Background: 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.Methods: 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], Ͻ25.0), overweight (BMI, 25.0-29.9), obese-insulin sensitive (IS) (BMI, Ն30.0 and placement in the upper quartile of insulin sensitivity), and obese-insulin resistant (IR) (BMI, Ն30.0 and placement in the lower 3 quartiles of insulin sensitivity).Results: Total body and visceral fat were higher in the overweight and obese groups compared with the normal-weight group (PϽ.05); however, no differences were observed between the obese groups. In contrast, ectopic fat in skeletal muscle (PϽ.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 (PϽ.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). Conclusions: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.

Background-Primary and secondary prevention trials suggest that statins possess favorable effects independent of cholesterol reduction. We investigated whether statin therapy may also accelerate reendothelialization after carotid balloon injury. Methods and Results-Simvastatin treatment in 34 male Sprague-Dawley rats accelerated reendothelialization of the balloon-injured arterial segments (reendothelialized area at 2 weeks, 12.3Ϯ1.8 versus 5.4Ϯ1.1 mm 2 , PϽ0.01) and resulted in a dose-dependent (0.2 or 1 mg/kg IP) significant reduction in neointimal thickening at 2, 3, and 4 weeks compared with saline-injected controls (nϭ18). To elucidate the mechanism, we investigated the contribution of bone marrow-derived endothelial progenitor cells (EPCs) by bone marrow transplantation from Tie2/lacZ mice to background mice or nude rats. X-gal staining of mouse carotid artery specimens revealed a 2.9-fold increase in the number of ␤-gal-positive cells per square millimeter appearing on the carotid artery luminal surface at 2 weeks, and double-fluorescence immunohistochemistry disclosed a significant 5-fold increase in the number of double-positive cells (␤-gal, isolectin B4) on the luminal surface in carotid arteries of statin-treated nude rats (20Ϯ3 versus 4Ϯ1 cells/mm surface length, PϽ0.005). Statins increased circulating rat EPCs (2.4-fold at 2 weeks and 2.5-fold at 4 weeks, PϽ0.001) and induced adhesiveness of cultured human EPCs by upregulation of the integrin subunits ␣ 5 , ␤ 1 , ␣ v , and ␤ 5 of human EPCs as shown by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting. Conclusions-These findings establish additional mechanisms by which statins may specifically preempt disordered vascular wall pathology and constitute physiological evidence that EPC mobilization represents a functionally relevant consequence of statin therapy.

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 Յ5.8 mL ⅐ kg Ϫ1 ⅐ min

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Febrile morbidity is the most commonly reported adverse event after hysterectomy. Its incidence ranges from 9.1 to 37.4%. Risk factors reported in the literature include prolonged operative time, history of previous surgery, higher parity, greater blood loss, abdominal approach, and no antibiotic prophylaxis.Antibiotic prophylaxis in abdominal hysterectomy may provide protection against febrile morbidity and reduce its incidence, but does not eliminate it. Limited data are available evaluating risk factors for febrile morbidity after hysterectomy. This historical cohort study assessed the incidence of febrile morbidity and associated risk factors in 1980 Thai women, who had an abdominal hysterectomy between 1998 and 2005.Of the 1980 women, febrile morbidity occurred in 517. This represents an overall incidence of 26.1%. Univariate analysis of potential risk factors showed that the incidence of febrile morbidity was higher in patients with lower preoperative hematocrit, more extensive surgery, longer operative time, greater intraoperative blood loss and malignant disease. Median intraoperative blood loss was lower in the nonfebrile group than the febrile group (400 versus 500 ml, P Յ .0005) and median operative time was shorter (135 versus 150 minute, P Յ .0005).When both pre and postoperative variables were included in the logistic regression model, the only two risk factors independently associated with febrile morbidity were intraoperative blood loss of Ն750 ml (odds ratio [OR],1.52; 95% confidence interval [CI], 1.08-2.13; P ϭ .036) and a diagnosis of malignant disease (OR 1.86; 95% CI 1.45-2.13, P Ͻ .0005). GYNECOLOGY Volume 64, Number 1 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACTAlternatives to hysterectomy such as medical treatment, uterine artery embolization (UAE), and ablative therapy have become available and widely used in the last 10 years. It is unclear if these alternatives are replacing hysterectomy or delaying it. To determine the effect of patient clinical factors on the utilization of hysterectomy and alternatives of hysterectomy, the investigators examined all claims relating to a hysterectomy procedure or a hysterectomy-associated diagnosis in the database of a large insurance provider for 48 consecutive months from 2001 to 2005. A total of 295,148 claim lines were abstracted and analyzed by CPT and diagnostic grouping codes.Of the 7049 procedures represented in the claim lines, 1972 were hysterectomies and 5077 were hysterectomy alternatives. The mean age of patients filing claims was 39.1 years. Patients submitting claims for a hysterectomy were older than those having an alternative procedure (mean age, 49.7 v 46.0 years, P Ͻ .0001). The diagnostic group associated with the majority of all claims was abnormal bleeding (33%); the inflammation/mass/pain/endometriosis group accounted for 32%. The most common diagnostic groups associated with a hysterectomy were fibroids (39.4%), the inflammation/mass/pain/endometriosis category (14.7%), and cancer (13.0%). Bleeding represented the majority o...

