The novel insulin resistance parameters RBP4 and GLP-1 in patients treated with valproic acid: just a sidestep?

Valproic acid (VPA), as one of the most widely prescribed antiepileptic drugs (AED) for many types of epilepsy in adults and children, is associated with weight gain, alteration of adipocytokine homeostasis, insulin resistance and Non-Alcoholic Fatty Liver Disease (NAFLD). Retinol-binding protein 4 (RBP4) and Glucagon-like peptide-1 (GLP-1) are considered as important new targets in modern type 2 diabetes mellitus therapy linked to insulin resistance, NAFLD and visceral obesity acting via peripheral or central mechanisms. We herein demonstrate the lack of an influence of VPA treatment on RBP4 and GLP-1 in otherwise healthy patients. In summary, the absence of any relationship with RBP4 and GLP-1 concentrations does not suggest a role of these novel insulin resistance parameters as potential regulators of glucose and fat metabolism during VPA-therapy.

Non-alcoholic fatty liver disease (NAFLD), insulin resistance and lipid profile in antiepileptic drug treatment.

PURPOSE: Patients undergoing long-term treatment with valproic acid (VPA) are prone to develop different features of the metabolic syndrome (MS). The aim of the present study was to evaluate the occurrence of non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and a pro-atherogenic lipid profile in patients undergoing VPA, carbamazepine (CBZ) and lamotrigine (LTG) monotherapy compared to healthy controls. METHODS: Abdominal ultrasound as well as measurement of serum fasting insulin and glucose, serum lipids and liver function parameters were performed in VPA (n=23), CBZ (n=22) and LTG (n=23) treated non-diabetic and non-obese epileptic patients compared to healthy controls (n=16). RESULTS: Ultrasound measurement demonstrated characteristics of fatty liver disease in 60.9% of VPA, in 22.7% of CBZ, in 8.7% of LTG treated patients and in 12.5% of the healthy controls, with highest level of steatosis seen in VPA treated patients. In addition, patients on VPA monotherapy showed a higher body-mass index (BMI) when compared to LTG treated patients and controls (p

Are plasma VEGF and its soluble receptor sFlt-1 atherogenic risk factors? Cross-sectional data from the SAPHIR study.

AIMS: Vascular endothelial growth factor (VEGF) is a potent hypoxia-regulated angiogenic factor. Its soluble receptor soluble (s)Flt-1 binds VEGF with high affinity inhibiting the angiogenic function of VEGF. The role of circulating VEGF in atherosclerosis is unclear. METHODS AND RESULTS: In 909 healthy subjects (511 male, 398 female) from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) we determined fasting plasma VEGF and sFlt-1 concentration, cardiovascular risk factors and carotid atherosclerosis. VEGF levels were lower and sFlt-1 levels higher in men than in women. VEGF and sFlt-1 showed a positive correlation. In the entire population VEGF correlated positively with age, BMI, insulin resistance, white blood cell and platelet count, C-reactive protein (CRP) and carotid intima media thickness (IMT). After adjustment for age, VEGF showed a weak positive correlation with BMI, liver enzymes, CRP and platelet count in males. In females VEGF correlated negatively with LDL-cholesterol and positively with insulin resistance and platelet count. After adjustment for age, no significant correlation with carotid atherosclerosis could be detected. CONCLUSION: Plasma VEGF and sFlt-1 are only weakly correlated with cardiovascular risk factors, suggesting that circulating VEGF levels do have only a minor impact on the development of atherosclerosis.

Effect of obesity and insulin sensitivity on adiponectin isoform distribution.

