The secretion pattern of perivascular fat cells is different from that of subcutaneous and visceral fat cells.

AIMS/HYPOTHESIS: We have previously found that the mass of perivascular adipose tissue (PVAT) correlates negatively with insulin sensitivity and post-ischaemic increase in blood flow. To understand how PVAT communicates with vascular vessels, interactions between perivascular, subcutaneous and visceral fat cells with endothelial cells (ECs) were examined with regard to inflammatory, metabolic and angiogenic proteins. To test for possible in vivo relevance of these findings, circulating levels of the predominant secretion product, hepatocyte growth factor (HGF), was measured in individuals carefully phenotyped for fat distribution patterns. METHODS: Mono- and co-cultures of human primary fat cells with ECs were performed. mRNA expression and protein production were studied using Luminex, cytokine array, RealTime Ready and ELISA systems. Effects of HGF on vascular cells were determined by WST assays. In patients, HGF levels were measured by ELISA, and the mass of different fat compartments was determined by whole-body MRI. RESULTS: In contrast with other fat cell types, PVAT cells released higher amounts of angiogenic factors, e.g. HGF, acidic fibroblast growth factor, thrombospondin-1, serpin-E1, monocyte chemotactic protein-1 and insulin-like growth factor-binding protein -3. Cocultures showed different expression profiles from monocultures, and mature adipocytes differed from pre-adipocytes. HGF was preferentially released by PVAT cells and stimulated EC growth and smooth muscle cell cytokine release. Finally, in 95 patients, only PVAT, not visceral or subcutaneous mass, correlated independently with serum HGF levels (p = 0.03; r = 0.225). CONCLUSIONS: Perivascular (pre-)adipocytes differ substantially from other fat cells with regard to mRNA expression and protein production of angiogenic factors. This may contribute to fat tissue growth and atherosclerotic plaque complications. Higher levels of angiogenic factors, such as HGF, in patients with increased perivascular fat mass may have pathological relevance.

Student tutors are able to teach basic sonographic anatomy effectively - a prospective randomized controlled trial.

PURPOSE: Ultrasound is a widely used diagnostic tool. In medical education, it can be used to teach sonographic anatomy as well as the basics of ultrasound diagnostics. Some medical schools have begun implementing student tutor-led teaching sessions in sonographic abdominal anatomy in order to meet the growing demand in ultrasound teaching. However, while this teaching concept has proven to be feasible and well accepted, there is limited data regarding its effectiveness. We investigated whether student tutors teach sonographic anatomy as effectively as faculty staff sonographers. MATERIALS AND METHODS: 50 medical students were randomly assigned to one of two groups. 46 of these could be included in the analysis. One group was taught by student tutors (ST) and the other by a faculty staff sonographer (FS). Using a pre/post-test design, students were required to locate and label 15 different abdominal structures. They printed out three pictures in three minutes and subsequently labeled the structures they were able to identify. The pictures were then rated by two blinded faculty staff sonographers. A mean difference of one point in the improvement of correctly identified abdominal structures between the pre-test and post-test among the two groups was regarded as equivalent. RESULTS: In the pre-test, the ST (FS) correctly identified 1.6 ± 1.0 (2.0 ± 1.1) structures. Both the ST and FS group showed improvement in the post-test, correctly identifying 7.8 ± 2.8 vs. 8.9 ± 2.9 structures, respectively (p < .0001 each). Comparing the improvement of the ST (6.2 ± 2.8 structures) versus the FS (6.9 ± 3.2) showed equivalent results between the two groups (p < .05 testing for equivalence). CONCLUSION: Basic abdominal sonographic anatomy can be taught effectively by student tutors.

[18F] FDG-PET/CT as a new and sensitive imaging method for the diagnosis of large vessel vasculitis.

