Search

Background and Aims: An appropriate diet is an essential component of the management of Type 2 Diabetes Mellitus (T2DM). However, for many people with T2DM, self-management is difficult. Therefore, the Beyond Good Intentions (BGI) education program was developed based on self-regulation and proactive coping theories to enhance people's capabilities for self-management. The aim of this study was to determine the effectiveness of the BGI program on improving dietary quality among a preselected group of people with T2DM after two-and-a-half years follow-up. Methods: In this randomized controlled trial, 108 people with T2DM were randomized (1:1) to the intervention ( n = 56) (BGI-program) or control group ( n = 52) (care as usual). Linear regression analyses were used to determine the effect of the BGI program on change in dietary quality between baseline and two-and-a-half years follow-up. In addition, potential effect modification by having a nutritional goal at baseline was evaluated. Multiple imputation ( n = 15 imputations) was performed to account for potential bias due to missing data. Results: According to intention-to-treat analysis, participants in the intervention group showed greater improvements in dietary quality score than participants in the control group (β = 0.71; 95%CI: 0.09; 1.33) after follow-up. Having a nutritional goal at baseline had a moderating effect on the effectiveness of the BGI program on dietary quality ( p -interaction = 0.01), and stratified results showed that the favorable effect of the intervention on dietary quality was stronger for participants without a nutritional goal at baseline (no nutritional goal: β = 1.46; 95%CI: 0.65; 2.27 vs. nutritional goal: β = -0.24; 95%CI: -1.17; 0.69). Conclusions: The BGI program was significantly effective in improving dietary quality among preselected people with T2DM compared to care as usual. This effect was stronger among participants without a nutritional goal at baseline. A possible explanation for this finding is that persons with a nutritional goal at baseline already started improving their dietary intake before the start of the BGI program. Future studies are needed to elucidate the moderating role of goalsetting on the effectiveness of the BGI program., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 van der Velde, Kiefte-de Jong, Rutten and Vos.)

Aims: Short-term weight loss may lead to remission of type 2 diabetes but the effect of maintained weight loss on cardiovascular disease (CVD) is unknown. We quantified the associations between changes in weight 5 years following a diagnosis of diabetes, and incident CVD events and mortality up to 10 years after diagnosis., Materials and Methods: Observational analysis of the ADDITION-Europe trial of 2730 adults with screen-detected type 2 diabetes from the UK, Denmark and the Netherlands. We defined weight change based on the maintenance at 5 years of weight loss achieved during the year after diabetes diagnosis, and as 5-year overall change in weight. Incident CVD events (n = 229) and all-cause mortality (n = 225) from 5 to 10 years follow-up were ascertained from medical records., Results: Gaining >2% weight during the year after diabetes diagnosis was associated with higher hazard of all-cause mortality versus maintaining weight [hazard ratio (95% confidence interval): 3.18 (1.30-7.82)]. Losing ≥5% weight 1 year after diagnosis was also associated with mortality, whether or not weight loss was maintained at 5 years: 2.47 (0.99-6.21) and 2.72 (1.17-6.30), respectively. Losing ≥10% weight over 5 years was associated with mortality among those with body mass index <30 kg/m 2 [4.62 (1.87-11.42)]. Associations with CVD incidence were inconclusive., Conclusions: Both weight loss and weight gain after screen-detected diabetes diagnosis were associated with higher mortality, but not CVD events, particularly among participants without obesity. The clinical implications of weight loss following a diagnosis of diabetes probably depend on its magnitude and timing, and may differ by body mass index status. Personalization of weight loss advice and support may be warranted., (© 2020 John Wiley & Sons Ltd.)

Background: Patients with chronic obstructive pulmonary disease (COPD) have an independent increased risk of cardiovascular (CV) disease. Cardiovascular risk (CVR) assessment should be offered to all patients with COPD, according to the new Dutch CVR management (CVRM) guideline (May 2019)., Aim: To evaluate the impact of the new CVRM guideline on the care of patients with COPD in primary care., Design & Setting: A retrospective study took place within five primary healthcare centres located in The Netherlands., Method: In accordance with the guideline, the CVR of all patients with COPD was estimated and categorised. Data from 2014-2019 were used for the qualitative risk assessment based on comorbidities, and the quantitative Systematic Coronary Risk Evaluation (SCORE). In addition, the guideline-based follow-up was investigated., Results: Of the 391 patients with COPD, 84.1% ( n = 329) had complete data on CVR assessment: 90.3% ( n = 297) had a (very) high risk, and 9.7% ( n = 32) a low-to-moderate risk. Of the patients with (very) high risk, 73.4% ( n = 218) received guideline-based follow-up (primary care: 95.4%, secondary care: 4.6%). In 15.9% ( n = 62) of all patients with COPD, the CVR profile was not measured and of the (very) high-risk patients, 26.6% ( n = 79) were not enroled in a CV care programme., Conclusion: Whereas in the majority of patients with COPD the CVR is already known, for one out of six patients this CVR still has to be assessed according to the recently updated guideline. Moreover, once a (very) high risk has been assessed, as a consequence CV treatment of risk factors should be intensified in one out of four patients with COPD. Adherence to the new CVRM guideline could provide improvement in CVRM in more than a third of all patients with COPD., (Copyright © 2020, The Authors.)

Aims: To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial., Methods: The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis., Results: There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)]., Conclusions: Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care., (© 2020 Diabetes UK.)

Introduction: With increased duration of type 2 diabetes, most people have a growing need of glucose-lowering medication and eventually might require insulin. Presumptive evidence is reported that early detection (eg, by population-based screening) and treatment of hyperglycemia will postpone the indication for insulin treatment. A treatment legacy effect of population-based screening for type 2 diabetes of about 3 years is estimated. Therefore, we aim to compare insulin prescription and glycemic control in people with screen-detected type 2 diabetes after 10 years with data from people diagnosed with type 2 diabetes seven (treatment legacy effect) and 10 years before during care-as-usual., Research Design and Methods: Three cohorts were compared: one screen-detected cohort with 10 years diabetes duration (Anglo-Danish-Dutch study of Intensive Treatment in People with Screen-Detected Diabetes in Primary care (ADDITION-NL): n=391) and two care-as-usual cohorts, one with 7-year diabetes duration (Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) and Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC): n=4473) and one with 10-year diabetes duration (GIANTT and ZODIAC: n=2660). Insulin prescription (primary outcome) and hemoglobin A1c (HbA1c) of people with a known diabetes duration of 7 years or 10 years at the index year 2014 were compared using regression analyses., Results: Insulin was prescribed in 10.5% (10-year screen detection), 14.7% (7-year care-as-usual) and 19.0% (10-year care-as-usual). People in the 7-year and 10-year care-as-usual groups had a 1.5 (95% CI 1.0 to 2.1) and 1.8 (95% CI 1.3 to 2.7) higher adjusted odds for getting insulin prescribed than those after screen detection. Lower HbA1c values were found 10 years after screen detection (mean 50.1 mmol/mol (6.7%) vs 51.8 mmol/mol (6.9%) and 52.8 mmol/mol (7.0%)), compared with 7 years and 10 years after care-as-usual (MD adjusted : 1.6 mmol/mol (95% CI 0.6 to 2.6); 0.1% (95% CI 0.1 to 0.2) and 1.8 mmol/mol (95% CI 0.7 to 2.9); and 0.2% (95% CI 0.1 to 0.3))., Conclusion: Population-based screen-detected type 2 diabetes is associated with less need for insulin after 10 years compared with people diagnosed during care-as-usual. Glycemic control was better after screen detection but on average good in all groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Overweight in children is a rising problem leading to serious consequences later in life. The Dutch guideline 'Obesity' for general practitioners recommends discussing obesity in children regardless of the reason of consultation and provides diagnostic and therapeutic tools. However, limited literature indicates that general practitioners experience barriers to discuss this topic. The aim of this study was to determine current perceived barriers of general practitioners in discussing overweight during a regular consultation in children aged 4 to 12 years and to what extent they discuss the topic. Furthermore, we attempt to get more insight in the specific needs and ideas for improvement among GPs., Methods: A semi-structured in-depth interview study was conducted. Dutch general practitioners with a broad range of demographic characteristics were invited to participate. The transcripts were analysed using a modified version of the constant comparative method. Using this method, we identified perceived barriers of general practitioners., Results: Ten general practitioners were included in the study. Four major themes were identified in the interviews: absence of physical or mental complaints related to overweight, internal barriers of the general practitioners, the child's family background and logistics. Major barriers appeared to be a low consultation rate of these children, the sensitivity of the topic (e.g. fear for children's or parents' reactions and/or disturbance of the relation, influence on the self-esteem of the child, resistance in the parents), the absence of a long-standing relation between general practitioner and child or parent, the background of the child and lack of time or prioritizing., Conclusion: Dutch general practitioners indicate to experience barriers and need tools for how to discuss children's overweight during regular consultations within the limited time available. The low consultation rate among children aged 4 to 12 years due to lack of physical complaints is mentioned as a new and important barrier. Therefore, the prior focus might be raising awareness among parents concerning overweight in children aged 4 to 12 years and, thereby, stressing the potential supporting role of primary care professionals in tackling the overweight of their child.

Diabetes is a strong risk factor for vascular disease. There is compelling evidence that the relative risk of vascular disease associated with diabetes is substantially higher in women than men. The mechanisms that explain the sex difference have not been identified. However, this excess risk could be due to certain underlying biological differences between women and men. In addition to other cardiometabolic pathways, sex differences in body anthropometry and patterns of storage of adipose tissue may be of particular importance in explaining the sex differences in the relative risk of diabetes-associated vascular diseases. Besides biological factors, differences in the uptake and provision of health care could also play a role in women's greater excess risk of diabetic vascular complications. In this review, we will discuss the current knowledge regarding sex differences in both biological factors, with a specific focus on sex differences adipose tissue, and in health care provided for the prevention, management, and treatment of diabetes and its vascular complications. While progress has been made towards understanding the underlying mechanisms of women's higher relative risk of diabetic vascular complications, many uncertainties remain. Future research to understanding these mechanisms could contribute to more awareness of the sex-specific risk factors and could eventually lead to more personalized diabetes care. This will ensure that women are not affected by diabetes to a greater extent and will help to diminish the burden in both women and men.

