anthropometric measures with HOMA, triglycerides, and HDL cholesterol are approximately as strong as MRI-measured whole-body adipose tissue depots in both HIV-infected and control subjects.

Insulin Resistance, Insulin Response, and Obesity as Indicators of Metabolic Risk

Insulin resistance (IR) and obesity, especially abdominal obesity, are regarded as central pathophysiological features of a cluster of cardiovascular risk factors (CVRFs), but their relative roles remain undefined. Moreover, the differential impact of IR viz. insulin response has not been evaluated. The objective of this study was to dissect out the impact of obesity, abdominal obesity, and IR/insulin response on CVRF. This was a cross-sectional study. The study was conducted at 21 research centers in Europe. The study included a cohort of 1308 nondiabetic subjects [718 women and 590 men, age 30-60 yr, body mass index (BMI) 17-44 kg.m(-2)]. We measured IR (by a standardized euglycemic insulin clamp), waist girth, insulin response to an oral glucose tolerance test, and major CVRF, and analyzed their associations by multivariate models and factor analysis. BMI was positively related to all CVRFs. Waist circumference was related to higher blood pressure and serum triglycerides and lower high-density lipoprotein-cholesterol, IR to reduced glucose tolerance, higher free fatty acids, triglyceride and low-density lipoprotein-cholesterol, and lower high-density lipoprotein-cholesterol, and insulin response to higher heart rate, blood pressure and fasting glucose, and the same dyslipidemic profile as IR (P < or = 0.05 for all). By factor analysis, three main factors (related to IR, age, and fatness, respectively) appeared to underlie this pattern of associations. Each of BMI, waist girth, IR, and insulin response was independently associated with total CVRF load (all P < 0.001). When IR, fat mass and distribution, and insulin response are measured simultaneously in a large cohort, no one factor stands out as the sole driving force of the CVRF cluster, each being associated with one or more physiological pathways according to known cause-effect relationships.

Fibrin Gel Architecture Influences Endogenous Fibrinolysis and May Promote Coronary Artery Disease

An altered fibrin network architecture has been associated with premature coronary artery disease (CAD).1,2 Hypofibrinolysis, ie, impaired dissolution of fibrin in blood clots, is another common finding in such patients. Hypofibrinolysis is associated with elevated activity of inhibitors of the fibrinolytic process, particularly of plasminogen activator inhibitor-1 (PAI-1)3 and thrombin activatable fibrinolysis inhibitor (TAFI),4 but it is also influenced by the characteristics of the fibrin network itself.5,6 However, previous studies on fibrin architecture, its regulation, and implications for CAD have been hampered by imperfect and/or incomplete methodology. Thus, the relationships between fibrin structure, fibrinolytic function, and premature CAD warrant further thorough examination. This issue of Arteriosclerosis, Thrombosis, and Vascular Biology features a comprehensive investigation of physical and viscoelastic characteristics of fibrin clots formed ex vivo from plasma samples, their relationships to fibrinolysis rate, and potential role in CAD.7 See page 2567 Both the morphology and mechanical properties of fibrin influence susceptibility to fibrinolysis. Fibrin structure is generally assessed by using liquid permeation, light scattering, scanning electron microscopy, and confocal microscopy, from which variables such as the fiber thickness, length and density, and the number of branch points and porosity of the network are derived.8 Blunted fibrinolysis is associated with a tight fibrin structure composed of thin and short fibers with increased number of branch points, and small pores.5,6 Individual thick fibers are actually lysed at a slower rate,9 but tight network configurations display a significantly higher fiber density …

Long-term health considerations in schizophrenia: Metabolic effects and the role of abdominal adiposity

Patients with schizophrenia have increased rates of morbidity and mortality compared with the general population, primarily due to cardiovascular disease. Thus there is an increasing need for clinicians in the psychiatric field to recognise and address cardiovascular risk factors such as abdominal obesity, dyslipidaemia, high blood pressure and elevated fasting blood glucose levels that contribute to this long-term health burden. The combination of three or more of these risk factors leads to a diagnosis of metabolic syndrome, further predisposing individuals to cardiovascular disease. A cluster of risk factors, such as in the metabolic syndrome, is being increasingly seen in patients with schizophrenia. Abdominal obesity is a key contributor to overall cardiovascular risk and is a particularly important consideration in schizophrenia as some atypical antipsychotics are associated with drug-induced weight gain. Lifestyle factors such as smoking, lack of exercise and poor diet undoubtedly contribute further. Psychiatrists need to be aware of metabolic risk when initiating treatment in patients with schizophrenia and should take steps to identify and monitor patients. A first step is to establish a risk profile for the patient based on medical, lifestyle and genetic factors, and measurement of waist circumference is a good indicator of overall cardiovascular and metabolic risk. Strategies recommended to reduce risk include promoting healthy lifestyle/behavioural habits and close monitoring of weight, glucose, and lipid profiles both before and during treatment. Established risk factors should also be considered when selecting the most appropriate antipsychotic medication for an individual patient, based on differences in the potential effect of individual medications to induce weight gain, risk of diabetes or worsening lipid profile.