OBJECTIVE: To determine the value of the new imaging modality positron-emission tomography/computed tomography (PET/CT) for the diagnosis and re-evaluation of large vessel vasculitis. METHODS: Thirteen patients newly diagnosed or re-evaluated for suspected clinical disease activity of Takayasu arteritis (TA, 3 patients) or giant cell arteritis (GCA, 10 patients) underwent PET/CT. Clinical activity status, serological markers, and alternative imaging methods were evaluated. RESULTS: In patients with clinical activity despite nearly normal erythrocyte sedimentation rate (ESR) and C reactive protein (CRP), disease activity could be shown by PET-CT. A long segmental, increased fluoro-deoxyglucose (FDG) uptake in the vessel wall served as confirmation of the vascular inflammation. The aortic arch was involved in all patients with active disease (n=12). In the complementary CT scans, stenotic lesions were found in 8 out of 13 patients. Duplex ultrasonography was performed in 11/13 patients and was positive in nine of these patients at least at one site. Magnetic resonance imaging (MRI) was done for confirmation in 10 patients. CONCLUSION: Doppler ultrasonography is a very useful and widely available method to confirm a first suspicion of vasculitis, but it has limitations especially at the large thoracic vessels, which are affected in many cases. ESR and CRP alone are not sufficient to evaluate disease activity. The new imaging modality PET/CT provides the additional information. It allows the evaluation of disease activity and vessel morphology as well as the localization of the inflammatory process in the same session.

Plasma homocysteine concentrations in young individuals at increased risk of type 2 diabetes are associated with subtle differences in glomerular filtration rate but not with insulin resistance.

Plasma homocysteine levels are elevated in individuals with type 2 diabetes contributing to the increased cardiovascular risk of these patients. As insulin resistance is a key feature in type 2 diabetic patients, hyperhomocysteinemia might be a consequence of insulin resistance. We studied this hypothesis in 839 individuals(male: 302, female: 537, mean age: 37.5 years) with a higher prevalence of insulin resistance (positive family history of type 2 diabetes, history of gestational diabetes, overweight). Subjects with overt type 2 diabetes or known kidney disease were excluded from the study. Mean plasma homocysteine concentration was 8.9 micromol/l (95% RCI 4.8-14.9). Adjusted for age and sex we could not find a significant correlation between homocysteine levels and BMI, insulin levels, or the insulin sensitivity-index (r = 0.35; p = 0.48). Furthermore, after a successful lifestyle intervention resulting in a significant decrease in BMI, body fat content and improved insulin sensitivity (p < 0.0001 each) no differences in homocysteine concentrations could be achieved. However,in the cross-sectional analysis we found a significant and independent, negative correlation between glomerular filtration rate (GFR) and homocysteine levels (r = -0.37; p < 0.0001). In conclusion, our study did not reveal a significant association between levels of homocysteine and insulin resistance in a population with an increased risk for type 2 diabetes. However, plasma homocysteine levels were related to subtle differences in kidney function at this early stage.

Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance.

BACKGROUND: Endothelial dysfunction (ED) is regarded as an early step in the development of atherosclerosis. Among the pathogenetic factors leading to atherosclerosis, the role of insulin resistance and hyperinsulinemia as independent risk factors is still under debate. In this study, we examined the association between ED and insulin resistance in normotensive and normoglycemic first-degree relatives (FDRs) of patients with type 2 diabetes mellitus (DM). METHODS AND RESULTS: Endothelium-dependent and -independent vasodilation of the brachial artery was measured with high-resolution ultrasound (13 MHz) in 53 normotensive FDRs (21 men, 32 women; mean age, 35 years) with normal oral glucose tolerance, 10 age- and sex-matched normal control subjects, and 25 DM patients (mean age, 57 years). According to the tertiles of the clamp-derived glucose metabolic clearance rate (MCR), the FDRs were further classified as insulin resistant with an MCR or =7.8 mL. kg(-1). min(-1), and borderline with an MCR of 5.9 to 7.7 mL. kg(-1). min(-1). Flow-associated dilation was 4.1+/-0.9% in insulin-resistant FDRs, 6.7+/-1.1% in borderline FDRs, 9.0+/-1.2% in insulin-sensitive FDRs (P=0.002), 7.7+/-2.9% in control subjects (P=NS versus FDRs), and 3.8+/-1.0% in DM patients (P=0.03). In multiple regression analysis, low MCR was significantly correlated with ED independent of age, sex, smoking, body mass index, percent body fat, serum insulin, and lipids. CONCLUSIONS: There is a significant association between ED and insulin resistance in young FDRs of DM subjects independent of the classic cardiovascular risk factors.

