Cardiovascular Events After Bariatric Surgery in Obese Subjects With Type 2 Diabetes

OBJECTIVE

Obese individuals with type 2 diabetes have an increased risk of cardiovascular disease. The effect of bariatric surgery on cardiovascular events in obese individuals with type 2 diabetes remains to be determined. The Swedish Obese Subjects (SOS) study is a prospective, controlled intervention study that examines the effects of bariatric surgery on hard end points. The aim of the present study was to examine the effect of bariatric surgery on cardiovascular events in the SOS study participants with type 2 diabetes.

RESEARCH DESIGN AND METHODS

All SOS study participants with type 2 diabetes at baseline were included in the analyses (n = 345 in the surgery group and n = 262 in the control group). Mean follow-up was 13.3 years (interquartile range 10.2–16.4) for all cardiovascular events.

RESULTS

Bariatric surgery was associated with a reduced myocardial infarction incidence (38 events among the 345 subjects in the surgery group vs. 43 events among the 262 subjects in the control group; log-rank P = 0.017; adjusted hazard ratio [HR] 0.56 [95% CI 0.34–0.93]; P = 0.025). No effect of bariatric surgery was observed on stroke incidence (34 events among the 345 subjects in the surgery group vs. 24 events among the 262 subjects in the control group; log-rank P = 0.852; adjusted HR 0.73 [0.41–1.30]; P = 0.29). The effect of surgery in reducing myocardial infarction incidence was stronger in individuals with higher serum total cholesterol and triglycerides at baseline (interaction P value = 0.02 for both traits). BMI (interaction P value = 0.12) was not related to the surgery outcome.

CONCLUSIONS

Bariatric surgery reduces the incidence of myocardial infarction in obese individuals with type 2 diabetes. Preoperative BMI should be integrated with metabolic parameters to maximize the benefits of bariatric surgery.Obesity is a growing burden for Western countries with approximately one-third of the population being affected in the U.S. (1). Excess body weight is associated with increased incidence of type 2 diabetes and cardiovascular disease (2–4). To date, bariatric surgery is the most effective treatment to achieve weight loss in obese individuals (5). The Swedish Obese Subjects (SOS) study is a nonrandomized but controlled, prospective, interventional trial on the effect of bariatric surgery on mortality and morbidity compared with conventional obesity treatment (6). We recently reported that bariatric surgery was associated with a decreased incidence of cardiovascular events in the overall SOS study (7).In individuals with type 2 diabetes, bariatric surgery results in sustained weight loss and also reduces blood glucose values (8–10). The American Diabetes Association (11), International Diabetes Federation (12), and other organizations (13,14) recommend bariatric surgery for adults with type 2 diabetes and BMI ≥35 kg/m², especially for those whose diabetes is difficult to control with a lifestyle and pharmacological approach. However, data on the long-term benefits of bariatric surgery on hard end points in individuals with type 2 diabetes are not available. Whether the metabolic improvement results in a reduced number of cardiovascular events in obese individuals with type 2 diabetes remains to be determined. Therefore, the aim of the present report was to examine the effect of bariatric surgery on cardiovascular events in SOS study participants with type 2 diabetes at baseline.     

Ultrastructural and Spectrophotometric Study on the Effects of Putative Triggers on Aortic Valve Interstitial Cells in In Vitro Models Simulating Metastatic Calcification