A diabetes risk score helps identify metabolic syndrome and cardiovascular risk in Indians – the Chennai Urban Rural Epidemiology Study (CURES‐38)

The aims of the study were to compare the recently evolved Indian Diabetes Risk Score (IDRS), in subjects with different grades of glucose intolerance and to evaluate its usefulness as an indicator of cardiovascular risk in Asian Indians, a high risk group for diabetes and coronary artery disease (CAD). The data for the present study were obtained from the Phase 3 (n = 2350, response rate: 90.4%) of the Chennai Urban Rural Epidemiology Study, a population-based study done in Chennai, the largest city in southern India. IDRS was developed based on multiple logistic regression analysis using four simple parameters namely age, abdominal obesity, family history of type 2 diabetes and physical activity. In all subjects, family history of diabetes was obtained, and details on physical activity were assessed using a validated questionnaire. Subjects with an IDRS of <30 was categorized as low risk, 30-50 as medium risk and those with > or =60 as high risk for diabetes. Biochemical and anthropometric measurements were done using standardized procedures. Minnesota coding was used to grade 12-lead electrocardiogram. The mean IDRS increased significantly with worsening glucose intolerance [normal glucose tolerance (NGT) subjects: 48 +/- 17, impaired glucose tolerance (IGT): 57 +/- 16, newly diagnosed diabetics (NDD): 61 +/- 15 and known diabetics (KD): 68 +/- 12; p for trend <0.001]. Among NGT group, the prevalence of cardiovascular risk factors increased progressively in low-, medium- to high-risk score groups; hypertension: 9.4, 22.1 and 38.2% (p for trend: < 0.001), hypertriglyceridemia: 8.8, 19.9 and 25.3% (p for trend: < 0.001), hypercholesterolemia: 7.2, 20.3 and 34.9% (p for trend: < 0.001) and metabolic syndrome: 1.8, 14.6 and 30.3% (p for trend: < 0.001), respectively. The prevalence of CAD was also significantly higher in individuals with high risk compared with those with low risk (p = 0.030) and the medium risk (p = 0.050) in the NGT group. The results suggest that in Asian Indians, (i) the diabetes risk score increases with increasing glucose intolerance, and (ii) it can serve as an effective indicator of metabolic syndrome and cardiovascular risk even among subjects with NGT.

Homocystéine et paramètres du syndrome métabolique et du risque cardiovasculaire chez 2045 militaires : étude EPIMIL

The aim of this present study is to investigate a possible relationship between plasma homocystein and biological indicators of metabolic syndrome and cardiovascular risk in a prospective epidemiological study; EPIMIL involving 2045 military subjects 20–58 years of age. Homocysteinemia measurements have been performed using automated chemiluminescent enzyme immunoassay on Immulite 2000 TM (DPC). According to NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel) definition, the prevalence of metabolic syndrome was 9%. Homocysteinemia was slightly related to some markers as cholesterol ( R = 0,04, p = 0,05), triglycerides ( R = 0,06, p = 0,004), free fatty acids ( R = 0,06, P = 0,004). When fasting homocysteinemia above 15 μmol/l (7,5% of the population), there is no relationship with syndrome metabolic components and cardiovascular risk biological markers except for cholesterol and blood pressure. The follow up of the EPIMIL population for ten years would predict if plasma homocysteine is or not an independent factor in the complex pathomecanism of atherosclerosis.

