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Background: A unique group of individuals termed metabolically obese but normal weight (MONW) has been identified in the general population. The present study examined phenotypic characteristics of MONW individuals in a sample of normal weight, non-diabetic patients with schizophrenia., Methods: Outpatients 19 to 75 years old diagnosed with schizophrenia or schizoaffective disorder participated in a multi-center, cross-sectional study. Those with normal weight (body-mass-index (BMI)<25 kg/m(2)) were included in the present analysis. Patients were further defined as MONW or metabolically nonobese based on a cut-off value of the homeostasis model assessment of insulin resistance (HOMA-IR = 1.86). Fasting blood samples were collected to determine levels of various metabolic parameters. In addition, lipoprotein subclass concentrations and sizes were analyzed using nuclear magnetic resonance (NMR) spectroscopy., Results: Seventeen MONW individuals and 17 metabolically nonobese individuals matched by BMI and gender were identified from a study sample of 206 patients with schizophrenia. There were no significant differences between the two groups on anthropometric measures (waist circumference and waist/hip ratio, ps>0.3). However, the MONW group had significantly higher levels of intermediate VLDL particle and Apolipoprotein B, and significantly lower levels of large HDL particle compared with the metabolically nonobese group (p = 0.012, p = 0.036 and p = 0.041 respectively)., Conclusion: The MONW individuals in non-diabetic schizophrenia patients seem to have an unfavorable metabolic profile and significant atherogenecity. Clinicians should be vigilant about the risk of cardiometabolic comorbidity even when the patient' body weight is normal., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: Lipoprotein concentrations are associated with the development of atherosclerosis in people with and without diabetes. The relative strength of these associations could differ by diabetes status as a result of diabetes-related lipoprotein modifications., Research Design and Methods: The associations between lipoprotein concentrations and internal and common carotid artery intimal-medial thickness (IMT) assessed by B-mode ultrasonography were examined by diabetes status in a cross-sectional analysis among 1,391 participants in the Insulin Resistance Atherosclerosis Study. Participants included 442 individuals with type 2 diabetes, 308 with impaired glucose tolerance, and 641 with normal glucose tolerance., Results: The differences in internal and common carotid IMT between the highest and lowest tertiles of LDL were 58.1 microm (P = 0.054) and 51.0 microm (P < 0.001), respectively. The differences in internal and common carotid IMT between the lowest and highest tertiles of HDL were 56.2 microm (P = 0.07) and 37.8 microm (P = 0.003), respectively Triglycerides and VLDL were not associated with IMT. These associations did not differ significantly because of diabetes status., Conclusions: These results support the importance of dyslipidemia as a major risk factor for atherosclerosis in people with diabetes. Future research in humans should measure lipoprotein oxidizability, glycation, size, and composition directly in people of differing glucose tolerance status to address the importance of diabetes-related lipoprotein modifications more conclusively.

The study purpose was to explore the association between dyslipidemia and insulin resistance in three ethnic groups. The Insulin Resistance Atherosclerosis Study (IRAS) is a multicenter epidemiologic study conducted at four clinical centers in California, Texas, and Colorado. The study population for this analysis consisted of 931 non-Hispanic white, African American, and Hispanic men and women (aged 45 to 64 years) without diabetes. The IRAS clinical examinations included lipoprotein measures, a 75-g glucose tolerance test, and the frequently sampled intravenous glucose tolerance (FSIGT) test. The results show a consistent relationship between insulin-mediated glucose disposal and dyslipidemia in African American, Hispanic, and non-Hispanic white men and women. Further, LDL size was inversely associated with insulin resistance in all three ethnic groups. These findings indicate that dyslipidemia is a fundamental part of the insulin resistance syndrome in all of the ethnic groups studied.

Using a density gradient ultracentrifugal procedure, we have separated equine plasma and follicular fluid high-density lipoproteins (HDL). The density distribution of the follicular fluid HDL was clearly displaced towards the highest densities in comparison with that of plasma HDL. Similarly, an analysis of size distributions showed a decrease in follicular fluid HDL diameters (4.2 to 9.2 nm) compared to plasma HDL (5.5 to 9.5 nm). HDL were isolated into three subfractions on the basis of the disposition of the Sudan Black stained bands in the centrifuge tubes. Concentrations of each subfraction were clearly lower in the follicular fluid, and the relative percentages with regard to the plasma equivalents were inversely proportional to the molecular weights (23.8% for HDL-1, 49.9% for HDL-2 and 63.7% for HDL-3). The cholesterol/phospholipid molar ratio and the esterified/free cholesterol molar ratio were clearly increased in the follicular HDL-2 and HDL-3 subfractions. The apolipoprotein distribution in follicular fluid HDL was very close to that in plasma HDL. LCAT activity measured in human as well as equine samples was weaker in follicular fluid compared to plasma in both species (4.0 nmol of free cholesterol esterified per h per ml vs. 24 nmol per h per ml). Theoretical concentrations of follicular fluid HDL were calculated assuming that the HDL particles would be merely a filtration product undergoing no detectable metabolic modifications. Biochemical measurements showed that the lightest particles (HDL-1) were less numerous than suggested by the theoretical calculation. Thus, although follicular fluid HDL appear to be a filtration product of plasma HDL, they undergo metabolic transformations that we suggest may be linked to hormonal synthesis and reverse cholesterol transport.

