Increasing fibre intake in the UK: lessons from the Danish Whole Grain Partnership.

Diets deficient in fibre are reported globally. The associated health risks of insufficient dietary fibre are sufficiently grave to necessitate large-scale interventions to increase population intake levels. The Danish Whole Grain Partnership (DWP) is a public-private enterprise model that successfully augmented whole-grain intake in the Danish population. The potential transferability of the DWP model to Slovenia, Romania and Bosnia-Herzegovina has recently been explored. Here, we outline the feasibility of adopting the approach in the UK. Drawing on the collaborative experience of DWP partners, academics from the Healthy Soil, Healthy Food, Healthy People (H3) project and food industry representatives (Food and Drink Federation), this article examines the transferability of the DWP approach to increase whole grain and/or fibre intake in the UK. Specific consideration is given to the UK's political, regulatory and socio-economic context. We note key political, regulatory, social and cultural challenges to transferring the success of DWP to the UK, highlighting the particular challenge of increasing fibre consumption among low socio-economic status groups - which were also most resistant to interventions in Denmark. Wholesale transfer of the DWP model to the UK is considered unlikely given the absence of the key 'success factors' present in Denmark. However, the DWP provides a template against which a UK-centric approach can be developed. In the absence of a clear regulatory context for whole grain in the UK, fibre should be prioritised and public-private partnerships supported to increase the availability and acceptability of fibre-rich foods.

A Framework for Standardizing Emergency Nursing Education and Training Across a Regional Health Care System: Programming, Planning, and Development via International Collaboration.

INTRODUCTION: The challenges related to providing continuing education and competence management for emergency nurses are not unique to any one organization, health system, or geographic location. These shared challenges, along with a desire to ensure high-quality practice of emergency nursing, were the catalyst for an international collaboration between emergency nurse leaders in Region Zealand, Denmark, and nurse leaders and educators from a large academic medical center in Boston, Massachusetts. The goal of the collaboration was to design a competency-based education framework to support high-quality emergency nursing care in Region Zealand. The core objectives of the collaboration included the following: (1) elevation of nursing practice, (2) development of a sustainable continuing education framework, and (3) standardization of training and nursing practice across the 4 emergency departments in Region Zealand. METHODS: To accomplish the core objectives, a multi-phased strategic approach was implemented. The initial phase, the needs assessment, included semi-structured interviews, a self-evaluation of skills of all regional emergency nurses, and a survey regarding nursing competency completed by emergency nurse leadership. Two hundred ninety emergency nurses completed the self-evaluation. The survey results were utilized to inform the strategic planning and design of a regional competency-based education framework. RESULTS: In 18 months, and through an international collaboration, emergency nursing education, training, and evaluation tools were developed and integrated into the 4 regional emergency departments. Initial feedback indicates that the education has had a positive impact. The annual competency day program has continued through 2021 and is now fully institutionalized within the regional emergency nursing continuing education program. Furthermore, use of this innovative education framework has expanded beyond the emergency department to other regional nursing specialties. DISCUSSION AND CONCLUSION: Through this unique collaboration with regional and international participants, a sustainable, regional emergency nursing education program was developed that has elevated and standardized the practice of emergency nurses in Region Zealand, Denmark. This program development can serve as a model for region-wide or health care system-wide collaborations in other countries.

GUB06-046, a novel secretin/glucagon-like peptide 1 co-agonist, decreases food intake, improves glycemic control, and preserves beta cell mass in diabetic mice.

