The prospective, controlled Swedish Obese Subjects study enrolled 4047 subjects who either underwent bariatric surgery or received conventional treatment. The results of follow-up for up to 15 years ...suggest that bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
The results suggest that bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
In the United States from 1980 through 2004, the prevalence of obesity — defined as a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30 or more — doubled, rising to include more than 30% of the population.
1
,
2
The majority of large and long-term epidemiologic studies have indicated that obesity is associated with increased mortality.
3
–
9
The life expectancy of severely obese persons is reduced by an estimated 5 to 20 years.
10
Weight loss is known to be associated with improvement of intermediate risk factors for disease,
11
suggesting that weight . . .
Debate continues as to whether acute bronchodilator responsiveness (BDR) predicts long-term outcomes in COPD. Furthermore, there is no consensus on a threshold for BDR.
At baseline and during the ...4-year Understanding Potential Long-term Improvements in Function with Tiotropium (UPLIFT®) trial, patients had spirometry performed before and after administration of ipratropium bromide 80 mcg and albuterol 400 mcg. Patients were split according to three BDR thresholds: ≥ 12% + ≥ 200 mL above baseline (criterion A), ≥ 15% above baseline (criterion B); and ≥ 10% absolute increase in percent predicted FEV1 values (criterion C). Several outcomes (pre-dose spirometry, exacerbations, St. George's Respiratory Questionnaire SGRQ total score) were assessed according to presence or absence of BDR in the treatment groups.
5783 of 5993 randomized patients had evaluable pre- and post-bronchodilator spirometry at baseline. Mean age (SD) was 64 (8) years, with 75% men, mean post-bronchodilator FEV1 1.33 ± 0.44 L (47.6 ± 12.7% predicted) and 30% current smokers. At baseline, 52%, 66%, and 39% of patients had acute BDR using criterion A, B, and C, respectively. The presence of BDR was variable at follow-up visits. Statistically significant improvements in spirometry and health outcomes occurred with tiotropium regardless of the baseline BDR or criterion used.
A large proportion of COPD patients demonstrate significant acute BDR. BDR in these patients is variable over time and differs according to the criterion used. BDR status at baseline does not predict long-term response to tiotropium. Assessment of acute BDR should not be used as a decision-making tool when prescribing tiotropium to patients with COPD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its ...etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a “hyperplastic” theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome.
Enlarged adipocytes are associated with insulin resistance and are an independent predictor of type 2 diabetes. To understand the molecular link between these diseases and adipocyte hypertrophy, we ...developed a technique to separate human adipocytes from an adipose tissue sample into populations of small cells (mean 57.6±3.54 μm) and large cells (mean 100.1±3.94 μm). Microarray analysis of the cell populations separated from adipose tissue from three subjects identified 14 genes, of which five immune-related, with more than fourfold higher expression in large cells than small cells. Two of these genes were serum amyloid A (SAA) and transmembrane 4 L six family member 1 (TM4SF1). Real-time RT-PCR analysis of SAA and TM4SF1 expression in adipocytes from seven subjects revealed 19-fold and 22-fold higher expression in the large cells, respectively, and a correlation between adipocyte size and both SAA and TM4SF1 expression. The results were verified using immunohistochemistry. In comparison with 17 other human tissues and cell types by microarray, large adipocytes displayed by far the highest SAA and TM4SF1 expression. Thus, we have identified genes with markedly higher expression in large, compared with small, human adipocytes. These genes may link hypertrophic obesity to insulin resistance/type 2 diabetes.--Jernås, M., Palming, J., Sjöholm, K., Jennische, E., Svensson, P.-A., Gabrielsson, B. G., Levin, M., Sjögren, A., Rudemo, M., Lystig, T. C., Carlsson, B., Carlsson, L. M. S., Lönn, M. Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression.
To the Editor:
In a phase 3 trial of acoramidis for transthyretin amyloid cardiomyopathy, Gillmore et al. (Jan. 11 issue)
1
used the Finkelstein–Schoenfeld test to assess the hierarchical composite ...primary outcome. They expressed the treatment effect as a win ratio, thereby following the initial presentation of the analysis of a prioritized outcome.
2
However, the generalized pairwise comparison method, to which the Finkelstein–Schoenfeld test and the win ratio belong, has evolved substantially since this first application.
3
To aid the interpretation of the results, it is now recommended that the proportions of wins and losses for each outcome are reported to understand the . . .
In patients with transthyretin amyloid cardiomyopathy, the TTR stabilizer acoramidis resulted in a better primary hierarchical outcome (including mortality, morbidity, and function) than placebo.
