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Increased perivascular fat mass contributes to cardiometabolic risk (CMR). High peribrachial adipose tissue (PBAT) associates with insulin resistance independently of established CMR parameters. It is unknown to what extent periaortic adipose tissue (PAAT) may have a similar impact. In 95 participants, precise quantification of total adipose tissue, PBAT, PAAT, visceral adipose tissue (VAT), and liver fat (LF) content was performed by whole-body magnetic resonance imaging. Insulin sensitivity was determined by oral glucose tolerance test and carotid intima–media thickness (cIMT) by high-resolution ultrasound. In univariate analyses, PAAT correlated with PBAT (β = .65, P < .0001). A negative correlation of PAAT (β = −.35, P = .0002) and PBAT (β = −.43, P < .0001) with insulin sensitivity was observed. While in a stepwise forward regression analysis the relationship of PAAT with insulin sensitivity was no longer significant after adjustment for VAT, LF content, and other CMR factors ( P = 0.42), PBAT still correlated with insulin sensitivity ( r2 = .35, P = .01). The association between PAAT and cIMT (β = .49, P < .0001) remained significant after adjustment for these variables ( r2 = .42, P = .0001). Although PAAT and PBAT strongly correlate, PAAT is not associated with insulin resistance, but with cIMT. Therefore, PAAT and PBAT may act differently as possible modulators of insulin resistance and subclinical atherosclerosis.

Summary. Arteriovenous fistulae are defined as congenital or acquired abnormal direct communications between an artery and a vein leading to abnormal blood circulation. This report describes an unusual manifestation of an acquired peripheral arteriovenous fistula with a high shunt volume of 410 ml/min following a fracture of the 5th finger.

Aim: The visceral adiposity index (VAI) has been proposed as an estimate of visceral adipose tissue (VAT) mass and as an indicator of VAT dysfunction. Both parameters are associated with cardiometabolic risk, including insulin resistance. In this study, we investigated whether VAI is associated with subclinical atherosclerosis in subjects who were free of cardiovascular disease but were at risk of developing diabetes mellitus.Methods: A total of 731 adults with a median age of 47 years old without diabetes mellitus were included in this cross-sectional study. The anthropometric data, blood pressure, and lipid profiles of 398 women and 333 men were measured. All subjects underwent an oral glucose tolerance test, and carotid intima -media thickness (cIMT) was evaluated by ultrasound. Insulin resistance was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR).Results: VAI and HOMA-IR (beta(st) = 0.44, p < 0.0001), VAI and cIMT (beta(st) = 0.17, p < 0.0001), and HOMA-IR and cIMT (beta(st) = 0.09, p = 0.0127) were correlated with each other. After adjusting for cofounding variables, VAI is still correlated with HOMA-IR (beta(st) = 0.42, p < 0.0001). Furthermore, VAI (beta(st) = 0.07, p = 0.0392) but not HOMA-IR (beta(st )= 0.03, p = 0.37) was correlated with cIMT independently of other established cardiovascular risk factors.Conclusion: The calculation of VAI may provide a better estimation of subclinical atherosclerosis than the calculation of HOMA-IR.

Klippel-Trénaunay syndrome (KTS) is a rare congenital anomaly characterized by malformation of lymph and blood vessels as well as growth disturbance of soft tissue and bone. The clinical picture is variable and associated with an increased risk of thromboembolic events mediated by intravascular coagulopathy in venous malformations. Here, we report on a male patient with KTS suffering from recurrent deep vein thrombosis (DVT) and life-threatening bleeding due to consumptive coagulopathy. Furthermore, we describe the successful long-term anticoagulant management with rivaroxaban.

The authors describe a case of an intrapancreatic gastroduodenal artery aneurysm in a pregnant woman. Successful endovascular therapy was performed for the first time in a visceral artery aneurysm during pregnancy as a bailout solution. The attributive risk to the fetus from scattered radiation during endovascular treatment did not exceed a critical level.

Aneurysms of the gluteal arteries are rare clinical findings. The majority of those aneurysms consist of pseudoaneurysms due to pelvic trauma [1–3]. True aneurysms of the gluteal arteries occur due to atherosclerosis, infections, polyarteritis nodosa, or are associated with arteriovenous malformations (AVM) [1]. AVMs are considered to be undifferentiated high-flow vascular malformations characterized by multiple abnormal communications between the arterial and venous system without an intervening capillary network [4–6]. AVMs can involve any area of the body; the extremities, head and neck, lung, and liver are most commonly affected [5, 6]. In the pelvic region, these lesions are rare and more often are acquired secondary to neoplasm, pelvic trauma, and surgical procedures or can be associated with congenital diseases, such as the Klippel-Trenauny syndrome or the Parks-Webber syndrome [6–8]. The following report will describe a case of congenital gluteal AVM associated with a giant true aneurysm of the ipsilateral inferior gluteal artery. Due to its size and the risk of rupture, the aneurysm demanded therapy that could be successfully performed with endovascular techniques.

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.

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.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.There was a mean decrease in body weight (-3%, p0.0001), TAT (-7.6%, p0.0001) and VAT (-12.5%, p0.0001), 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).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.