BACKGROUND: Adiponectin is an insulin-sensitizing, antiatherogenic and anti-inflammatory adipocytokine that circulates in three isoforms: a trimer [low-molecular weight (LMW)], a hexamer (trimer-dimer) of medium molecular weight (MMW) and a multimeric high molecular weight (HMW) isoform. Evidence is accumulating that HMW adiponectin is the active isoform of the adipocytokine. We investigated the impact of adipose tissue and insulin sensitivity on adiponectin isoform distribution. MATERIALS AND METHODS: One hundred and eighty-seven normolipidaemic, non-diabetic lean or obese subjects with or without insulin resistance participating in the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk (SAPHIR) were included in the study. Insulin sensitivity was determined by the short insulin tolerance test and the homeostasis model assessment (HOMA) index. Serum adiponectin isoform distribution was determined by an enzyme immunoassay. RESULTS: Total adiponectin as well as HMW/total adiponectin ratio was significantly increased in female subjects. Circulating total adiponectin levels were lowest in obese patients due to reduced concentrations of HMW adiponectin. As determined by stepwise regression analysis, besides age and high density lipoprotein (HDL) cholesterol, visceral fat area and waist-to-hip ratio predicted concentrations of HMW adiponectin, while insulin sensitivity had no influence on either total adiponectin or its isoforms. CONCLUSIONS: Our results underline that determination of adiponectin isoforms are more useful than measurement of total adiponectin in clinical settings. Our data suggest that adiponectin concentrations are strongly associated with visceral fat area but not with insulin sensitivity. Thus, we hypothesize that insulin resistance is a consequence rather than the cause of hypoadiponectinaemia in obese subjects.

[Respiratory symptoms in the general practice. An analysis of the Leipzig SESAM Study]. / Atemwegsbeschwerden in der allgemeinärztlichen Sprechstunde. Eine Auswertung der Leipziger SESAM-Studie.

The Saxon Study of General Medicine (SESAM) investigated the reasons why patients consulted the general practitioner, which diagnoses were established and how the patients were subsequently treated. In the majority of cases, the respiratory symptoms were simple infections of the upper and lower respiratory tract. Pneumonia must always be considered, while severe pulmonary diseases are of no significance in the differential diagnosis of respiratory complaints in the general practice.

Effect of pronounced weight loss on visceral fat, liver steatosis and adiponectin isoforms.

BACKGROUND: Weight loss induced by bariatric surgery is an effective method to reverse obesity and comorbidities. The aim of this prospective weight loss study was to investigate changes of body fat distribution in relation to adiponectin and its isoforms and further to investigate the influence of both body fat distribution and adiponectin on the degree of liver steatosis. DESIGN: Fifteen severely obese female patients (body mass index 43.1 +/- 4.1, mean age 34.5 +/- 8.6 years) were examined before and after surgical treatment. Grading of fatty liver disease and the subcutaneous and visceral fat diameters were determined by abdominal ultrasonography. Metabolic parameters were determined using standard methods; serum total adiponectin and its isoforms were detected by enzyme immuno assay (EIA). RESULTS: Mean weight loss was 28.3 kg, which was mostly due to a loss in fat mass, accompanied by an increase in total adiponectin and the high molecular weight (HMW) adiponectin isoform. Visceral adipose tissue (VAT) diameter was highly correlated with liver steatosis, even more strongly than the parameters of liver function. In addition, liver steatosis correlated negatively with HMW adiponectin and binary logistic regression revealed that changes in fat mass, HMW adiponectin and alanine aminotransferase (ALT) were the best predictors for changes in the degree of hepatic steatosis. CONCLUSIONS: Our results suggest that circulating HMW adiponectin is associated with both VAT and liver steatosis. In summary, the major findings were that the VAT diameter is highly correlated with liver steatosis, even stronger than the parameters of liver function and the association of HMW adiponectin with liver steatosis was better than with total adiponectin.

Comparison of different definitions of the metabolic syndrome.

