Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Aims/hypothesis

Oxidative stress plays a key role in the development of type 2 diabetes mellitus. We previously showed that the circulating antioxidant peroxiredoxin 4 (Prx4) is associated with cardiometabolic risk factors. We aimed to evaluate the association of Prx4 with type 2 diabetes risk in the general population.

Methods

We analysed data on 7,972 individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (49% men, aged 28–75 years) with no diabetes at baseline. Logistic regression models adjusted for age, sex, smoking, waist circumference, hypertension and family history of diabetes were used to estimate the ORs for type 2 diabetes.

Results

During a median follow up of 7.7 years, 496 individuals (288 men; 58%) developed type 2 diabetes. The median (Q1–Q3) Prx4 level was 0.84 (0.53–1.40) U/l in individuals who developed type 2 diabetes and 0.68 (0.43–1.08) U/l in individuals who did not develop type 2 diabetes. For every doubling of Prx4 levels, the adjusted OR (95% CI) for type 2 diabetes was 1.16 (1.05–1.29) in the whole population; by sex, it was 1.31 (1.14–1.50) for men and 1.03 (0.87–1.21) for women. Further adjustment for other clinical measures did not materially change the results. The addition of Prx4 to a validated diabetes risk score significantly improved the prediction of type 2 diabetes in men (p?=?0.002 for reclassification improvement).

Conclusions/interpretation

Our findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes. For men, taking Prx4 into consideration can improve type 2 diabetes prediction over a validated diabetes risk score; in contrast, there is no improvement in risk prediction for women.     

Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised,placebo-controlled study

Aims/hypothesis

Liraglutide can modulate insulin secretion by directly stimulating beta cells or indirectly through weight loss and enhanced insulin sensitivity. Recently, we showed that liraglutide treatment in overweight individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) led to greater weight loss (?7.7% vs ?3.9%) and improvement in insulin resistance compared with placebo. The current study evaluates the effects on beta cell function of weight loss augmented by liraglutide compared with weight loss alone.

Methods

This was a parallel, randomised study conducted in a single academic centre. Both participants and study administrators were blinded to treatment assignment. Individuals who were 40–70 years old, overweight (BMI 27–40 kg/m²) and with prediabetes were randomised (via a computerised system) to receive liraglutide (n?=?35) or matching placebo (n?=?33), and 49 participants were analysed. All were instructed to follow an energy-restricted diet. Primary outcome was insulin secretory function, which was evaluated in response to graded infusions of glucose and day-long mixed meals.

Results

Liraglutide treatment (n?=?24) significantly (p?≤?0.03) increased the insulin secretion rate (% mean change [95% CI]; 21% [12, 31] vs ?4% [?11, 3]) and pancreatic beta cell sensitivity to intravenous glucose (229% [161, 276] vs ?0.5% (?15, 14]), and decreased insulin clearance rate (?3.5% [?11, 4] vs 8.2 [0.2, 16]) as compared with placebo (n?=?25). The liraglutide-treated group also had significantly (p?≤?0.03) lower day-long glucose (?8.2% [?11, ?6] vs ?0.1 [?3, 2]) and NEFA concentrations (?14 [?20, ?8] vs ?2.1 [?10, 6]) following mixed meals, whereas day-long insulin concentrations did not significantly differ as compared with placebo. In a multivariate regression analysis, weight loss was associated with a decrease in insulin secretion rate and day-long glucose and insulin concentrations in the placebo group (p?≤?0.05), but there was no association with weight loss in the liraglutide group. The most common side effect of liraglutide was nausea.

Conclusions/interpretation

A direct stimulatory effect on beta cell function was the predominant change in liraglutide-augmented weight loss. These changes appear to be independent of weight loss.

Trial registration

ClinicalTrials.gov NCT01784965

Funding

The study was funded by the ADA.     

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Aims/hypothesis

Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately.

Methods

From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7?years.