Intense cholesterol lowering therapy with a HMG-CoA reductase inhibitor does not improve nitric oxide dependent endothelial function in type-2-diabetes--a multicenter, randomised, double-blind, three-arm placebo-controlled clinical trial.

Disturbances in nitric oxide (NO) metabolism resulting in endothelial dysfunction play a central role in the pathogenesis of atherosclerosis in hypercholesterolemia and in individuals with type 2 diabetes. It is unclear whether lipid lowering therapy with HMG-CoA-reductase inhibitors might improve endothelial function in subjects with type 2 diabetes as it is demonstrated in non-diabetic subjects with hypercholesterolemia. We examined the influence of 0.2 mg and 0.8 mg cerivastatin on endothelial function in a multicenter, randomised, double-blind, and three-arm placebo-controlled clinical trial. Endothelial function was assessed by nitric oxide-dependent flow mediated vasodilatation (FMD) of the brachial artery. A total of 103 patients with type 2 diabetes were enrolled in the study. Bayer Company undertook a voluntary action to withdraw cerivastatin from market, therefore the study was terminated earlier. At this point 77 patients were randomised, of which 58 completed the study (mean age 60 +/- 8 years, HbA1c 7.4 +/- 0.9 %). At baseline mean FMD was disturbed in all three therapy arms (5.18 +/- 2.31 % in the placebo group, 3.88 +/- 1.68 in the 0.2-mg cerivastation group, and 4.86 +/- 2.25 in the 0.8-mg cerivastatin group). Despite a significant reduction in cholesterol and LDL-cholesterol-levels after 12 weeks of treatment (decrease in LDL-cholesterol - 26.8 +/- 13.9 % in the 0.2-mg group and - 40.3 +/- 16.0 % in the 0.8-mg group, p = 0.0001, ANCOVA) there was no difference in flow mediated vasodilatation (p = 0.52 and p = 0.56 vs. placebo, respectively, ANCOVA). HbA1c, CRP, and HDL-cholesterol did not change during the study. Furthermore no difference in safety profile between cerivastatin and placebo was found. Despite a significant improvement in lipid profile under statin therapy, no improvement of endothelial dysfunction in terms of nitric oxide bioavailability could be detected.

Acute improvement of peripheral endothelial function in postmenopausal women with coronary artery disease after single oral intake of 17beta-estradiol valerate.

Chronic estrogen supplementation is known to improve endothelial function in postmenopausal women. We studied the acute effect of a single dose of orally administered 17beta-estradiol valerate (E2) on the peripheral endothelial dependent and independent vasodilatation in postmenopausal women with coronary artery disease (CAD). 20 postmenopausal women (age: 64.9 (7.2) y, height: 1.61 (0.04) m. weight: 68.6 (10.6) kg) with angiographically confirmed CAD were randomly examined for flow-associated vasodilatation (= FAD%, a marker for endothelial dependent vasodilatation) and for glyceryltrinitrate (400 microg, p.o.) induced vasodilatation (= GTN%, representing endothelial independent vasodilatation) two hours after placebo controlled, randomized crossover intake of 4 mg E2 p.o. After placebo FAD% was impaired (3.5 (1.7)%) compared to historic controls. After the oral intake of 4 mg E2, FAD% improved to 5.0 (2.8)% (P=0.02). GTN% was not significantly influenced by the oral E2 (E2: 12.6 (5.7) v placebo: 11.2 (6.9)%, P=0.14). Endothelial dysfunction can partially be restored by a single oral dose of 4 mg E2. This indicates an acute vasoprotective effect of E2 beyond its genomic and lipid modifying actions. It remains to be investigated if estrogen might play a beneficial role in the acute treatment of symptomatic coronary artery disease such as angina pectoris or preinfarct syndrome.

