Chemerin: a potential endocrine link between obesity and type 2 diabetes

Obesity and type 2 diabetes have reached epidemic levels and account for a substantial portion of the annual health expenditures of developed nations. While there is an abundance of epidemiological evidence demonstrating that obesity is a primary risk factor for developing type 2 diabetes, the mechanism(s) underlying this linkage are not completely understood. Given the enormous impact of these disorders on global health, considerable research effort has been devoted to elucidate the pathophysiological relationship between these two disorders. Two factors believed to contribute to the causal link between obesity and type 2 diabetes are chronic inflammation and altered secretion of adipose-derived signaling molecules (adipokines). Independent lines of investigation have implicated the novel adipokine chemerin as a regulator of adipogenesis, inflammation, and glucose metabolism through interactions with the cognate cell surface receptor chemokine-like receptor 1. Increased levels of chemerin that occur with obesity are hypothesized to be a causal factor in the development of type 2 diabetes as a consequence of dysregulation of the key physiological processes regulated by this adipokine. This review summarizes current research on the biological roles of chemerin and chemokine-like receptor 1, and highlights key questions to guide future research on the role of this adipokine in mediating obesity and the development of type 2 diabetes.     

GLP1 and cancer: friend or foe?

The new incretin-based therapies, dipeptidyl peptidase-4 (DPP4) inhibitors and glucagon like peptide 1 (GLP1) receptor agonists are widely used for the treatment of type 2 diabetes because of their glucose-lowering capacity with low risk of hypoglycemia. As they are weight neutral or induce weight loss in this mostly overweight population, they are popular among clinicians and patients alike. Nonetheless, concerns have been raised about GLP1's trophic effects. While increased β cell mass observed in rodents sounds appealing for treatment of diabetes, there was also an increased incidence of medullary thyroid cancer (MTC) in some species. We reviewed literature available in the Medline database until March 2012. Safety signals have emerged for MTC and pancreatic carcinoma from adverse event databases in the United States and Europe. Considering the relatively short duration of these studies, it is more likely that premalignant lesions are stimulated in presence of GLP1, rather than new neoplasms induced. Moreover, interpreting results of animal studies is difficult because of species-specific differences in presence and density of GLP1 receptors. Furthermore, data are emerging suggesting beneficial effects of GLP1 on colon and breast cancer. In conclusion, presently, the benefits of using DPP4 inhibitors or GLP1 receptor agonists for treatment of type 2 diabetes outweigh the risks. Nonetheless, their safety profile should be monitored and their indications should be widened cautiously. At present they remain contra-indicated in patients with a personal or family history of MTC or multiple endocrine neoplasia type 2.     

Perioperative risk factors for 30-day mortality after bariatric surgery: is functional status important?

Background

Although the mortality from bariatric surgery is low, perioperative determinants of morbidity and mortality in the bariatric surgery population to date have not been fully defined. This study aimed to evaluate the factors capable of predicting perioperative mortality based on preoperative characteristics with a national patient sample.

Methods

From the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, all the primary bariatric procedures performed between 2007 and 2009 were identified. Using univariate analysis, factors associated with increased perioperative (30-day) mortality were identified. Logistic regression was used to select correlates of 30-day mortality, which were subsequently integrated into a simplified clinical scoring system based on the number of comorbid risk factors.

Results

The study identified 44,408 patients (79 % women, 21 % men) with a mean age of 45 ± 11 years. The cumulative 30-day perioperative mortality rate was 0.14 %. The majority of the procedures performed included laparoscopic gastric bypass (54 %) followed by laparoscopic gastric banding (33 %) and open gastric bypass (7 %). Independent predictors associated with significantly increased mortality included age >45 years [adjusted odds ratio (AOR), 2.45], male gender (AOR = 1.77), a body mass index (BMI) of 50 kg/m² or higher (AOR, 2.48), open bariatric procedures (AOR, 2.34), diabetes (AOR, 2.88), functional status of total dependency before surgery (AOR, 27.6), prior coronary intervention (AOR, 2.66), dyspnea at preoperative evaluation (AOR, 4.64), more than 10 % unintentional weight loss in 6 months (AOR, 13.5), and bleeding disorder (AOR, 2.63). Ethnicity, hypertension, alcohol abuse, liver disease, and smoking had no significant association with mortality in this study. Risk stratification based on the number of preoperative comorbid factors showed an exponential increase in mortality as follows: 0–1 comorbidities (0.03 %), 2–3 comorbidities (0.16 %), and 4 comorbidities or more (7.4 %).

Conclusion

This model provides a straightforward, precise, and easily applicable tool for identifying bariatric patients at low, intermediate, and high risk for in-hospital mortality. Notably, baseline functional status before surgery is the single most powerful predictor of perioperative survival and should be incorporated into risk stratification models.     

A cross-cultural replication of an interactive model of anxiety sensitivity relevant to suicide

Recent findings indicate a relationship between anxiety sensitivity (AS) and suicide in a variety of populations in the United States. However, the link between AS and suicide has not been evaluated in other cultures. Suicide rates in Russia are among the highest worldwide making it an excellent choice to evaluate the cross-cultural robustness of these findings. The current investigation sought to replicate and extend the investigation of AS subfactors (i.e., cognitive, physical, and their interaction) in relation to suicidality in a sample of Russian adults. Participants were 390 adults recruited from Moscow using a geographic sampling method. Findings from the current study indicate that the interaction of AS cognitive concerns and AS physical concerns are associated with elevated rates of suicidality and previous suicide attempt, above and beyond negative affectivity and hazardous alcohol use. Clinicians may benefit from implementing AS reduction strategies with individuals who endorse elevated suicide risk as well as elevated AS cognitive concerns and low AS physical concerns.     

How might financial pressures have impacted brachytherapy? A proposed narrative to explain the declines in cervical and prostate brachytherapy utilization

Rates of brachytherapy administration in the United States have declined for both cervical and prostate cancers, and we argue that the available facts suggest financial considerations are a major contributor to this issue. In this narrative, we discuss financial pressures that have existed for cervical and prostate brachytherapy and how they may have influenced their declining usage, consider other proposed influences, and provide suggestions for future research to understand the scope of the issue.