A Leitz-Tas automatic image analysis system has been used to investigate the size distributions of human lipoprotein particles isolated by density gradient ultracentrifugation. Computerized image analysis enabled us to obtain more precise determinations of modal diameter and overall range in diameter for each lipoprotein subspecies than those determined by classical methods. In addition, lipoprotein molecular weight distributions were calculated from measurements of flotation density and particle size distributions. This method offers certain advantages over other procedures used to characterize mean molecular weight with regard to the ability to define lipoprotein polydispersity. The method and its limitations are discussed and illustrated with results obtained with human lipoproteins.

1. Plasma lipoproteins from six calves at 8, 43 and 118 days old, six heifers and six cows were separated by density gradient ultracentrifugation. For each sample lipoproteins bands were visualized by prestained control and characterized by electrophoretic, chemical and morphological analysis. 2. Two resolved bands were detected in the low density lipoprotein fraction (LDL). At an early stage of development, LDLI and LDLII were present with almost equal concentration. With ageing, LDLII became the major fraction of LDL lipoproteins. 3. HDL were isolated as a single band distributed over the range 1.064-1.166 mg/ml in young calf and 1.050-1.152 mg/ml in adult. This progressive decrease of density limits with ageing, associated with a decrease of protein content and an increase of phospholipids and cholesteryl esters content, was consistent with higher HDL particle diameters in adult. 4. With ageing, free cholesterol/esterified cholesterol ratio decreased in LDL fractions and increased in HDL fractions.

1. Plasma lipoproteins from six thoroughbred horses were separated by density gradient ultracentrifugation. For each sample, lipoprotein bands were visualized by means of a prestained plasma control and characterized by electrophoretic, chemical and morphological analysis. 2. Very low density lipoproteins (VLDL) were isolated at d less than 1.018 g/ml. 3. Two clearly resolved bands were detected in the low density lipoprotein fraction (LDL). The density limits were evaluated as follows: LDL1(1.028 less than d less than 1.045 g/ml) and LDL2(1.045 less than d less than 1.070 g/ml). Marked differences were observed in the chemical composition and particle size of LDL1 and LDL2 fractions. 4. High density lipoprotein fraction (HDL) was usually isolated as a single band, distributed over the range 1.075 less than d less than 1.180 g/ml. However, chemical composition and particle size revealed heterogeneity in HDL subfractions. 5. The density limit of LDL and HDL bands varied in each animal, indicating differences in equine lipoprotein distribution.

Six 8-day-old female calves were treated with a subcutaneous implant of 200 mg testosterone + 20 mg estradiol-17 beta. Thirty-five days following implantation, plasma lipoproteins were compared to those in control calves of the same age. The LDL exhibited a slight change in protein and lipid concentrations and no change in particle size. The effects of steroid therapy on HDL and particularly on the lighter density HDL were characterized by a reduction of densities associated with a decrease in protein content, and by a rise in lipids and an increase in particle size. The changes in HDL composition but not in LDL alterations were consistent with those associated with sexual maturation described previously. Although testosterone is the predominant component of our combined preparation, the effects of our treatment on young female calves is not consistent with the data reported for human lipoproteinemia. The high levels of urinary estradiol in treated calves suggest that these effects result more likely from the aromatization of the injected testosterone.

1. Equine lipoproteins were isolated from plasma by density gradient ultracentrifugation and apolipoprotein composition determined by SDS-polyacrylamide gel electrophoresis. 2. VLDL and IDL were present at low concentration (0.2 mg/ml). Two apoB components of Mr corresponding to human apoB-100 and one apoB-48-like component were represented in VLDL fraction. 3. LDL-1 and LDL-2 subfractions have displayed an almost equal concentration (0.4 mg/ml). Two apoB-100-like components were the major apolipoproteins in each fraction. Small amounts of apoB-48-like component were detectable in LDL-1 and LDL-2. 4. HDL-2 represented a major class of equine lipoproteins (1.8 mg/ml). ApoA-1-like component was the dominant protein in HDL-1, HDL-2 and HDL-3. Dimeric apoA-II-like components were slightly represented in HDL subfractions. 5. HDL-3 displayed the same apolipoprotein pattern as HDL-1 and HDL-2, but two further minor proteins of Mr 20,000 and 14,000 were detected. 6. VHDL represented a minor class of lipoprotein (0.2 mg/ml). ApoA-I-like component was the major apolipoprotein of VHDL. Small amounts of apoA-IV-like, apoE-like, and Mr 55,000 protein were detectable. 7. ApoC-like of Mr lower than 10,000 was represented in all equine lipoprotein classes.

Objective: The primary purpose of this 8-week double-blind, placebo-controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine-treated subjects with schizophrenia with insulin resistance. Method: Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI. Results: Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non-significant improvement in SG (0.016 ± 0.006–0.018 ± 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 ± 2.8–7.8 ± 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low-density lipoprotein cholesterol (LDL-C) particle number (987 ± 443–694 ± 415, effect size = 0.30, P = 0.04). Conclusion: Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine. [ABSTRACT FROM AUTHOR]