Insulin action and secretion in healthy, glucose tolerant first degree relatives of patients with type 2 diabetes mellitus. Influence of body weight.

It is a matter of controversy, whether insulin action or secretion - or both - are disturbed in first degree relatives of patients with type 2 diabetes. We intended to assess both the compensatory and the obesity-related part of insulin secretion. In order to dissect out the latter, matching for insulin sensitivity was mandatory to normalize for the compensatory part of hyperinsulinemia. In 154 healthy, glucose tolerant first degree relatives of patients with type 2 diabetes we directly quantified both insulin sensitivity (by euglycemic-glucose-clamp technique) and insulin secretion (oral glucose load; stimulated serum c-peptide). Insulin sensitivity was scattered over a wide range with a considerable overlap of both first degree relatives of patients with type 2 diabetes and 97 controls without a family history of diabetes. Average insulin sensitivity was higher in controls (8.0+/-0.3 vs. 7.1 + 0.2 ml x kg-l x min-1, p < 0.05). Prevalence of insulin resistance (defined as controls, lowest tertile for insulin sensitivity) was 40% in first degree relatives of patients with type 2 diabetes. Insulin secretion after oral glucose was significantly increased in insulin resistant first degree relatives of patients with type 2 diabetes compared to insulin sensitive first degree relatives of patients with type 2 diabetes. Early phase relative insulin secretion (30 min) expressed as x-fold increase above basal was smaller in insulin resistant first degree relatives of patients with type 2 diabetes than in insulin sensitive counterparts (5.3+/-0.4 vs. 7.3+/-0.5; p < 0.01). Body mass index was distributed over the whole range in insulin resistant first degree relatives of patients with type 2 diabetes. In the insulin sensitive subgroup absolute and relative secretion did not differ in obese (Body mass index >25 kg/m2) and insulin sensitivity-matched lean. In obese insulin resistant first degree relatives of patients with type 2 diabetes absolute hyperinsulinemia was combined with reduced and delayed relative early insulin release. In summary, degree and prevalence of insulin resistance is higher in first degree relatives of patients with type 2 diabetes than in controls. However, both groups are of heterogenous metabolic composition and family history as major discriminator should not be overestimated. Our data suggest, that hyperinsulinemia cannot simply be explained as a compensatory event to balance insulin resistance. Hypersecretion is associated with insulin resistance predominantly in combination with obesity. It might be speculated that adipose tissue derived signals to the beta-cell might lead to hypersecretion only in the genetic background that also leads to insulin resistance.

Acute adrenocortical insufficiency due to heparin-induced thrombocytopenia with subsequent bilateral haemorrhagic infarction of the adrenal glands.

A 56 year old male developed bilateral massive adrenal haemorrhage (BMAH) resulting in chronic adrenal insufficiency in the course of heparin-induced thrombocytopenia (HIT)-syndrome. Thrombosis of the central adrenal vein (CAV) with subsequent adrenal haemorrhagic infarction is the most probable cause of the rare association of HIT and BMAH. The exorbitantly high catecholamine plasma levels within the CAV in addition to immunogenic platelet activation are discussed as possible underlying pathophysiological mechanisms.

Flow associated (endothelium dependent) vasodilation and TSH-levels in young normotensive and normoglycemic subjects.

