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PubMed2000

Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with type II diabetes.

AIMS/HYPOTHESIS: Non-alcoholic steatohepatitis is frequent in Type II (non-insulin-dependent) diabetes mellitus and can lead to fibrosis and cirrhosis. The interindividual variability in the occurrence of nonalcoholic steatohepatitis suggests, however, a genetic modulation. Microsomal triglyceride transfer protein (MTP) is necessary for the assembly and secretion of VLDL and when the protein is not functional, such as in abetalipoproteinaemia, a steatohepatitis occurs. We therefore assessed the association between a functional polymorphism in the promoter region of MTP gene (-493 G/T) and the biological features of steatohepatitis in Type II diabetic patients. METHODS: We studied 271 patients with Type II diabetes. Determination of -493 G/T polymorphism was made by PCR-RFLP. Increased liver enzymes were used as surrogates of liver steatosis and alanine aminotransferase concentration was the outcome variable for the multivariate analysis. Liver ultrasonography was available for a subgroup of patients with newly diagnosed diabetes. RESULTS: The proportion of patients with increased alanine aminotransferase was higher in GG than in GT and TT subgroups (23%, 11% and 6%, respectively, p = 0.01). Additionally, patients with high alanine aminotransferase concentrations were more likely to be young (p = 0.01), male (p = 0.001), obese (p = 0.04) and have low HDL-cholesterol (p = 0.01). In multivariate analysis, the MTP genotype was independently associated with alanine aminotransferase concentration (p = 0.0023) as well as sex and body mass index but not HDL-cholesterol. CONCLUSION/INTERPRETATION: The -493 G/T MTP gene polymorphism is associated with biological surrogates of steatohepatitis in patients with Type II diabetes. The G allele which is responsible for a decrease in MTP gene transcription is prone to increase the intrahepatic triglycerides content, conferring by this a genetic susceptibility for steatohepatitis.

Adult↗

PubMed2001

On the use of surrogate respondents for controls in a case-control study of Alzheimer's disease.

OBJECTIVE: To examine the presence and extent of bias introduced by using surrogate respondents for healthy controls in a case-control study of Alzheimer's disease (AD). DESIGN: Comparative study of matched responses to questionnaire ascertaining lifestyle issues. SETTING: University Hospitals/Case Western Reserve University Alzheimer Center. PARTICIPANTS: Controls (n = 50) were identified through the Research Registry. Surrogates (n = 50) were their healthy relatives or friends. MEASUREMENTS: Answers in the areas of demographic and occupational history, smoking habits, medical history, dietary intake, and leisure and work activities were recorded. The analysis was based on methods for paired data. Continuous variables were analyzed, focusing on paired differences between self and surrogate responses. RESULTS: For occupations and exposures, over 80% of the surrogates agreed with the subjects on over 80% of the questions. On smoking history, over 90% of the surrogates agreed with the subjects on over 70% of the questions. On leisure and work activities, over 70% of the surrogates agreed with the subjects on over 50% of the questions. There was less agreement regarding medical history. For continuous variables, most paired t-tests of zero mean difference between self and surrogate responses resulted in nonrejection of this hypothesis. Computed mean differences were not always positive or always negative. CONCLUSION: We did not find systematic under- or overreporting by the surrogates of the controls. Therefore, if there are biases in the responses of surrogates of the AD cases in our case-control study, they would not be canceled out by using surrogates for the controls.

Aged↗

PubMed1989

Poisson regression with a surrogate X: an analysis of vitamin A and Indonesian children's mortality.

"A Poisson regression model with a surrogate X variable is proposed to help to assess the efficacy of vitamin A in reducing child mortality in Indonesia. In a recent community trial, the mortality rate in villages receiving vitamin A supplementation was 35% less than in control villages. However, at base-line, control villages were found to have slightly higher rates of xerophthalmia, an ocular disease caused by vitamin A deficiency. It was therefore desirable to adjust the mortality comparison for base-line vitamin A levels as indicated by xerophthalmia prevalence. This paper presents a parametric errors-in-X regression model developed for this purpose. Likelihood methods for fitting and inference are discussed. The model is illustrated on the Indonesian data set."

Asia↗

PubMed2006

Regular heartbeat dynamics are associated with cardiac health.

