Is Glycemic Control the Primary Goal in Diabetes Treatment?

The prevalence of Diabetes is steadily increasing, raising public health concerns. Hyperglycemia leads to microvascular and macrovascular diseases through several metabolic and biochemical pathways. Previous clinical trials and observational studies have demonstrated that tight glycemic control can reduce the incidence of diabetic complications, with the greatest benefit shown in younger patients with diabetes of shorter duration and those who have no prior history of cardiovascular disease. Moreover, previous studies highlight the concept of metabolic memory and legacy effect, since controlling diabetes early can have an impact on long-term prognosis of the disease. As to whether it is time to consider shifting the treatment focus for patients with type 2 diabetes from a glucose-centric to a weight-centric or a cardio-centric approach, the dilemma remains theoretical; glucose control, weight loss and effective treatment of metabolic and cardio-vascular co-morbidities are interrelated components of an integrated plan of care that should be addressed simultaneously and effectively

Ιnternists’ and Endocrinologists’ Knowledge and Attitudes Regarding Periodontal Disease, Caries, Xerostomia and Diabetes Mellitus: A National Survey

Objectives: The present study aims to investigate the current knowledge, attitudes and behaviors of clinicians dealing with diabetes regarding the relationship of Diabetes Mellitus (DM) and odostomatological diseases, such as periodontal disease, xerostomia and caries. Methods:  A twenty-four item closed-ended multiple-choice questionnaire was completed by 225 Greek medical doctors. The sample was divided into three groups according to specialty: a) Endocrinologists; b) Internists; c) Internal medicine registrars. Bivarate analysis, Fisher test, and Spearman correlation were used for statistical analysis. Results:  Most doctors were aware of the bi-directional relationship between periodontal disease and DM. Regarding the relationship between DM and xerostomia, 50% of doctors were unaware that patients with DM have an increased risk of xerostomia and were unfamiliar with the relevant studies. Nearly 50% of doctors agreed that patients with diabetes are at increased risk of developing caries. Age, specialty, and years of expertise have an impact on the way of doctors' answer. Finally, 78,6% of doctors treating diabetes should cooperate with dentists to reduce their patients' risk of odontostomatological complications. Conclusions: The relationship between diabetes and dental problems is often underestimated. Implementation of medical and dental educational programs oriented in increasing inter-professional education as well as collaboration between dentists and doctors dealing with diabetes, are needed in order to achieve the goal of better care of patients with diabetes

Effect of polydispersity and bubble clustering on the steady shear viscosity of semidilute bubble suspensions in Newtonian media

In this work, we examine the steady shear rheology of semidilute polydisperse bubble suspensions to elucidate the role of polydispersity on the viscosity of these systems. We prove theoretically that the effect of polydispersity on suspension viscosity becomes apparent only if the bubble size distribution is bimodal, with very small and very large bubbles having similar volume fractions. In any other case, we can consider the polydisperse suspension as monodisperse, with the average bubble diameter equal to the De Brouckere mean diameter (d43). To confirm the theoretical results, we carried out steady shear rheological tests. Our measurements revealed an unexpected double power-law decay of the suspension relative viscosity at average capillary numbers between 0.01 and 1. To investigate this behavior further, we visualized the produced bubble suspensions under shear. The visualization experiments revealed that bubbles started forming clusters and threads at an average capillary number around 0.01, where we observed the first decay of viscosity. Clustering and alignment have been associated with shear-thinning behavior in particle suspensions. We believe that the same holds for bubble suspensions, where bubble clusters and threads align with the imposed shear flow, reducing the streamline distortions and, in turn, resulting in a decrease in the suspension viscosity. Consequently, we can attribute the first decay of the relative viscosity to the formation of bubble clusters and threads, proving that the novel shear-thinning behavior we observed is due to a combination of bubble clustering and deformation

Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk study.

BACKGROUND: BRAF and K-ras proto-oncogenes encode components of the ERK signalling pathway and are frequently mutated in colorectal cancer. This study investigates the associations between BRAF and K-ras mutations and clinicopathological, lifestyle and dietary factors in colorectal cancers. METHODS: 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for BRAF and K-ras mutations. Diet and lifestyle data were collected prospectively using seven day food diaries. RESULTS: BRAF V600E mutation was found in 15.6% of colorectal cancers but at higher frequencies in cancers with proximal location, poor differentiation and microsatellite instability (MSI) (all p < 0.001). K-ras mutation (mostly in codons 12 and 13) was found in 22.0% of colorectal cancers but at higher frequencies in cancers of more advanced Dukes' stage (p = 0.001), microsatellite stable (MSS) status (p = 0.002) and in individuals with lower blood high-density lipoprotein concentrations (p = 0.04). Analysis of dietary factors demonstrated no link between BRAF mutation and any specific dietary constituent, however, K-ras mutation was found at higher frequencies in individuals with higher white meat consumption (p < 0.001). Further analysis of specific mutation type demonstrated that G to A transitions in K-ras were observed at higher frequencies in individuals consuming lower amounts of fruit (p = 0.02). CONCLUSION: These data support the model of BRAF and K-ras mutations arising in distinct colorectal cancer subsets associated with different clinicopathological and dietary factors, acting as mutually exclusive mechanisms of activation of the same signalling pathway.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors.