To assess thyroid perfusion in patients with autoimmune thyroid diseases compared with that in healthy control subjects by using an arterial spin-labeling (ASL) magnetic resonance (MR) technique and to assess whether thyroid perfusion is associated with endocrine laboratory abnormalities.This study was approved by the local institutional review board. All participants gave written informed consent. Perfusion imaging of the thyroid gland was performed in 10 patients with Graves disease (GD) and 10 patients with Hashimoto thyroiditis (HT). Ten healthy individuals served as control subjects. Perfusion imaging was performed with a 1.5-T MR unit by using a flow-sensitive alternating inversion recovery-true fast imaging with steady-state precession technique. Perfusion maps of the entire thyroid gland were calculated on the basis of extended Bloch equations. Analysis of variance with a post hoc test (Tukey honestly significant difference) was performed to assess differences in perfusion between groups. Associations between perfusion and laboratory parameters were analyzed with univariate regression analysis.Mean thyroid perfusion was 1596 mL/min/100 g +/- 436 (standard deviation) in patients with GD, 825 mL/min/100 g +/- 264 in patients with HT, and 491 mL/min/100 g +/- 89 in healthy control subjects. Perfusion was significantly higher in patients with GD (P.0001) and those with HT (P.05) than in control subjects. A significant difference in thyroid perfusion was detected between the two autoimmune entities (P.0001). In patients with GD, significant associations were found between perfusion and serum concentrations of free thyroid hormones and anti-thyroid-stimulating hormone receptor antibodies (P.05 for all).Quantitative ASL perfusion imaging of the thyroid gland revealed significant perfusion differences in the autoimmune thyroid diseases GD and HT. Absolute quantification of thyroid perfusion may be useful in the clinical assessment of autoimmune thyroid disorders and when monitoring therapeutic treatment in GD.

To longitudinally assess the value of cardiac functional and viability imaging as a supplement to MR angiography in patients with atherosclerotic disease.Cardiac MRI was performed in 195 consecutive patients with symptomatic peripheral arterial disease. Of these, 186 patients were followed for 22 +/- 5 months for the presence of cardiac events (cardiac death, acute coronary syndrome and hospitalisation as a result of congestive heart failure).Myocardial viability imaging showed a high prevalence of known (n = 31) and occult myocardial infarctions (MI) (n = 26). Cardiac events occurred more often in patients with reduced ventricular function (ejection fraction (EF) less than 40%, cardiac event in 4/8 patients; EF 40-55%, cardiac event in 10/40 patients; EF greater than 55%, cardiac event in 15/138 patients) as well as in patients with occult MI (8/25 patients) and known MI (11/30 patients). In patients with normal function, the detection of a previous MI was of high relevance to prognosis.Both reduced EF and the presence of MI influence patients' prognoses. Performing cardiac MRI in this patient population may influence further patient management including intensified risk factor intervention.

Udgivelsesdato: 2008-Nov 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.

Monocyte-chemoattractant-protein (MCP)-1 and its receptor CCR2 have been shown to play a pivotal role in vascular inflammation and atherosclerotic plaque formation. However, it is currently unclear whether MCP-1/CCR2 triggered inflammation affects nitric oxide (NO)-bioavailability, hence influencing vascular function, a sign of early atherosclerosis. Therefore, we sought to investigate the association between serum levels of MCP-1 and NO-bioavailability, expressed as flow mediated dilation (FMD) in vivo, and the impact of CCR2 gene variations on FMD. We studied a German population of 242 prediabetic individuals (144 women, 98 men; mean age 45+/-0.8 years) via FMD by high-resolution ultrasound (13MHz). In order to replicate our findings, a second, independent population (n=115; 44 women, 77 men; mean age 48+/-1.0 years) (total=357 individuals) from Italy was studied. Vascular function in the Italian population was studied via intra-arterial application of acetylcholine. MCP-1 serum-levels were assessed by ELISA and CCR2 polymorphisms were determined by sequencing. MCP-1 serum levels showed no association with FMD (p=0.90), whereas the CCR2 promoter polymorphism was associated with elevated FMD (T/T: 5.6+/-0.3%; T/A: 6.7+/-0.4%; A/A: 8.3+/-0.8%; p=0.01) after adjusting for possible confounders. These results were confirmed in the independent Italian population (A/A: 97.1+/-20.3 vs. T/T: 60.5+/-5.6% forearm blood-flow increase; p

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.

Circulating trimethylamine N-Oxide (TMAO) levels predict cardiovascular disease (CVD), possibly by impacting on cholesterol metabolism and oxidative stress. Because hepatic TMAO production is regulated by insulin signalling and it is unclear whether and to what extent circulating TMAO levels associate with CVD risk, independently of insulin resistance and its important determinants fatty liver and visceral obesity, we have now addressed this question in 220 subjects who participated in the Tübingen Lifestyle Intervention Program. Visceral fat mass (r = 0.40, p 20%). We provide novel information that increased serum TMAO levels associate with increased cIMT, independently of established cardiovascular risk markers, including insulin resistance, visceral obesity and fatty liver. Furthermore, the decrease of cIMT during a lifestyle intervention may be related to the decrease of TMAO levels.