The human heartbeat series is more variable and, hence, more complex in healthy subjects than in congestive heart failure (CHF) patients. However, little is known about the complexity of the heart rate variations on a beat-to-beat basis. We present an analysis based on symbolic dynamics that focuses on the dynamic features of such beat-to-beat variations on a small time scale. The sequence of acceleration and deceleration of eight successive heartbeats is represented by a binary sequence consisting of ones and zeros. The regularity of such binary patterns is quantified using approximate entropy (ApEn). Holter electrocardiograms from 30 healthy subjects, 15 patients with CHF, and their surrogate data were analyzed with respect to the regularity of such binary sequences. The results are compared with spectral analysis and ApEn of heart rate variability. Counterintuitively, healthy subjects show a large amount of regular beat-to-beat patterns in addition to a considerable amount of irregular patterns. CHF patients show a predominance of one regular beat-to-beat pattern (alternation of acceleration and deceleration), as well as some irregular patterns similar to the patterns observed in the surrogate data. In healthy subjects, regular beat-to-beat patterns reflect the physiological adaptation to different activities, i.e., sympathetic modulation, whereas irregular patterns may arise from parasympathetic modulation. The patterns observed in CHF patients indicate a largely reduced influence of the autonomic nervous system. In conclusion, analysis of short beat-to-beat patterns with respect to regularity leads to a considerable increase of information compared with spectral analysis or ApEn of heart-rate variations.

Adult↗

PubMed2000

Analysis and modeling of the variability associated with UV inactivation of Escherichia coli in apple cider.

Raw data from validation studies of UV tubes used for nonthermal pathogen reduction in apple cider underwent comprehensive statistical analysis. Data from each tube that demonstrated at least a 5-log reduction of Escherichia coli ATCC 25922, a surrogate for E. coli O157:H7, in each of three trials were used in the analysis. The within- and between-tube variability was calculated for 70 tubes. The mean log reductions of the tubes fit a Beta distribution (Kolmogorov-Smirnov test, 0.0246), and the between-replicate variability followed a logistic distribution (Kolmogorov-Smirnov test, 0.0305). These two distributions can be used together to model UV cider treatment as part of an overall E. coli O157:H7 in cider risk assessment. Examples of codes from @RISK and Analyticato describe these distributions, such as one would find in a quantitative risk assessment, are included.

Beverages↗

PubMed1998

Short-term variability of blood pressure and heart rate in hyperthyroidism.

The effect of hyperthyroidism on the short-term memory variability of blood pressure and heart rate was evaluated in 12 untreated hyperthyroid patients during thyrotoxicosis and after a 6 1/2 month treatment designed to achieve a stable euthyroid state. Beat-by-beat finger blood pressure was measured with a Finapres device. The pulse interval, from which pulse rate was derived, was obtained from the blood pressure signal. Due to the significant change in heart rhythm associated with thyrotoxicosis, both pulse interval (taken as a surrogate of heart period) and pulse rate (taken as a surrogate of heart rate) were computed. Power spectral analysis showed a reduction in the overall heart period variability in the supine position in the hyperthyroid compared to the euthyroid state. This effect was observed in the low-frequency (0.005-0.068 Hz), mid-frequency (0.068-0.127 Hz) and high-frequency (respiratory) domains as well, with a significant reduction of the modulus of these bands of 31%, 35% and 47%, respectively. The heart rate spectral modulus also exhibited a reduction of the high-frequency component (31%) in the supine position in the hyperthyroid subjects. These changes in heart rhythmicity corroborate a vagal deficit in hyperthyroidism. In addition, blood pressure spectral power exhibited a significant deficit in the orthostatism-induced mid-frequency systolic blood pressure rise in the hyperthyroid state (64%) compared with the euthyroid state. This observation may reflect a reduced vascular sympathetic activation with standing. The resulting vasodilatation could well contribute to normalize blood pressure in thyrotoxicosis in which cardiac output is increased.

Adult↗

PubMed2006

Kolmogorov-Smirnov statistical test for analysis of ZAP-70 expression in B-CLL, compared with quantitative PCR and IgV(H) mutation status.

BACKGROUND: ZAP-70 has been proposed as a surrogate marker for immunoglobulin heavy-chain variable region (IgV(H)) mutation status, which is known as a prognostic marker in B-cell chronic lymphocytic leukemia (CLL). The flow cytometric analysis of ZAP-70 suffers from difficulties in standardization and interpretation. We applied the Kolmogorov-Smirnov (KS) statistical test to make analysis more straightforward. METHODS: We examined ZAP-70 expression by flow cytometry in 53 patients with CLL. Analysis was performed as initially described by Crespo et al. (New England J Med 2003; 348:1764-1775) and alternatively by application of the KS statistical test comparing T cells with B cells. Receiver-operating-characteristics (ROC)-curve analyses were performed to determine the optimal cut-off values for ZAP-70 measured by the two approaches. ZAP-70 protein expression was compared with ZAP-70 mRNA expression measured by a quantitative PCR (qPCR) and with the IgV(H) mutation status. RESULTS: Both flow cytometric analyses correlated well with the molecular technique and proved to be of equal value in predicting the IgV(H) mutation status. Applying the KS test is reproducible, simple, straightforward, and overcomes a number of difficulties encountered in the Crespo-method. CONCLUSIONS: The KS statistical test is an essential part of the software delivered with modern routine analytical flow cytometers and is well suited for analysis of ZAP-70 expression in CLL.