Background: The multicentre, international ADDITION-Europe study investigated the effect of promoting intensive treatment of multiple risk factors among people with screen-detected type 2 diabetes over 5 years. Here we report the results of a post-hoc 10-year follow-up analysis of ADDITION-Europe to establish whether differences in treatment and cardiovascular risk factors have been maintained and to assess effects on cardiovascular outcomes., Methods: As previously described, general practices from four centres (Denmark, Cambridge [UK], Leicester [UK], and the Netherlands) were randomly assigned by computer-generated list to provide screening followed by routine care of diabetes, or screening followed by intensive multifactorial treatment. Population-based stepwise screening programmes among people aged 40-69 years (50-69 years in the Netherlands), between April, 2001, and December, 2006, identified patients with type 2 diabetes. Allocation was concealed from patients. Following the 5-year follow-up, no attempts were made to maintain differences in treatment between study groups. In this report, we did a post-hoc analysis of cardiovascular and renal outcomes over 10 years following randomisation, including a 5 years post-intervention follow-up. As in the original trial, the primary endpoint was a composite of first cardiovascular event, including cardiovascular mortality, cardiovascular morbidity (non-fatal myocardial infarction and non-fatal stroke), revascularisation, and non-traumatic amputation, up to Dec 31, 2014. Analyses were based on the intention-to-treat principle. ADDITION-Europe is registered with ClinicalTrials.gov, NCT00237549., Findings: 343 general practices were randomly assigned to routine diabetes care (n=176) or intensive multifactorial treatment (n=167). 317 of these general practices (157 in the routine care group, 161 in the intensive treatment group) included eligible patients between April, 2001, and December, 2006. Of the 3233 individuals with screen-detected diabetes, 3057 agreed to participate (1379 in the routine care group, 1678 in the intensive treatment group), but at the 10-year follow-up 14 were lost to follow-up and 12 withdrew, leaving 3031 to enter 10-year follow-up analysis. Mean duration of follow-up was 9·61 years (SD 2·99). Sustained reductions over 10 years following diagnosis were apparent for bodyweight, HbA 1c , blood pressure, and cholesterol in both study groups, but between-group differences identified at 1 and 5 years were attenuated at the 10-year follow-up. By 10 years, 443 participants had a first cardiovascular event and 465 died. There was no significant difference between groups in the incidence of the primary composite outcome (16·1 per 1000 person-years in the routine care group vs 14·3 per 1000 person-years in the intensive treatment group; hazard ratio [HR] 0·87, 95% CI 0·73-1·04; p=0·14) or all-cause mortality (15·6 vs 14·3 per 1000 person-years; HR 0·90, 0·76-1·07)., Interpretation: Sustained reductions in glycaemia and related cardiovascular risk factors over 10 years among people with screen-detected diabetes managed in primary care are achievable. The differences in prescribed treatment and cardiovascular risk factors in the 5 years following diagnosis were not maintained at 10 years, and the difference in cardiovascular events and mortality remained non-significant., Funding: National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Novo Nordisk, Novo Nordisk Foundation, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, UK National Health Service, Merck, Julius Center for Health Sciences and Primary Care, UK Department of Health, and Nuts-OHRA., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To investigate whether adverse differences in levels of cardiovascular risk factors in women than men, already established when comparing individuals with and without diabetes, are also present before type 2 diabetes onset., Research Design and Methods: In a population-based cohort study of individuals aged 40-75 years (n=3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated associations with cardiometabolic and lifestyle risk factors of (1) pre-diabetes and type 2 diabetes (reference category: normal glucose metabolism) and (2) among non-diabetic individuals, of continuous levels of hemoglobin A1c (HbA1c). Age-adjusted sex differences were analyzed using linear and logistic regression models with sex interaction terms., Results: In pre-diabetes, adverse differences in cardiometabolic risk factors were greater in women than men for systolic blood pressure (difference, 3.02 mm Hg; 95% CI:-0.26 to 6.30), high-density lipoprotein (HDL) cholesterol (difference, -0.10 mmol/L; 95% CI: -0.18 to -0.02), total-to-HDL cholesterol ratio (difference, 0.22; 95% CI: -0.01 to 0.44), triglycerides (ratio: 1.11; 95% CI: 1.01 to 1.22), and inflammation markers Z-score (ratio: 1.18; 95% CI: 0.98 to 1.41). In type 2 diabetes, these sex differences were similar in direction, and of greater magnitude. Additionally, HbA1c among non-diabetic individuals was more strongly associated with several cardiometabolic risk factors in women than men: per one per cent point increase, systolic blood pressure (difference, 3.58 mm Hg; 95% CI: -0.03 to 7.19), diastolic blood pressure (difference, 2.10 mm Hg; 95% CI: -0.02 to 4.23), HDL cholesterol (difference, -0.09 mmol/L; 95% CI: -0.19 to 0.00), and low-density lipoprotein cholesterol (difference, 0.26 mmol/L; 95% CI: 0.05 to 0.47). With regard to lifestyle risk factors, no consistent pattern was observed., Conclusion: Our results are consistent with the concept that the more adverse changes in cardiometabolic risk factors in women (than men) arise as a continuous process before the onset of type 2 diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine at what glycated haemoglobin (HbA1c) level physicians from eight European countries would initiate insulin in type 2 diabetes, which physician or practice related factors influenced this level and whether physicians would differentiate between a younger uncomplicated patient and an older patient with comorbidities., Design: Cross-sectional study with data from the Guideline Adherence to Enhance Care study., Setting and Participants: 410 physicians from both primary and secondary care from Belgium, France, Germany, Italy, Ireland, Sweden, the Netherlands and the UK., Outcome Measures: Physicians were asked at which HbA1c level they would initiate insulin for a young, uncomplicated patient (vignette 1) and for an older, complicated patient (vignette 2). We evaluated differences in HbA1c levels between physicians from different countries using analysis of variance. To identify physician and practice related factors associated with HbA1c level at initiation of insulin, we performed multivariable linear regression. Multiple imputation was used to deal with missing data., Results: In Germany, Ireland, Sweden, the Netherlands and the UK, the HbA1c levels for initiating insulin in vignette 2 (range: 60.0 to 66.0 mmol/mol; 7.6% to 8.2%) were higher than for vignette 1 (range: 57.2 to 64.2 mmol/mol; 7.4% to 8.0%). In multivariable analysis, the HbA1c level at which insulin was initiated only differed between countries (vignette 1): Dutch physicians initiated insulin at a lower HbA1c level compared with Belgium, France and the UK. No physician or practice factors were independently associated with HbA1c level at insulin initiation., Conclusions: When deciding on individualised HbA1c targets for insulin initiation, physicians from five countries took patient's age and comorbidity into account. The HbA1c level at which physicians would initiate insulin therapy differed between countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Diabetes is a stronger risk factor for cardiovascular complications in women than men., Aim: To evaluate whether there are sex differences in cardiovascular risk management in patients with diabetes in primary care., Design & Setting: A cross-sectional study was undertaken using data from 12 512 individuals with diabetes within the Dutch Julius General Practitioners Network (JGPN) from 2013., Method: Linear and Poisson regression analyses were used to assess sex differences in risk factor levels, assessment, treatment, and control., Results: No sex differences were found in HbA1c levels and control, while small differences were found for cardiovascular risk management. Blood pressure levels were higher (mean difference [MD] 1.09 mmHg; 95% confidence intervals [CI] = 0.41 to 1.77), while cholesterol levels (MD -0.38 mmol/l; 95% CI = -0.42 to -0.34) and body mass index ([BMI] MD -1.79 kg/m 2 ; 95% CI = -2.03 to 1.56) were lower in men than women. Risk factor assessment was similar between sexes, apart from high-density lipoprotein cholesterol (HDL-c), which was more commonly assessed in women (risk ratio [RR] 1.16; 95% CI = 1.13 to 1.20). Among those with a treatment indication for prevention, women with cardiovascular disease (CVD) were less likely to receive lipid-lowering drugs (RR 0.84; 95% CI = 0.76 to 0.93) than men, while women without CVD were more likely to receive lipid-lowering drugs (RR 1.16; 95% CI = 1.04 to 1.2). Among those treated, women were more likely to achieve systolic blood pressure (SBP) control (RR 1.06; 95% CI = 1.02 to 1.10) and less likely to achieve low-density lipoprotein cholesterol (LDL-c) control (RR 0.88; 95% CI = 0.85 to 0.91) than men., Conclusion: In this Dutch primary care setting, sex differences in risk factor assessment and treatment of people with diabetes were small. However, women with diabetes were less likely to achieve control for LDL-c and more likely to achieve blood pressure control than men with diabetes., (Copyright © 2019, The Authors.)

Aims: To evaluate the (cost-)effectiveness of Beyond Good Intentions (BGI), a 12-week group-based, nurse-led self-management programme, in terms of cardiovascular risk factors, self-management and quality of life, after 2.5 years of follow-up in pre-selected individuals with known Type 2 diabetes of up to 5 years' duration., Methods: A parallel randomized controlled trial comparing BGI with usual care, based on a self-management screening questionnaire, was conducted in 43 general practices after pre-selection of participants. After 2.5 years of follow-up, the between-group changes in the abovementioned variables were assessed using analysis of covariance., Results: A total of 108 participants (BGI group, n =56; control group, n =52) were included. Changes over time in BMI (-0.4 vs -0.5 kg/m 2 ) were similar in the two groups. Median HbA 1c [BGI group 47 mmol/mol (6.5%); control group: 49 mmol/mol (6.6%)] and mean systolic blood pressure (BGI group: 132±13 mmHg; control group: 133±14 mmHg) were well controlled at baseline and no intervention effect was found. LDL cholesterol levels decreased from 2.4 to 2.2 mmol/l in the control group and remained stable at 2.6 mmol/l in the intervention group (P=0.032). No intervention effect was found for self-management or quality of life., Conclusion: In contrast to the first BGI study, we did not observe significant effects of the BGI intervention, despite pre-selection of individuals. In diabetes populations with target levels for HbA 1c , systolic blood pressure and LDL cholesterol, no further beneficial effects can be expected from self-management programmes with regard to biomedical factors and quality of life., (© 2019 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: Diabetes distress (DD) is an increasingly important part of clinical medicine, diabetes self-management and research topic in people with diabetes mellitus. The present study evaluated the effectiveness of a value-based emotion-focused educational program in Malay adults with type 2 diabetes (VEMOFIT) at 12-month follow-up compared with a program with systematic attention to participants' emotions (attention-control)., Methods: VEMOFIT consisted of four biweekly group sessions and a booster session after 3 months; the attention-control program consisted of three sessions over the same period. Intention-to-treat analysis with multilevel mixed modelling was done to estimate the intervention effect., Results: Participants ( n  = 124) randomized to VEMOFIT ( n  = 53) or attention-control ( n  = 71). Mean (SD) age 55.7 (9.7) years, median diabetes duration 7.0 (8.0) years and mean HbA1c level 9.7% (82 mmol/mol). The mean DD (DDS-17 scale) level decreased in both groups (from 3.4 to 3.3 versus 3.1-2.5, respectively), significantly more in the attention-control group [adjusted difference -0.6, 95% confidence interval (CI) -1.1, -0.2]. The VEMOFIT group had a significant improvement in self-efficacy (DMSES, range 0-200; adjusted difference 16.4, 99.4% CI 1.9, 30.9). Other outcomes did not differ., Conclusions: Because the attention-control program resulted in a decreased DD 1 year later, its implementation on a larger scale seems justified., Trial Registration: NCT02730078; NMRR-15-1144-24803., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