Metastatic calcification of cardiac valves is a common complication in patients affected by chronic renal failure. In this study, primary bovine aortic valve interstitial cells (AVICs) were subjected to pro‐calcific treatments consisting in cell stimulation with (i) elevated inorganic phosphate (Pi = 3 mM), to simulate hyperphosphatemic conditions; (ii) bacterial endotoxin lipopolysaccharide (LPS), simulating direct effects by microbial agents; and (iii) conditioned media (CM) derived from cultures of either LPS‐stimulated heterogenic macrophages (commercial murine RAW264.7 cells) or LPS‐stimulated fresh allogenic monocytes/macrophages (bCM), simulating consequent inflammatory responses, alone or combined. Compared to control cultures, spectrophotometric assays revealed shared treatment‐dependent higher values of both calcium amounts and alkaline phosphatase activity for cultures involving the presence of elevated Pi. Ultrastructurally, shared peculiar pro‐calcific degeneration patterns were exhibited by AVICs from these latter cultures irrespectively of the additional treatments. Disappearance of all cytomembranes and concurrent formation of material showing positivity to Cuprolinic Blue and co‐localizing with silver precipitation were followed by the outcropping of such a material, which transformed in layers outlining the dead cells. Subsequent budding of these layers resulted in the formation of bubbling bodies and concentrically laminated calcospherulae mirroring those in actual soft tissue calcification. In conclusion, the in vitro models employed appear to be reliable tools for simulating metastatic calcification and indicate that hyperphosphatemic‐like conditions could trigger valve calcification per se, with LPS and allogenic macrophage‐derived secretory products acting as possible calcific enhancers via inflammatory responses. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Human dedifferentiated adipocytes show similar properties to bone marrow-derived mesenchymal stem cells

Mature adipocytes are generally considered terminally differentiated because they have lost their proliferative abilities. Here, we studied the gene expression and functional properties of mature adipocytes isolated from human omental and subcutaneous fat tissues. We also focused on dedifferentiated adipocytes in culture and their morphologies and functional changes with respect to mature adipocytes, stromal-vascular fraction (SVF)-derived mesenchymal stem cells (MSCs) and bone marrow (BM)-derived MSCs. Isolated mature adipocytes expressed stem cell and reprogramming genes. They replicated in culture after assuming a fibroblast-like shape and expanded similarly to SVF- and BM-derived MSCs. During the dedifferentiation process, mature adipocytes lost their lineage gene expression profile, assumed the typical mesenchymal morphology and immunophenotype, expressed stem cell genes and differentiated into multilineage cells. Moreover, during the dedifferentiation process, we showed changes in the epigenetic status of mature adipocytes, which led dedifferentiated adipocytes to display a similar DNA methylation condition to BM-derived MSCs. Like SVF- and BM-derived MSCs, dedifferentiated adipocytes were able to inhibit the proliferation of stimulated lymphocytes in coculture while mature adipocytes stimulated their growth. Furthermore, dedifferentiated adipocytes maintained the survival and complete differentiation characteristic of hematopoietic stem cells. This is the first study that in addition to characterizing isolated and dedifferentiated adipocytes also reports on the immunoregulatory and hematopoietic supporting functions of these cells. This structural and functional characterization might have clinical applications of both mature and dedifferentiated adipocytes in such fields, as regenerative medicine.     

Immunological Comorbity in Coeliac Disease: Associations, Risk Factors and Clinical Implications

Purpose

Coeliac disease is frequently associated with other immunomediated diseases. Our aim was to identify immunological comorbidities and possible risk factors for their development in coeliac patients.

Methods

We recruited a cohort of 1,015 coeliac patients followed from 0 to 46?years in a single tertiary referral centre. Data were collected from the yearly scheduled clinical and serological evaluations. Possible risk factors such as demographic parameters, type of symptomatic presentation, gluten exposure, gluten-free diet compliance and family history were all evaluated. Subjects (848,606) from the regional health registry were investigated as controls.

Results

The prevalence of immunomediated diseases was higher in patients with coeliac disease compared to the registry population (23?% vs 0.4?%, p?p?=?0.0061). Type of presentation and dietetic compliance did not represent risk factors. Long-standing gluten exposure reduced the risk of developing immunomediated diseases in coeliac subjects (hazard ratio for 1?year longer exposure 0.23, 95?% confidence interval 0.16–0.33, p?Conclusions Our study suggests the need to investigate coeliac patients for other associated immunomediated diseases, independently of sex, gluten exposure and compliance to therapy; also subjects diagnosed in paediatric age should be carefully screened during follow up.     