Adult↗

PubMed2006

Structural and serum surrogate markers of cerebrovascular disease in obstructive sleep apnea (OSA): association of mild OSA with early atherosclerosis.

There is increasing evidence of a causal interaction between obstructive sleep apnea (OSA) and cerebrovascular disease. The aim of the study was to elucidate the relationship between the polysomnographically (PSG) measured severity of OSA and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. 147 patients (102 males, 45 females) referred to our sleep laboratory for evaluation of snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein (hs-CRP) and fibrinogen and four sonographic indices: intima-media thickness (IMT) of the common carotid artery (CCA), IMT from bulb to internal carotid artery (Bulb-ICA), combined IMT measurements from all segments and a plaque score (PlaS). Pearson correlation analysis, intergroup comparison (ANOVA), covariance analysis and a multiple regression were performed to assess the association between surrogate markers and respiratory variables. 44 patients had no OSA (apnea-hypopnea index AHI < 5/h), 27 mild (AHI 5-15), 25 moderate (AHI 15-30) and 51 severe OSA (AHI > 30). After adjusting for potential confounders, significant differences between the controls and all three OSA groups were observed in the CCA-IMT (p = 0.032) and in the PlaS between the controls and the severe group (p = 0.034). Multiple regression revealed the AHI as an independent predictor of CCA-IMT (p = 0.001) and combined IMT (p = 0.001), whereas the percentage of total sleep time with an oxygen saturation below 90 % was associated with Bulb-ICA IMT (p = 0.018) and hs-CRP (p = 0.015). OSA is associated with higher surrogate levels of cerebrovascular disease. Even mild OSA seems to predispose to early atherosclerosis.

Adult↗

PubMed1996

Prognosis versus actual outcome. III. The effectiveness of clinical parameters in accurately predicting tooth survival.

Tooth loss for 100 treated periodontal patients (2,509 teeth) under maintenance care was evaluated to determine the effectiveness of commonly taught clinical parameters utilized in the assignment of prognosis in accurately predicting tooth survival. Previous studies in this series evaluated prognosis as a surrogate variable representing the condition of the tooth at a particular point. In this study, survival analysis was used to evaluate the relationship of these common clinical parameters to an actual end point, tooth loss. Robust log rank tests indicated that initial probing depth, initial furcation involvement, initial mobility, initial crown-to-root ratio, and initial root form were all associated with tooth loss. In addition, smoking and increased initial bone loss were both found to be associated with increased risk of tooth loss while fixed abutment status was associated with a decreased risk of tooth loss. A Cox proportional hazards regression model showed that initial probing depth, initial furcation involvement, initial mobility, initial percent bone loss, presence of a parafunctional habit without a biteguard, and smoking were all associated with an increased risk of tooth loss. This model suggests that patients are twice as likely to loose their teeth if there is increasing mobility, if they have a parafunctional habit and do not wear a biteguard, or if they smoke. From these data there does appear to be a relationship between the assigned prognosis and tooth loss. Teeth with worse prognosis have a worse survival rate, but the commonly taught clinical parameters used in the traditional method of assignment of prognosis do not adequately explain that relationship. Furthermore, initial prognosis did not adequately explain the condition of the tooth or accurately predict the tooth's survival. These results seem to indicate that the effect of these clinical parameters on tooth survival is only partially reflected in the assigned prognosis initially, suggesting that perhaps some of the clinical parameters should be weighed more heavily than others when assigning prognosis. Further studies are needed to develop a more accurate method for the assignment of prognosis.

Alveolar Bone Loss↗

PubMed2002

An analysis of patient compliance with nurse recommendations from an after-hours call center.