Summary Background Gender differences may occur in many chronic diseases. We have examined the influence of gender in chronic obstructive pulmonary disease (COPD) on long-term responses to ...tiotropium. Methods Subgroup analysis of data from the Understanding the Potential Long-term Impact of Tiotropium (UPLIFT® ) trial (4-year, randomized, double-blind, placebo-controlled trial of tiotropium in patients with COPD). Results Of 5992 patients, 75% were men and 25% women. Mean age was 65 and 63 years, respectively. Baseline post-bronchodilator forced expiratory volume in 1 s (FEV1 ) = 47% predicted(men) and 49% predicted(women). St George’s Respiratory Questionnaire (SGRQ) total score was 44.9 and 48.7 units, respectively. At 48 months, improvement in trough FEV1 over control was 92 mL(men) and 77 mL(women) ( p < 0.001 for both), with no differences in the rate of decline (trial primary endpoint). Hazard ratio (HR) (95% confidence interval CI) for first exacerbation (tiotropium/placebo) was 0.87(0.81, 0.93)(men) and 0.83(0.74, 0.94)(women). Number of exacerbations (per patient-year) was reduced with tiotropium in men (from 0.82 to 0.71) and women (from 0.92 to 0.77) ( p < 0.005 for both). HR (95% CI) for a hospitalized exacerbation was 0.89(0.79, 0.99) and 0.77(0.62, 0.94), respectively. HR (95% CI) for mortality during treatment was 0.85(0.72, 0.99)(men) and 0.85(0.62, 1.18)(women). Improvements in SGRQ total score (tiotropium–control) at 1, 2, 3 and 4 years were: −2.8, −2.3, −3.6, −2.4(men) and −2.7, −2.6, −2.6, −2.1(women) ( p < 0.05 for all). Conclusion Long-term treatment of COPD with tiotropium improves lung function, exacerbations and health status in men and women, with similar magnitudes of benefit. Boehringer Ingelheim trial 205.235; ClinicalTrials.gov: NCT00144339.
To identify genes predominantly expressed in omental adipocytes, microarray expression profiles from 33 human tissues or cell types were analyzed, using an algorithm developed for identification of ...transcripts predominantly expressed in a certain tissue. Both known adipocyte-specific and more unexpected genes were among the 28 genes identified. To validate the approach, adipocyte expression of three of these genes, acute-phase serum amyloid A (A-SAA), aquaporin 7, and transport secretion protein-2.2, was compared with 17 other human tissues by real-time PCR. The unexpectedly high expression of A-SAA in adipocytes was further verified by Northern blot and immunohistochemistry. The liver, reported to be the main production site for A-SAA, displayed the second highest expression using microarray and real-time PCR. In obese subjects, adipose tissue mRNA and serum A-SAA levels were down-regulated during an 18-wk diet regime (P < 0.05 and P < 0.0001, respectively). A-SAA serum levels were highly correlated to adipose tissue mRNA levels (P < 0.001) and to the total (P < 0.0001) and sc (P < 0.0001) adipose tissue areas, as analyzed by computed tomography.
We show that adipose tissue is a major expression site of A-SAA during the nonacute-phase reaction condition. This provides a direct link between adipose tissue mass and a marker for low-grade inflammation and cardiovascular risk.
Postnatal events contribute to features of the metabolic syndrome in adulthood. In this study, postnatally administered testosterone reduced insulin sensitivity and increased the mesenteric fat ...depot, the size of mesenteric adipocytes, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and the atherogenic index in adult female rats. To assess the involvement of estrogen and androgen receptors in these programming effects, we compared testosterone-exposed rats to rats exposed to estradiol or dihydrotestosterone (DHT). Estradiol-treated rats had lower insulin sensitivity than testosterone-treated rats and, like those rats, had enlarged mesenteric adipocytes and increased triglyceride levels. DHT also reduced insulin sensitivity but did not mimic the other metabolic effects of testosterone. All treated rats were probably anovulatory, but only those treated with testosterone had reduced testosterone levels. This study confirms our previous finding that postnatal administration of testosterone reduces insulin sensitivity in adult female rats and shows that this effect is accompanied by unfavorable changes in mesenteric fat tissue and in serum lipid levels. The findings in the estradiol and DHT groups suggest that estrogen receptors exert stronger metabolic programming effects than androgen receptors. Thus, insults such as sex hormone exposure in early life may have long-lasting effects, thereby creating a predisposition to disturbances in insulin sensitivity, adipose tissue, and lipid profile in adulthood.
PDF