BACKGROUND: The International Diabetes Federation (IDF) published a new definition of the metabolic syndrome (MetS). For this definition we compared frequency, concordance, clinical and laboratory stigmata and carotid atherosclerosis with those of the established definitions by the National Cholesterol Education Program (NCEP) and World Health Organization (WHO). MATERIALS AND METHODS: A total of 1518 subjects (943 men, 575 women) from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR), free of clinical atherosclerosis, were included in this study. To estimate insulin sensitivity two methods, i.e. homeostasis model assessment of insulin resistance (HOMA-IR) and the short insulin tolerance test, were employed. Carotid intima media thickness (IMT) and plaque extent were quantified for all subjects using high-resolution ultrasound. RESULTS: Prevalence of the MetS was 18.7% for men and 16.2% for women for the WHO definition, 18.9% and 17.0%, respectively, for the NCEP definition, and 25.8% and 19.5%, respectively, for the IDF definition. Concordance was lower between the definitions of WHO and IDF (< 50%) than between NCEP and IDF (> 67%). Compared to subjects identified by NCEP definition, subjects identified in excess by IDF (3.1-11.7%) showed less insulin resistance and lower IMT and plaque extent indistinguishable from MetS-free subjects. CONCLUSIONS: Our data suggest that the IDF definition includes subjects as MetS sufferers above these detected by NCEP or WHO, who exhibit considerably less insulin resistance and carotid atherosclerosis blurring the distinction between health and disease.

Plasma cholesteryl ester transfer protein concentrations predict cardiovascular events in patients with coronary artery disease treated with pravastatin.

OBJECTIVE: The B1B1 variant of the cholesteryl ester transfer protein (CETP) TaqIB polymorphism and high plasma CETP concentrations are associated with favourable angiographic outcomes in pravastatin-treated patients suffering from coronary artery disease (CAD). The purpose of the present study was to test whether CETP TaqIB genotypes and/or plasma CETP concentrations at baseline also predict clinical end-points in patients with CAD. DESIGN: Prospective longitudinal observational study. SETTING: Primary care doctors (n=88) and hospitals (n=7) in Austria. SUBJECTS: A total of 1620 men and women with preexisting CAD were recruited and plasma lipids were determined at study entry. 1389 hypercholesterolaemic patients were included and 1002 patients completed the follow-up. INTERVENTIONS: In all patients treatment with pravastatin was started and patients were followed up for 2 years. MAIN OUTCOME MEASURES: Cardiovascular events. RESULTS: One hundred patients suffered at least one cardiovascular event. We observed significantly more events in patients within the lowest compared with the highest quartile of plasma CETP concentrations (odds ratio 3.20, CI95 1.65-6.23; P=0.001, adjusted for known risk factors of CAD). No significantly different numbers of cardiovascular events were found between CETP TaqIB genotypes. CONCLUSIONS: Plasma CETP concentrations, but not CETP TaqIB genotypes, predict cardiovascular events in patients with CAD treated with pravastatin. Despite higher LDL cholesterol concentrations, high plasma CETP concentrations at baseline are associated with fewer cardiovascular events compared with low plasma CETP concentrations in CAD patients treated with pravastatin.

Effect of pronounced weight loss on the nontraditional cardiovascular risk marker matrix metalloproteinase-9 in middle-aged morbidly obese women.

OBJECTIVE: Obesity is associated with increased morbidity and mortality from atherosclerotic disease. Nontraditional cardiovascular risk factors such as C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated in obese subjects and weight loss is associated with an attenuation of these risk factors. Matrix metalloproteinase-9 (MMP-9) has been linked to plaque rupture, and is, thus, a candidate marker of future myocardial events. The aim of this study was to determine the influence of weight loss on MMP-9 plasma concentrations. METHODS AND RESULTS: CRP, IL-6 and MMP-9 were analyzed from samples of 45 morbidly obese, middle-aged women before gastric banding and 1 y postsurgical treatment in this prospective study. The body mass index (BMI) of subjects decreased from 42.5+/-4.9 to 32.3+/-5.3 kg/m(2) 1 y after gastric banding. In parallel, both MMP-9 and CRP were reduced by 23 and 41%, respectively. A positive relationship was found between BMI and MMP-9 (r=0.312, P<0.05), and between CRP and IL-6 (r=0.508, P<0.05), whereas no correlation was found between CRP and MMP-9. CONCLUSIONS: We conclude that weight loss is associated with a pronounced decrease in the nontraditional cardiovascular risk markers MMP-9 and CRP, which could indicate future beneficial effects of weight loss on the cardiovascular risk in weight loosing subjects.