The authors report on a case of arterial embolism caused by bone entrapment of the popliteal artery due to a protrusion of a hydroxyl-apatite wedge. The wedge had been placed 4 years earlier during the course of a valgus osteotomy procedure. Thrombolytic therapy was performed, and the wedge was removed. Because causes for arterial embolism vary, the knowledge of its underlying mechanism is necessary to avoid recurring events. Bone entrapment after knee surgery is a differential diagnosis that should be taken into account, even years after surgery.

Abstract. Background: There is a widely approved influence of novel risk factors like the body fat distribution and the associated metabolic syndrome, subclinical inflammation, insulin resistance and prediabetic disturbances in glucose metabolism on the progression of atherosclerosis. Former studies examining normal values for intima-media thickness (IMT) did not consider all of these new study results in detail. We therefore aimed to assess an update on age- and gender-specific normal values for IMT accounting for these novel risk factors. Patients and methods: We evaluated IMT by high-resolution ultrasound (13 MHz) on the far wall of the common carotid artery in 801 subjects without cardiovascular disease (428 women aged 46.2±12.9 years; 373 men aged 47.3±13.3 years). After precise evaluation and exclusion of 14 cardiovascular risk factors, 90% limits of IMT were determined by parametric statistics. Results: The reference limits of IMT according to the age classes 18-29, 30-39, 40-49 and 50-59 years were estimated as 0.47, 0.59, 0.67 and 0.70 mm in women and 0.47, 0.62, 0.72 and 0.80 mm in men. Conclusions: Age and gender-specific normal values for IMT are lower than reported in former studies after additionally accounting for novel cardiovascular risk factors. The still widely regarded upper IMT limit of 1 mm must be strictly regarded as obsolete.

Background: The metabolic effects of adiponectin, including insulin sensitivity, seem to become stronger with increasing adiposity. Adiposity may also affect the relationship of adiponectin concentrations with serum lipid profile; markers of inflammation, atherosclerosis, and endothelial function; and ectopic fat accumulation. Methods: We measured plasma adiponectin concentrations, serum lipids, and serum markers of inflammation, atherosclerosis, and endothelial function in 242 Caucasians without type 2 diabetes. We also measured visceral adipose tissue with magnetic resonance tomography and liver and intramyocellular fat with 1H magnetic resonance spectroscopy. Results: We divided the study participants into 2 groups: lean [mean (SE) total body fat, 26% (0.6%); n = 119] and obese [36% (0.6%); n = 123]. In the obese group, plasma adiponectin concentrations showed a strong positive association with concentrations of HDL cholesterol (P 0.10). High visceral adipose tissue was a strong predictor of low adiponectin concentrations, particularly in the obese group, and attenuated many of the significant relationships. Conclusions: High adiponectin plasma concentrations are associated with favorable lipid profiles, decreased subclinical inflammation, decreased markers of atherosclerosis and endothelial function, and low ectopic fat accumulation, particularly in obese persons. Adiponectin may also have a concentration-related effect on the relationship between visceral adipose tissue and these metabolic characteristics, especially in obese persons.

Single low density lipoprotein (LDL) fibrinogen apheresis has shown beneficial effects in the treatment of patients with sudden sensorineural hearing loss (SSHL). Pathophysiologically, a microcirculatory disorder of the inner ear, probably caused by disturbed endothelial function, is discussed as a final common pathway of a variety of SSHL etiologies. Thus, we carried out a prospective pilot study on the efficacy of Rheopheresis on vascular function in these patients, embedded into an ongoing randomized controlled multicenter trial investigating the efficacy of Rheopheresis for the treatment of SSHL. Potential modulation of systemic endothelial dysfunction by Rheopheresis was examined by measuring flow-associated vasodilatation of the brachial artery (according to the criteria of the American College of Cardiology) in a small group of patients suffering from SSHL (N = 6, 5m/1f, mean age 56 ± 11 years) within the last 3 days. At baseline, five of the six patients with acute hearing loss showed endothelial dysfunction as evidenced by diminished flow-mediated vasodilatation (FMD

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.

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.

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. Citation Format: • Ketelsen D, Thomas C, Schmehl J et al. Endovascular Aneurysm Repair of Abdominal Aortic Aneurysms: Standards, Technical Options and Advanced Indications. Fortschr Rontgenstr 2014; 186: 337 – 347

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.