PI3KCA mutations and/or PTEN loss in Her2-positive breast carcinomas treated with trastuzumab are not related to resistance to anti-Her2 therapy

The purpose of this study is to evaluate whether activating mutations of the p110α catalytic subunit of class A phosphoinositide 3-kinases (PI3KCA) or complete loss of phosphatase and tensin homolog (PTEN) is associated with response to anti-human epidermal growth factor receptor 2 (Her2) treatment in breast cancer (BC). We analysed PI3KCA hot-spot mutations and PTEN immunohistochemical expression in 129 Her2-positive infiltrating BC treated with trastuzumab, including 26 cases treated with neoadjuvant therapy, 48 metastatic infiltrating breast cancer (IBC; MBC) and 55 early-stage IBC, with complete clinical information (mean follow-up 37, 66 and 32?months, respectively). PI3KCA hot-spot mutations were observed in 25 cases (19?%): 12 (9?%) in exon 9 and 13 (10?%) in exon 20. No correlations were observed between mutations and pathological and biological parameters. In patients treated with neoadjuvant therapy and in MBC, we did not observe any relationship with response to trastuzumab-based therapy. PTEN loss was observed in 24 out of 86 informative cases (28?%), 3 (13?%) of which were also mutated for PI3KCA. PI3K pathway activation, defined as PI3KCA mutation and/or PTEN loss, was not associated with response to treatment or clinical outcome in MBC. PI3KCA mutation and/or PTEN loss should not exclude patients from potentially beneficial anti-Her2 therapy.     

Evaluation of the new test VERSANT CT/GC DNA 1.0 assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are the two most common sexually transmitted bacterial infections in developed countries. The purpose of the present study was evaluating a new system for CT/GC detection in urine specimens. A total of 700 urine specimens were obtained from patients attending the STD Outpatients Clinic of St. Orsola University Hospital, Bologna, Italy. Samples were tested by VERSANT? CT/GC DNA 1.0 Assay (Siemens Healthcare Diagnostics Inc., Tarrytown, NY), a multiplex Real-Time PCR assay, for simultaneous CT/GC detection. Results obtained by VERSANT assay were compared with those obtained by culturing genital secretions of the same patients. Moreover, urine specimens testing positive in VERSANT assay were retested by in-house PCR assays, used as confirmatory tests. VERSANT? CT/GC DNA 1.0 Assay performed with 99.4% and 99.2% of specificity for GC and CT detection, respectively, whereas sensitivity was 100% both for CT and GC. Culture methods were 100% specific, but far less sensitive than VERSANT assay. VERSANT? CT/GC DNA 1.0 Assay demonstrated to be a highly sensitive and specific technique for CT/GC detection.     

Multiple cycles of repeated treatments with a Phaseolus vulgaris dry extract reduce food intake and body weight in obese rats

Previous lines of experimental evidence have suggested that Phaseolus vulgaris extracts reduce food intake, body weight, lipid accumulation, hedonic properties of food, carbohydrate absorption and metabolism, and glycaemia in rats. The present study was designed to assess the effect of multiple cycles of repeated treatments with a standardised P. vulgaris dry extract on daily food intake and body weight in genetically obese Zucker fa/fa rats (Expt 1). Additionally, the study tested the effect of acute treatment with P. vulgaris dry extract on postprandial glycaemia in Zucker fa/fa rats (Expt 2). In Expt 1, P. vulgaris dry extract was administered daily, at doses of 50 and 500 mg/kg, in three 5 d treatment periods followed by three 20 d off-treatment periods. Administration of P. vulgaris dry extract resulted in dose-dependent decreases in daily food intake and body weight in each treatment phase. Reductions in food intake were of comparable magnitude in each treatment phase. In Expt 2, food-deprived rats were acutely treated with 50 and 500 mg P. vulgaris dry extract per kg immediately before access to a fixed amount of a starch-enriched chow. Treatment with P. vulgaris dry extract resulted in a dose-dependent suppression of glycaemia. These results extend previous data on the anorectic and hypoglycaemic effects of the P. vulgaris dry extract to a validated animal model of obesity. Together with data published previously in the literature, these results strengthen the hypothesis that potentially effective, novel pharmacotherapies for obesity and related disorders may originate from extracts and derivatives of P. vulgaris.