L-ascorbate (ASC) is essential for human health. Therefore, there is interest in increasing the ASC content of crops like tomato. High irradiance induces accumulation of ASC in green tomato fruits. The D-mannose/L-galactose biosynthetic pathway accounts for the most ASC in plants. The myo-inositol and galacturonate pathways have been proposed to exist but never identified in plants. The D-mannose/L-galactose starts from D-glucose. In a series of experiments, we tested the hypothesis that ASC levels depend on soluble carbohydrate content when tomato fruits ripen under irradiances that stimulate ASC biosynthesis. We show that ASC levels considerably increased when fruits ripened under light, but carbohydrate levels did not show a parallel increase. When carbohydrate levels in fruits were altered by flower pruning, no effects on ASC levels were observed at harvest or after ripening under irradiances that induce ASC accumulation. Artificial feeding of trusses with sucrose increased carbohydrate levels, but did not affect the light-induced ASC levels. We conclude that light-induced accumulation of ASC is independent of the carbohydrate content in tomato fruits. In tomato fruit treated with light, the increase in ASC was preceded by a concomitant increase in myo-inositol.

Aims: Information and communications technology (ICT) could support care organisations to cope with the increasing number of patients with diabetes mellitus. We aimed to aid diabetes care providers in allocating patients to the preferred treatment setting (hospital outpatient clinic or primary care practice), by using the Electronic Medical Record (EMR)., Methods: A cluster randomised controlled trial. Physicians in primary and secondary care practices of the intervention group received an advisory message in the EMR during diabetes consultations if patients were treated in the 'incorrect' setting according to national management guidelines. Primary outcome: the proportion of patients that shifted to the correct treatment setting at one year follow-up., Results: 47 (38 primary care and 9 internist) practices and 2778 patients were included. At baseline, 1197 (43.1%) patients were in the correct treatment setting (intervention 599; control 598). Advice most often (68.4%) regarded a consultation with the internist. After one year 12.4% of the patients in the intervention and 10.6% in the control group (p = 0.30) had shifted to the correct setting. Main reasons for not following advice were: 1. physician's preference to consider other treatment options; 2. patients' preferences., Conclusions: We could not find evidence that using the EMR to send consultation-linked advice to physicians resulted in a shift in patients. Physicians will not follow the advice, at least partly due to patients' preferences., Competing Interests: The authors have declared that no competing interests exist.

This observational study with a pre-post design, conducted in two Dutch primary healthcare centres, aimed to evaluate the effect of a supervised walking programme in highly motivated individuals with or at risk for type 2 diabetes mellitus (T2DM). Those able and willing to walk at least 6 km, were invited for a 28-week walking programme (February to August 2017), in which participants walked in groups, once weekly under supervision of volunteer healthcare professionals. Changes in bodyweight, BMI, waist circumference, HbA1c, blood pressure, well-being, health status and patient activation were analysed using paired t -tests and the Wilcoxon signed-rank test. Fifty-six people were included (30 T2DM; 26 at risk), of whom 60.7% were female. Mean age was 60.6 years, median BMI 30.8 kg/m 2 and mean systolic blood pressure 146.9 mm Hg. Participants with T2DM had median HbA1c of 50.0 mmol/mol. Post-challenge, BMI had decreased to 29.7 kg/m 2 , and waist circumference decreased 3.4 cm (95% CI 2.1-4.8), both p  < 0.01. Systolic and diastolic blood pressure decreased significantly (mean difference 6.5 mm Hg (95% CI 1.6-11.3, p  = 0.01) and 3.5 mm Hg (95% CI 1.0-6.0, p  < 0.01), respectively). Participants with HbA1c >53 mmol/mol at baseline ( n  = 8), had median decrease in HbA1c of 6.5 mmol/mol ( p  = 0.03). Well-being, but not health status and patient activation, improved significantly. In conclusion, in highly motivated individuals with or at risk for T2DM, this simple to implement and low-cost, but intensive, volunteer-based supervised walking programme is favourable, and therefore, can be seen as an option for clinical programs to implement to support highly motivated patients.

Aims: To examine whether diabetes distress (DD), when measured by three different instruments, was associated differently with self-efficacy, self-care activity, medication adherence and disease control in people with Type 2 diabetes mellitus., Methods: A cross-sectional study in three health clinics. DD was assessed with the 17-item Diabetes Distress Scale, the 2-item DDS-2 (DDS-2) and the 5-item Problem Areas in Diabetes Scale (PAID-5). Dependent variables included self-efficacy, self-care activities, medication adherence, HbA 1c , systolic and diastolic blood pressure (SBP, DBP). Multiple linear and logistic regression were used in analyses., Results: In total 338 participants (56% women), with a mean age of 61 years and diabetes duration of 9.8 years, were included. DDS-2 was an independent determinant of SBP (β = 1.89, 95% CI 0.14, 3.64), DBP (β = 1.19, 95% CI 0.16, 2.21) and blood pressure target (OR = 2.09, 95% CI 1.12, 3.83). PAID-5 was an independent determinant of medication adherence (adjusted β = -0.05, 95% CI -0.08, -0.01) and self-care activities (OR = 0.50, 95% CI 0.26, 0.99)., Conclusions: Associations of DD with important aspects of diabetes care are substantially influenced by confounders and depend on the way DD is measured. Our findings call for a judicious use of different DD measures in clinical practice and research. The study is registered on ClinicalTrials.gov (NCT02730754)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: To gain insight into the opinions and working methods of diabetes care providers after using a diabetes web portal for 4 years in order to understand the role of the provider in patients' web portal use., Methods: Survey among physicians and nurses from general practices and an outpatient clinic, correlated with data from the common web portal., Results: One hundred twenty-eight questionnaires were analysed (response rate 56.6%). Responders' mean age was 46.2 ± 9.8 years and 43.8% were physicians. The majority was of opinion that the portal improves patients' diabetes knowledge (90.6%) and quality of care (72.7%). Although uploading glucose diary (93.6%) and patient access to laboratory and clinical notes (91.2 and 71.0%) were considered important, these features were recommended to patients in only 71.8 and 19.5% respectively. 64.8% declared they informed their patients about the portal and 45.3% handed-out the information leaflet and website address. The portal was especially recommended to type 1 diabetes patients (78.3%); those on insulin (84.3%) and patients aged< 65 years (72.4%). Few found it timesaving (21.9%). Diabetes care providers' opinions were not associated with patients' portal use., Conclusions: Providers are positive about patients web portals but still not recommend or encourage the use to all patients. There seems room for improvement in their working methods.

Aims: To evaluate the effectiveness of a brief, value-based emotion-focused educational programme (VEMOFIT) in Malay adults with Type 2 diabetes mellitus compared with a programme of active listening to participants' emotional experiences, social support and their opinion on the health clinic diabetes care services (attention control)., Methods: Malay adults with severe diabetes distress [Diabetes Distress Scale (DDS-17) mean score ≥ 3] were included. VEMOFIT consisted of four biweekly group sessions, a booster session after 3 months and a follow-up 6 months post intervention. The attention control programme consisted of three sessions over the same period. Outcomes included diabetes distress, depressive symptoms, self-efficacy and disease control. Required total sample size was 165., Results: Participants (n = 124) were randomized to either VEMOFIT (n = 53) or the attention control programme (n = 71). Participants had a mean (sd) age of 55.7 (9.7) years, median diabetes duration of 7.0 (8.0) years and mean HbA 1c level of 82 mmol/mol (9.7%). The mean DDS-17 level decreased significantly in both the VEMOFIT and the attention control programmes (3.4 to 2.9 vs. 3.1 to 2.7, respectively). The adjusted between-group DDS-17 difference was not significant [-0.01, 95% confidence interval (CI) -0.38, 0.35]. The proportion of individuals with severe diabetes distress decreased in both groups, from 89% to 47% vs. 69% to 39% (odds ratio 0.88; 95% CI 0.26, 2.90). Other outcomes did not differ between groups., Conclusions: Both interventions decreased diabetes distress significantly. The theory-based VEMOFIT programme was not superior to the attention control programme. The latter approach is a simpler way to decrease severe diabetes distress (Trial registration: NCT02730078; NMRR-15-1144-24803)., (© 2018 Diabetes UK.)

Given that there are indications of overtreatment in older patients with type 2 diabetes in both the United States and Europe, we assessed the level of personalized diabetes treatment for older patients in primary care, focusing on overtreatment. Based on Dutch guidelines individuals aged ≥70 years were classified into 3 glycated haemoglobin (HbA1c) treatment target groups: 7% (53 mmol/mol), 7.5% (58 mmol/mol) and 8% (64 mmol/mol). In our cohort of 1002 patients (n = 319 aged ≥70 years), the 165 patients with HbA1c targets >7% had more micro- and macrovascular complications, more often used ≥5 medicines and were more often frail compared with those with an HbA1c target ≤7%. Of these 165 patients, 64 (38.8%) were overtreated; that is, 20% of all people aged ≥70 years. The majority of overtreated people were frail and used ≥5 medicines. Hypoglycaemia occurred in 20.3% of these patients and almost 30% reported accidents involving falls. Personalized treatment in older people with type 2 diabetes is not common practice. A substantial number of older people are overtreated, with probable harmful consequences. To prevent overtreatment, definition of lower HbA1c limits might be helpful., (© 2017 John Wiley & Sons Ltd.)