UNLABELLED The non-invasive evaluation of endothelial dysfunction with high-resolution ultrasound has become a widely accepted tool in determination of high-risk subjects for early atherosclerosis. Furthermore it is often used as intermediate outcome in intervention studies. AIM We examined the influence of examiner experience on intra- and inter-individual variability in the measurement of flow-associated vasodilation (FAD) independent of automated analysis systems. METHOD FAD was measured on two occasions in 7 and 8 subjects respectively (mean age 32 +/- 3 years) by two investigators after different prior training procedures with a 13 MHz linear transducer (LA14A, ESAOTE Biomedica). RESULTS The intra-individual variability expressed as median absolute difference in the measurements of FAD was 1.1 % (range from 0.03 % to 3.2 %) for examiner one with an experience of more than 50 FAD measurements through former studies and 2.9 % (range from 1.6 % to 9.2 %) for examiner two with only 10 training examinations under supervision. By a further training period of two months, with an increase of examinations of additional 20 measurements by both examiners, the intra-observer variability could be dropped to 0.9 % (range from 0.03 % to 1.3 %) for examiner two (p = 0.0025) with no significant change for examiner one (median 0.6 % with a range from 0.14 % to 3.7 %). As expected, the inter-individual variability was not influenced by this further training (median 1.0 % with a range of 0.5 % to 3.6 % versus a median of 1.6 % with a range from 0.15 % to 7.5 %). CONCLUSION 30 training measurements of FAD under supervision should be regarded as minimum requirement for valid determination of endothelial function. The reachable result for the intra-observer variability is thereby within the range of computed analysis systems.

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. Therfore 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 thyroptropin level was 1.43 ± 0.11 muU/ml (range 0.18–3.52 muU/ml). Results: Comparing subjects in the upper, middle and lower tertile of TSH (2.38 ± 0.14 muU/ml, 1.23 ± 0.04 muU/ml and 0.65 ± 0.06 muU/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.

Diabetes mellitus and impaired glucose tolerance are linked to increased cardiovascular morbidity and mortality. Vascular disease is directly associated with plasma glucose levels, and reduction of these levels forestalls to a certain extent the vascular complications of diabetes, such as myocardial infarction, nephropathies, and retinopathies. In addition to hyperglycemia, there are other risk factors that play a prominent role, such as hypertension, hyperlipidemia, and genetic factors. Endothelial dysfunction is one of the major factors in the development of cardiovascular disease. The vascular endothelium regulates the blood flow by tightly controlling the coagulation system, cell-cell interaction, and vascular tone. These functions are disturbed in diabetic patients. In diabetics, endothelin-1 levels are increased, leading to vasoconstriction. Endothelin levels are directly related to plasma glucose levels. In addition, the endothelial cell-NO axis is disturbed. NO release and function are impaired. This seems to be dependent upon hyperglycemia and genetic factors. Impaired NO function also results in vasoconstriction. Furthermore, enhanced vascular permeability is seen in diabetics. This appears to be related to impaired endothelial cell relaxation and reactive oxygen species as well as advanced glycosylated end products (AGEs). The complex changes seen in diabetes and even prediabetes are therefore related to numerous derailments related to endothelial dysfunction, and no single therapeutic approach is likely to solve the problem of vascular complications.

Studienziel: Die endothelial Dysfunktion (ED) gilt als frühfunktioneller, die Intima-Media-Dicke (IMT) als frühmorphologischer Marker der Atherogenese. Gibt es ein einfaches, nichtinvasives, routinemaßig einsetzbares Ver-fahren zur Darstellung des Atherosklerosestatus, welches die frühfunktionellen Veränderungen z.B. bei Typ II-Diabetikern mitberücksichtigt? Methode: Wir untersuchten mittels hochauflosendem Ultraschall bei 25 Typ II-Diabetikern und gematchten Kontrollpersonen die periphere Endothelfunktion (ausgedrückt durch die flußassoziierte Vasodilatation nach Ischämie = FAD %) und die endothelunabhangige Vasodilatation nach Gabe von 400 μg Glyceroltrinitrat (Postnitro %) an der A. brachialis sowie die IMT an der A. carotis communis. Ergebnisse (Mittelwerte ± SD): Die Typ II-Diabetiker zeigen eine deutliche Endothelschadigung (FAD %: 3,8 ±3,3 vs. 6,9 ± 4,4%, p = 0,01) sowie eine bereits verdickte IMT (0,72 ±0,14 vs. 0,62 ± 0,10 mm, p > 0,01). Die Vasodilatation nach Nitrogabe als Ausdruck eines prinzipiell noch dilatierfähigen Gefäßsystems unterscheidet sich nicht von der der Gesunden (Postnitro %: 14,3 ±9,4 vs. 14,9 ±8,5%, p = ns). Schlußfolgerung: Die hier verwendete diagnostische Trias ermöglicht die Darstellung des Atherosklerosestatus unter Berücksichtigung der frühfunktionellen Störungen bei Typ II-Diabetikern.

Background: In patients with arterial hypertension, increased blood pressure (BP) variability contributes to end organ damage independently from mean levels of arterial BP. Increased BP variability has been linked to alterations in autonomic function including sympathetic overdrive. We hypothesized that catheter-based renal sympathetic denervation (RDN) confers beneficial effects on BPV. Methods and Results: Eleven consecutive patients with therapy-refractory arterial hypertension (age 68.9±7.0 years; baseline systolic BP 189±23mmHg despite medication with 5.6±2.1 antihypertensive drugs) underwent bilateral RDN. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed before RDN and six months thereafter. BPV was primarily assessed by means of standard deviation of 24-hour systolic arterial blood pressures (SDsys). Secondary measures of BPV were maximum systolic blood pressure (MAXsys) and maximum difference between two consecutive readings of systolic BP (deltamaxsys) over 24 hours. Six months after RDN, SDsys, MAXsys and deltamaxsys were significantly reduced from 16.9±4.6mmHg to 13.5±2.5mmHg (p=0.003), from 190±22mmHg to 172±20mmHg (p

