Toxicity profile of bevacizumab in the UK Neurofibromatosis Type 2 cohort

Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis Type 2(NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event(CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32female), median age 24.5 years (range 11-66years), were followed for a median of 32.7 months (range 12.0–60.2months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24%) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5%) had proteinuria. Of 36 patients followed for 36 months, 78% were free from hypertension and 86% were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be predictors of development of hypertension with dose of 7.5mg/kg three weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.

Development and Evaluation of a Computer-Based, Self-Management Tool for People Recently Diagnosed with Type 2 Diabetes

Aim. The purpose of this study was to develop and evaluate a computer-based, dietary, and physical activity self-management program for people recently diagnosed with type 2 diabetes. 
Methods. The computer-based program was developed in conjunction with the target group and evaluated in a 12-week randomised controlled trial (RCT). Participants were randomised to the intervention (computer-program) or control group (usual care). Primary outcomes were diabetes knowledge and goal setting (ADKnowl questionnaire, Diabetes Obstacles Questionnaire (DOQ)) measured at baseline and week 12. User feedback on the program was obtained via a questionnaire and focus groups. Results. Seventy participants completed the 12-week RCT (32 intervention, 38 control, mean age 59 (SD) years). After completion there was a significant between-group difference in the “knowledge and beliefs scale” of the DOQ. Two-thirds of the intervention group rated the program as either good or very good, 92% would recommend the program to others, and 96% agreed that the information within the program was clear and easy to understand. 
Conclusions. The computer-program resulted in a small but statistically significant improvement in diet-related knowledge and user satisfaction was high. With some further development, this computer-based educational tool may be a useful adjunct to diabetes self-management.

The relationship between adipokines and the onset of type 2 diabetes in middle-aged men: The PRIME study

Aims: Epidemiological evidence suggests that adipokines may be associated with the onset of type 2 diabetes, but the evidence to date is limited and inconclusive. This study examined the association between adiponectin and leptin and the subsequent diagnosis of type 2 diabetes in a UK population based cohort of non-diabetic middle-aged men.
Methods: Baseline serum levels of leptin and adiponectin were measured in 1839 nondiabetic men aged 50–60 years who were participating in the prospective populationbased PRIME study. Over a mean follow-up of 14.7 years, new cases of type 2 diabetes were determined from self-reported clinical information with subsequent validation by general practitioners.
Results: 151 Participants developed type 2 diabetes during follow-up. In Cox regression models adjusted for age, men in the top third of the leptin distribution were at increased risk (hazard ratio (HR) 4.27, 95% CI 2.67–6.83) and men in the top third of the adiponectin
distribution at reduced risk (HR 0.24, 95% CI 0.14–0.42) relative to men in the bottom third. However, significance was lost for leptin after additional adjustment for BMI, waist to hip ratio, lifestyle factors and biological risk factors, including C-reactive protein (CRP). Further adjustment for HOMA-IR also resulted in loss of significance for adiponectin.
Conclusions: This study provides evidence that adipokines are associated with men’s future type 2 diabetes risk but not independently of other risk factors.

Fruit and vegetable intake and risk of incident of type 2 diabetes: results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES)

BACKGROUND/OBJECTIVES: There is limited information to support definitive recommendations concerning the role of diet in the development of type 2 Diabetes mellitus (T2DM). The results of the latest meta-analyses suggest that an increased consumption of green leafy vegetables may reduce the incidence of diabetes, with either no association or weak associations demonstrated for total fruit and vegetable intake. Few studies have, however, focused on older subjects.

SUBJECTS/METHODS: The relationship between T2DM and fruit and vegetable intake was investigated using data from the NIH-AARP study and the EPIC Elderly study. All participants below the age of 50 and/or with a history of cancer, diabetes or coronary heart disease were excluded from the analysis. Multivariate logistic regression analysis was used to calculate the odds ratio of T2DM comparing the highest with the lowest estimated portions of fruit, vegetable, green leafy vegetables and cabbage intake.