BACKGROUND: Endothelial dysfunction (ED) is regarded as an early step in the development of atherosclerosis. Recent experimental data showed a crosstalk between endothelial NO-synthase activity and thyrotropin production. Therefore we studied whether basal TSH can predict flow associated vasodilation (FAD) in a cohort of healthy young subjects with normal TSH levels. PATIENTS AND METHODS: FAD was evaluated in 60 normotensive and normoglycemic subjects (mean age 34 years; range 18-50). The mean thyrotropin level was 1.43 +/- 0.11 microU/ml (range 0.18-3.52 microU/ml). RESULTS: Comparing subjects in the upper, middle and lower tertile of TSH (2.38 +/- 0.14 microU/ml, 1.23 +/- 0.04 microU/ml and 0.65 +/- 0.06 microU/ml respectively) there was no difference in terms of the classical cardiovascular risk factor profiles (24 h blood pressure, HDL- and LDL-cholesterol, triglycerides, oral glucose load and body fat content). Regarding the vascular parameters, we could neither find an independent association with FAD (7.0 +/- 1.1%, 6.4 +/- 1.0% and 5.8 +/- 1.1% respectively) nor with endothelial independent vasodilation (after application of glycerol trinitrate GTN, 17.3 +/- 1.9%, 18.4 +/- 1.7% bzw. 17.5 +/- 1.6% respectively) between the groups. Furthermore, we could not find a significant association between free thyroid hormones (fT3/fT4) and FAD or GTN-induced vasodilation. CONCLUSION: TSH has no predictive value towards endothelial dysfunction in subjects with thyrotropin levels within the normal range.

Endovascular aneurysm repair of abdominal aortic aneurysms: standards, technical options and advanced indications.

UNLABELLED: Since the introduction of endovascular aneurysm repair (EVAR) in 1991, the endovascular therapy with newest stent grafts has assumed a prominent role in the clinical management of abdominal aortic aneurysms (AAA) with a superior perioperative mortality of EVAR and an equivalent mid-term outcome, compared to open surgery. Newest techniques using chimney or periscope grafts and customized fenestrated and branched stent grafts allow the endovascular treatment of complex pararenal AAA. This article reviews EVAR in the treatment of AAA, evidence based results and advanced indication by newest interventional techniques and technical developments. KEY POINTS: • EVAR has become standard treatment of abdominal aortic aneurysm with equivalent results to open surgery.• Technical advancements and the introduction of newest stent grafts continually expand the indication of EVAR.• Chimney- and periscope grafts as well as custom-made prothesis systems allow endovascular treatment of complex para- and suprarenal aneurysms.

Thyroid perfusion imaging as a diagnostic tool in Graves' disease--arterial spin labeling magnetic resonance imaging vs. colour-coded Doppler ultrasound.

PURPOSE: Though increased thyroid perfusion assessed by colour-coded Doppler ultrasound (CDUS) is characteristic of Graves' disease (GD), sometimes perfusion assessment by CDUS is not possible. In these cases, arterial spin labelling (ASL), a novel magnetic resonance imaging (MRI) technique allowing non-invasive thyroid perfusion quantification, may have additional diagnostic value. We aimed to evaluate the potential of ASL-MRI for assessment of increased blood perfusion in patients with GD compared to CDUS. MATERIALS AND METHODS: Thyroid perfusion was measured by CDUS (volume flow rate calculated from pulsed wave Doppler signals and vessel diameter) and ASL-MRI at 1.5 T in 7 patients with GD and 10 healthy controls. RESULTS: In patients with GD, average perfusion in both thyroid lobes was markedly increased compared to controls. Both techniques applied for volume related perfusion as well as absolute volume flow in thyroid feeding vessels provided similar results (all p=0.0008). Using a cut-off value of 22 ml/min for the volume flow rate assessed by CDUS in the four feeding vessels allowed discrimination between patients with GD and controls in all cases. After adjusting thyroid perfusion for the differences in organ volume, both CDUS and ASL revealed also complete discrimination between health and disease. CONCLUSION: Thyroid perfusion measurement by ASL-MRI reliably discriminate GD from normal thyroid glands. In patients in whom thyroid arteries cannot be depicted by CDUS for technical or anatomical reasons, ASL-MRI may have additional diagnostic value.