Antidiabetic thiazolidinediones (TZDs) improve endothelial function in patients with or without type 2 diabetes. The present randomised, placebo-controlled, double-blind study examined the time course of a single dose of rosiglitazone on flow-mediated endothelium-dependent vasodilation (FMD), metabolic parameters, and its effect on inflammatory markers in non-diabetic men. Forty non-obese, healthy men with normal glucose tolerance were randomised to a single dose of rosiglitazone (8 mg) or placebo, and FMD was assessed at baseline as well as after 6 h and 24 h. Rosiglitazone did not significantly affect blood glucose and insulin levels or lipid parameters after 6 and 24 h compared with placebo. Treatment with rosiglitazone significantly increased FMD after 6 h from 4.3% (3.3; 4.9) to 7.6% (5.6; 9.2) ( p

Obesity represents a risk factor for insulin resistance, type 2 diabetes mellitus, and atherosclerosis. In addition, for any given amount of total body fat, an excess of visceral fat or fat accumulation in the liver and skeletal muscle augments the risk. Conversely, even in obesity, a metabolically benign fat distribution phenotype may exist.In 314 subjects, we measured total body, visceral, and subcutaneous fat with magnetic resonance (MR) tomography and fat in the liver and skeletal muscle with proton MR spectroscopy. Insulin sensitivity was estimated from oral glucose tolerance test results. Subjects were divided into 4 groups: normal weight (body mass index [BMI] [calculated as weight in kilograms divided by height in meters squared],25.0), overweight (BMI, 25.0-29.9), obese-insulin sensitive (IS) (BMI,or = 30.0 and placement in the upper quartile of insulin sensitivity), and obese-insulin resistant (IR) (BMI,or = 30.0 and placement in the lower 3 quartiles of insulin sensitivity).Total body and visceral fat were higher in the overweight and obese groups compared with the normal-weight group (P.05); however, no differences were observed between the obese groups. In contrast, ectopic fat in skeletal muscle (P.001) and particularly the liver (4.3% +/- 0.6% vs 9.5% +/- 0.8%) and the intima-media thickness of the common carotid artery (0.54 +/- 0.02 vs 0.59 +/- 0.01 mm) were lower and insulin sensitivity was higher (17.4 +/- 0.9 vs 7.3 +/- 0.3 arbitrary units) in the obese-IS vs the obese-IR group (P.05). Unexpectedly, the obese-IS group had almost identical insulin sensitivity and the intima-media thickness was not statistically different compared with the normal-weight group (18.2 +/- 0.9 AU and 0.51 +/- 0.02 mm, respectively).A metabolically benign obesity that is not accompanied by insulin resistance and early atherosclerosis exists in humans. Furthermore, ectopic fat in the liver may be more important than visceral fat in the determination of such a beneficial phenotype in obesity.

Fatty liver is associated with insulin resistance, atherosclerosis, and the metabolic syndrome (1–7) and predicts future cardiovascular events (4–8). The pro-atherogenic serum lipid profile in subjects with fatty liver is characterized by elevated levels of triglycerides, low HDL cholesterol, and an increase in small dense LDL particles (9–12). Regarding HDL, not only quantitative, but also qualitative and compositional alterations are related to its antiatherogenic properties (13–16). In particular, circulating HDL2 was found to protect from atherosclerosis (17,18). In the present study, we first investigated whether fatty liver is associated with altered circulating HDL cholesterol subfractions and second whether this relationship is independent of insulin sensitivity, thus possibly representing a direct link between fatty liver and cardiovascular disease. In our ongoing study on the pathophysiology of type 2 diabetes, ∼300 Caucasians were carefully characterized for fatty liver and its associated metabolic characteristics (19). To select a subgroup that was representative for the percentage of subjects having fatty liver (liver fat >5.56%) (20) in our large cohort (∼40%) and in whom enough sample volume was available to measure the HDL cholesterol subfractions, we randomly selected 8 men and 8 women with fatty liver and 24 control subjects. The subjects underwent a 75-g oral glucose tolerance test to exclude diabetes and calculate insulin sensitivity (21). Total body fat was measured by bioelectrical impedance, visceral fat by magnetic resonance (MR) tomography, and liver fat by 1H-MR spectroscopy (19). Serum total, HDL, and LDL cholesterol, as well as triglyceride concentrations, were measured by standard colorimetry, plasma adiponectin …

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.

The feasibility of self-expanding nitinol stents for treatment of infragenicular arteries following unsuccessful balloon angioplasty was assessed. Options for lower limb percutaneous revascularization are limited, especially for complex vessel obstruction. Depending on the lesion and the experience of the interventionalist, the failure rate of balloon angioplasty (PTA) ranges between 10 and 40%. Until recently, no self-expanding stent for the use in the infragenicular arteries was available. This is the first report of the results for 18 consecutive patients who received 4F sheath compatible self-expanding nitinol stents following unsuccessful PTA or early restenosis. Twenty-four stents were implanted in 21 lesions for various indications residual stenosis >50% due to heavy calcification, flow-limiting dissection, occluding thrombus resistant to thrombolyis, thrombaspiration, and PTA, and early restenosis after previous PTA. Stent implantation was feasible in all cases. No complications occurred. After the stent implantation, all primarily unsuccessful interventions could be transformed into successful procedures with no residual stenosis >30% in any case. After 6 ± 2 months, two of the 18 patients died, and 14 of the 16 remaining patients improved clinically. At follow-up, the patency could be assessed in 14 stented arteries. Three stents were occluded, one stent showed some neointimal hyperplasia (50–70% restenosis), the remaining ten stents showed no restenosis (0–30%). The use of self-expanding nitinol stents in tibioperoneal and popliteal arteries is a safe and feasible option for the treatment of unsuccessful PTA. The 6-months patency is high.

Background— Antidiabetic thiazolidinediones (TZDs), like rosiglitazone or pioglitazone, improve endothelial function in patients with type 2 diabetes or metabolic syndrome, but it is currently unknown, whether these beneficial effects of TZDs depend on their metabolic action or may be caused by direct effects on the endothelium. Therefore, the present study examined whether short-term rosiglitazone treatment influences endothelium-dependent vasodilation as well as serum levels of vascular disease biomarkers in healthy, nondiabetic subjects. Methods and Results— Short-term treatment (21 days) of healthy subjects (n=10) did not significantly change blood glucose levels or lipid profile. In contrast, rosiglitazone significantly increased flow-mediated, endothelium-dependent vasodilation already within the first day from 5.3±2.7% at baseline to 7.8±2.6%, further increasing it to 9.4±3.0% at day 21. In addition, the early improvement of endothelium-dependent vasodilation was paralleled by a rapid reduction of serum levels of the biomarkers C-reactive protein (CRP), serum amyloid A (SAA), and sE-selectin. Moreover, after drug withdrawal all markers remained suppressed for the whole follow-up period of 7 days. In contrast, rosiglitazone treatment did not significantly affect tumor necrosis factor (TNF)-α, interleukin (IL)-6, sICAM-1, sVCAM-1, and sCD40L levels. Conclusions— Our study suggests a direct effect of TZD treatment on endothelial function and inflammatory biomarkers of arteriosclerosis, promoting the concept that TZDs, independent of their metabolic action, may exhibit protective effects in the vessel wall.

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.

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). 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. 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. 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.

Reduced bio-availability of nitric oxide leading to disturbed flow mediated (endothelial dependent) vasodilation (FMD) has been shown to be an early functional abnormality of the vascular system in insulin resistant individuals and other subjects at high risk for accelerated atherosclerosis. In addition, an increase of the intima-media thickness (IMT) is regarded as an early marker of morphological alterations of the vessel wall. Whether endothelial dysfunction (ED) is evident already at an early stage when morphological changes of the vessel wall are not apparent is still an open question. We, therefore, examined IMT and peripheral endothelial function in a group of young insulin resistant subjects in a cross-sectional study and compared these results with a metabolically healthy (insulin sensitive) control group. We measured IMT (distal common carotid arteries), endothelium-dependent and endothelium-independent vasodilation (flow mediated and glyceroltrinitrate induced vasodilation of the brachial artery) non-invasively with high resolution ultrasound (13 MHz) in 91 young normoglycemic subjects (40/51 M/F, median: 31 years, range 18-50 years). Insulin sensitivity was measured with a euglycemic, hyperinsulinemic glucose clamp. Despite a marked reduction in flow-mediated vasodilation in insulin resistant (IR) subjects (FMD: median 3.4%, range -4.0 to 12.5 in IR versus 6.6%, range -1.2 to 20.1% in insulin sensitive subjects; P = 0.017), there was no difference in endothelial independent vasodilation (16.3%, range 5.7-41.0% versus 16.1%, range 0.5-39.2%) and in IMT (0.50 mm, range 0.39-0.66 and 0.51, 0.40-0.70 mm, respectively). These data suggest that ED can be detected very early in the life of insulin resistant subjects whereas no significant structural changes, indicated by a thickening of the intima-media layer, could be found. We therefore conclude that for identification of subjects with a high risk for accelerated atherosclerosis at an early stage, measurement of flow mediated vasodilation of the brachial artery may be more helpful than measuring thickness of the vascular wall.

In a recent study, we found a significant association between insulin resistance (IR) and disturbed flow-associated (endothelial-dependent) vasodilation in first-degree relatives of subjects with type 2 diabetes. However, the mechanisms linking insulin resistance and endothelial dysfunction (ED) have not been fully elucidated. Experimental data have pointed out that non-esterified fatty acids (NEFA) have a modulating effect on NO-synthase activity, and therefore on endothelial function. The aim of our study was to evaluate whether insulin resistance associated impaired NEFA suppression is present in subjects with ED. We examined 53 first-degree relatives (FDR) of patients with type 2 diabetes (32f, 21 m, mean age 35 years). Endothelial function was measured as flow-associated vasodilation (FAD%) of the brachial artery. Insulin sensitivity was evaluated with a standard hyperinsulinemic glucose clamp (insulin infusion rate of 1 mU/kg/min). While under fasting conditions, NEFA did not differ between groups with high or low FAD (0.415+/-0.033 vs. 0.394 +/- 0.040 mmol/l; p = n. s.), reduced FAD% was significantly associated with higher non-esterified fatty acids concentrations during steady state of the glucose clamp (0.072+/-0.022 vs. 0.039+/-0.016mmol/l; p=0.04). This association was independent of insulin levels under fasting conditions and during the glucose clamp. In conclusion, our results reveal a significant association between endothelial dysfunction and impaired non-esterified fatty acid suppression in insulin resistant subjects. As insulin resistance of lipolysis is a feature of the insulin resistance syndrome, these results suggest that elevated NEFA concentrations could play a role linking endothelial dysfunction and insulin resistance in vivo.

Recently, a highly prevalent polymorphism of the PPARgamma2-receptor (Pro12Ala) was described and found to be associated with reduced transcriptional activity. Both human and animal studies suggested that this polymorphism may be associated with increased insulin sensitivity. However, an effect independent of other factors known to influence insulin sensitivity has yet to be demonstrated. Therefore, we compared insulin sensitivity using the hyperinsulinemic-euglycemic clamp technique in 37 subjects heterozygous for the PPARgamma2-Pro12Ala mutation and 37 control subjects negative for the PPARgamma2-Pro12Ala. The control group was selected from 190 subjects by pair-matching for sex, BMI, fat distribution and body composition. In the group heterozygous for the polymorphism steady-state plasma insulin during the clamp was significantly lower (63.3 microU/ml +/- 2.8) than in the control group (74.9 microU/ml +/- 4.0, p = 0.02). While MCR of glucose was similar in the PPARgamma2-Pro12Ala group (8.1 ml/kg x min x 100 +/- 0.5) and the control group (7.6 ml/kg x min x 100 +/- 3.0, p = 0.7), the insulin sensitivity index was significantly higher in the PPARgamma2-Pro12Ala group (12.5 mg/kg x min x microU/ml +/- 0.9 vs. 9.7 mg/kg x min x microU/ml +/- 0.8, p = 0.039). In addition, an arbitrary lipolysis index (decrease in FFA divided by increase in insulin) was also found to be marginally higher in the PPARgamma2-Pro12Ala group (8.0 +/- 0.9) compared to the control group (6.1 +/- 0.7, p = 0.097). In conclusion, these data suggest that the PPARgamma2-Pro12Ala mutation is associated with better insulin sensitivity of glucose disposal and possibly, also of antilipolysis.

Essential hypertension is--at least in many subjects--associated with a decrease in insulin sensitivity, while glycaemic control is (still) normal. It seems that in hypertensive patients, two major functions of insulin are impaired: there is insulin resistance of peripheral glucose uptake (primarily skeletal muscle) and insulin resistance of insulin-stimulated vasodilation. In view of some retrospective data and meta-analyses, which showed a less than expected reduction in coronary events (coronary paradox), the metabolic side effects of the antihypertensive treatment have received more attention. Many groups have shown that conventional antihypertensive treatment, both with beta-blockers and/or diuretics, decreases insulin sensitivity by various mechanisms. While low-dose diuretics seem to be free of these metabolic effects, there is no evidence for this in the beta-adrenergic blockers. However, recent metabolic studies evaluated the effects of vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. None of them decreased insulin sensitivity, as has been described for the beta-blockers with and without beta1 selectivity. This supports the idea that peripheral vascular resistance and peripheral blood flow play a central role in mediating the metabolic side effects of the beta-blocking agents, as the vasodilating action (either via beta2 stimulation or alpha1-blockade) seems to more than offset the detrimental effects of the blockade of beta (or beta1) receptors. Further studies are needed to elucidate the relevance of the radical scavenging properties of these agents and their connection to their metabolic effects. Therefore, the beneficial characteristics of these newer beta-adrenoreceptor blockers suggest that the vasodilating beta-blocking agents could be advantageous for hypertensive patients with insulin resistance or type 2 diabetes.

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 ≤5.8 mL · kg −1 · min −1 , insulin sensitive (IS) with an MCR ≥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.

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, p0.05). 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; p0.01). 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 index25 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.

HISTORY AND ADMISSION FINDINGS: We report on a young female patient with flank pain and a swelling of the lower limb of the left side. INVESTIGATIONS: In magnetic resonance angiography as well as Doppler-duplex ultrasound an iliofemoral phlebothrombosis of the left side due to vena cava inferior hypoplasia with collateral circulation was diagnosed. Oral contraception could play a role as a trigger. The patient also presented activated protein C resistance/ heterozygous factor V Leiden mutation. DIAGNOSIS TREATMENT AND COURSE: According to the CaVenT study we treated the patient successfully with catheter-directed thrombolysis. Follow-ups presented a patency of the iliofemoral vein. CONCLUSIONS: In young patients with short duration of a proximal deep vein thrombosis and after exclusion of contraindications a catheter-directed lysis should be considered as a treatment option. The differential diagnostic of a (bilateral) ilio-femoral vein thrombosis in young patients should include an anomaly of the venous system.