RESULTS: Comparing people with the highest and lowest estimated portions of fruit, vegetable or green leafy vegetable intake indicated no association with the risk of T2DM. However, although the pooled OR across all studies showed no effect overall, there was significant heterogeneity across cohorts and independent results from the NIH-AARP study showed that fruit and green leafy vegetable intake was associated with a reduced risk of T2DM OR 0.95 (95% CI 0.91,0.99) and OR 0.87 (95% CI 0.87,0.90) respectively.

CONCLUSIONS: Fruit and vegetable intake was not shown to be related to incident T2DM in older subjects. Summary analysis also found no associations between green leafy vegetable and cabbage intake and the onset of T2DM. Future dietary pattern studies may shed light on the origin of the heterogeneity across populations.European Journal of Clinical Nutrition advance online publication, 17 August 2016; 

HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes

OBJECTIVE: Low HDL cholesterol (HDL-C) and small HDL particle size may directly promote hyperglycemia. We evaluated associations of HDL-C, apolipoprotein A-I (apoA-I), and HDL-C/apoA-I with insulin secretion, insulin resistance, HbA1c, and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control.

RESEARCH DESIGN AND METHODS: The 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study followed 9,795 type 2 diabetic subjects. We calculated baseline associations of fasting HDL-C, apoA-I, and HDL-C/apoA-I with HbA1c and, in those not taking exogenous insulin (n = 8,271), with estimated β-cell function (homeostasis model assessment of β-cell function [HOMA-B]) and insulin resistance (HOMA-IR). Among the 2,608 subjects prescribed lifestyle only, Cox proportional hazards analysis evaluated associations of HDL-C, apoA-I, and HDL-C/apoA-I with subsequent initiation of oral hypoglycemic agents (OHAs) or insulin.

RESULTS: Adjusted for age and sex, baseline HDL-C, apoA-I, and HDL-C/apoA-I were inversely associated with HOMA-IR (r = -0.233, -0.134, and -0.230; all P < 0.001; n = 8,271) but not related to HbA1c (all P > 0.05; n = 9,795). ApoA-I was also inversely associated with HOMA-B (r = -0.063; P = 0.002; n = 8,271) adjusted for age, sex, and HOMA-IR. Prospectively, lower baseline HDL-C and HDL-C/apoA-I levels predicted greater uptake (per 1-SD lower: hazard ratio [HR] 1.13 [CI 1.07-1.19], P < 0.001; and HR 1.16 [CI 1.10-1.23], P < 0.001, respectively) and earlier uptake (median 12.9 and 24.0 months, respectively, for quartile 1 vs. quartile 4; both P < 0.01) of OHAs and insulin, with no difference in HbA1c thresholds for initiation (P = 0.87 and P = 0.81). Controlling for HOMA-IR and triglycerides lessened both associations, but HDL-C/apoA-I remained significant.

CONCLUSIONS: HDL-C, apoA-I, and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA1c. However, lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control.

Alleles that increase risk for type 2 diabetes mellitus are not associated with increased risk for Alzheimer's disease