Apelin serum levels are not associated with early atherosclerosis or fat distribution in young subjects with increased risk for type 2 diabetes.

Apelin is proposed to possess protective cardiovascular properties and may furthermore promote favorable effects on glucose metabolism. First data in humans seem to support this hypothesis. Therefore we aimed to assess the meaning of apelin as an early risk indicator in young subjects prone to atherosclerosis and type 2 diabetes. Furthermore we examined the association of apelin serum levels with insulin sensitivity/resistance and body fat distribution as probably dependent cardiovascular risk factors. We examined 344 individuals (f/m=216/128, mean age 46±1 years) with an increased risk for type 2 diabetes. Apelin-36 serum levels were measured via ELISA. Endothelial dysfunction and intima media thickness (IMT) were assessed using high resolution ultrasound. Visceral adipose tissue (VAT) was measured with an axial T1-weighted fast spin echo technique with a 1.5 T whole-body imager. According to the study population's age, FMD (6.4±0.2%) and IMT (0.56±0.01 mm) were within the expected ranges. Gender or age had no influence on serum apelin levels. When looked at early stages of atherosclerosis, we could not detect a significant correlation between apelin serum levels and FMD or IMT. Blood pressure as well was unaffected by serum apelin levels. Furthermore, neither parameters of insulin sensitivity like insulin sensitivity index (ISI), nor fat distribution like BMI, grade of adiposity, total adipose tissue or VAT were associated with apelin serum levels. We conclude that apelin serum levels do not add further information on the cardiovascular-, or diabetes risk pattern in a diabetes prone population.

Reducing visceral adipose tissue mass is essential for improving endothelial function in type 2 diabetes prone individuals.

OBJECTIVE: In obesity, particularly increased visceral- (VAT), but not total (TAT) adipose tissue mass is a major source of proinflammatory cytokine expression and secretion. VAT, more than TAT, is associated with endothelial dysfunction (ED), which is an accepted risk factor for atherosclerosis. Consequently, we hypothesized that during a lifestyle intervention specifically a decrease in VAT, rather than TAT, is associated with improved ED and vascular adhesion molecules in type 2 diabetes prone subjects. METHODS: Analyses were done in 189 individuals (age: 45.4±0.8 years) at increased risk of type 2 diabetes, who underwent a 9-month lifestyle intervention. ED expressed as flow mediated dilation (FMD) of the brachial artery, sE-selectin, sV-CAM, sI-CAM, TAT and VAT (measured by magnetic resonance tomography) was determined. RESULTS: There was a mean decrease in body weight (-3%, p<0.0001), TAT (-7.6%, p<0.0001) and VAT (-12.5%, p<0.0001), while FMD increased (+9.1%, p=0.04). The change in FMD was not associated with change in body weight (p=0.35) or TAT (p=0.21) but with a decrease in VAT (r=-0.19, p=0.009). In a post hoc analysis, the subjects were divided by the median change in VAT into responders and non-responders. FMD increased only in the responders (from 6.2±0.4% to 8.0±0.5%, p=0.0005) but not in the non-responders (p=0.15). Also sE-selectin significantly decreased only in the responders (from 54±4 ng/ml to 47±3 ng/ml; p=0.03). CONCLUSION: During a lifestyle intervention, not weight loss or decrease in TAT, but decrease in VAT is associated with improved ED in individuals prone to type 2 diabetes. Therefore, primary cardiovascular prevention should focus specifically on reducing VAT rather than body weight alone.

[Unusual reason for unilateral (corrected) Raynaud's phenomenon with intensification when the arms are elevated]. / Einseitiges Raynaud-Phänomen mit Verstärkung bei Elevation des Arms.