Bariatric surgery is currently the most effective treatment of obesity, which has spurred an interest in developing pharmaceutical mimetics. It is thought that the marked body weight-lowering effects of bariatric surgery involve stimulated secretion of appetite-regulating gut hormones, including glucagon-like peptide 1. We here report that intestinal expression of secretin is markedly upregulated in a rat model of Roux-en-Y gastric bypass, suggesting an additional role of secretin in the beneficial metabolic effects of Roux-en-Y gastric bypass. We therefore developed novel secretin-based peptide co-agonists and identified a lead compound, GUB06-046, that exhibited potent agonism of both the secretin receptor and glucagon-like peptide 1 receptor. Semi-acute administration of GUB06-046 to lean mice significantly decreased cumulative food intake and improved glucose tolerance. Chronic administration of GUB06-046 to diabetic db/db mice for 8 weeks improved glycemic control, as indicated by a 39% decrease in fasting blood glucose and 1.6% reduction of plasma HbA1c levels. Stereological analysis of db/db mice pancreata revealed a 78% increase in beta-cell mass after GUB06-046 treatment, with no impact on exocrine pancreas mass or pancreatic duct epithelial mass. The data demonstrate beneficial effects of GUB06-046 on appetite regulation, glucose homeostasis, and beta-cell mass in db/db mice, without proliferative effects on the exocrine pancreas and the pancreatic duct epithelium. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Menu labelling is effective in reducing energy ordered and consumed: a systematic review and meta-analysis of recent studies.

OBJECTIVE: Menu labelling is a practical tool to inform consumers of the energy content of menu items and help consumers make informed decisions in the eating-out environment, and the volume of studies published recently regarding its effects is expanding, both quantitatively and geographically. The aim of the present review and meta-analysis is to consider the most recent evidence which assesses the effect of menu labelling regarding changes in energy consumed, ordered or selected in both real-world and experimental settings. DESIGN: The review included fifteen peer-reviewed, full-text articles published between 2012 and 2014. Pertinent methodological information was extracted from each of the included studies and a quality assessment scheme was applied to classify the studies, after which systematic across-study comparisons were conducted. A meta-analysis was conducted including twelve of the fifteen studies, and stratified according to type of research setting and outcome: energy consumed, ordered or selected. RESULTS: The rating yielded studies categorized by study quality: good (n 3), fair (n 9) and weak (n 3). Overall nine studies showed statistically significant reductions in energy consumed, ordered or selected. Three articles reported no effect of menu labelling. The meta-analysis showed statistically significant effects of menu labelling: overall energy consumed was reduced by a mean of 419·5 kJ (100·2 kcal) and energy ordered in real-world settings decreased by a mean of 325·7 kJ (77·8 kcal). CONCLUSIONS: The review supports that menu labelling can effectively reduce energy ordered and consumed in the away-from-home food environment.

Impact of source data verification on data quality in clinical trials: an empirical post hoc analysis of three phase 3 randomized clinical trials.

AIM: The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach. METHODS: We used data from three randomized phase III trials monitored with a combination of complete SDV or partial SDV. After database lock, individual subject data were extracted from the clinical database and subjected to post hoc complete SDV. Error rates were calculated with focus on the degree of on study monitoring and relevance and analyzed for potential impact on end points. RESULTS: Data from a total of 2566 subjects including more than 3 million data fields were 100% source data verified post hoc. An overall error rate of 0.45% was found. No sites had 0% errors. 100% SDV yielded an error rate of 0.27% as compared with partial SDV having an error rate of 0.53% (P < 0.0001). Comparing partly and fully monitored subjects, minor differences were identified between variables of major importance to efficacy or safety. CONCLUSIONS: The findings challenge the notion that a 0% error rate is obtainable with on site monitoring. Data indicate consistently low error rates across the three trials analyzed. The use of complete vs. partial SDV offers a marginal absolute error rate reduction of 0.26%, i.e. a need to perform complete SDV of about 370 data points to avoid one unspecified error and does not support complete SDV as a means of providing meaningful improvements in data accuracy.

Conceptions of how a learning or teaching curriculum, workplace culture and agency of individuals shape medical student learning and supervisory practices in the clinical workplace.