Although epidemiological studies suggest that type 2 diabetes mellitus (T2DM) increases the risk of late-onset Alzheimer's disease (LOAD), the biological basis of this relationship is not well understood. The aim of this study was to examine the genetic comorbidity between the 2 disorders and to investigate whether genetic liability to T2DM, estimated by a genotype risk scores based on T2DM associated loci, is associated with increased risk of LOAD. This study was performed in 2 stages. In stage 1, we combined genotypes for the top 15 T2DM-associated polymorphisms drawn from approximately 3000 individuals (1349 cases and 1351 control subjects) with extracted and/or imputed data from 6 genome-wide studies (>10,000 individuals; 4507 cases, 2183 controls, 4989 population controls) to form a genotype risk score and examined if this was associated with increased LOAD risk in a combined meta-analysis. In stage 2, we investigated the association of LOAD with an expanded T2DM score made of 45 well-established variants drawn from the 6 genome-wide studies. Results were combined in a meta-analysis. Both stage 1 and stage 2 T2DM risk scores were not associated with LOAD risk (odds ratio = 0.988; 95% confidence interval, 0.972-1.004; p = 0.144 and odds ratio = 0.993; 95% confidence interval, 0.983-1.003; p = 0.149 per allele, respectively). Contrary to expectation, genotype risk scores based on established T2DM candidates were not associated with increased risk of LOAD. The observed epidemiological associations between T2DM and LOAD could therefore be a consequence of secondary disease processes, pleiotropic mechanisms, and/or common environmental risk factors. Future work should focus on well-characterized longitudinal cohorts with extensive phenotypic and genetic data relevant to both LOAD and T2DM.

A systematic review of the effectiveness of lifestyle interventions for the prevention of type 2 diabetes mellitus (T2DM) in routine practice.

This document updates and extends a previously conducted systematic review and meta-analysis assessing the effectiveness of ‘real-world’ interventions for the prevention of type 2 diabetes mellitus (T2DM) in high risk populations.

Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low

[EN]Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet).

Adhésion au traitement antidiabétique oral chez les adultes atteints de diabète de type 2 : déterminants et interventions visant à l'améliorer

Introduction : Le diabète de type 2 est une maladie évolutive débilitante et souvent mortelle qui atteint de plus en plus de personnes dans le monde. Le traitement antidiabétique non-insulinique (TADNI) notamment le traitement antidiabétique oral (TADO) est le plus fréquemment utilisé chez les adultes atteints de cette maladie. Toutefois, plusieurs de ces personnes ne prennent pas leur TADO tel que prescrit posant ainsi la problématique d’une adhésion sous-optimale. Ceci entraîne des conséquences néfastes aussi bien pour les patients que pour la société dans laquelle ils vivent. Il serait donc pertinent d’identifier des pistes de solution à cette problématique. Objectifs : Trois objectifs de recherche ont été étudiés : 1) Explorer la capacité de la théorie du comportement planifié (TCP) à prédire l’adhésion future au TADNI chez les adultes atteints de diabète de type 2, 2) Évaluer l’efficacité globale des interventions visant à améliorer l’adhésion au TADO chez les adultes atteints de diabète de type 2 et étudier l’influence des techniques de changement de comportement sur cette efficacité globale, et 3) Évaluer l’efficacité globale de l’entretien motivationnel sur l’adhésion au traitement médicamenteux chez les adultes atteints de maladie chronique et étudier l’influence des caractéristiques de cette intervention sur son efficacité globale. Méthodes : Pour l’objectif 1 : Il s’agissait d’une enquête web, suivie d’une évaluation de l’adhésion au TADNI sur une période de 30 jours, chez des adultes atteints de diabète de type 2, membres de Diabète Québec. L’enquête consistait à la complétion d’un questionnaire auto-administré incluant les variables de la TCP (intention, contrôle comportemental perçu et attitude) ainsi que d’autres variables dites «externes». Les informations relatives au calcul de l’adhésion provenaient des dossiers de pharmacie des participants transmis via la plateforme ReMed. Une régression linéaire multivariée a été utilisée pour estimer la mesure d’association entre l’intention et l’adhésion future au TADNI ainsi que l’interaction entre l’adhésion passée et l’intention. Pour répondre aux objectifs 2 et 3, deux revues systématiques et méta-analyses ont été effectuées et rapportées selon les lignes directrices de PRISMA. Un modèle à effets aléatoires a été utilisé pour estimer l’efficacité globale (g d’Hedges) des interventions et son intervalle de confiance à 95 % (IC95%) dans chacune des revues. Nous avons également quantifié l’hétérogénéité (I2 d’Higgins) entre les études, et avons fait des analyses de sous-groupe et des analyses de sensibilité. Résultats : Objectif 1 : Il y avait une interaction statistiquement significative entre l’adhésion passée et l’intention (valeur-p= 0,03). L’intention n’était pas statistiquement associée à l’adhésion future au TADNI, mais son effet était plus fort chez les non-adhérents que chez les adhérents avant l’enquête web. En revanche, l’intention était principalement prédite par le contrôle comportemental perçu à la fois chez les adhérents [β= 0,90, IC95%= (0,80; 1,00)] et chez les non-adhérents passés [β= 0,76, IC95%= (0,56; 0,97)]. Objectif 2 : L’efficacité globale des interventions sur l’adhésion au TADO était de 0,21 [IC95%= (-0,05; 0,47); I2= 82 %]. L’efficacité globale des interventions dans lesquelles les intervenants aidaient les patients et/ou les cliniciens à être proactifs dans la gestion des effets indésirables était de 0,64 [IC95%= (0,31; 0,96); I2= 56 %]. Objectif 3 : L’efficacité globale des interventions (basées sur l’entretien motivationnel) sur l’adhésion au traitement médicamenteux était de 0,12 [IC95%= (0,05; 0,20); I2= 1 %. Les interventions basées uniquement sur l’entretien motivationnel [β= 0,18, IC95%= (0,00; 0,36)] et celles dans lesquelles les intervenants ont été coachés [β= 0,47, IC95%= (0,03; 0,90)] étaient les plus efficaces. Aussi, les interventions administrées en face-à-face étaient plus efficaces que celles administrées par téléphone [β= 0,27, IC95%=(0,04; 0,50)]. Conclusion : Il existe un écart entre l’intention et l’adhésion future au TADNI, qui est partiellement expliqué par le niveau d’adhésion passée. Toutefois, il n’y avait pas assez de puissance statistique pour démontrer une association statistiquement significative entre l’intention et l’adhésion future chez les non-adhérents passés. D’un autre côté, quelques solutions au problème de l’adhésion sous-optimale au TADO ont été identifiées. En effet, le fait d’aider les patients et/ou les cliniciens à être proactifs dans la gestion des effets indésirables contribue efficacement à l’amélioration de l’adhésion au TADO chez les adultes atteints de diabète de type 2. Aussi, les interventions basées sur l’entretien motivationnel améliorent efficacement l’adhésion au traitement médicamenteux chez les adultes atteints de maladie chronique. L’entretien motivationnel pourrait donc être utilisé comme un outil clinique pour soutenir les patients dans l’autogestion de leur TADO.

Type 2 Diabetes Mellitus: Risk Evaluation and Advice in Undergraduate Students in Ashrafieh, Lebanon

Type 2 diabetes mellitus (T2DM) is a chronic lifestyle disease. It has become evident that T2DM occurs even among the younger age groups.1 In Lebanon, T2DM has a major public health impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities.2

Cost-effectiveness Study of Antidiabetic Drugs in Type 2 Diabetes Mellitus Patients From Mumbai, India

Diabetes is fast gaining the status of a potential epidemic in India, with >62 million individuals currently diagnosed with the disease.1 India currently faces an uncertain future in relation to the potential burden that diabetes may impose on the country. An estimated US$ 2.2 billion would be needed to sufficiently treat all cases of type 2 diabetes mellitus (T2DM) in India.2 Many interventions can reduce the burden of this disease. However, health care resources are limited; thus, interventions for diabetes treatment should be prioritized.

Body image perception in people with type 2 diabetes: does perceived image match reality?

Rationale: Body image misperception and body image dissatisfaction can lead to underestimation of weight and less predisposition to weight control.

Impact of a community-based exercise programme on physical fitness in middle-aged and older patients with type 2 diabetes

Objectives: Physical fitness is related to all-cause mortality, quality of life and risk of falls in patients with type 2 diabetes. This study aimed to analyse the impact of a long-term community-based combined exercise program (aerobic + resistance + agility/balance + flexibility) developed with minimum and low-cost material resources on physical fitness in middle-aged and older patients with type 2 diabetes. Methods: This was a non-experimental pre-post evaluation study. Participants (N = 43; 62.92 ± 5.92 years old) were engaged in a community-based supervised exercise programme (consisting of combined aerobic, resistance, agility/balance and flexibility exercises; three sessions per week; 70 min per session) of 9 months' duration. Aerobic fitness (6-Minute Walk Test), muscle strength (30-Second Chair Stand Test), agility/balance (Timed Up and Go Test) and flexibility (Chair Sit and Reach Test) were assessed before (baseline) and after the exercise intervention. Results: Significant improvements in the performance of the 6-Minute Walk Test (Δ = 8.20%, p < 0.001), 30-Second Chair Stand Test (Δ = 28.84%, p < 0.001), Timed Up and Go Test (Δ = 14.31%, p < 0.001), and Chair Sit and Reach Test (Δ = 102.90%, p < 0.001) were identified between baseline and end-exercise intervention time points. Conclusions: A long-term community-based combined exercise programme, developed with low-cost exercise strategies, produced significant benefits in physical fitness in middle-aged and older patients with type 2 diabetes. This supervised group exercise programme significantly improved aerobic fitness, muscle strength, agility/balance and flexibility, assessed with field tests in community settings.

Analyse des facteurs pouvant contribuer à l’augmentation de la prévalence du diabète de type 2 au Nouveau-Brunswick

Résumé : Problématique : Une augmentation importante de la prévalence du diabète a été observée au Nouveau-Brunswick au cours de la dernière décennie. Sachant que le diabète est associé à des complications de santé nombreuses et à des coûts élevés infligés au système de soins de santé, il devient important d’identifier les facteurs pouvant expliquer l’augmentation de la prévalence du diabète. L’étude a pour objectif de décrire l’évolution de ces facteurs afin de prioriser les interventions en lien avec cette maladie. Méthodes : Une revue critique de la littérature a permis l’identification de l’ensemble des facteurs pouvant expliquer l’augmentation de la prévalence du diabète. Des données administratives disponibles au Nouveau-Brunswick et des données tirées d’enquêtes de Statistique Canada ont été utilisées afin de décrire l’évolution de plusieurs des facteurs tirés de la revue critique de la littérature. Résultats : Une augmentation de 120% de la prévalence du diabète de type 2 au Nouveau-Brunswick a été observée entre 2001 et 2014. Cette augmentation pourrait être explicable par l’ensemble des cinq catégories de facteurs pouvant expliquer une augmentation de la prévalence dont plusieurs facteurs de risque individuels (dont l’obésité, le prédiabète et l’hypertension), de facteurs de risque environnementaux (dont l’urbanisation), de l’évolution de la maladie (exprimée par une diminution du taux de mortalité et une augmentation de l’incidence), de l’effet de détection (augmentation du nombre de personnes testées, diminution de la valeur d’HbA1c et de l’âge à la détection) et d’un effet du changement dans l’environnement (exprimé par un effet de période et de cohorte). Conclusion: L’augmentation de la prévalence du diabète notée au Nouveau-Brunswick pourrait s’expliquer par plusieurs facteurs de risque individuels, environnementaux, de l’évolution de la maladie, de l’effet de détection et d’un effet du changement dans l’environnement. Cette étude permettra de guider les actions sur le diabète au Nouveau-Brunswick et d’inspirer les autres provinces et pays à identifier les facteurs pouvant contribuer à l’augmentation de la prévalence du diabète grâce à la liste de l’ensemble des facteurs potentiellement explicatifs.

Preventing type 2 diabetes : a guide to refer your patients with prediabetes to an evidence-based diabetes prevention program

This document describes steps to take in preventing type 2 diabetes. Included is a risk test, a prediabetes screening test and BMI calculation chart.