Effects of weight loss on PLTP activity and HDL particle size.

OBJECTIVE: Dyslipidaemia in obesity is characterized by hypertriglyceridaemia, low HDL-C levels, small, dense HDL particles and increased phospholipid transfer protein (PLTP) activity. METHODS: In the present study, we investigated PLTP activity and HDL particle size in 16 morbidly obese, middle-aged women, who underwent Swedish Adjustable Gastric Banding surgery. Study subjects were tested within 2 months before and 1 y after surgery. PLTP activity was determined by exogenous substrate assay and HDL particle size by gradient gel electrophoresis, respectively. RESULTS: Pronounced weight loss after gastric banding surgery resulted in a significant decrease of PLTP activity from 8.42+/-2.04 to 7.43+/-2.21 micromol/ml/h (P=0.02). The size of HDL(2) particles increased signficantly from 14.04+/-0.86 to 14.28+/-0.64 nm (P=0.02) after body weight reduction, while no change in HDL(3) particle size was apparent. DISCUSSION: Our results suggest that dyslipidaemia in obesity is--at least partially--reversible by weight loss. We hypothesize that reduction of PLTP activity and increase of HDL particle size are important component factors in converting the atherogenic lipoprotein profile of obese subjects into a less atherogenic profile with weight loss.

Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro.

Resistin is a recently discovered polypeptide that induces insulin resistance in rodents. While in rodents resistin is predominantly expressed in adipocytes, in humans peripheral blood mononuclear cells (PBMC) seem to a be a major source of resistin. In the present study, we show that in human PBMC resistin mRNA expression-determined by fluorescence-based real-time polymerase chain reaction-is strongly increased by the proinflammatory cytokines interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-alpha), and also by lipopolysaccharides (LPS), respectively, while no effect was found by interferon-gamma (IFN-gamma) or leptin. Our results suggest that in humans resistin may be a link in the well-known association between inflammation and insulin resistance.

Phospholipid and cholesteryl ester transfer are increased in lipoprotein lipase deficiency.

OBJECTIVES: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism by mediating the transfer and exchange of phospholipids (PL) and neutral lipids between lipoproteins. Lipoprotein lipase (LPL) deficiency is associated with low HDL-cholesterol (HDL-C) levels in both, the homozygous and heterozygous state. In the present study we set out to investigate the role of lipid transfer proteins, which are known to strongly determine HDL-C levels, in LPL deficiency. DESIGN/SUBJECTS: Phospholipid acceptor and donor properties of lipoproteins, PLTP activity, CETP mass, activity and cholesteryl ester (CE) transfer were determined in two homozygous and six heterozygous LPL-deficient subjects and in 10 healthy, normolipidaemic controls, respectively. RESULTS: The HDL isolated from LPL-deficient subjects showed strongly increased PL-acceptance when compared with controls (homozygotes versus heterozygotes versus control: 26.46 +/- 15.26 vs. 3.41 +/- 1.61 vs. 1.89 +/- 0.33 micromol mL-1 h-1/micromol mL-1 PL; all P < 0.05). Phospholipid transfer from apolipoprotein B containing lipoproteins was increased in heterozygotes when compared with controls (46.66 +/- 23.3 vs. 28.91 +/- 18.05 micromol mL-1 h-1/micromol mL-1 PL, P = 0.05). PLTP activity, however, was similar in LPL-deficient subjects and controls. CETP mass was highest in homozygotes, whilst enzyme activity was similar in LPL-deficient subjects and controls. CE transfer was highest in homozygotes (72.5 +/- 8.8%) and lowest in controls (28.7 +/- 5.2%, P < 0.01). CONCLUSIONS: In conclusion, PL and CE transfer are increased in LPL deficiency and thus, partly explain low HDL-levels in LPL-deficient subjects. Enhanced transfer seems rather to be the result of altered lipoprotein composition and concentration than altered enzyme activity. Our findings on mechanisms leading to low HDL-C levels might show another aspect in atherogenesis in LPL deficiency.