Results

In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p _interaction?p?=?0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p?Conclusions/interpretation The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women.     

Treatment and outcomes of acute coronary syndrome in the cancer population

Background:

Randomized trials have established the benefit of medical therapy and revascularization in the treatment of acute myocardial infarction (MI). Cancer and cardiovascular disease are the 2 most common diseases worldwide. In clinical practice, cancer patients are frequently afflicted with MI. The benefit of medical and/or revascularization therapy in the cancer population with MI is less well known.

Hypothesis:

Medical and revascularization therapy reduces mortality in cancer patients with MI.

Methods:

After approval by the institutional review board, we retrospectively reviewed all patients with a discharge diagnosis of acute MI who were admitted to the University of Texas MD Anderson Cancer Center between December 2000 and October 2006 and evaluated the association between cardiac treatments with survival outcomes.

Results:

A total of 456 patients with a discharge diagnosis of acute MI were identified and included in the study, of which 386 had non–ST‐segment elevation MI (NSTEMI) and 70 had ST‐segment elevation MI (STEMI). Compared with patients with NSTEMI, patients who had STEMI were more often prescribed aspirin (66% vs 43%; P = 0.004), β‐blockers (61% vs 46%; P = 0.018), and thrombolytic therapy (9% vs 0.3%; P = 0.0001). In the multivariable analysis, aspirin use was associated with a 23% decreased risk of death (hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.60‐0.98, P = 0.033) and β‐blocker use was associated with a 36% decreased risk of death (HR: 0.64, 95% CI: 0.51–0.81, P = 0.0002). Statins (HR: 0.82, P = 0.18) and catheter‐based revascularization (HR: 0.57, P = 0.09) did not have an impact on the risk of death. Compared with patients with limited cancer, advanced cancer patients were twice as likely to die (HR: 2.12, 95 CI: 1.47–3.04, P < 0.0001). Previous chemotherapy (P = 0.005) and chest radiotherapy (P = 0.017) were associated with increased 1‐year mortality, whereas hyperlipidemia (P = 0.018) was protective.

Conclusions:

In this study of cancer patients with MI, medical therapy with aspirin and β‐blockers was associated with improved survival. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Ultrasound-guided simultaneous irrigation and drainage of facial abscess

The establishment of drainage and the elimination of the origin of infection are essential procedures for successful management of odontogenic infections. Irrigation and aspiration are considered as the 2 main procedures for the treatment of facial space infections; we invented a new method named simultaneous irrigation and aspiration. The simultaneous irrigation and aspiration method is significantly less painful and less invasive compared with the standard surgical incision and drainage. This method was thought to be useful for managing facial infections if proper patient selection is performed.     

Spatiotemporal distribution of cortical processing of first and second languages in bilinguals. I. Effects of proficiency and linguistic setting

The study determined how spatiotemporal distribution of cortical activity to words in first and second language is affected by language, proficiency, and linguistic setting. Ten early bilinguals and 14 late adult bilinguals listened to pairs of words presented in Arabic (L1), Hebrew (L2), or in mixed pairs and indicated whether both words had the same meaning or not. Source current densities of event‐related potentials were estimated. Activity to first words in the pair lateralized to right hemisphere, higher to L1 than L2 during early processing (<300 ms) among both groups but only among late bilinguals during late processing (>300 ms). During early and late processing, activities were larger in mixed than monolinguistic settings among early bilinguals but lower in mixed than in monolinguistic settings among late bilinguals. Late processing in auditory regions was of larger magnitude in left than right hemispheres among both groups. Activity to second words in the pair was larger in mixed than in monolinguistic settings during both early and late processing among both groups. Early processing of second words in auditory regions lateralized to the right among early bilinguals and to the left among late bilinguals, whereas late processing did not differ between groups. Wernicke's area activity during late processing of L2 was larger on the right, while on the left no significant differences between languages were found. The results show that cortical language processing in bilinguals differs between early and late processing and these differences are modulated by linguistic proficiency and setting. Hum Brain Mapp 34:2863–2881, 2013. © 2012 Wiley Periodicals, Inc.     

股骨近端锁定加压钢板治疗股骨转子间骨折

目的 探讨股骨近端锁定加压钢板（LCP）内固定治疗股骨转子间骨折的临床疗效.方法 采用股骨近端LCP治疗23例股骨转子间骨折的患者.随访观察骨折愈合时间,按Harris评分标准评价疗效.结果 23例均获随访,时间6~12（9±1.4）个月.骨折愈合时间14~20（17±1.7）周.髋关节Harris评分：优13例,良9例,一般1例.结论 股骨近端LCP内固定治疗股骨转子间骨折创伤小、出血少、对骨膜影响小,符合解剖形态,临床疗效满意.     

Comparison between Gallbladder Serosal and Mucosal Patch in Duodenal Injuries Repair in Dogs

Background: One of the most challenging problems in clinical surgery is management of an extensive duodenal injury. In its management, there are limitations in using jejunal serosal patch and other conventional methods in specific conditions. This study was performed to compare treatment of large duodenal defects by a gallbladder serosal patch and the gallbladder mucosal patch in a dog as an animal model. Methods: A duodenal defect (2 cm, about 50% of the total circumference) was created in the second portion of the duodenum in eight dogs. The animals were divided into two equal groups, with group 1 undergoing serosal patch repair and group 2 undergoing mucosal patch repair. The macroscopic and microscopic healing features of the gallbladder serosal and mucosal patch were compared. Results: None of the dogs died due to surgical complications. The whole grafted area was covered by neomucosa at the end of the third week in all animals with the gallbladder serosal patch (group 1). In this group, the scar was small; no significant narrowing of lumen was noted and serosal healing was uniformly complete. In histological examination, a complete coverage of the gallbladder serosal patch by neomucosa consisting of columnar epithelium with short villous formations was observed. In mucosal patch models (group 2), complete epitheliazation, mild fibrosis, and incomplete repair were visible. In histological examination, severe inflammation was noticed too. Conclusion: In patients with multiple trauma affecting upper gastrointestinal tracts, use of the gallbladder serosal patch method is easy and reliable. So it may be considered in the surgical management of large duodenal defects, which cannot be repaired by available conventional methods.     

Electrophysiological and morphological characterization of cells in superficial layers of rat presubiculum

The presubiculum (PrS) plays critical roles in spatial information processing and memory consolidation and has also been implicated in temporal lobe epileptogenesis. Despite its involvement in these processes, a basic structure–function analysis of PrS cells remains far from complete. To this end, we performed whole‐cell recording and biocytin labeling of PrS neurons in layer (L)II and LIII to examine their electrophysiological and morphological properties. We characterized the cell types based on electrophysiological criteria, correlated their gross morphology, and classified them into distinct categories using unsupervised hierarchical cluster analysis. We identified seven distinct cell types: regular‐spiking (RS), irregular‐spiking (IR), initially bursting (IB), stuttering (Stu), single‐spiking (SS), fast‐adapting (FA), and late‐spiking (LS) cells, of which RS and IB cells were common to LII and LIII, LS cells were specific to LIII, and the remaining types were identified exclusively in LII. Recorded neurons were either pyramidal or nonpyramidal and, except for Stu cells, displayed spine‐rich dendrites. The RS, IB, and IR cells appeared to be projection neurons based on extension of their axons into LIII of the medial entorhinal area (MEA) and/or angular bundle. We conclude that LII and LIII of PrS are distinct in their neuronal populations and together constitute a more diverse population of neurons than previously suggested. PrS neurons serve as major drivers of circuits in superficial (LII–III) entorhinal cortex (ERC) and couple neighboring structures through robust afferentation, thereby substantiating the PrS's critical role in the parahippocampal region. J. Comp. Neurol. 521: 3116–3132, 2013. © 2013 Wiley Periodicals, Inc.