Thoracic outlet syndrome (TOS) is a broad term for compression of the neurovascular structures in the area of the 1. rib and the clavicle. The cause can be either fibrous bands, cervical ribs, anomalous muscles or posttraumatic changes as well as tumors. Symptoms depend on the affected structure, in most cases (up to 97% of TOS patients) neurologic symptoms are present. In case of an arterial compression, for example due to a cervical rib like in our case, embolism of the arm and finger arteries can occur. For mild or moderate symptoms a conservative approach with physiotherapy can be helpful. For severe cases surgical resection of the compressing structure and the first rib is necessary. In our case, the cervical and first rib were excised after an initial lysis therapy. Furthermore, the aneurysm of the subclavian artery was excised.

Endothelial NO-synthase intron 4 polymorphism is associated with disturbed in vivo nitric oxide production in individuals prone to type 2 diabetes.

Insulin resistance, as well as vascular disease, both share a relevant genetic background taking the influence of a positive family history of these disorders. On the other hand, insulin resistance is associated with a proatherosclerotic disturbance in nitric oxide dependent vasodilation, probably contributing to the link between these two disorders. We examined the association between nitric oxide dependent vasodilation (measured with high resolution ultrasound at 13 MHz) and three relevant NO-synthase (eNOS)-polymorphisms in 200 insulin resistant subjects participating in the Tuebinger Lifestyle Intervention Program (TULIP). This study revealed that carriers of the eNOS intron 4 polymorphism (aa 2.16%; ab 24.2%; bb 73.2%) show significantly worse endothelial, and thereby eNOS dependent vasodilation (p=0.03, multivariate ANOVA), as compared to wildtype carriers. The 5' UTR T-786C and the G894 T polymorphism did not show any influence on eNOS-activity. In subjects at increased risk to develop type 2 diabetes, the eNOS intron 4 polymorphism is independently associated with endothelial function as indicated by disturbed endothelial NO production. Due to the high prevalence and the relatively strong effect, this polymorphism might help to identify subjects at increased risk for atherosclerosis associated with overweight and insulin resistance.

Perivascular fatty tissue at the brachial artery is linked to insulin resistance but not to local endothelial dysfunction.

AIMS/HYPOTHESIS: Different ectopic fat depots, such as visceral or hepatic fat, are known to affect whole body insulin sensitivity. It has recently been hypothesised that differences in perivascular adipose tissue (PVAT) mass around resistance vessels may also contribute to insulin resistance, possibly via direct vascular effects leading to reduced capillary cross-sectional area in the muscle, which in turn affects muscular blood flow and glucose uptake. Based on this, the aim of the present study was to test whether PVAT around conduit arteries (i.e. the brachial artery) influences NO bioavailability, expressed as flow-mediated dilation (FMD), or insulin sensitivity in humans in vivo. METHODS: Insulin sensitivity was measured by OGTT in all 95 participants (59 women, 36 men; median age 47 years, range 19-66 years) and by the gold standard, a euglycaemic-hyperinsulinaemic clamp, in a randomly selected subgroup of 33 participants. Quantification of the different fat compartments, including PVAT around the brachial artery, was achieved by high-resolution magnetic resonance imaging (1.5 T). Blood flow and FMD were measured at the brachial artery using high-resolution (13 MHz) ultrasound, after 5 min of forearm occlusion. RESULTS: PVAT was negatively correlated with insulin sensitivity and the post-ischaemic increase in blood flow. The association between PVAT and insulin sensitivity (r = -0.54, beta = -0.37, p = 0.009) was independent of age, sex, visceral adipose tissue, liver fat, BMI and further cardiovascular risk factors. No correlation could be detected between PVAT and local endothelial function. However, we observed an independent association between PVAT and post-ischaemic increase in blood flow (r = -0.241; beta = -1.69; p = 0.02). CONCLUSIONS/INTERPRETATION: PVAT seems to play an independent role in the pathogenesis of insulin resistance. This may be due to direct vascular effects influencing muscular blood flow.

[Early systolic notched peripheral Doppler flow pattern as an indicator of functional obstruction of the common iliac artery after iatrogenic aortic dissection: a case report]. / Frühsystolisch eingekerbte periphere Dopplerflusssignale als Hinweis auf eine funktionelle Obstruktion der Arteria iliaca communis bei iatrogener Aortendissektion: ein Fallbericht.