Sex Hormone-Binding Globulin and Insulin-Like Growth Factor-Binding Protein-1 as Indicators of Metabolic Syndrome, Cardiovascular Risk, and Mortality in Elderly Men

Two binding proteins, SHBG and IGF-binding protein-1 (IGFBP-1), are both down-regulated by insulin and therefore could serve as potential indicators of the metabolic syndrome and hyperinsulinemia-related cardiovascular risk. We compared serum SHBG and IGFBP-1 as potential markers of abnormal glucose tolerance, the metabolic syndrome, diabetes mellitus, cardiovascular risk factors, and total, cardiovascular, and coronary heart disease mortality in elderly men. Of the original cohort of 1711 men, 524 were alive on January 1, 1989, and 413 participated in the 30-yr examination, of whom 335 men, aged 70-89 yr, formed the study group for the present analysis. Low SHBG and IGFBP-1 were both associated with an increased prevalence of abnormal glucose tolerance and the metabolic syndrome, but only SHBG was associated with diabetes mellitus. SHBG was less influenced by body mass index than IGFBP-1. Low SHBG indicated increased cardiovascular and coronary disease mortality; the association remained after adjustment for abnormal glucose tolerance, but not after adjustment for prevalent cardiovascular disease. IGFBP-1 had no association with mortality. It is concluded that low SHBG is a better indicator of increased cardiovascular mortality than low or high IGFBP-1.

Microarousals During Sleep Are Associated With Increased Levels of Lipids, Cortisol, and Blood Pressure

Previous work has demonstrated a link between restricted sleep and risk indicators for cardiovascular and metabolic disease, such as levels of cortisol, lipids, and glucose. The present study sought to identify relations between polysomnographic measures of disturbed sleep (frequency of arousals from sleep, total sleep time, and sleep efficiency) and a number of such indicators. A second purpose was to relate the number of arousals to mood, stress, work characteristics, and other possible predictors in daily life. Twenty-four people (10 men, 14 women; mean age 30 years), high vs. low on burnout, were recruited from a Swedish IT company. Polysomnographically recorded sleep was measured at home before a workday. Blood pressure, heart rate, morning blood sample, and saliva samples of cortisol were measured the subsequent working day. They were also recorded for diary ratings of sleep and stress, and a questionnaire with ratings of sleep, stress, work conditions, and mood was completed. A stepwise regression analysis using sleep parameters as predictors brought out number of arousals as the best predictor of morning cortisol (serum and saliva), heart rate, systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)-cholesterol, and LDL/HDL-ratio. Work stress/unclear boundaries between work and leisure time was the best predictor of arousals among the stress variables. Consistent with sleep restriction experiments, sleep fragmentation was associated with elevated levels of metabolic and cardiovascular risk indicators of stress-related disorders. Number of arousals also seems to be related to workload/stress.

Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction.

To validate transthoracic echocardiography as an easy and reliable imaging method for visceral adipose tissue (VAT) prediction. VAT is recognized as an important indicator of high cardiovascular and metabolic risk. Several methods are applied to estimate VAT, with different results. We selected 60 healthy subjects (29 women, 31 men, 49.5 +/- 16.2 years) with a wide range of body mass indexes. Each subject underwent transthoracic echocardiogram and magnetic resonance imaging (MRI) to measure epicardial fat thickness on the right ventricle. Measurements of epicardial adipose tissue thickness were obtained from the same echocardiographic and MRI views and points. MRI was also used to measure VAT cross-sectional areas at the level of L4 to L5. Anthropometric indexes were also measured. Subjects with predominant visceral fat accumulation showed higher epicardial adipose tissue thickness than subjects with predominant peripheral fat distribution: 9.97 +/- 2.88 vs. 4.34 +/- 1.98 (p = 0.005) and 7.19 +/- 2.74 vs. 3.43 +/- 1.64 (p = 0.004) in men and women, respectively. Simple linear regression analysis showed an excellent correlation between epicardial adipose tissue and waist circumference (r = 0.895, p = 0.01) and MRI abdominal VAT (r = 0.864, p = 0.01). Multiple regression analysis showed that epicardial adipose tissue thickness (r(2) = 0.442, p = 0.02) was the strongest independent variable correlated to MRI VAT. Bland test confirmed the good agreement between the two methods. Epicardial adipose tissue showed a strong correlation with anthropometric and imaging measurements of VAT. Hence, transthoracic echocardiography could be an easy and reliable imaging method for VAT prediction.