The role of workplace supervisors in the clinical education of medical students is currently under debate. However, few studies have addressed how supervisors conceptualize workplace learning and how conceptions relate to current sociocultural workplace learning theory. We explored physician conceptions of: (a) medical student learning in the clinical workplace and (b) how they contribute to student learning. The methodology included a combination of a qualitative, inductive (conventional) and deductive (directed) content analysis approach. The study triangulated two types of interview data from 4 focus group interviews and 34 individual interviews. A total of 55 physicians participated. Three overarching themes emerged from the data: learning as membership, learning as partnership and learning as ownership. The themes described how physician conceptions of learning and supervision were guided by the notions of learning-as-participation and learning-as-acquisition. The clinical workplace was either conceptualized as a context in which student learning is based on a learning curriculum, continuity of participation and partnerships with supervisors, or as a temporary source of knowledge within a teaching curriculum. The process of learning was shaped through the reciprocity between different factors in the workplace context and the agency of students and supervising physicians. A systems-thinking approach merged with the "co-participation" conceptual framework advocated by Billet proved to be useful for analyzing variations in conceptions. The findings suggest that mapping workplace supervisor conceptions of learning can be a valuable starting point for medical schools and educational developers working with changes in clinical educational and faculty development practices.

The sodium glucose cotransporter type 2 inhibitor empagliflozin preserves ß-cell mass and restores glucose homeostasis in the male zucker diabetic fatty rat.

Type 2 diabetes is characterized by impaired ß-cell function associated with progressive reduction of insulin secretion and ß-cell mass. Evidently, there is an unmet need for treatments with greater sustainability in ß-cell protection and antidiabetic efficacy. Through an insulin and ß cell-independent mechanism, empagliflozin, a specific sodium glucose cotransporter type 2 (SGLT-2) inhibitor, may potentially provide longer efficacy. This study compared the antidiabetic durability of empagliflozin treatment (10 mg/kg p.o.) against glibenclamide (3 mg/kg p.o.) and liraglutide (0.2 mg/kg s.c.) on deficient glucose homeostasis and ß-cell function in Zucker diabetic fatty (ZDF) rats. Empagliflozin and liraglutide led to marked improvements in fed glucose and hemoglobin A1c levels, as well as impeding a progressive decline in insulin levels. In contrast, glibenclamide was ineffective. Whereas the effects of liraglutide were less pronounced at week 8 of treatment compared with week 4, those of empagliflozin remained stable throughout the study period. Similarly, empagliflozin improved glucose tolerance and preserved insulin secretion after both 4 and 8 weeks of treatment. These effects were reflected by less reduction in ß-cell mass with empagliflozin or liraglutide at week 4, whereas only empagliflozin showed ß-cell sparing effects also at week 8. Although this study cannot be used to dissociate the absolute antidiabetic efficacy among the different mechanisms of drug action, the study demonstrates that empagliflozin exerts a more sustained improvement of glucose homeostasis and ß-cell protection in the ZDF rat. In comparison with other type 2 diabetic treatments, SGLT-2 inhibitors may through insulin-independent pathways thus enhance durability of ß-cell protection and antidiabetic efficacy.

Development and psychometric evaluation of the Undergraduate Clinical Education Environment Measure (UCEEM).

BACKGROUND: There is a paucity of instruments designed to evaluate the multiple dimensions of the workplace as an educational environment for undergraduate medical students. AIM: The aim was to develop and psychometrically evaluate an instrument to measure how undergraduate medical students perceive the clinical workplace environment, based on workplace learning theories and empirical findings. METHOD: Development of the instrument relied on established standards including theoretical and empirical grounding, systematic item development and expert review at various stages to ensure content validity. Qualitative and quantitative methods were employed using a series of steps from conceptualization through psychometric analysis of scores in a Swedish medical student population. RESULTS: The final result was a 25-item instrument with two overarching dimensions, experiential learning and social participation, and four subscales that coincided well with theory and empirical findings: Opportunities to learn in and through work & quality of supervision; Preparedness for student entry; Workplace interaction patterns & student inclusion; and Equal treatment. Evidence from various sources supported content validity, construct validity and reliability of the instrument. CONCLUSION: The Undergraduate Clinical Education Environment Measure represents a valid, reliable and feasible multidimensional instrument for evaluation of the clinical workplace as a learning environment for undergraduate medical students. Further validation in different populations using various psychometric methods is needed.

Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats.

AIM: To validate the gubra DIO-rats as a useful animal model of human obesity. METHODS: The gubra diet-induced obesity (DIO) rat model was based on male Sprague-Dawley rats with ad libitum access to regular chow and a palatable diet rich in fat and sugar. To evaluate the versatility of the gubra DIO-rats as a valid model of human obesity syndrome, the efficacy of 2 weight loss compounds liraglutide and sibutramine with different mechanisms of action were examined in 7-month-old gubra DIO-rats. Liraglutide (200 µg/kg, sc) was administered bi-daily, and sibutramine (5 mg/kg, po) was administered once daily for 23 d. RESULTS: Both the compounds effectively reduced the food intake, body weight and total fat mass as measured by nuclear magnetic resonance. Whereas the 5-HT reuptake inhibitor/5-HT receptor agonist sibutramine reduced the intake of both chow and the gubra-diet, the GLP-1 analogue liraglutide predominantly reduced the intake of the highly palatable diet, indicating a shift in food preference. Sibutramine lowered the insulin sensitivity index, primarily via reductions in glucose-stimulated insulin secretion. CONCLUSION: This animal model responds well to 2 weight loss compounds with different mechanisms of action. Moreover, the gubra DIO-rat can be particularly useful for the testing of compounds with potential effects on diet preference.

Effectiveness of a Canteen Take Away concept in promoting healthy eating patterns among employees.

OBJECTIVE: To investigate the effectiveness of a relatively novel concept of providing employees with healthy ready-to-heat meals to bring home to their families, here referred to as Canteen Take Away (CTA). DESIGN: Employees' dietary intake on two weekdays when they received free CTA was compared with that on weekdays when they did not receive CTA. Four non-consecutive 24 h dietary recalls were applied to assess dietary intake on a daily basis. Moreover, a digital photographic method was used to assess evening meal intake for three consecutive weeks. Data were analysed using a mixed-effects model. SETTING: A financial worksite offering CTA. SUBJECTS: Twenty-seven employees. RESULTS: Overall dietary quality as expressed by the energy density of the food (excluding beverages) was found to be significantly lower on days consuming CTA meals compared to days not consuming CTA with regard to evening meal intake (average difference: -187 (95 % CI -225, -149) kJ/100 g) and on a daily basis (average difference: -77 (95 % CI -132, -21) kJ/100 g). Other favourable differences included increased vegetable intake (average difference: 83 (95 % CI 67, 98) g/evening meal, 109 (95 % CI 62, 155) g/d). CONCLUSION: The present study shows that providing healthy take-away dinners has potential for promoting healthy dietary habits among employees. This reinforces the importance of availability and convenience as effective tools to promote healthy eating habits.

Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy.

BACKGROUND: Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a clinical trial. The BALaglitazone glucose Lowering Efficacy Trial aimed to establish the glucose-lowering effects and safety parameters of the perioxisome proliferator-activated receptor-γ partial agonist balaglitazone in diabetic patients on stable insulin therapy. METHODS: Four hundred and nine subjects from three countries with type 2 diabetes on stable insulin therapy were randomized to 26 weeks of double-blind treatment with once daily doses of 10 or 20 mg balaglitazone, 45 mg pioglitazone, or matching placebo (n ≥ 99 in each group). The primary endpoint was the efficacy of balaglitazone 10 and 20 mg versus placebo on the absolute change in haemoglobin A(1c) . Secondary endpoints included levels of fasting serum glucose, and changes in body composition and bone mineral density as measured by dual energy X-ray absorptiometry, in comparison to pioglitazone 45 mg. This study is registered with Clinicaltrials.gov identifier: NCT00515632. RESULTS: In the 10- and 20-mg balaglitazone groups, and in the 45-mg pioglitazone group, significant reductions in haemoglobin A(1c) levels were observed (−0.99, −1.11, and −1.22%, respectively; p < 0.0001) versus placebo. Fasting serum glucose was similarly reduced in all treatment arms. Dual energy X-ray absorptiometry analyses showed that, while balaglitazone at 10 mg caused weight gain and fluid retention compared to placebo, the magnitude of these effects was significantly smaller than that of pioglitazone 45 mg and balaglitazone 20mg. Balaglitazone at either dose did not appear to reduce bone mineral density, while Pioglitazone showed a trend towards a reduction. CONCLUSION: Patients treated with balaglitazone at 10 mg and 20 mg and pioglitazone at 45 mg showed clinically meaningful improvements in glucose levels and HbA(1c) . With the 10 mg dose, the benefits (glucose & HgA(1c) lowering) and untoward effects (fluid and fat accumulation) were less, results that encourage further studies of this drug candidate.