Impaired glucose tolerance (IGT) which precedes overt type 2 diabetes (T2DM) for decades is associated with multiple metabolic alterations in insulin sensitive tissues. In an UPLC-qTOF-mass spectrometrydriven non-targeted metabonomics approach we investigated plasma as well as spot urine of 51 non-diabetic, overnight fasted individuals aiming to separate subjects with IGT from controls thereby identify pathways affected by the pre-diabetic metabolic state. We could clearly demonstrate that normal glucose tolerant (NGT) and IGT subjects clustered in two distinct groups independent of the investigated metabonome. These findings reflect considerable differences in individual metabolite fingerprints, both in plasma and urine. Pre-diabetes associated alterations in fatty acid-, tryptophan-, uric acid-, bile acid-, and lysophosphatidylcholine-metabolism, as well as the TCA cycle were identified. Of note, individuals with IGT also showed decreased levels of gut flora-associated metabolites namely hippuric acid, methylxanthine, methyluric acid, and 3-hydroxyhippuric acid. The findings of our non-targeted UPLC-qTOF-MS metabonomics analysis in plasma and spot urine of individuals with IGT vs NGT offers novel insights into the metabolic alterations occurring in the long, asymptomatic period preceding the manifestation of T2DM thereby giving prospects for new intervention targets.

Aims/hypothesis We and others recently characterised metabolically benign or healthy obesity (MHO). In the present study we investigated whether a lifestyle intervention is sufficient to place obese insulin-resistant (OIR) individuals in a position where the possible metabolic consequences are similar to those for MHO individuals. Methods A total of 262 non-diabetic individuals participated in a 9 month lifestyle intervention programme. Obese individuals (BMI≥30.0 kg/m 2 ) were stratified, based on their insulin sensitivity (IS) estimated from an OGTT, into MHO (IS in the upper quartile, n=26) and OIR (IS in the lower three quartiles, n=77). Total body and visceral fat were measured by magnetic resonance (MR) tomography and liver fat by 1 H-MR spectroscopy. Results During the intervention, visceral fat decreased significantly in both groups (both p≤0.009), whereas total body and liver fat decreased only in the OIR group (p< 0.0001; MHO p=0.12 for total body fat and p=0.47 for liver fat). IS improved in the OIR group (p<0.0001), but remained essentially unchanged in the MHO group (p= 0.30). However, despite the significant increase in the OIR group, IS at follow-up barely exceeded 50% of the IS of the MHO group (OIR 9.30±0.53 arbitrary units [AU]; MHO 16.41±1.05 AU; p<0.0001). Conclusions/interpretation IS improves during the lifestyle intervention in OIR individuals. However, it does not reach a level where adequate protection from type 2 diabetes and cardiovascular disease is expected. Thus, stratification of obese individuals based on their metabolic phenotype is important to identify those who are likely to need early pharmacological treatment in addition to the lifestyle intervention.

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.