Covariance of metabolic and hemostatic risk indicators in men and women

Background and objective: Multivariate analyses on clusters of metabolic and hemostatic risk indicators implicitly assume good test–retest reliability of these variables, substantial covariance among the various indicators, stability of covariance structure over time, and comparable covariance structure in different subpopulations. The aim of the present study is to investigate these assumptions.Methods: Repeated samples were taken of fasting insulin, triglycerides (TG), high-density cholesterol (HDL-C), low-density cholesterol (LDL-C), fibrinogen, tissue-type plasminogen activator (t-PA) antigen, t-PA activity, plasminogen activator inhibitor-1 (PAI-1)antigen to address their intra-week reliability and covariance structure. In the same workweek blood was drawn three times from 125 sedentary males (age 45.2±5.3 years) and twice from 132 female nurses (age 33.7±8.0 years).Results: About half(44.8%) of these women were oral contraceptives (OC) users. Only minor intra-week changes in absolute levels were found. Intra-week test-retest correlations varied between 0.52 (t-PA activity) and 0.94 (HDL-C) with an average value of 0.81. In men, and non-OC using women, and OC using women, the covariance matrices of the eight risk indicators were equal at day 1 and day 3, testifying the good stability of covariance structure over time. Differences in covariance structure of all three groups were observed, which remained after correction for BMI and age. In men and non-OC-using women, significant correlation was found on all days between insulin and the other risk indicators with exception of fibrinogen and LDL-C. In OC users, insulin was correlated with TG, LDL-C, and fibrinogen.Conclusion: The metabolic and hemostatic risk indicators showed good test-retest reliability, and their covariance is stable over time. Multivariate analyses of this cluster should be performed separately for men, non-OC-using women, and OC-using women.

Waist circumference and VO2max are associated with metabolic and hemostatic risk in premenopausal nurses.

In 21 nurses (34.4+/-3.9 yr), VO2max physical activity, body composition and lifestyle parameters were measured to determine which of these characteristics are related to metabolic and hemostatic risk for cardiovascular disease. Physical activity was assessed with the 7-day recall interview. VO2max was measured in a progressive and continuous treadmill test to volitional fatigue. Fasting insulin, total cholesterol, HDL-C, triglycerides, fibrinogen, tPA-act, tPA-ag, and PAI-1-ag were determined from fasting blood samples. Contrary to our expectation, there was no association of physical activity with any of these risk indicators. High VO2max was associated with lower levels of insulin and fibrinogen. Regression analyses indicated that metabolic and hemostatic risk indicators, as measured in healthy premenopausal nurses, were mainly predicted by waist circumference and oral contraceptive use.

Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity.

Plasminogen activator inhibitor-1 (PAI-1), a rapid inhibitor of tissue-type plasminogen activator, has been shown to be an independent risk factor for recurrent myocardial infarction (MI) at a young age. To investigate whether genetic variation in the PAI-1 gene is affecting plasma PAI-1 levels, a sample of 145 patients with an MI before the age of 45 years was genotyped for two polymorphisms at the PAI-1 locus, together with a sample of 95 healthy individuals of a similar age. All individuals were measured for plasma PAI-1 levels as well as for other fibrinolytic and metabolic risk indicators. A HindIII restriction fragment length polymorphism (RFLP) was used in this study in conjunction with a previously unreported eight-allele dinucleotide repeat polymorphism at the PAI-1 locus. The dinucleotide repeat polymorphism and HindIII RFLP were in strong linkage disequilibrium. There was no difference in the frequency of alleles of either polymorphism between patient and control groups. However, the smaller dinucleotide repeat alleles were significantly associated (p = 0.03) with higher plasma PAI-1 levels in the patient sample. This association was also apparent in the control sample but not at significant levels. Differences in regression coefficients for the effect of triglycerides on plasma PAI-1 levels suggest that triglyceride regulation of PAI-1 is genotype specific. Our data suggest that genetic variation at this locus contributes to between-individual differences in the level of plasma PAI-1, which is important in fibrinolysis and the pathogenesis of MI.

Risk factors for coronary artery disease in families of young men with myocardial infarction

Familial clustering of coronary artery disease (CAD) and familial influences on various clinical and metabolic risk factors were investigated in 85 male survivors of acute myocardial infarction younger than 45 years. The study also involved 85 age-matched men randomly selected from the general population and the first-degree relatives of both patients and control subjects. Presence of CAD was assessed by an angina questionnaire and from rest and exercise electrocardiograms. There was an apparent aggregation of premature CAD in 38% of the case families. A familial clustering of hyperlipoproteinemia was present in 58% of the case families and 15% of the control families. Systemic hypertension and cigarette smoking also were clustered in the case families. Multivariate statistical analyses of clinical and metabolic risk indicators in patients with and without a family history of CAD and in control subjects indicated that familial aggregation of CAD is independently related to MI at a young age. Degree and extent of coronary atheromatosis and number and severity of hemodynamically significant stenoses did not differ between young patients with and without a familial aggregation of CAD. The absence of a relation between the family history and severity of CAD implies that other underlying mechanisms are involved.