Relationship between cholesteryl ester transfer protein and atherogenic lipoprotein profile in morbidly obese women.

OBJECTIVE: Obesity is associated with increased morbidity and mortality from atherosclerotic disease. Lipid abnormalities contribute to the increased relative risk in obese subjects. Cholesteryl ester transfer protein (CETP) mass is increased in these patients and might mediate the atherogenic lipoprotein pattern observed in obesity. METHODS AND RESULTS: Twenty-one morbidly obese, middle-aged, female subjects participated in this prospective study. Subjects were examined before and 1 year after surgical treatment. Fat mass was determined by body impedance analysis; CETP mass, by ELISA; CETP activity, by exogenous substrate assay; and LDL particle diameter, by gradient gel electrophoresis. Mean weight loss after 1 year was 28.7 kg; mean fat mass loss was 22.6 kg. Mean CETP mass decreased from 1.81 to 1.32 microg/mL (P=0.008); mean CETP activity decreased from 244 to 184 nmol x mL(-1) x h(-1) (P=0.004); and in parallel, the mean diameter of LDL particles increased (256.8 to 258.4 A, P=0.04). CONCLUSIONS: We conclude that weight loss is associated with a pronounced decrease in CETP mass and activity and a consistent increase in LDL particle diameter. After 1 year of this prospective study in morbidly obese subjects undergoing weight loss by surgical treatment, it has been determined that some features of the atherogenic lipoprotein profile can be reversed.

Antithrombin and near-fatal exertional heat stroke.

Heat waves result in excess deaths, excess emergency department visits, and intensive care unit admissions for heat stroke. We describe the clinical features and 3-month outcome of a patient with near-fatal heat stroke, admitted to our intensive care unit in July, 2001. After heavily working for hours at a construction site during a heat wave, the 28-year-old male presented with 41.4 degrees C body temperature and multiorgan failure, consisting of neurological impairment, rhabdomyolysis, acute renal failure, disseminated intravascular coagulation, and acute respiratory distress syndrome (ARDS). In the first week there was no evidence of infection. Treatment included cooling, aggressive volume resuscitation, administration of antithrombin-III concentrates and steroids. The patient survived and recovered normal neurological, renal, respiratory and haematological function, and no disability persisted. This case illustrates survival and complete recovery after multiorgan failure in heat stroke with vigorous intensive care. Treatment with antithrombin and steroids and may well have contributed to the favourable outcome. Correction of reduced antithrombin III levels to supranormal by therapeutic administration of antithrombin III concentrate in disseminated intravascular coagulation of heat stroke was not associated with any bleeding complications.

Markers of chronic inflammation and obesity: a prospective study on the reversibility of this association in middle-aged women undergoing weight loss by surgical intervention.

BACKGROUND: Human adipose tissue expresses and releases proinflammatory cytokines and these measures of chronic inflammation have recently been associated with obesity. HYPOTHESIS: To test whether the proinflammatory state is reversible in subjects undergoing weight loss by surgical measures. SUBJECTS AND METHODS: Twenty morbidly obese women participated in this prospective study. Subjects were examined for fat mass, high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) before and 1 y after Swedish adjustable gastric banding. RESULTS: Anthropometric measures displayed a significant reduction of the body mass index (BMI) from 41.6+/-5.4 to 30.8+/-6.1 kg/m(2) and the fat mass from 53.9+/-10.3 to 29.8+/-12.1 kg (mean+/-s.d.). Hs-CRP levels decreased significantly from 1.33+/-1.21 mg/dl in pre-gastric banding subjects to 0.40+/-0.61 mg/dl in post-gastric banding subjects, respectively. IL-6 and TNF-alpha levels did not differ significantly between pre- and post-gastric banding subjects. CONCLUSIONS: We speculate that in these patients the marked reduction in C-reactive protein might be beneficial in reducing their cardiovascular risk and is not solely mediated by IL-6 and TNF-alpha.

Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency.