Background: Chronically ill patients such as people with type 2 diabetes develop perceptions of their illness, which will influence their coping behaviour. Perceptions are formed once a health threat has been recognised. Many people with type 2 diabetes suffer from multimorbidity, for example the combination with cardiovascular disease. Perceptions of one illness may influence perceptions of the other condition. The aim of the current study was to evaluate the effect of an intervention in type 2 diabetes patients with a first acute coronary event on change in illness perceptions and whether this mediates the intervention effect on health status. The current study is a secondary data analysis of a RCT., Methods: Two hundred one participants were randomised (1:1 ratio) to the intervention (n = 101, three home visits) or control group (n = 100). Outcome variables were diabetes and acute coronary event perceptions, assessed with the two separate Brief Illness Perceptions Questionnaires (BIPQs); and health status (Euroqol Visual Analog Scale (EQ-VAS)). The intervention effect was analysed using ANCOVA. Linear regression analyses were used to assess whether illness perceptions mediated the intervention effect on health status., Results: A positive intervention effect was found on the BIPQ diabetes items coherence and treatment control (F = 8.19, p = 0.005; F = 14.01, p < 0.001). No intervention effect was found on the other BIPQ diabetes items consequence, personal control, identity, illness concern and emotional representation. Regarding the acute coronary event, a positive intervention effect on treatment control was found (F = 7.81, p = 0.006). No intervention effect was found on the other items of the acute coronary event BIPQ. Better diabetes coherence was associated with improved health status, whereas perceiving more treatment control was not. The mediating effect of the diabetes perception 'coherence' on health status was not significant., Conclusion: Targeting illness perceptions of people with diabetes after an acute coronary event has no effect on most domains, but can improve the perceived understanding of their diabetes. Discussing perceptions prevents people with type 2 diabetes who recently experienced an acute coronary event from the perception that they will lose control of both their diabetes and the acute coronary event. Illness perceptions of diabetes patients should therefore be discussed in the dynamic period after an acute coronary event., Trial Registration: Nederlands trial register; NTR3076 , Registered September 20 2011.

Clinical Question: Among patients with type 2 diabetes mellitus who do not achieve optimal glycemic control with insulin monotherapy, is the addition of oral hypoglycemic agents associated with benefits (measured by lowering of hemoglobin A1c) or adverse effects?, Bottom Line: Adding a sulfonylurea to insulin was associated with more hypoglycemic events compared with insulin alone, but this association was not observed for metformin. Adding a sulfonylurea or metformin to insulin was associated with a decrease in hemoglobin A1c of approximately 1.0%.

For people with type 2 diabetes mellitus (T2DM) the daily maintenance of physical and psychological health is challenging. However, the interrelatedness of these two health domains, and of diabetes-related distress (DRD) and depressive symptoms, in the Asian population is still poorly understood. DRD and depressive symptoms have important but distinct influences on diabetes self-care and disease control. Furthermore, the question of whether changes in DRD or depressive symptoms follow a more or less natural course or depend on disease and therapy-related factors is yet to be answered. The aim of this study was to identify the factors influencing changes in DRD or depressive symptoms, at a 3-year follow-up point, in Malaysian adults with T2DM who received regular primary diabetes care. Baseline data included age, sex, ethnicity, marital status, educational level, employment status, health-related quality of life (WHOQOL-BREF), insulin use, diabetes-related complications and HbA1c. DRD was assessed both at baseline and after 3 years using a 17-item Diabetes Distress Scale (DDS-17), while depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). Linear mixed models were used to examine the relationship between baseline variables and change scores in DDS-17 and PHQ-9. Almost half (336) of 700 participants completed both measurements. At follow-up, their mean (SD) age and diabetes duration were 60.6 (10.1) years and 9.8 (5.9) years, respectively, and 54.8% were women. More symptoms of depression at baseline was the only significant and independent predictor of improved DRD at 3 years (adjusted β = -0.06, p = 0.002). Similarly, worse DRD at baseline was the only significant and independent predictor of fewer depressive symptoms 3 years later (adjusted β = -0.98, p = 0.005). Thus, more "negative feelings" at baseline could be a manifestation of initial coping behaviors or a facilitator of a better psychological coaching by physicians or nurses that might be beneficial in the long term. We therefore conclude that initial negative feelings should not be seen as a necessarily adverse factor in diabetes care.

Objective: About 20% of patients with type 2 diabetes achieve all their treatment targets. Shared decision making (SDM) using a support aid based on the 5-years results of the ADDITION study on multifactorial treatment, could increase this proportion., Research Design and Methods: Cluster-randomized trial in 35 former ADDITION primary care practices. Practices were randomized to SDM or care as usual (1:1). Both ADDITION and non-ADDITION type 2 diabetes patients, 60-80 years, known with diabetes for 8-12 years, were included. In the intervention group, patients were presented evidence about the relationship between treatment intensity and cardiovascular events. They chose intensive or less intensive treatment and prioritized their targets. After 1 year priorities could be rearranged., Follow-Up: 24 months. Intention-to-treat analysis., Main Outcome Measure: proportion of patients that achieved all three treatment targets., Results: At baseline 26.4% in the SDM group (n=72) had already achieved all three treatment goals (CG: 23.5%, n=81). In the SDM group 44 patients chose intensive treatment, 25 continued their former less intensive treatment and three people switched from the more to the less intensive protocol. After 24 months 31.8% of the patients in the SDM group achieved all three treatment targets (CG: 25.3%), RR 1.26 (95% CI 0.81-1.95). Mean systolic blood pressure decreased in the SDM group (-5.4 mm Hg, P<.01), mean HbA1c and total cholesterol did not change., Conclusions: Despite an already high baseline level of diabetes care, we found strong indications that SDM on both intensity of treatment and prioritizing treatment goals further improved outcomes., (© 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.)

Background: Many adults with type 2 diabetes mellitus (T2DM) experience a psychosocial burden and mental health problems associated with the disease. Diabetes-related distress (DRD) has distinct effects on self-care behaviours and disease control. Improving DRD in adults with T2DM could enhance psychological well-being, health-related quality of life, self-care abilities and disease control, also reducing depressive symptoms., Objectives: To assess the effects of psychological interventions for diabetes-related distress in adults with T2DM., Search Methods: We searched the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, BASE, WHO ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was December 2014 for BASE and 21 September 2016 for all other databases., Selection Criteria: We included randomised controlled trials (RCTs) on the effects of psychological interventions for DRD in adults (18 years and older) with T2DM. We included trials if they compared different psychological interventions or compared a psychological intervention with usual care. Primary outcomes were DRD, health-related quality of life (HRQoL) and adverse events. Secondary outcomes were self-efficacy, glycosylated haemoglobin A1c (HbA1c), blood pressure, diabetes-related complications, all-cause mortality and socioeconomic effects., Data Collection and Analysis: Two review authors independently identified publications for inclusion and extracted data. We classified interventions according to their focus on emotion, cognition or emotion-cognition. We performed random-effects meta-analyses to compute overall estimates., Main Results: We identified 30 RCTs with 9177 participants. Sixteen trials were parallel two-arm RCTs, and seven were three-arm parallel trials. There were also seven cluster-randomised trials: two had four arms, and the remaining five had two arms. The median duration of the intervention was six months (range 1 week to 24 months), and the median follow-up period was 12 months (range 0 to 12 months). The trials included a wide spectrum of interventions and were both individual- and group-based.A meta-analysis of all psychological interventions combined versus usual care showed no firm effect on DRD (standardised mean difference (SMD) -0.07; 95% CI -0.16 to 0.03; P = 0.17; 3315 participants; 12 trials; low-quality evidence), HRQoL (SMD 0.01; 95% CI -0.09 to 0.11; P = 0.87; 1932 participants; 5 trials; low-quality evidence), all-cause mortality (11 per 1000 versus 11 per 1000; risk ratio (RR) 1.01; 95% CI 0.17 to 6.03; P = 0.99; 1376 participants; 3 trials; low-quality evidence) or adverse events (17 per 1000 versus 41 per 1000; RR 2.40; 95% CI 0.78 to 7.39; P = 0.13; 438 participants; 3 trials; low-quality evidence). We saw small beneficial effects on self-efficacy and HbA1c at medium-term follow-up (6 to 12 months): on self-efficacy the SMD was 0.15 (95% CI 0.00 to 0.30; P = 0.05; 2675 participants; 6 trials; low-quality evidence) in favour of psychological interventions; on HbA1c there was a mean difference (MD) of -0.14% (95% CI -0.27 to 0.00; P = 0.05; 3165 participants; 11 trials; low-quality evidence) in favour of psychological interventions. Our included trials did not report diabetes-related complications or socioeconomic effects.Many trials were small and were at high risk of bias for incomplete outcome data as well as possible performance and detection biases in the subjective questionnaire-based outcomes assessment, and some appeared to be at risk of selective reporting. There are four trials awaiting further classification. These are parallel RCTs with cognition-focused and emotion-cognition focused interventions. There are another 18 ongoing trials, likely focusing on emotion-cognition or cognition, assessing interventions such as diabetes self-management support, telephone-based cognitive behavioural therapy, stress management and a web application for problem solving in diabetes management. Most of these trials have a community setting and are based in the USA., Authors' Conclusions: Low-quality evidence showed that none of the psychological interventions would improve DRD more than usual care. Low-quality evidence is available for improved self-efficacy and HbA1c after psychological interventions. This means that we are uncertain about the effects of psychological interventions on these outcomes. However, psychological interventions probably have no substantial adverse events compared to usual care. More high-quality research with emotion-focused programmes, in non-US and non-European settings and in low- and middle-income countries, is needed.

Background: Illness perceptions involve the personal beliefs that patients have about their illness and may influence health behaviours considerably. Since an instrument to measure these perceptions for Malay population in Malaysia is lacking, we translated and examined the psychometric properties of the Malay version of the Brief Illness Perception Questionnaire (MBIPQ) in adult patients with type 2 diabetes mellitus., Methods: The MBIPQ has nine items, all use a 0-10 response scale, except the ninth item about causal factors, which is an open-ended item. A standard procedure was used to translate and adapt the English BIPQ into Malay language. Construct validity was examined comparing item scores and scores on the Diabetes Management Self-Efficacy Scale, the Morisky Medication Adherence Scale, the World Health Organization Quality of Life-brief, the 9-item Patient Health Questionnaire, the 17-item Diabetes Distress Scale, HbA1c and the presence of complications. In addition, 2-week and 4-week test-retest reliability were studied., Results: A total of 312 patients completed the MBIPQ. Out of this, 97 and 215 patients completed the 2- or 4-weeks test-retest reliability questionnaire, respectively. Moderate inter-items correlations were observed between illness perception dimensions (r = -0.31 to 0.53). MBIPQ items showed the expected correlations with self-efficacy (r = 0.35), medication adherence (r = 0.29), quality of life (r = -0.17 to 0.31) and depressive symptoms (r = -0.18 to 0.21). People with severe diabetes-related distress also were more concern (t-test = 4.01, p < 0.001) and experienced lower personal control (t-test = 2.07, p = 0.031). People with any diabetes-related complication perceived the consequences as more serious (t-test = 2.04, p = 0.044). The 2-week and 4-week test-retest reliabilities varied between ICC agreement 0.39 to 0.70 and 0.58 to 0.78, respectively., Conclusions: The psychometric properties of items in the MBIPQ are moderate. The MBIPQ showed good cross-cultural validity and moderate construct validity. Test-retest reliability was moderate. Despite the moderate psychometric properties, the MBIPQ may be useful in clinical practice as it is a useful instrument to elicit and communicate on patient's personal thoughts and feelings. Future research is needed to establish its responsiveness and predictive validity., Trial Registration: ClinicalTrials.gov NCT02730754 registered on March 29, 2016; NCT02730078 registered on March 29, 2016.