OBJECTIVES: To demographically and clinically describe the callers who use an after-hours call center (AHCC); to estimate the level of patient satisfaction with the AHCC; to determine caller compliance with the AHCC nurse's recommendation; and to examine the relationship between compliance and selected demographic and clinical characteristics, including caller satisfaction. STUDY DESIGN: A prospective, quasi-experimental telephone survey. PATIENTS AND METHODS: Randomly selected callers (n = 427) to an AHCC were surveyed by telephone to determine their satisfaction with the services provided and their compliance with the AHCC nurse's recommendation. RESULTS: Overall, 88.2% of the AHCC clients were compliant with the nurse's recommendations. Logistic regression analysis revealed that 2 patient variables had a statistically significant impact on compliance. Patients or their surrogates (eg, parents/guardians, caregivers) who were "very satisfied" were more than 4 times more likely to be compliant, and the surrogates of the patients under the age of 1 year were more than 20 times more likely to be compliant. The greatest level of patient dissatisfaction was with the time it took to make contact with the nurse. Decreasing this response time may improve satisfaction, which in turn may increase compliance and lead to more desirable health outcomes. CONCLUSIONS: The level of compliance was found to be favorable for all levels of acuity. However, the results indicate a further need for quality improvement activities.

Data Collection↗

PubMed2004

Macro- and mesomorphology of frontal sinuses in humans: noisiness models relating to their ontogeny.

The debate about the role of the frontal sinuses remains unresolved. In this paper, I explore several statistical and fractal features of the frontal sinus outlines in order to better assess the spatial models of supraorbital torus formation. Although the analyses are restricted to a suite of techniques dealing with two-dimensional projections of the frontal sinuses, here I report many features that explain why it is so difficult to describe the spatial models. I show how the outline circumference scales with enclosed area, how the fractal dimensions of the outlines are distributed, how the method of singular value decomposition is used to define surrogate landmarks, and how a principal component analysis of vectors between these landmarks indicates directions of high variability in some of the inferior-distal directions. All these analysis techniques reveal regularities underlying the statistical noise. I believe that uncovering them necessitates a fresh look at the biology of noisy ontogeny phenomena.

Asian People↗

PubMed2002

Helicobacter pylori does not play a part in the dyspeptic complaints of rheumatology patients receiving long term treatment with non-steroidal anti-inflammatory drugs.

BACKGROUND: The presence of dyspeptic symptoms is a common finding in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). Some studies seem to support the involvement of Helicobacter pylori infection in the dyspeptic symptoms reported by these patients, and suggest that eradication may be useful. OBJECTIVE: To determine the variables related to dyspepsia in rheumatology patients requiring NSAID treatment, assessing in particular the role of Helicobacter pylori infection. METHODS: One hundred and eighty six consecutive patients with a rheumatological disorder requiring NSAID treatment (68 male, 118 female; mean (SD) age 55 (15) years) were included in a cross sectional study; dyspeptic symptoms were measured by a previously validated scale. Helicobacter pylori infection was determined by serology. Variables related to the severity of symptoms and the need for antisecretory drugs were determined by multivariate analysis. RESULTS: No relation was found between Helicobacter pylori infection and dyspepsia or any of its surrogate markers (antisecretory drug use or NSAID intolerance). Female sex and treatment with antisecretory drugs were found to be independent predictors for the appearance and severity of dyspeptic symptoms. The only independent predictive variables of the requirement for antisecretory drugs were age, previous ulcer disease, taking NSAIDs with a medium or high anti-inflammatory potential, and the symptoms score. CONCLUSION: Helicobacter pylori infection does not seem to play any part in the gastric symptoms of patients treated long term with NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Factors influencing preoperative stress response in coronary artery bypass graft patients.

BACKGROUND: In many studies investigating measures to attenuate the hemodynamic and humoral stress response during induction of anaesthesia, primary attention was paid to the period of endotracheal intubation since it has been shown that even short-lasting sympathetic cardiovascular stimulation may have detrimental effects on patients with coronary artery disease. The aim of this analysis was, however, to identify the influencing factors on high catecholamine levels before induction of anaesthesia. METHODS: Various potential risk factors that could impact the humoral stress response before induction of anaesthesia were recorded in 84 males undergoing coronary aortic bypass surgery, and were entered into a stepwise linear regression analysis. The plasma level of norepinephrine measured immediately after radial artery canulation was chosen as a surrogate marker for the humoral stress response, and it was used as the dependent variable in the regression model. Accordingly, the mean arterial blood pressure, heart rate and the calculated pressure-rate product were taken as parameters of the hemodynamic situation. RESULTS: Stepwise regression analysis revealed that the oral administration of low-dose clonidine (mean dose 1.75 μg.kg-1) on the morning of surgery was the only significant predictor (p = 0.004) of the high variation in preoperative norepinephrine plasma levels. This intervention decreased norepinephrine levels by more than 40% compared to no clonidine administration, from 1.26 to 0.75 nmol.l-1. There was no evidence for dose-responsiveness of clonidine. All other potential predictors were removed from the model as insignificant (p > 0.05). The use of beta-blocker, ace-inhibitors, ejection fraction, and body mass index were significant determinants for the hemodynamic situation (heart rate, mean arterial pressure, pressure rate product) of the patient during the pre-induction period. CONCLUSION: The oral administration of clonidine is the only significant predictor for the observed variation of norepinephrine levels during the preoperative period. Lack of significant dose responsiveness suggests that even a low dose of the drug can attenuate the preoperative stress response and thus is recommended in cardiovascular high risk patients.

