BACKGROUND: Recent studies show an increased adipose production of tumor necrosis factor-alpha (TNF-a) in human obesity. It was hypothesized from this ®nding and other data, that TNF-a may be a mediator of obesity-linked insulin resistance. OBJECTIVE: The aim of this study was to measure plasma concentrations of the two soluble TNF-a receptors, together with those of TNF-a in subjects with severe obesity with and without type 2 diabetes mellitus, in comparison to a lean control group, to examine whether plasma concentrations re¯ect an up-regulation of the TNF system in adipose tissue. PATIENTS AND METHODS: Plasma concentrations of the two soluble TNF-a receptors were measured in 49 obese subjects (mean body mass index (BMI): 44.9 kgam 2 , 95% con®dence intervals (CI) 42.3 ± 47.5 kgam 2 , including 19 type 2 diabetic individuals) and 28 lean controls, by using a highly sensitive enzyme-linked immunoassay (ELISA) technique. TNF-a concentrations were determined in 28 obese (10 with diabetes) and 23 lean subjects. RESULTS: The obese subjects showed signi®cantly higher plasma concentrations of the soluble p60 and p80 TNF receptor, respectively, compared to the lean control group, independent of the presence of diabetes. Multiple regression analysis, with the p80 TNF receptor as dependent variable, revealed that BMI and log insulin signi®cantly affected the plasma concentration of this soluble receptor subtype, explaining 46% of the variance, whereas for the p60 TNF receptor, only BMI turned out to in¯uence plasma concentrations. TNF-a plasma concentrations were not different between the three groups (Kruskal-Wallis test: P 0.34), but due to the low power of the test, an effect of obesity on TNF-a is not excluded. CONCLUSION: These data indicate that plasma concentrations of both soluble TNF receptors are elevated in obesity and insulin resistance, possibly as a function of excess body fat. The reported adipose overexpression of TNF-a does not seem to be re¯ected by elevated plasma concentrations, suggesting a primarily local role of the cytokine.
Total cost and cost per case of diabetes avoided was high. Staff education and screening had a considerable impact. In view of the low participation in a routine healthcare setting, with both strategies only a small number of cases of diabetes would be prevented. Before implementing the programme, efforts should be made to improve patient participation in order to achieve better clinical and cost-effectiveness of the prevention of Type 2 diabetes in 'real world' clinical practice.
Definitions of the metabolic syndrome (MetS) include obesity, dyslipidemia, elevated levels of fasting blood glucose, and blood pressure as criteria, but it is also known that the MetS is associated with chronic, subclinical inflammation. Hyperglycemia (fasting and postprandial) may be important in exacerbating this proinflammatory state. We aimed to assess the impact of oral glucose challenge and in vitro glucose-stimulation on gene expression and secretion of inflammatory parameters in peripheral blood leukocytes and to investigate whether presence of the MetS could "prime" leukocytes to up-regulate proinflammatory markers in response to glucose. Using quantitative real-time PCR, we could show that the expression of intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) significantly increased in peripheral blood leukocytes from "MetS" subjects (n=39) compared to "no MetS" subjects (n=35) 2 h after an oral glucose tolerance test (ICAM-1 +52%, TNF-alpha +107%, and IL-6 +38%) and also in vitro after 72 h cultivation in high-glucose medium (ICAM-1 +74%, TNF-alpha +71%, and IL-6 +44%). Using ELISA and Luminex technique, we further observed a trend towards increased immune mediator concentrations in the corresponding cell culture supernatants from MetS patients (ICAM-1 +21%, TNF-alpha +31%, and IL-6 +175%). Thus, the MetS may support peripheral inflammation by sensitizing leukocytes to up-regulate proinflammatory markers in response to glucose, which in turn increases the risk for type-2 diabetes mellitus and cardiovascular disease.
Among the direct medical costs of childhood diabetes, the highest economic burden was due to glucose self measurement, hospitalization, and insulin. The costs were considerably higher in adolescents with poor metabolic control, especially the costs for hospitalization. Outpatient education programs in pediatric diabetes care, in particular targeting children with poor metabolic control, should be encouraged, including their evaluation with respect to cost and effectiveness.
In line with most European countries, the overall hip fracture incidence in Germany no longer increases. However, differences between age, sex, and region exist.
The population-based data regarding indicators of type 2 diabetes care processes and outcome in a defined region in Germany show that the treatment of hypertension and hypercholesterolemia was highly inappropriate, as was the frequency of medical control investigations. The high proportion of subjects who did not know the term "HbA(1c)" was striking, particularly among those of a low social status. A significant proportion had severe late complications. The mean HbA(1c), however, was better than had been reported in some previous German practice-based studies.
The purpose of this study was to assess the accuracy of multi-parameter measurements with color-coded duplex sonography (CCDS) for the diagnosis of venous leakage in patients with erectile dysfunction. Sixty patients with repeated unsatisfactory reactions after intracavernous injection of vasoactive substances underwent CCDS. Following intracavernous injection of prostaglandin E1, peak systolic velocity (PSV), enddiastolic velocity (EDV), time averaged velocity (TAV), resistance index (RI), and pulsatility index (PI) were measured in the cavernous arteries over 30 min (one measurement per minute). The results were compared with independent measurements based on dynamic pharmaco-cavernosometry/cavernosography (DPCC). Dynamic pharmaco-cavernosometry/cavernosography revealed venous leakage in 33 patients. Of 48 patients with normal PSV ( > 25 cm/s), 25 had veno-occlusive dysfunction and the remainder presented normal venous function. No statistically significant differences between these groups were found in EDV, RI, and PI measurements. In contrast, differences in TAV were significant between patients with (mean 9.4 +/- 4.6 cm/s) and without venous leakage (mean 5.5 +/- 2.2 cm/s; p = 0.001). Analysis of relative frequencies revealed a broad overlap of EDV, TAV, RI, and PI measurements between both groups. Sensitivities and specificities determined from receiver-operating-characteristic curves were > 80 % and > 50% for a TAV threshold of 5 cm/s, and an RI threshold of 1.0. Measurements of EDV, TAV, RI, and PI in patients with repeated unsatisfactory reactions on intracavernous prostaglandin injection are poor predictors of venous leakage and should not replace DPCC in the investigation of vasculogenic impotence.
Numbers of prescriptions and costs in primary care patients with future diabetes diagnosis in Germany were already increased six years before clinical detection, reflecting increased cardiovascular risk even before clinical diabetes diagnosis.
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