Objective: Patients with type 2 diabetes (T2DM) on insulin therapy are less satisfied with their diabetes treatment than those on oral hypoglycaemic therapies or lifestyle advice only. Determinants of satisfaction in patients with T2DM on insulin therapy are not clearly known. The aim of this study was to determine the association of treatment satisfaction with demographic and clinical characteristics of patients with T2DM., Design: For this study we used data from the GUIDANCE (Guideline Adherence to Enhance Care) study, a cross-sectional study among 7597 patients with T2DM patients from Belgium, France, Germany, Ireland, Italy, Sweden, the Netherlands and the UK. The majority of patients were recruited from primary care. Treatment satisfaction was assessed by the Diabetes Treatment Satisfaction Questionnaire (DTSQ, score 0-36; higher scores reflecting higher satisfaction). To determine which patient characteristics and laboratory values were independently associated with treatment satisfaction, a linear mixed model analysis was used., Participants: In total, 1984 patients on insulin were analysed; the number of included patients per country ranged from 166 (the Netherlands) to 384 (Italy)., Results: The mean DTSQ score was 28.50±7.52 and ranged from 25.93±6.57 (France) to 30.11±5.09 (the Netherlands). Higher DTSQ scores were associated with having received diabetes education (β 1.64, 95% CI 0.95 to 2.32), presence of macrovascular complications (β 0.76, 95% CI 0.21 to 1.31) and better health status (β 0.08 for every one unit increase on a 0-100 scale, 95% CI 0.07 to 0.10). Lower DTSQ scores were associated with more frequently perceived hyperglycaemia (β -0.32 for every 1 unit increase on a seven-point Likert scale, 95% CI -0.50 to -0.13), and higher glycated haemoglobin (β -0.52 for every percentage increase, 95% CI -0.75 to -0.29)., Conclusions: A number of factors including diabetes education, perceived and actual hyperglycaemia and macrovascular complications are associated with treatment satisfaction. Self-management education programmes should incorporate these factors for ongoing support in patients with T2DM., Competing Interests: Competing interests: AMB reports an unrestricted grant from Sanofi-Aventis for a study in type 2 diabetes patients on insulin therapy (support of self-management by mHealth), outside the submitted work. RCV reports an unrestricted grant from Sanofi-Aventis for a study in type 2 diabetes patients on insulin therapy (support of self-management by mHealth). Also an unrestricted grant is received from European Foundation for the Study of Diabetes for a study on the long-term effects of a self-management education course for patients with type 2 diabetes. Both outside the submitted work. TGTH, NPAZ and NM have nothing to disclose. KK is supported by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care, East Midlands (NIHR CIAHRC, EM) and the NIHR Leicester–Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University and the University of Leicester, UK (outside the submitted work). GEHMR received an unrestricted research grant from Sanofi-Aventis and fees from Novo Nordisk for consultancy and lecturing, outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Type 2 diabetes mellitus (T2DM) patients experience many psychosocial problems related to their diabetes. These often lead to emotional disorders such as distress, stress, anxiety and depression, resulting in decreased self-care, quality of life and disease control. The purpose of the current study is to evaluate the effectiveness of a brief value-based emotion-focused educational programme in adults with T2DM on diabetes-related distress (DRD), depressive symptoms, illness perceptions, quality of life, diabetes self-efficacy, self-care and clinical outcomes., Methods: A cluster randomised controlled trial will be conducted in 10 public health clinics in Malaysia, all providing diabetes care according to national clinical practice guidelines. Patients' inclusion criteria: Malay, ≥ 18 years with T2DM for at least 2 years, on regular follow-up with one of three biomarkers HbA1c, systolic blood pressure and LDL-cholesterol sub-optimally controlled, and with a mean 17-item Diabetes Distress Scale (DDS-17) score ≥ 3. The intervention consists of four sessions and one booster over a period of 4 months that provide information and skills to assist patients in having proper perceptions of their T2DM including an understanding of the treatment targets, understanding and managing their emotions and goal-setting. The comparator is an attention-control group with three meetings over a similar period. With an estimated intra-cluster correlation coefficient ρ of 0.015, a cluster size of 20 and 20% non-completion, the trial will need to enroll 198 patients., Primary Outcome: the between groups difference in proportion of patients achieving a mean DDS-17 score < 3 (non-significant distress) at 6 months post-intervention. Secondary outcomes will be the differences in the above mentioned variables between groups., Discussion: We hypothesize that primary and secondary outcomes will improve significantly after the intervention compared to the comparator group. The results of this study can contribute to better care for T2DM patients with DRD., Trial Registration: ClinicalTrials.gov NCT02730078 . Registered on 29 March 2016, last updated on 4 January 2017.

Background: Little attention has been paid to self-management support of patients with well-controlled type 2 diabetes mellitus (T2DM). Most studies evaluated the addition of self-management support to regular diabetes care, but self-management as an alternative for part of regular diabetes care has hardly been studied. In this study, we offered patients with well-controlled T2DM the opportunity to perform the 3 quarterly monitoring sessions at home using an Internet-based self-management program, resulting in online personalized advice., Objective: The aim of our study was to assess the reach and feasibility of an Internet-based diabetes self-management support program for patients with well-controlled T2DM, addressing both primary care providers' (PCPs) opinions and patients' willingness to participate in such a support program., Methods: PCPs assessed patients' eligibility for Internet-based self-management, and patients were offered the opportunity to participate. Characteristics of eligible and ineligible patients were compared, as well as those of participants and nonparticipants, also with regard to quality of life, treatment satisfaction, and illness perceptions. Multivariate logistic regression models were performed and odds ratios (ORs) calculated with 95% CIs., Results: Almost half (128/282, 45.4%) of the patients with well-controlled T2DM were considered ineligible by their PCPs mainly because of cognitive impairment and language barriers (8.2% and 8.9%). Older patients (OR for each year 1.06, 95% CI 1.03-1.09, P<.001), non-Western European patients (OR 3.64, 95% CI 1.67-7.92, P=.001), and patients with a longer diabetes duration (OR for each year 1.56, 95% CI 1.04-2.34, P=.03) were more often regarded as ineligible. Of the 154 patients considered eligible, 57 (37.0%) consented to participate and 30 (10.6%) started the program. Of 57 participants, 45 returned the 3 questionnaires; 21 of 97 nonparticipants returned the questionnaires. Nonparticipants less often thought that their disease would last their entire life (median 8.0 vs 10.0, P=.03) and they were more satisfied with their current treatment than participants (DTSQ total score 44.0 vs 40.0, P=.05). There was no significant difference in quality of life between the 2 groups., Conclusions: PCPs considered half of their patients with well-controlled T2DM incapable of Internet-based self-management mainly because of cognitive impairment and language barriers; of the selected patients, about 1 out of 3 was willing to participate. Older patients, non-Western European patients, and patients with a higher BMI were less likely to participate. Predominantly, practical issues (such as Internet problems) hindered implementation of the Internet-based self-management program., (©Huberta E Hart, Inge ETM Geilen, Elke de Leeuw, Guy EHM Rutten, Rimke C Vos. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 23.03.2017.)

Aims: To compare the proportion of cardiometabolic well-controlled type 2 diabetes mellitus (T2DM) patients according to a clearly defined, simple personalised approach, versus the 'one-size-fits-all' approach., Methods: Observational study using routine data of primary care type 2 diabetes patients in the Netherlands. The proportions of patients that reach the targets for HbA1c, systolic blood pressure and low-density lipoprotein cholesterol in the two different approaches were compared., Results: Of the 890 patients (54.7% men, mean age 62.7 years), 31.8% were well-controlled according to the individualised approach and 24.8% according to the 'one-size-fits-all' approach. For specific subgroups personalising the treatment led to a 5.2%, 27.3% and 45.6% increase of patients achieving low-density lipoprotein cholesterol, HbA1c and systolic blood pressure goals respectively., Conclusions: A clearly defined and relatively simple personalised approach leads to a higher proportion of T2DM patients considered as cardiometabolic well-controlled. This approach may especially be beneficial for patients aged ≥70 years on more than metformin monotherapy (HbA1c) and for patients aged ≥80 years (SBP). Precisely these patients are suggested not to benefit from stricter HbA1c or SBP targets, whereas they may experience more adverse effects (e.g. hypoglycaemia, postural hypotension) when a stricter target value is pursued., (Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Many self-management programs have been developed so far. Their effectiveness varies. The program 'Beyond Good Intentions' (BGI) is based on proactive coping and has proven to be (cost-) effective in achieving reductions in BMI and blood pressure in screen-detected type 2 diabetes patients up until nine months follow-up. However, its long-term effectiveness in people already known with diabetes is lacking. In addition, its (cost-) effectiveness might increase if people who are likely not to be benefit from the program are excluded in a valid way. Therefore it was aimed to investigate the long-term effects of the educational program BGI on cardiovascular risk, quality of life and diabetes self-management behaviour in a pre-selected group of patients known with type 2 diabetes up to 5 years., Methods: Randomised controlled trial with 2.5 year follow-up. Adults (≤75 years) with a type 2 diabetes duration between 3 months and 5 years will be included. With the use of a self-management screening tool (SeMaS) their potential barriers of self-management due to depression and/or anxiety will be determined. Based on the results of the SeMaS selection patients will be randomised (1:1) to the BGI-group (n = 53) or the control-group (n = 53). In addition to receiving usual care, patients in the BGI-group will follow the 12-week theory-based self-management program and a booster session a few months thereafter. The control-group will receive care as usual. The primary outcome is change in Body Mass Index after 2.5 years follow-up. Secondary outcomes are HbA1c, lipid profile and systolic blood pressure, (diabetes) quality of life, level of physical activity, dietary intake and medication adherence and proactive coping. Cost-effectiveness will be based on total use of health care resources during the entire study period. Difference between groups in change over time will be analysed according to intention-to-treat analysis., Conclusions: By differentiating between patients who will and those who are likely not to benefit from the educational program, a more (cost-) effective self-management program might be designed, also on the long-run. Trial registration NTR 5330.