Journal Article↗

PubMed2001

Quantification and variability analysis of bacterial cross-contamination rates in common food service tasks.

This study investigated bacterial transfer rates between hands and other common surfaces involved in food preparation in the kitchen. Nalidixic acid-resistant Enterobacter aerogenes B199A was used as a surrogate microorganism to follow the cross-contamination events. Samples from at least 30 different participants were collected to determine the statistical distribution of each cross-contamination rate and to quantify the natural variability associated with that rate. The transfer rates among hands, foods, and kitchen surfaces were highly variable, being as low as 0.0005% and as high as 100%. A normal distribution was used to describe the variability in the logarithm of the transfer rates. The mean +/- SD of the normal distributions were, in log percent transfer rate, chicken to hand (0.94 +/- 0.68), cutting board to lettuce (0.90 +/- 0.59), spigot to hand (0.36 +/- 0.90), hand to lettuce (-0.12 +/- 1.07), prewashed hand to postwashed hand (i.e., hand washing efficiency) (-0.20 +/- 1.42), and hand to spigot (-0.80 +/- 1.09). Quantifying the cross-contamination risk associated with various steps in the food preparation process can provide a scientific basis for risk management efforts in both home and food service kitchens.

Animals↗

PubMed2005

Characterization of EEG--a comparative study.

The Electroencephalogram (EEG) is a representative signal containing information about the condition of the brain. The shape of the wave may contain useful information about the state of the brain. However, the human observer cannot directly monitor these subtle details. Besides, since bio-signals are highly subjective, the symptoms may appear at random in the time scale. Therefore, the EEG signal parameters, extracted and analyzed using computers, are highly useful in diagnostics. Chaotic measures like correlation dimension (CD), largest Lyapunov exponent (LLE), Hurst exponent (H) and entropy are used to characterize the signal. Results indicate that these nonlinear measures are good discriminators of normal and epileptic EEG signals. These measures distinguish epileptic EEG and alcoholic from normal EEG with an accuracy of more than 90%. The dynamical behavior is less random for alcoholic and epileptic compared to normal. This indicates less of information processing in the brain due to the hyper-synchronization of the EEG. Hence, the application of nonlinear time series analysis to EEG signals offers insight into the dynamical nature and variability of the brain signals. As a pre-analysis step, the EEG data is tested for nonlinearity using surrogate data analysis and the results exhibited a significant difference in the correlation dimension measure of the actual data and the surrogate data.

Alcoholism↗

PubMedDate not supplied

[Use of regression analysis in the study of the association between different mercury exposure routes and some functional variables].

AIMS: The "Mercury Multicentric Project" data-set was analysed with the aim to identify a group of biological variables associated with different types of Hg exposure (occupational exposure, fish dietary intake, exposure due to amalgam restorations). The distribution of socio-demographic, biological and surrogate outcome variables was rather different among the collaborating Units. METHODS: Mixed linear models (MLM) were used to overcome the problems related to the heterogeneity of variances among Units. MLM are a generalization of the standard linear models, the generalization being that the data are permitted to exhibit correlation and non constant variability. MLM therefore provide with the flexibility of modelling not only the means of the dependent variable, but also their variances and co-variances as well. This allows to represent the total variability of the dependent variable as a sum of two components: the first attributable to the Units and the other one to the random error. RESULTS AND CONCLUSIONS: A set of biological variables significantly associated with at least one of the Hg exposure variables or with the HgU/creatinine ratio (as surrogate variable for Hg exposure) was identified by means of MLM. This set includes beta 2-MG, sIL8, CD4+, sPRL, FT dominant, BAMT, and some variables related to neurological behaviour. An extension of this analysis will be performed with a structural equations approach in order to study the dose-response relationships among the various variables according to a hierarchical path defined on biological basis. One of the possible simplified general models including all the selected variables is described.