BACKGROUND: The PTEN tumour suppressor gene and PIK3CA proto-oncogene encode proteins which contribute to regulation and propagation of signal transduction through the PI3K/AKT signalling pathway. This study investigates the prevalence of loss of PTEN expression and mutations in both PTEN and PIK3CA in colorectal cancers (CRC) and their associations with tumour clinicopathological features, lifestyle factors and dietary consumptions. METHODS: 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for PTEN and PIK3CA mutations by DNA sequencing and PTEN expression changes by immunohistochemistry. Dietary and lifestyle data were collected prospectively using seven day food diaries and lifestyle questionnaires. RESULTS: Mutations in exons 7 and 8 of PTEN were observed in 2.2% of CRC and PTEN loss of expression was identified in 34.9% CRC. Negative PTEN expression was associated with lower blood low-density lipoprotein concentrations (p = 0.05). PIK3CA mutations were observed in 7% of cancers and were more frequent in CRCs in females (p = 0.04). Analysis of dietary intakes demonstrated no link between PTEN expression status and any specific dietary factor. PTEN expression negative, proximal CRC were of more advanced Dukes' stage (p = 0.02) and poor differentiation (p < 0.01). Testing of the prevalence of PIK3CA mutations and loss of PTEN expression demonstrated that these two events were independent (p = 0.55). CONCLUSION: These data demonstrated the frequent occurrence (34.9%) of PTEN loss of expression in colorectal cancers, for which gene mutations do not appear to be the main cause. Furthermore, dietary factors are not associated with loss of PTEN expression. PTEN expression negative CRC were not homogenous, as proximal cancers were associated with a more advanced Dukes' stage and poor differentiation, whereas distal cancers were associated with earlier Dukes' stage.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Operationalizing the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations: A Standardized Scoring System

Background: Following the publication of the 2018 World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) Third Expert Report, a collaborative group was formed to develop a standardized scoring system and provide guidance for research applications. Methods: The 2018 WCRF/AICR Cancer Prevention Recommendations, goals, and statements of advice were examined to define components of the new Score. Cut-points for scoring were based on quantitative guidance in the 2018 Recommendations and other guidelines, past research that operationalized 2007 WCRF/AICR Recommendations, and advice from the Continuous Update Project Expert Panel. Results: Eight of the ten 2018 WCRF/AICR Recommendations concerning weight, physical activity, diet, and breastfeeding (optional), were selected for inclusion. Each component is worth one point: 1, 0.5, and 0 points for fully, partially, and not meeting each recommendation, respectively (Score: 0 to 7–8 points). Two recommendations on dietary supplement use and for cancer survivors are not included due to operational redundancy. Additional guidance stresses the importance of accounting for other risk factors (e.g., smoking) in relevant models. Conclusions: The proposed 2018 WCRF/AICR Score is a practical tool for researchers to examine how adherence to the 2018 WCRF/AICR Recommendations relates to cancer risk and mortality in various adult populations.

Latest data on metabolic diseases: Diabetes Mellitus

With such a high cost in money and human lives, diabetes mellitus (DM) is a major challenge for health care systems and an obstacle to sustainable economic growth. The pathophysiological disorders of diabetes include, besides the defect in pancreatic insulin secretion and insulin resistance in peripheral tissues (liver, muscle and adipose tissue), increased lipolysis, increased glucagon secretion, impaired secretion and action of incretin hormones, increased glucose resorption by the kidney and defects in the central nervous system. The therapeutic intervention must be timely and personalized. Lifestyle interventions (diet, exercise, smoking cessation) are the cornerstone of treatment. Treatment should begin with metformin unless there is a contraindication (eg renal failure) or intolerance (eg, gastrointestinal disorders). If HbA1c remains off target a second or a third treatment may be added, orally (glitazone, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylurea) or by injection (GLP-1 agonist or basal insulin). On failure to achieve glycemic target combinations of injectable treatments (combination of agonist GLP-1 with basal insulin, intensified insulin therapy or in some cases insulin mixtures) are recommended. New treatments (weekly administered GLP-1 analogs, combination of a basal insulin / GLP-1 in one injection, SGLT-2 inhibitors, long acting basal insulins) in combination with the old tried treatments (e.g. metformin, pioglitazone, inhibitors DPP-4) can contribute to human-centered and individualized management of patients with diabetes. The cardiovascular safety of antidiabetic treatment should be considered. There is a need for early diagnosis and treatment of glucose metabolism disorders during pregnancy (before 24 to 28 weeks of gestation) in women at high risk for developing gestational diabetes