Both physical barriers and reactive phytochemicals represent two important components of a plant's defence system against environmental stress. However, these two defence systems have generally been studied independently. Here, we have taken an exclusive opportunity to investigate the connection between a chemical-based plant defence system, represented by the glucosinolate-myrosinase system, and a physical barrier, represented by the cuticle, using Arabidopsis myrosinase (thioglucosidase; TGG) mutants. The tgg1, single and tgg1 tgg2 double mutants showed morphological changes compared to wild-type plants visible as changes in pavement cells, stomatal cells and the ultrastructure of the cuticle. Extensive metabolite analyses of leaves from tgg mutants and wild-type Arabidopsis plants showed altered levels of cuticular fatty acids, fatty acid phytyl esters, glucosinolates, and indole compounds in tgg single and double mutants as compared to wild-type plants. These results point to a close and novel association between chemical defence systems and physical defence barriers.

An ethnopharmacological survey indicates that the genus Byrsonima has some medicinal species that are commonly found in the Brazilian Cerrado and has been used as an anti-inflammatory and for gastroduodenal disorders. The aim of this study was to evaluate the anti-inflammatory and antioxidant activity along with qualitative chemical characterization of the methanolic extract of the leaves of Byrsonima verbascifolia (BvME) obtained by exhaustive percolation. The data from the chemical analyses by liquid chromatography-mass spectrometry led to tentative identification of 42 compounds belonging to proanthocyanidins, galloyl quinic acid derivatives, flavonoids, and triterpene glycoside derivatives. BvME contain flavonoids and show an antioxidative activity. The methanolic extract administered intraperitoneally at doses of 50, 100, or 300 mg/kg showed a significant reduction in paw edema and modulated the neutrophil influx in a mouse model. Furthermore, the anti-edematogenic activity of the extract provided in smaller doses (12.5 and 25 mg/kg) was also demonstrated in a mouse paw edema model. The extract inhibited NO production by macrophages induced by lipopolysaccharide. We presume that the anti-inflammatory effects of BvME are due to a combination of compounds present in B. verbascifolia, including catechins (procyanidins), flavonoids, and triterpene glycosides and that these anti-inflammatory actions should be mediated, at least partly, through the inhibition of NO production. This study supports and validates the ethnopharmacological uses of B. verbascifolia as an anti-inflammatory.

Background: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy., Objectives: To assess the effects of insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin monotherapy for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and reference lists of articles. The date of the last search was November 2015 for all databases., Selection Criteria: Randomised controlled clinical trials of at least two months' duration comparing insulin monotherapy with combinations of insulin with one or more oral glucose-lowering agent in people with type 2 diabetes., Data Collection and Analysis: Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated overall quality of the evidence using GRADE. We summarised data statistically if they were available, sufficiently similar and of sufficient quality. We performed statistical analyses according to the statistical guidelines in the Cochrane Handbook for Systematic Reviews of Interventions., Main Results: We included 37 trials with 40 treatment comparisons involving 3227 participants. The duration of the interventions ranged from 2 to 12 months for parallel trials and two to four months for cross-over trials.The majority of trials had an unclear risk of bias in several risk of bias domains. Fourteen trials showed a high risk of bias, mainly for performance and detection bias. Insulin monotherapy, including once-daily long-acting, once-daily intermediate-acting, twice-daily premixed insulin, and basal-bolus regimens (multiple injections), was compared to insulin in combination with sulphonylureas (17 comparisons: glibenclamide = 11, glipizide = 2, tolazamide = 2, gliclazide = 1, glimepiride = 1), metformin (11 comparisons), pioglitazone (four comparisons), alpha-glucosidase inhibitors (four comparisons: acarbose = 3, miglitol = 1), dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) (three comparisons: vildagliptin = 1, sitagliptin = 1, saxagliptin = 1) and the combination of metformin and glimepiride (one comparison). No trials assessed all-cause mortality, diabetes-related morbidity or health-related quality of life. Only one trial assessed patients' treatment satisfaction and showed no substantial differences between the addition of either glimepiride or metformin and glimepiride to insulin compared with insulin monotherapy.Insulin-sulphonylurea combination therapy (CT) compared with insulin monotherapy (IM) showed a MD in glycosylated haemoglobin A1c (HbA1c) of -1% (95% confidence interval (CI) -1.6 to -0.5); P < 0.01; 316 participants; 9 trials; low-quality evidence. Insulin-metformin CT compared with IM showed a MD in HbA1c of -0.9% (95% CI -1.2 to -0.5); P < 0.01; 698 participants; 9 trials; low-quality evidence. We could not pool the results of adding pioglitazone to insulin. Insulin combined with alpha-glucosidase inhibitors compared with IM showed a MD in HbA1c of -0.4% (95% CI -0.5 to -0.2); P < 0.01; 448 participants; 3 trials; low-quality evidence). Insulin combined with DPP-4 inhibitors compared with IM showed a MD in HbA1c of -0.4% (95% CI -0.5 to -0.4); P < 0.01; 265 participants; 2 trials; low quality evidence. In most trials the participants with CT needed less insulin, whereas insulin requirements increased or remained stable in participants with IM.We did not perform a meta-analysis for hypoglycaemic events because the included studies used different definitions.. In most trials the insulin-sulphonylurea combination resulted in a higher number of mild episodes of hypoglycaemia, compared to the IM group (range: 2.2 to 6.1 episodes per participant in CT versus 2.0 to 2.6 episodes per participant in IM; low-quality evidence). Pioglitazone CT also resulted in more mild to moderate hypoglycaemic episodes compared with IM (range 15 to 90 episodes versus 9 to 75 episodes, respectively; low-quality evidence. The trials that reported hypoglycaemic episodes in the other combinations found comparable numbers of mild to moderate hypoglycaemic events (low-quality evidence).The addition of sulphonylureas resulted in an additional weight gain of 0.4 kg to 1.9 kg versus -0.8 kg to 2.1 kg in the IM group (220 participants; 7 trials; low-quality evidence). Pioglitazone CT caused more weight gain compared to IM: MD 3.8 kg (95% CI 3.0 to 4.6); P < 0.01; 288 participants; 2 trials; low-quality evidence. Metformin CT was associated with weight loss: MD -2.1 kg (95% CI -3.2 to -1.1), P < 0.01; 615 participants; 7 trials; low-quality evidence). DPP-4 inhibitors CT showed weight gain of -0.7 to 1.3 kg versus 0.6 to 1.1 kg in the IM group (362 participants; 2 trials; low-quality evidence). Alpha-glucosidase CT compared to IM showed a MD of -0.5 kg (95% CI -1.2 to 0.3); P = 0.26; 241 participants; 2 trials; low-quality evidence.Users of metformin CT (range 7% to 67% versus 5% to 16%), and alpha-glucosidase inhibitors CT (14% to 75% versus 4% to 35%) experienced more gastro-intestinal adverse effects compared to participants on IM. Two trials reported a higher frequency of oedema with the use of pioglitazone CT (range: 16% to 18% versus 4% to 7% IM)., Authors' Conclusions: The addition of all oral glucose-lowering agents in people with type 2 diabetes and inadequate glycaemic control who are on insulin therapy has positive effects on glycaemic control and insulin requirements. The addition of sulphonylureas results in more hypoglycaemic events. Additional weight gain can only be avoided by adding metformin to insulin. Other well-known adverse effects of oral glucose-lowering agents have to be taken into account when prescribing oral glucose-lowering agents in addition to insulin therapy.

Objective: To examine associations over longitudinal measurements between neuromusculoskeletal function and gross motor capacity in children and youth with cerebral palsy (CP)., Design: A prospective cohort study., Setting: Rehabilitation departments of university medical centers and rehabilitations centers., Participants: A sample (N=327) consisting of 148 children (aged 5-9y) and 179 youth (aged 11-20y) with CP, Gross Motor Function Classification System level I (n=180), level II (n=44), level III (n=36), level IV (n=34), and level V (n=33)., Interventions: Not applicable., Main Outcome Measures: Gross motor capacity was assessed with the Gross Motor Function Measure-66 over a period of 2 to 4 years in different age cohorts. Neuromusculoskeletal function included selective motor control (SMC), muscle strength, spasticity, and range of motion (ROM) of the lower extremities., Results: Multilevel analyses showed that SMC was significantly associated with gross motor capacity in children and youth with CP, showing higher values and a more favorable course of gross motor capacity in those with better SMC. Strength was only associated with gross motor capacity in youth. Reduced ROM of hip (children) and knee extension (youth) and spasticity of the hip adductors (youth) were additionally-but more weakly-associated with lower values and a less favorable course of gross motor capacity., Conclusions: Results indicate that children and youth with more severely impaired SMC and youth with reduced muscle strength have a less favorable course of gross motor capacity, while spasticity and reduced ROM are less determinative., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Aims: To explore differences in clinical characteristics of patients with and without type 2 diabetes (T2DM) hospitalized with a first myocardial infarction (MI)., Methods: In this cross-sectional study we examined differences between patients with and without T2DM hospitalized with a first MI (n=563). Multiple linear regression modeling was used to examine the association between T2DM and age of occurrence of MI. We adjusted for gender, systolic blood pressure (BP), lipids and creatinine level to examine whether these variables explained the association between T2DM and age of occurrence of MI., Results: Among 563 patients with a first MI, T2DM patients (n=77) were older than non-diabetic patients (67.8±10.9 vs. 64.4±13.4years, p<0.05), had lower LDL (2.5±0.8 vs. 3.4±1.1mmol/l, p<0.001) and total cholesterol levels (4.4±0.9 vs. 5.4±1.2mmol/l, p<0.001), but higher systolic BP (150.3±29.9 vs. 141.7±27.5mmHg, p<0.05). The association between T2DM and age of occurrence of MI was largely explained by cholesterol levels., Conclusions: T2DM patients were older when hospitalized with a first MI. This difference was largely explained by differences in cholesterol levels. The lower cholesterol levels in T2DM patients compared to non-diabetic patients, and maybe also the older age of occurrence of MI, might reflect the results successful primary prevention and systematic monitoring in T2DM., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To examine the efficacy of child-focused, context-focused, and regular care approaches, delivered in a rehabilitation setting by physical or occupational therapists to preschool children with cerebral palsy (CP), in optimizing the child's self-care and mobility capabilities., Method: A multicentre randomized controlled trial clustered at therapist level was conducted in 13 rehabilitation centres. It included 68 children with CP (38 males, 30 females; mean age 3y, SD 6mo, range 1y 11mo-4y), classified as Gross Motor Function Classification System levels I to IV, who were already receiving therapy. Children received a child-focused, context-focused, or regular care approach during a 6-month period. Self-care and mobility capabilities were assessed with the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory., Results: The child-focused, context-focused, and regular care approaches all resulted in significant but similar improvements in self-care (regular: reference; child-focused: β=-0.11, 95% confidence interval [CI] -0.68 to 0.46; context-focused: β=0.13, CI -0.38 to 0.64) and mobility (regular: reference; child-focused: β=-0.09, CI=-0.93 to 0.75; and context-focused: β=0.14, CI -0.65 to 0.94) capabilities., Interpretation: The results suggest that the three therapy approaches were equally efficacious for preschool children with CP. Depending on a child's individual situation each approach can be selected., (© 2015 Mac Keith Press.)