Adult↗

PubMed1996

Sex-specific associations of magnetic resonance imaging-derived intra-abdominal and subcutaneous fat areas with conventional anthropometric indices. The Atherosclerosis Risk in Communities Study.

Accurate measurement of central fat patterning is difficult to obtain by conventional anthropometry. Direct measurement of intra-abdominal fat area by magnetic resonance imaging, while accurate, is impractical for large-scale observational studies. This report examines the sex-specific associations of conventional anthropometric indices with intra-abdominal fat and subcutaneous fat areas measured by magnetic resonance imaging. A total of 157 volunteers (97 men and 60 women) aged 48-68 years of predominately white ethnicity had intra-abdominal fat and subcutaneous fat areas measured as part of the Atherosclerosis Risk in Communities (ARIC) Study. Weight, body mass index, waist circumference, waist : hip ratio, and subscapular skinfold thickness were measured or calculated by a standardized protocol. On average, women had a lower intra-abdominal fat area than men (109.5 cm2 vs. 152.9 cm2) but a higher mean subcutaneous fat area (287.8 cm2 vs. 214.6 cm2). After adjustment for age, intra-abdominal fat area was quadratically associated with body mass index, waist circumference, weight, and subscapular skinfold thickness in men; in women, these associations were best modeled by a positive linear equation. Waist : hip ratio was linearly related to intra-abdominal fat area in both sexes. In general, anthropometric measures predicted lower percentages of the total variance in intra-abdominal fat area for men than for women. For subcutaneous fat area, all anthropometric indices were linearly associated and predicted more of the variance in subcutaneous fat area than in intra-abdominal fat area. These results indicate that among men, greater intra-abdominal fat deposition rates occur at relatively low body weights and fat is more uniformly deposited at higher weights. Women appear to deposit intra-abdominal fat at a constant rate as they gain weight, even after menopause. The authors conclude that when waist circumference or body mass index is used as a surrogate for intra-abdominal fat area in men, a quadratic term should be included in the analysis as a predictor variable. Subcutaneous fat area can be estimated well by linear measures commonly employed in epidemiologic studies.

Adipose Tissue↗

PubMed2004

Metabolic and inflammation variable clusters and prediction of type 2 diabetes: factor analysis using directly measured insulin sensitivity.

Factor analysis, a multivariate correlation technique, has been used to provide insight into the underlying structure of the metabolic syndrome. The majority of previous factor analyses, however, have used only surrogate measures of insulin sensitivity; very few have included nontraditional cardiovascular disease (CVD) risk factors such as plasminogen activator inhibitor (PAI)-1, fibrinogen, and C-reactive protein (CRP); and only a limited number have assessed the ability of factors to predict type 2 diabetes. The objective of this study was to investigate, using factor analysis, the clustering of metabolic and inflammation variables using data from 1,087 nondiabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS) and to determine the association of these clusters with risk of type 2 diabetes at follow-up. This study includes information on directly measured insulin sensitivity (S(i)) from the frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years. Principal factor analysis of data from nondiabetic subjects at baseline (1992-1994) identified three factors, which explained 28.4, 7.4, and 6% of the total variance in the dataset, respectively. Based on factor loadings of >or= 0.40, these factors were interpreted as 1) a "metabolic" factor, with positive loadings of BMI, waist circumference, 2-h glucose, log triglyceride, and log PAI-1 and inverse loadings of log S(i) + 1 and HDL; 2) an "inflammation" factor, with positive loadings of BMI, waist circumference, fibrinogen, and log CRP and an inverse loading of log S(i) + 1; and 3) a "blood pressure" factor, with positive loadings of systolic and diastolic blood pressure. The results were similar within strata of ethnicity, and there were only subtle differences in sex-specific analyses. In a prospective analysis, each of the factors was a significant predictor of diabetes after a median follow-up period of 5.2 years, and each factor remained significant in a multivariate model that included all three factors, although this three-factor model was not significantly more predictive than models using either impaired glucose tolerance or conventional CVD risk factors. Factor analysis identified three underlying factors among a group of inflammation and metabolic syndrome variables, with insulin sensitivity loading on both the metabolic and inflammation variable clusters. Each factor significantly predicted diabetes in multivariate analysis. The findings support the emerging hypothesis that chronic subclinical inflammation is associated with insulin resistance and comprises a component of the metabolic syndrome.

Adult↗