We report on a 57-year-old male patient with typical claudication localised in the right thigh, following aortic valve replacement. The ankle brachial index under resting conditions is within normal range on both sides. A conspicuous monomorphic double-humped peripheral Doppler flow pattern with an early systolic notch extending to the baseline can be registered in all the arteries of the right lower limb. The flow patterns of all other peripheral arteries are properly configured and of triphasic morphology. As the underlying cause of the pathologically altered Doppler flow morphology, aortic dissection Type A can be detected, extending from the former cannulation site of the ascending aorta into the right common iliac artery. Its dissection membrane functionally occludes the right common iliac artery in the early systole, the effect being brief and reversible. The pathogenesis of this morphologically altered Doppler flow pattern and potential differential diagnoses are discussed in this case report, also considering the current literature.

Early carotid atherosclerosis in overweight non-diabetic individuals is associated with subclinical chronic inflammation independent of underlying insulin resistance.

Overweight in children and young adults is an increasing problem in Western industrialized countries with potential impact on cardiovascular morbidity. Whether early arterial wall thickening in these subjects mainly results from the often associated insulin resistance syndrome or from increased subclinical chronic inflammation probably triggered by adipose tissue is still under discussion. We therefore determined insulin sensitivity index (ISI) by performing an euglycaemic hyperinsulinaemic glucose clamp (insulin infusion rate 1 mU/kg/min) and high-sensitivity C-reactive protein (hsCRP) levels in relation to the intima-media thickness (IMT) at the common carotid artery (high resolution ultrasound; 13 MHz) in 81 young (age 33 +/- 1 years), moderately overweight subjects. To reduce the number of confounding variables, subjects with disturbances in glucose metabolism (75 g oral glucose tolerance test) and hypertension were excluded. As expected, higher BMI was positively correlated with increased IMT (r = 0.358; p = 0.001). After multiple regression analysis, hsCRP levels independently correlated to IMT (r = 0.251; p = 0.03), even after adjusting for age, sex, BMI, ISI, LDL cholesterol and smoking as cofactors. However, taking all above listed factors into account, glucose-clamp assessed insulin sensitivity was not correlated with IMT. Thus, overweight might trigger inflammatory mechanisms leading to vascular wall hypertrophy independent of the insulin resistance syndrome already early in life.

Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells.

AIMS/HYPOTHESIS: Present guidelines for the treatment of type 2 diabetes recommend HbA1c values of less than 7%. As beta cell function worsens during progress of the disease, insulin therapy is often necessary to achieve this ambitious goal. However, due to peripheral insulin resistance, many patients need rather high insulin dosages. In the light of the extremely high cardiovascular risk of diabetic patients, it is important to determine whether high concentrations of insulin or its frequently used analogues are harmful to the cardiovascular system. We therefore investigated the modulatory effects of regular human insulin and its analogue glargine on proliferation and apoptosis of human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs). METHODS: Cells were treated with regular human insulin or insulin glargine. Proliferation was determined by [3H]thymidine incorporation and by flow cytometric analysis of Ki-67 expression. Apoptosis was assessed by flow cytometry (cell cycle analysis and annexin V staining) and determination of caspase-3 activity. RESULTS: HCAECs and HCASMCs treated with regular human insulin or insulin glargine did not show significant increases in DNA synthesis or Ki-67 expression. Administration of regular human insulin or insulin glargine did not modulate the extent of apoptotic events. No influence of insulin on lipoapoptotic vascular cell death could be detected. CONCLUSIONS/INTERPRETATION: Taken together, neither regular human insulin nor insulin glargine influences growth and apoptosis of human coronary artery cells in vitro. Our data do not suggest that regular human insulin or insulin glargine promote atherosclerosis through mechanisms affecting the cellularity of human coronary arteries.