Development and validation of a new simple Healthy Meal Index for canteen meals.

OBJECTIVE: Nutrition evaluation tools should be developed both for scientific purposes and to encourage and facilitate healthy nutritional practices. The purpose of the present study was to develop and validate a simple food-based Healthy Meal Index (HMI) reflecting the nutritional profile of individual canteen meals. DESIGN: The development process included overall model selection, setting nutritional goals and defining scoring systems and thresholds. Three index components were included: (i) contents of fruit and vegetables, (ii) fat content and quality and (iii) contents of wholegrain products and potatoes. The development was built on the principles embodied by the Plate Model, but providing more specificity in some areas. The simple HMI was validated against weighed and chemically analysed food and nutrient content of a representative sample of canteen meals. The sample was split into four categories according to the total index score and compared across categories. SETTING: A total of 180 meals from fifteen worksite canteens. RESULTS: Average energy density decreased significantly across categories (from 876 kJ/100 g to 537 kJ/100 g, P < 0.001). Also, the content of total and saturated fat, carbohydrate and fruit and vegetables varied across categories with higher score values being closer to dietary guidelines (P < 0.001). CONCLUSIONS: The simple HMI was successful in ranking canteen meals according to their nutritional quality. The index provides a valuable tool to both researchers and food and nutrition professionals, e.g. caterers and dietitians, who wish to evaluate nutritional quality of meals in line with the recommendations for healthier eating without the use of nutrition calculation programs.

Immunoelectrophoresis for the Characterization of Allergen Extracts.

Immunoelectrophoresis can be used for analysis of individual proteins in complex mixtures. The conditions involved in immunoelectrophoresis are mild, avoiding the risk of denaturation, and it is possible to perform relative quantification of individual components. The fundamental disadvantage is the dependence on rabbit antisera as reagents. The usefulness of immunoelectrophoresis in allergy research is greatly enhanced by the possibility of identification of allergens to which the individual in question has IgE.The common principle is characterized by two independent electrophoreses having direction of current perpendicular to each other, i.e., crossed immunoelectrophoresis (CIE). This ultimately results in the formation of characteristic bell-shaped precipitates, each precipitate representing one antigen. There is a linear relationship between the amount of antigen and size of precipitate for a given antibody concentration for each precipitate and so relative quantification can be performed. The sensitivity and resolution power of CIE are very high and there are multiple variations of the technique, some of which will be illustrated in this chapter.

The role of C16:0 ceramide in the development of obesity and type 2 diabetes: CerS6 inhibition as a novel therapeutic approach.