ANAMNESE UND KLINISCHER BEFUND: Patient1, 73 Jahre, litt unter Schmerzen und diskreter Umfangsvermehrungdes linken Unterschenkels. Aufgrund einer spontanen zerebralen Blutungskomplikation beieinem cavernosen Hamangiom 5 Jahre zuvor bestandeine absolute Kontraindikation gegen eine antithrombozytareTherapie bzw. Antikoagulation. Patient 2, 79 Jahre, stellte sichwegen zunehmender Dyspnoe vor. Zwei bzw. vier Monate zuvor waren tiefeBeinvenenthrombosen aufgetreten, die mit Phenprocoumon behandeltwurden (gesichert suffiziente Antikoagulation) UNTERSUCHUNGEN: Bei Patient 1 wurde mittels Doppler-Sonographieeine tiefe Beinvenenthrombose diagnostiziert. Bei Folgeuntersuchungenzeigte sich eine Thrombus-Aszension. Bei Patient 2 wurden mittelsDopplersonographie und Kontrastmittel-verstarkter Thorax-Computertomographie (CT)eine tiefe Beinvenenthrombose und eine Lungenarterienembolie diagnostiziert.Bei dem zweiten Fall wurde schlieslich mit 18F-Fluordesoxyglukose-Positronenemissionstomographie/CTund histologischer Untersuchung eines Biopsats ein bronchiales Adenokarzinomauf dem Boden einer Silikose nachgewiesen. THERAPIE UND VERLAUF: Beide Patientenwurden mit einem passageren Vena-cava-Filter versorgt. Die Interventionenwaren bei beiden Patienten komplikationslos. Auch im Kurzzeitverlaufergaben sich keine mit den Vena-cava-Filtern in Zusammenhang stehendeKomplikationen. FOLGERUNG: Diese zwei Fallberichte veranschaulichenunterschiedliche Situationen, in denen der Einsatz eines Vena-cava-Filters uberlegtwerden kann. Auserdem enthalt der Bericht einekurze Zusammenfassung uber die verschiedenen Filterarten,die derzeit geltenden Leitlinien zur Implantation, den klinischenNutzen sowie mogliche Risiken durch die Implantation vonVena-cava-Filtern. HISTORY, INVESTIGATIONS AND DIAGNOSIS: Patient 1, 73 years, suffered from pain in the left lower leg showing discretely increased circumference. Due to a spontaneous cerebral bleeding of a cavernous malformation five years ago there was an absolute contraindication against anti-platelet therapy and anticoagulation. Patient 2, 79 years, presented with increasing dyspnoea. Two and four months ago deep venous thromboses had been diagnosed and he was therefore treated with phenprocoumon (secured sufficient anticoagulation). DIAGNOSTICS: In patient 1, deep venous thrombosis was diagnosed with Doppler-ultrasound. Further examinations showed thrombus ascension. In patient 2, deep venous thrombosis and pulmonary artery embolism were diagnosed with Doppler-ultrasound and contrast medium enhanced thoracic computed tomography (CT). In the second case, a bronchial adenocarcinoma associated with silicosis was finally diagnosed with 18F-fluordeoxyglukose positron emission tomography/CT and histological investigation of a biopsy sample. TREATMENT AND COURSE: Retrievable vena cava filters were implanted in both patients. The interventions and course were without vena cava filter associated complications in both patients. CONCLUSIONS: These two case reports reflect different clinical situations in which the implantation of vena cava filters may be considered. Furthermore, this report gives a short overview about the different types of vena cava filters, the current guidelines for the implantation, the clinical benefits and possible adverse events associated with the use of vena cava filters.

HISTORY AND ADMISSION FINDINGS: We report on a patient with known hypertension, who presented to his general practitioner with severe thoracic pain of sudden onset. The aches had started during a dental treatment. Immediately, the patient was admitted to hospital by the general practitioner because myocardial ischemia was suspected. INVESTIGATIONS: Neither the electrocardiogram nor the laboratory findings (creatin kinase, troponin I) argued for an acute coronary syndrome. Since the plasma D-dimer level was increased and the transthoracic echocardiography showed discrete signs of right ventricular strain, pulmonary embolism could not be ruled out. Because of the high intensity of pain and for further diagnostics the patient underwent a contrast medium-enhanced computed tomography (CT). DIAGNOSIS, TREATMENT AND COURSE: The contrast medium-enhanced CT showed a type B acute aortic dissection. According to the current guidelines for the treatment of type B aortic dissection, a conservative therapeutic regimen was applied. Antihypertensive therapy was escalated. Furthermore, the patient transiently received analgesic drugs. After three weeks the patient was released from hospital without pain and with physiologic blood pressure under intensified antihypertensive therapy. A follow up examination three months after the acute aortic dissection showed a constant aortic diameter. Therefore, surgical treatment was not indicated. CONCLUSIONS: This case report illustrates a typical clinical picture of acute aortic dissection and gives an overview about its epidemiology, classification, pathogenesis, and prognosis. Furthermore, the diagnostic opportunities and the current guidelines for the treatment of acute aortic dissection are discussed.

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.