AIMS/HYPOTHESIS: Several studies have investigated the lipoprotein phenotype in heterozygous carriers of a defective lipoprotein lipase allele. We studied whether heterozygosity for lipoprotein lipase deficiency also affects glucose metabolism beyond its effect on plasma lipids. METHODS: To address this question 85 heterozygous carriers of either a missense mutation (Gly188Glu) or a splice site mutation (C-->A in position -3 at the acceptor splice site of intron 6) in the LPL gene which both result in a catalytically inactive product were compared with 108 unaffected subjects from the same families. RESULTS: Carriers for one of these mutations had higher fasting insulin levels but only a trend towards increased fasting blood glucose concentrations could be detected. HOMA index values were significantly higher in carriers than in non-carriers. Furthermore, in carriers, a significantly higher BMI and a trend towards higher systolic and diastolic blood pressure were observed. Carriers also had significantly higher fasting triglycerides, lower HDL cholesterol, and lipoprotein lipase particles of smaller size, confirming previous reports. Among carriers, subjects with one rare allele of the SstI polymorphism in the apo CIII gene had significantly higher plasma triglyceride levels than those with two common SstI alleles. This difference could not be observed in non-carriers of a mutant lipoprotein-lipase allele. The mean intima media thickness of the carotid arteries was slightly, but not significantly higher in carriers when compared with non-carriers. CONCLUSION/INTERPRETATION: This study shows that carrier status of one defective lipoprotein-lipase allele is associated with impaired insulin sensitivity, an atherogenic lipoprotein profile and other characteristics of the metabolic syndrome, which are risk factors for atherosclerotic vascular disease. A higher incidence of atherosclerotic vascular disease, however, could not be firmly established in carriers of this study population.

Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2.

AIM: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism facilitating the transfer and exchange of cholesteryl esters, triglycerides and phospholipids between lipoproteins. In the study presented here, we investigated the influence of two hormones-the adipocyte-derived hormone leptin as well as insulin on the hepatic secretion of both, PLTP and CETP. METHODS: PLTP activity and CETP concentration-measured by exogenous substrate assay and enzyme-linked immunosorbent assay-were determined in supernatant of human hepatoma cell line HepG2 after single or combined exposure to leptin and insulin at physiological and supraphysiological concentrations, respectively. Messenger-RNA of PLTP and CETP was quantified by Northern blot analysis. RESULTS: Leptin suppressed PLTP activity and CETP-concentration by up to 33% and 23%, respectively. Insulin also suppressed PLTP activity by up to 11% and CETP-concentration by up to 16%. In combination, the two hormones had additive suppressive effects for both, PLTP activity and CETP-concentration. Northern blot analysis showed no difference in m-RNA levels after exposure to leptin or insulin. CONCLUSIONS: Leptin and insulin, both known to increase with body fat mass, suppress production of PLTP and CETP in HepG2 cells. When extrapolated to the in vivo situation, this suppressive effect may constitute a mechanism counteracting the potentially harmful action of lipid transfer proteins, particularly reduction of HDL-cholesterol, in conditions frequently associated with increased plasma triglyceride levels such as obesity and insulin resistance.

Influence of obesity and insulin sensitivity on phospholipid transfer protein activity.