OBJECTIVE: Ectopic fat deposition is associated with increased tissue production of ceramides. Recent genetic mouse studies suggest that specific sphingolipid C16:0 ceramide produced by ceramide synthase 6 (CerS6) plays an important role in the development of insulin resistance. However, the therapeutic potential of CerS6 inhibition not been demonstrated. Therefore, we pharmacologically investigated the selective ablation of CerS6 using antisense oligonucleotides (ASO) in obese insulin resistance animal models. METHODS: We utilized ASO as therapeutic modality, CerS6 ASO molecules designed and synthesized were initially screened for in-vitro knock-down (KD) potency and cytotoxicity. ASOs with >85% inhibition of CerS6 mRNA were selected for further investigations. Most promising ASOs verified for in-vivo KD efficacy in healthy mice. CerS6 ASO (AAGATGAGCCGCACC) was found most active with hepatic reduction of CerS6 mRNA expression. Prior to longitudinal metabolic studies, we performed a dose titration target engagement analysis with CerS6 ASO in healthy mice to select the optimal dose. Next, we utilized leptin deficiency ob/ob and high fat diet (HFD) induced obese mouse models for pharmacological efficacy study. RESULTS: CerS6 expression were significantly elevated in the liver and brown adipose, this was correlated with significantly elevated C16:0 ceramide concentrations in plasma and liver. Treatment with CerS6 ASO selectively reduced CerS6 expression by ∼90% predominantly in the liver and this CerS6 KD resulted in a significant reduction of C16:0 ceramide by about 50% in both liver and plasma. CerS6 KD resulted in lower body weight gain and accompanied by a significant reduction in whole body fat and fed/fasted blood glucose levels (1% reduction in HbA1c). Moreover, ASO-mediated CerS6 KD significantly improved oral glucose tolerance (during oGTT) and mice displayed improved insulin sensitivity. Thus, CerS6 appear to play an important role in the development of obesity and insulin resistance. CONCLUSIONS: Our investigations identified specific and selective therapeutic valid ASO for CerS6 ablation in in-vivo. CerS6 should specifically be targeted for the reduction of C16:0 ceramides, that results in amelioration of insulin resistance, hyperglycemia and obesity. CerS6 mediated C16:0 ceramide reduction could be a potentially attractive target for the treatment of insulin resistance, obesity and type 2 diabetes.

Pancreatic ß-Cell Rest Replenishes Insulin Secretory Capacity and Attenuates Diabetes in an Extreme Model of Obese Type 2 Diabetes.

The onset of common obesity-linked type 2 diabetes (T2D) is marked by exhaustive failure of pancreatic ß-cell functional mass to compensate for insulin resistance and increased metabolic demand, leading to uncontrolled hyperglycemia. Here, the ß-cell-deficient obese hyperglycemic/hyperinsulinemic KS db/db mouse model was used to assess consequential effects on ß-cell functional recovery by lowering glucose homeostasis and/or improving insulin sensitivity after treatment with thiazolidinedione therapy or glucagon-like peptide 1 receptor agonism alone or in combination with sodium/glucose cotransporter 2 inhibition (SGLT-2i). SGLT-2i combination therapies improved glucose homeostasis, independent of changes in body weight, resulting in a synergistic increase in pancreatic insulin content marked by significant recovery of the ß-cell mature insulin secretory population but with limited changes in ß-cell mass and no indication of ß-cell dedifferentiation. Restoration of ß-cell insulin secretory capacity also restored biphasic insulin secretion. These data emphasize that by therapeutically alleviating the demand for insulin in vivo, irrespective of weight loss, endogenous ß-cells recover significant function that can contribute to attenuating diabetes. Thus, this study provides evidence that alleviation of metabolic demand on the ß-cell, rather than targeting the ß-cell itself, could be effective in delaying the progression of T2D.

Immunoelectrophoresis for the characterization of allergen extracts.

Immunoelectrophoresis can be used for analysis of individual proteins in complex mixtures. The conditions involved in immunoelectrophoresis are mild, avoiding the risk of denaturation, and it is possible to perform relative quantification of individual components. The principle disadvantage is the dependence on rabbit antisera as reagents. The usefulness of immunoelectrophoresis in allergy research is greatly enhanced by the possibility of identification of allergens to which the individual in question has IgE. The common principle is characterized by two independent electrophoreses having direction of current perpendicular to each other, i.e., crossed immunoelectrophoresis (CIE). This ultimately results in the formation of characteristic bell-shaped precipitates, each precipitate representing one antigen. There is a linear relationship between the amount of antigen and size of precipitate for a given antibody concentration for each precipitate and so relative quantification can be performed. The sensitivity and resolution power of CIE is very high and there are multiple variations of the technique, some of which will be illustrated in this chapter.