Aims: To evaluate the effectiveness of a tailored, supportive intervention strategy in influencing diabetes-related distress, health status, well-being and clinical outcomes in people with Type 2 diabetes shortly after a first acute coronary event., Methods: People with Type 2 diabetes and a recent first acute coronary event (n = 201) were randomized to the intervention group (three home visits by a diabetes nurse) or the attention control group (one telephone consultation). Outcomes were measured after discharge (baseline) and at 5 months (follow-up) using validated questionnaires for diabetes-related distress (Problem Areas in Diabetes), well-being (WHO Well-Being Index) and health status (Euroqol 5 Dimensions; Euroqol Visual Analogue Scale). ancova was used to analyse change-over-time differences between groups., Results: Follow-up data were available for 81 participants in the intervention group (66.0 ± 9.3 years, 76% male) and 80 in the control group (65.6 ± 9.4 years, 75% male) participants. Mean diabetes-related distress was low after hospital discharge (intervention group: 8.2 ± 10.1; control group: 9.2 ± 12.4) and did not change after 5 months (intervention group: 9.2 ± 12.4; control group: 9.0 ± 11.2). Baseline well-being was less favourable but improved significantly in the intervention group (baseline: 58.5 ± 28.0; follow-up: 65.5 ± 23.7; P = 0.005), but not in the control group (baseline: 57.5 ± 25.2; follow-up: 59.6 ± 24.4; P = 0.481). Health status also improved in the intervention group (baseline: 69.9 ± 17.3; follow-up: 76.8 ± 15.6; P < 0.001) but not in the control group (baseline: 68.6 ± 15.9; follow-up: 69.9 ± 16.7; P = 0.470). A significant group effect was found for health status (F = 7.9; P = 0.006)., Conclusions: Although the intervention had no effect on diabetes-related distress, this might be at least partially attributable to very low levels of diabetes-related distress at baseline. Interestingly, health status scores and well-being, which were less favourable at baseline, both improved after the tailored support intervention., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Introduction: Batch effects in large untargeted metabolomics experiments are almost unavoidable, especially when sensitive detection techniques like mass spectrometry (MS) are employed. In order to obtain peak intensities that are comparable across all batches, corrections need to be performed. Since non-detects, i.e., signals with an intensity too low to be detected with certainty, are common in metabolomics studies, the batch correction methods need to take these into account., Objectives: This paper aims to compare several batch correction methods, and investigates the effect of different strategies for handling non-detects., Methods: Batch correction methods usually consist of regression models, possibly also accounting for trends within batches. To fit these models quality control samples (QCs), injected at regular intervals, can be used. Also study samples can be used, provided that the injection order is properly randomized. Normalization methods, not using information on batch labels or injection order, can correct for batch effects as well. Introducing two easy-to-use quality criteria, we assess the merits of these batch correction strategies using three large LC-MS and GC-MS data sets of samples from Arabidopsis thaliana ., Results: The three data sets have very different characteristics, leading to clearly distinct behaviour of the batch correction strategies studied. Explicit inclusion of information on batch and injection order in general leads to very good corrections; when enough QCs are available, also general normalization approaches perform well. Several approaches are shown to be able to handle non-detects-replacing them with very small numbers such as zero seems the worst of the approaches considered., Conclusion: The use of quality control samples for batch correction leads to good results when enough QCs are available. If an experiment is properly set up, batch correction using the study samples usually leads to a similar high-quality correction, but has the advantage that more metabolites are corrected. The strategy for handling non-detects is important: choosing small values like zero can lead to suboptimal batch corrections.

Background: Perceptions of illness are important determinants of health behaviour. A better understanding of perceptions of obesity might allow more effective interventions that challenge these perceptions through lifestyle modification programs. Although several studies have evaluated causal attributions with regard to obesity, other domains of illness perception, such as the perceived consequences of obesity and perceived controllability, have not yet been studied. The aim of the current study was to explore perceptions regarding causes, consequences, control, concerns and time course of obesity of centrally obese adults, with and without an elevated cardiometabolic risk and with or without weight loss, 3 years after screening for metabolic syndrome, and to compare these perceptions., Methods: Three groups were selected from a longitudinal study dependent on the baseline and 3-year follow-up profiles: individuals with central obesity and metabolic syndrome at both time points ('persistent cardiometabolic-risk group', n = 80), those with central obesity but without metabolic syndrome on either occasion ('persistent obese group', n = 63), and formerly obese individuals ('improved cardiometabolic-risk group', n = 49). Perceptions of obesity were assessed using an adapted version of the Brief Illness Perception Questionnaire (BIPQ, range 0-10). Chi-square and Kruskal-Wallis tests were performed to compare the 'persistent cardiometabolic risk' group with the other two groups with regard to patient characteristics and BIPQ scores., Results: Both males and females who improved their cardiometabolic risk perceived their obesity as shorter (median (IQR): 3.0 (4.0) vs. 6.0 (3.0), p < 0.001) and experienced greater personal control over their weight (7.0 (3.0) vs. 5.0 (3.0), p = 0.002) compared to those who did not improve. Females who improved their cardiometabolic risk experienced fewer identity and illness concerns, this was not found for males. Other scores did not differ between groups., Conclusion: Obese adults with an improved cardiometabolic risk profile felt greater personal control and considered their obesity to be of shorter duration. Persistence of central obesity with additional cardiometabolic risk factors had a larger impact on female than male participants with respect to identity and illness concerns. Whether discussing 'personal control' is a favourable element in lifestyle intervention should now be assessed in the setting of a controlled trial.

Aims: To investigate the relationship between diabetes duration and diabetes-related distress and to examine the impact of micro- and macrovascular complications and blood glucose-lowering treatment on this relationship., Methods: We conducted a cross-sectional study in people with Type 2 diabetes who participated in the Dutch Diacourse study (n = 590) and completed the Problem Areas in Diabetes questionnaire. Data on diabetes duration, micro- and macrovascular complications and blood glucose-lowering treatment were collected. Multiple linear regression analysis was used to investigate the association between diabetes duration and diabetes-related distress, and to examine whether complications and treatment could explain this association., Results: A significant linear and quadratic association between diabetes duration and diabetes-related distress was found (duration: β = 0.27, P = 0.005; duration(2): β = -0.21, P = 0.030). The association between duration and distress could be explained by microvascular complications and insulin treatment, which were both more often present in people with a longer diabetes duration, and were associated with higher levels of diabetes-related distress (β = 0.20, P < 0.001 and β = 0.16, P = 0.006 respectively). Duration, age, gender, complications and treatment together explained 13.1% of the variance in distress., Conclusions: Diabetes duration was associated with diabetes-related distress. This association can be explained largely by the presence of diabetes-related microvascular complications and insulin treatment. Healthcare providers should focus on distress in people with Type 2 diabetes in different stages over the course of illness, especially when complications are present or when people are on insulin treatment. As well as diabetes duration, complications and blood glucose-lowering treatment, diabetes-related distress is likely to be influenced by many other factors., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Laser-ablation electrospray ionization (LAESI)-mass spectrometry imaging has been applied to contrasting plant organs to assess its potential as a procedure for performing in vivo metabolomics in plants. In a proof-of-concept experiment, purple/white segmented Phalaenopsis spp. petals were first analyzed using standard liquid chromatography-mass spectrometry analyses of separate extracts made specifically from the purple and white regions. Discriminatory compounds were defined and putatively annotated. LAESI analyses were then performed on living tissues, and these metabolites were then relocalized within the LAESI-generated data sets of similar tissues. Maps were made to illustrate their locations across the petals. Results revealed that, as expected, anthocyanins always mapped to the purple regions. Certain other (nonvisible) polyphenols were observed to colocalize with the anthocyanins, whereas others were found specifically within the white tissues. In a contrasting example, control and Cladosporium fulvum-infected tomato (Solanum lycopersicum) leaves were subjected to the same procedures, and it could be observed that the alkaloid tomatine has clear heterogeneous distribution across the tomato leaf lamina. Furthermore, LAESI analyses revealed perturbations in alkaloid content following pathogen infection. These results show the clear potential of LAESI-based imaging approaches as a convenient and rapid way to perform metabolomics analyses on living tissues. However, a range of limitations and factors have also been identified that must be taken into consideration when interpreting LAESI-derived data. Such aspects deserve further evaluation before this approach can be applied in a routine manner., (© 2015 American Society of Plant Biologists. All Rights Reserved.)

Carnosic acid (CA) is a phenolic diterpene with anti-tumour, anti-diabetic, antibacterial and neuroprotective properties that is produced by a number of species from several genera of the Lamiaceae family, including Salvia fruticosa (Cretan sage) and Rosmarinus officinalis (Rosemary). To elucidate CA biosynthesis, glandular trichome transcriptome data of S. fruticosa were mined for terpene synthase genes. Two putative diterpene synthase genes, namely SfCPS and SfKSL, showing similarities to copalyl diphosphate synthase and kaurene synthase-like genes, respectively, were isolated and functionally characterized. Recombinant expression in Escherichia coli followed by in vitro enzyme activity assays confirmed that SfCPS is a copalyl diphosphate synthase. Coupling of SfCPS with SfKSL, both in vitro and in yeast, resulted in the synthesis miltiradiene, as confirmed by 1D and 2D NMR analyses (1H, 13C, DEPT, COSY H-H, HMQC and HMBC). Coupled transient in vivo assays of SfCPS and SfKSL in Nicotiana benthamiana further confirmed production of miltiradiene in planta. To elucidate the subsequent biosynthetic step, RNA-Seq data of S. fruticosa and R. officinalis were searched for cytochrome P450 (CYP) encoding genes potentially involved in the synthesis of the first phenolic compound in the CA pathway, ferruginol. Three candidate genes were selected, SfFS, RoFS1 and RoFS2. Using yeast and N. benthamiana expression systems, all three where confirmed to be coding for ferruginol synthases, thus revealing the enzymatic activities responsible for the first three steps leading to CA in two Lamiaceae genera.

Background: No more than 10-15% of type 2 diabetes mellitus (T2DM) patients achieve all treatment goals regarding glycaemic control, lipids and blood pressure. Shared decision making (SDM) should increase that percentage; however, not all support decision tools are appropriate. Because the ADDITION-Europe study demonstrated two (almost) equally effective treatments but with slightly different intensities, it may be a good starting point to discuss with the patients their diabetes treatment, taking into account both the intensity of treatment, clinical factors and patients' preferences. We aim to evaluate whether such an approach increases the proportion of patients that achieve all three treatment goals., Methods: In a cluster-randomised trial including 40 general practices, that participated until 2009 in the ADDITION Study, 150 T2DM patients 60-80 years, known with T2DM for 8-15 years, will be included. Practices are randomised a second time, i.e. intervention practices in the ADDITION study could be control practices in the current study and vice versa. For the GPs from the intervention group a 2-hour training in SDM was developed as well as a decision support tool to be used during the consultation. GPs plan the first visit with the patients to decide on the intensity of the treatment, personalised targets and the priorities of treatment. The control group will continue with the treatment they were allocated to in the ADDITION study., Follow-Up: 24 months. The primary outcome is the proportion of patients who achieve all three treatment goals. Secondary outcomes are the proportion of patients who achieve five treatment goals (HbA1c, blood pressure, total cholesterol, body weight, not smoking), evaluation of the SDM process (SDM-Q9 and CPS), satisfaction with the treatment (DTSQ), wellbeing and quality of life (W-BQ12, ADD QoL-19), health status (SF-36, EQ-5D) and coping (DCMQ). The proportions of achieved treatment goals will be compared between both groups. For the secondary outcomes mixed models will be used. The Medical Research Ethics Committee of the University Medical Centre Utrecht has approved the study protocol (Protocol number: 11-153)., Discussion: This trial will provide evidence whether an intervention with a multi-faceted decision support tool increases the proportion of achieved personalised goals in type 2 diabetes patients., Trial Registration: NCT02285881, November 4, 2014.

The effects of conventional industrial processing steps on global phytochemical composition of broccoli, tomato and carrot purees were investigated by using a range of complementary targeted and untargeted metabolomics approaches including LC-PDA for vitamins, (1)H NMR for polar metabolites, accurate mass LC-QTOF MS for semi-polar metabolites, LC-MRM for oxylipins, and headspace GC-MS for volatile compounds. An initial exploratory experiment indicated that the order of blending and thermal treatments had the highest impact on the phytochemicals in the purees. This blending-heating order effect was investigated in more depth by performing alternate blending-heating sequences in triplicate on the same batches of broccoli, tomato and carrot. For each vegetable and particularly in broccoli, a large proportion of the metabolites detected in the purees was significantly influenced by the blending-heating order, amongst which were potential health-related phytochemicals and flavour compounds like vitamins C and E, carotenoids, flavonoids, glucosinolates and oxylipins. Our metabolomics data indicates that during processing the activity of a series of endogenous plant enzymes, such as lipoxygenases, peroxidases and glycosidases, including myrosinase in broccoli, is key to the final metabolite composition and related quality of the purees., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Secondary prevention is efficient in reducing morbidity and mortality after a myocardial infarction (MI). However, both short-term and long-term mortality after MI remains relativity high in type 2 diabetes patients., Objective: To evaluate repeat prescriptions of secondary prevention medication (anti-thrombotic agent, beta-blocker and statin) in type 2 diabetes patients with a previous MI., Methods: Data of 1009 type 2 diabetes patients with a previous MI were extracted from the Julius General Practitioners' Network database. The proportion of patients with recent repeat prescriptions of guideline-based medication was determined. Furthermore, repeat prescriptions was determined 6 months, 1 year, 2 years and 5 years after MI. Generalized linear models were used to examine changes over time. Multivariate logistic regression analysis was used to analyse the association between patient characteristics and prescription., Results: Only 46% of all type 2 diabetes patients with a previous MI had a recent repeat prescription for all three medicines. An increase in prescription over time was found for statins (P = 0.001). Older aged people [odds ratio (OR): 0.99, 95% confidence interval (CI): 0.98-1.00] were less likely to receive the combination of all three., Conclusion: A substantial proportion of type 2 diabetes patients with a previous MI did not receive guideline-based secondary prevention. Prescription rates were quite stable over time. This study confirms the need for a different approach to achieve an improvement of secondary prevention in type 2 diabetes patient with a previous MI. GPs can play an important role in this respect by being extra alert that prescription occurs according to the guidelines., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Scope: Genistein from foods or supplements is metabolized by the gut microbiota and the human body, thereby releasing many different metabolites into systemic circulation. The order of their appearance in plasma and the possible influence of food format are still unknown. This study compared the nutrikinetic profiles of genistein metabolites., Methods and Results: In a randomized cross-over trial, 12 healthy young volunteers were administered a single dose of 30 mg genistein provided as a genistein tablet, a genistein tablet in low fat milk, and soy milk containing genistein glycosides. A high mass resolution LC-LTQ-Orbitrap FTMS platform detected and quantified in human plasma: free genistein, seven of its phase-II metabolites and 15 gut-derived metabolites. Interestingly, a novel metabolite, genistein-4'-glucuronide-7-sulfate (G-4'G-7S) was identified. Nutrikinetic analysis using population-based modeling revealed the order of appearance of five genistein phase II metabolites in plasma: (1) genistein-4',7-diglucuronide, (2) genistein-7-sulfate, (3) genistein-4'-sulfate-7-glucuronide, (4) genistein-4'-glucuronide, and (5) genistein-7-glucuronide, independent of the food matrix., Conclusion: The conjugated genistein metabolites appear in a distinct order in human plasma. The specific early appearance of G-4',7-diG suggests a multistep formation process for the mono and hetero genistein conjugates, involving one or two deglucuronidation steps., (© 2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Coloration of plant organs such as fruit, leaves and flowers through anthocyanin production is governed by a combination of MYB and bHLH type transcription factors (TFs). In this study we introduced Rosea1 (ROS1, a MYB type) and Delila (DEL, a bHLH type), into Nicotiana benthamiana leaves by agroinfiltration. ROS1 and DEL form a pair of well-characterized TFs from Snapdragon (Antirrhinum majus), which specifically induce anthocyanin accumulation when expressed in tomato fruit. In N. benthamiana, robust induction of a single anthocyanin, delphinidin-3-rutinoside (D3R) was observed after expression of both ROS1 and DEL. Surprisingly in addition to D3R, a range of additional metabolites were also strongly and specifically up-regulated upon expression of ROS1 and DEL. Except for the D3R, these induced compounds were not derived from the flavonoid pathway. Most notable among these are nornicotine conjugates with butanoyl, hexanoyl, and octanoyl hydrophobic moieties, and phenylpropanoid-polyamine conjugates such as caffeoyl putrescine. The defensive properties of the induced molecules were addressed in bioassays using the tobacco specialist lepidopteran insect Manduca sexta. Our study showed that the effect of ROS1 and DEL expression in N. benthamiana leaves extends beyond the flavonoid pathway. Apparently the same transcription factor may regulate different secondary metabolite pathways in different plant species.

Aim: The aim of this study was to determine the developmental trajectories of expressive (speech) and receptive (spoken and written language) communication by type of motor disorder and intellectual disability in individuals with cerebral palsy (CP)., Method: The development of 418 participants (261 males, 157 females; mean age 9y 6mo [SD 6y 2mo], range 1-24y; Gross Motor Function Classification System (GMFCS) level I [n=206], II [n=57], III [n=59], IV [n=54], V [n=42]) was followed for 2 to 4 years in a longitudinal study. Communication performance was measured using the Vineland Adaptive Behavior Scales. The type of motor disorder was differentiated by type of CP as unilateral spastic (USCP, n=161), bilateral spastic (BSCP, n=202), and non-spastic (NSCP, n=55), while intellectual disability was determined by IQ or school type (regular or special). A multilevel analysis was then used to model the developmental trajectories., Results: The most favourable development of expressive communication was seen in USCP (vs BSCP β [SE]-2.74 [1.06], NSCP β [SE]-2.67 [1.44]). The difference between the development trajectory levels of children with and without intellectual disability was smaller for children with USCP than for those with BSCP and NSCP. For receptive communication, the most favourable development was found for all children with USCP and for BSCP or NSCP without intellectual disability (vs intellectual disability β [SE]-4.00 [1.16]). Development of written language was most favourable for children without intellectual disability (vs intellectual disability β [SE]-23.11 [2.85])., Interpretation: The development of expressive communication was found to be most closely related to type of motor disorder, whereas the development of receptive communication was found to be most closely related to intellectual disability., (© 2014 Mac Keith Press.)

Aims: Despite diabetes patients' efforts to control their disease, many of them are confronted with an acute coronary event. This may evoke depressive feelings and self-management may be complicated. According to the American Diabetes Association, the transition from hospital to home after an acute coronary event (ACE) is a high-risk time for diabetes patients; it should be improved. Before developing an intervention for diabetes patients with an ACE in the period after discharge from hospital, we want to gain a detailed understanding of patients' views, perceptions and feelings in this respect., Methods: Qualitative design. Two semi-structured focus groups were conducted with 14 T2DM patients (71% male, aged 61-77 years) with a recent ACE. One focus group with partners (67% male, aged 64-75 years) was held. All interviews were transcribed verbatim and analyzed by two independent researchers., Results: Patients believed that coping with an ACE differs between patients with and without T2DM. They had problems with physical exercise, sexuality and pharmacotherapy. Patients and partners were neither satisfied with the amount of information, especially on the combination of T2DM and ACE, nor with the support offered by healthcare professionals after discharge. Participants would appreciate tailored self-management support after discharge from hospital., Conclusions: Patients with T2DM and their partners lack tailored support after a first ACE. Our findings underpin the ADA recommendations to improve the transition from hospital to home. The results of our study will help to determine the exact content of a self-management support program delivered at home to help this specific group of patients to cope with both conditions., (Copyright © 2013 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)