AIMS/HYPOTHESIS: Phospholipid transfer protein plays a key role in lipoprotein metabolism by catalysing the transfer of phospholipids from triglyceride-rich lipoproteins to high-density lipoproteins and, also, within the high-density lipoprotein family, from particle to particle. This transfer results in a change of HDL particle size and the generation of pre-beta-high-density lipoproteins which function as initial lipid acceptors in the process of reverse cholesterol transport. Because adipose tissue is a source of phospholipid transfer protein we investigated the influence of obesity and insulin sensitivity on phospholipid transfer protein activity. METHODS: Using an exogenous substrate assay phospholipid transfer protein activity was measured in plasma specimens of 190 normolipidaemic, non-diabetic subjects with BMI ranging from 19 to 43 kg/m2. Insulin sensitivity was measured by the short insulin tolerance test. RESULTS: Phospholipid transfer protein activity was associated with BMI (r = 0.46, p < 0.01), body fat mass (r = 0.39, p < 0.01), subcutaneous fat area (r = 0.32, p < 0.01) and plasma leptin concentration (r = 0.24, p < 0.01) but not with insulin sensitivity expressed as the k(s) of the insulin tolerance test (kITT value) (r = -0.14, p = 0.40). Accordingly, phospholipid transfer protein activity was higher in obese than in nonobese subjects. As determined by linear regression analysis, BMI was the sole predictor of phospholipid transfer protein activity in plasma explaining 22.2% of the activity (p< 0.01). CONCLUSIONS/INTERPRETATIONS: This data suggests that increased phospholipid transfer protein activity in obese subjects is a consequence of obesity itself without the contribution of insulin resistance and can be explained by increased synthesis of phospholipid transfer protein from the enlarged mass of adipose tissue.

Flow-mediated, endothelium-dependent vasodilatation is impaired in male body builders taking anabolic-androgenic steroids.

Self-administration of anabolic-androgenic steroids to increase muscular strength and lean body mass has been used widely among athletes. Flow mediated dilatation (FMD) determined by ultrasound of the brachial artery is accepted as both an in vivo index of endothelial function and an indicator for future atherosclerosis. FMD was calculated in 20 male non-smoking body builders in different phases of their training cycle and in six male non-smoking control athletes. Ultrasound studies of the brachial artery were performed according to the protocol of Celermajer et al. Of the entire training cycle, work-out phase was training phase without actual intake of anabolic-androgenic steroids over 8 weeks; build-up phase included actual intake of anabolic-androgenic steroids; and competition phase consisted of 8 weeks post intake of anabolic-androgenic steroids. Baseline characteristics did not differ between body builder groups except for a higher weight in competition phase body builders. Hormonal analysis revealed suppressed luteinizing hormone and follicle stimulating hormone levels in build-up phase body builders. The lipid profiles showed a marked reduction of HDL-C in build-up phase body builders. FMD was reduced in body builders of all phases when compared to control athletes (work-out phase: 2.5+/-2.7%; build-up phase: 2.1+/-3.0%; competition phase: 0.4+/-2.9% vs. 10.9+/-4.4%, P<0.05 by pairwise comparison using Scheffe's test for work-out phase, build-up phase and competition phase vs. control athletes). The glyceryl trinitrate-induced vasodilatation was diminished, though not statistically significantly, in body builders when compared with control athletes. The differences in FMD persisted after adjustment for vessel size. Our data indicate that intake of anabolic-androgenic steroids is associated with both an atherogenic blood lipid profile and endothelial dysfunction and thus may pose an increased risk of atherosclerosis.

Lipoprotein profile and cholesteryl ester transfer protein in neonates.

Undernourishment in utero appears to be associated with persisting changes in the metabolic, endocrine, and immune functions. In this study, we determined the influence of birth weight on the lipoprotein profile and cholesteryl ester transfer protein (CETP), which promotes a proatherogenic lipoprotein profile in plasma by determining the chemical, physical, and biologic properties of the respective lipoprotein particles. Triglyceride (TG) concentrations were highest and high-density lipoprotein (HDL)(2)-cholesterol levels were lowest in small for gestational age (SGA) neonates. CETP-mass was determined by enzyme-linked immunosorbent assay (ELISA) and CETP-activity by using exogenous lipoproteins. Cholesteryl ester transfer was determined as transfer of radiolabeled cholesteryl esters (CE) from HDL to apolipoprotein B-containing lipoproteins. CETP mass was lowest and cholesteryl ester transfer was highest in SGA neonates. CETP-activity did not differ among the neonates. Our results suggest that increased and decreased nourishment in utero affects the lipoprotein profile and CETP in neonates. High TG and low HDL(2) levels in SGA neonates might result from increased cholesteryl ester transfer and, may in part, explain the increased risk of coronary heart disease (CHD) of small for gestational age neonates in later life.