Novel GLP-1/GLP-2 co-agonists display marked effects on gut volume and improves glycemic control in mice.

AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice. RESULTS: Sub-chronic administration of GUB09-123 to lean mice significantly reduced food intake, improved glucose tolerance, and increased gut volume, superior to monotherapy with the GLP-2 analogue teduglutide. Chronic administration of GUB09-123 to diabetic mice significantly improved glycemic control and showed persistent effects on gastric emptying, superior to monotherapy with the GLP-1 analogue liraglutide. Due to the short-acting nature of the molecule, no effects on body weight were observed, whereas a marked and robust intestinotrophic effect on mainly the small intestine volume and surface area was obtained. In contrast to GUB09-123, sub-chronic administration of a half-life extended GUB09-145 to lean mice caused marked dose-dependent effects on body weight while maintaining its potent intestinotrophic effect. CONCLUSION: Our data demonstrate that the GLP-1/GLP-2 co-agonists have effects on gut morphometry, showing a marked increase in intestinal volume and mucosal surface area. Furthermore, effects on glucose tolerance and long-term glycemic control are evident. Effects on body weight and gastric emptying are also observed depending on the pharmacokinetic properties of the molecule. We suggest that this novel co-agonistic approach could exemplify a novel concept for treatment of T2DM or SBS.

Avoidable colorectal cancer cases in Denmark - The impact of red and processed meat.

BACKGROUND: High red and processed meat intakes are associated with increased colorectal cancer (CRC) risk. The effect of eliminating or reducing red and processed meat consumption on CRC burden was not previously quantified in Denmark. The aim of this study was to calculate the possible effects of reductions in red and processed meat consumption on future CRC incidence in the Danish adult population. METHODS: Under six scenarios of prevalence exposure (meat consumption) the number of CRC cases in Denmark for a 30-year period (2016-2045) was estimated and compared to the projected number of CRCs if the prevalence of meat consumption remains constant. Data was obtained from the NORDCAN register, Statistics Denmark, and from the Danish dietary survey data (DANSDA). Analyses were conducted using the Prevent model. RESULTS: During the 30-year period, a total of 36,767 (19.8%) CRC cases out of 185,937 expected could be avoided in Denmark by eliminating the consumption of both red and processed meat. For the same period, a modest reduction in both red and processed meat consumption could lead to the prevention of 16,964 (9.1%) CRC cases. The greatest reductions were seen among men, and the highest impact was estimated for the elimination or reduction of processed meat consumption. CONCLUSION: Decreased red and processed meat consumption could reduce the burden of CRC markedly in Denmark. These results can assist public health planners and help highlight the important role of a modest but realistic reduction in meat consumption in the prevention of CRC.

The IL-1ß Receptor Antagonist SER140 Postpones the Onset of Diabetes in Female Nonobese Diabetic Mice.

The cytokine interleukin-1ß (IL-1ß) is known to stimulate proinflammatory immune responses and impair ß-cell function and viability, all critical events in the pathogenesis of type 1 diabetes (T1D). Here we evaluate the effect of SER140, a small peptide IL-1ß receptor antagonist, on diabetes progression and cellular pancreatic changes in female nonobese diabetic (NOD) mice. Eight weeks of treatment with SER140 reduced the incidence of diabetes by more than 50% compared with vehicle, decreased blood glucose, and increased plasma insulin. Additionally, SER140 changed the endocrine and immune cells dynamics in the NOD mouse pancreas. Together, the data suggest that SER140 treatment postpones the onset of diabetes in female NOD mice by interfering with IL-1ß activated pathways.

A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents.

AIM: Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet-induced obesity (DIO) and hypercholesterolemia Golden Syrian hamster model. METHODS AND RESULTS: Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS) for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days), normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin (3.0 mg/kg, PO, QD) also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day) or neuromedin U (NMU, 1.5 mg/kg/day), continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD) for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents.