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Aims/hypothesisType 2 diabetes, particularly with concomitant CVD, is associated with an increased risk of cognitive impairment. We assessed the effect on accelerated cognitive decline (ACD) of the DPP-4 inhibitor linagliptin vs the sulfonylurea glimepiride in individuals with type 2 diabetes.MethodsThe CAROLINA-COGNITION study was part of the randomised, double-blind, active-controlled CAROLINA trial that evaluated the cardiovascular safety of linagliptin vs glimepiride in individuals with age ≥40 and ≤85 years and HbA1c 48–69 mmol/mol (6.5–8.5%) receiving standard care, excluding insulin therapy. Participants were randomised 1:1 using an interactive telephone- and web-based system and treatment assignment was determined by a computer-generated random sequence with stratification by center. The primary cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression-based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning, in participants with a baseline MMSE score ≥24. Prespecified additional analyses included effects on ACD at week 160, in subgroups (sex, age, race, ethnicity, depressive symptoms, cardiovascular risk, duration of type 2 diabetes, albuminuria), and absolute changes in cognitive performance. Participants, caregivers, and people involved in measurements, examinations or adjudication, were all masked to treatment assignment.ResultsOf 6033 participants recruited from hospital and primary care sites, 3163 (38.0% female, mean age/diabetes duration 64/7.6 years, MMSE score 28.5, HbA1c 54 mmol/mol [7.1%]) represent the CAROLINA-COGNITION cohort. Over median 6.1 years, ACD occurred in 27.8% (449/1618, linagliptin) vs 27.6% (426/1545, glimepiride), OR 1.01 (95% CI 0.86, 1.18). Also, no differences in ACD were observed at week 160 (OR 1.07 [0.91, 1.25]), between treatments across subgroups, or for absolute cognitive changes.Conclusions/interpretationIn a large, international outcome trial in people with relatively early type 2 diabetes at elevated cardiovascular risk, no difference in risk for ACD was observed between linagliptin and glimepiride over 6.1 years.FundingThis study was sponsored by Boehringer Ingelheim.Trial registrationClinicalTrials.gov NCT01243424.

Food insecurity is an important public health concern; however, research into this phenomenon within the Netherlands is limited. Food insecurity is not solely related to individual factors, but can also be influenced by various factors in the social and physical environment. Therefore, this study aimed to identify determinants of food insecurity within the personal, social and physical environment, based on the social ecological model (SEM), and to identify their relative importance for experiencing food insecurity. The study population consisted of 307 participants living in disadvantaged neighbourhoods of the Dutch city The Hague, of which approximately one-quarter were food insecure. Participant characteristics showing bivariate associations P < 0⋅20 were placed in a predetermined level of the SEM, after which a multivariate logistic regression was performed for each level and the Nagelkerke pseudo R2 was presented. Determinants of food insecurity were BMI, gross monthly income, highest educational attainment, smoking status, diet quality, employment status, marital status and religion (P < 0⋅05). The results showed that 29⋅7 % of the total variance in food insecurity status was explained by all included determinants together. The personal, social and physical environment explained 20⋅6, 14⋅0 and 2⋅4 % of the total variance, respectively. Our findings suggest that determinants within the personal environment are most important for explaining differences in experienced food insecurity. The present study contributes to furthering the knowledge about the relative importance of the personal, social and physical environment, indicating that determinants within the personal environment may be most promising for developing targeted interventions to reduce food insecurity.

Phytoextraction could be a potential management option for diffusely Cd-Zn-Pb-polluted agricultural land in Northeast Belgium. The use of high yielding crops with a sufficiently high metal accumulation is preferred as these are expected to both gradually decontaminate the soil while generating an income through biomass valorization. To find out which high biomass crop possessed the highest and most constant (in time) phytoextraction potential on these soils, different plant species and different mutants or clones of each species, were evaluated during consecutive years. Biomass production and metal accumulation of pre-selected tobacco somaclonal variants ( L.) and pre-selected sunflower mutants ( L.) were investigated for two productivity years, while the phytoextraction potential of experimental poplar ( ) and willow ( ) in short rotation coppice (SRC) was assessed at the end of the second cutting cycle (after two times four growing seasons). The tobacco clones and the sunflower mutants showed efficient extraction of, respectively, Cd and Zn, while the highest simultaneous extractions of Cd and Zn were gained with some SRC clones. Variation in biomass production and metal accumulation were high for all crops over the years. The highest biomass production was observed for the experimental poplar clone of the crossing type ( ) with 9.9 ton DW per ha per year. The remediation period to reach legal threshold values for the pseudo-total content of Cd in this specific soil was estimated to be at least 60 years. Combining estimated phytoextraction potential and economic and environmental aspects, the SRC option is proposed as the most suitable crop for implementing metal phytoextraction in the investigated area.

Background Type 2 diabetes mellitus is associated with cognitive dysfunction and an increased risk of dementia. Linagliptin is a glucose-lowering agent of the dipeptidyl peptidase-IV (DPP-IV) inhibitor class that is of particular interest for the prevention of accelerated cognitive decline, because it may potentially benefit the brain through pleiotropic effects, beyond glucose lowering. This paper presents the design of a study that aims to establish if linagliptin is superior to the sulfonylurea glimepiride in the prevention of accelerated cognitive decline in patients with type 2 diabetes mellitus. Methods The cognition substudy is an integral part of the ongoing event-driven, randomised, double blind CARdiOvascular safety of LINAgliptin (CAROLINA®) trial, which evaluates the effect of treatment with linagliptin versus glimepiride on cardiovascular outcomes. CAROLINA® includes patients with type 2 diabetes mellitus with sub-optimal glycaemic control at elevated cardiovascular risk. The substudy will evaluate patients randomised and treated who have a baseline Mini Mental State Examination (MMSE) score ≥ 24, documented years of formal education with at least one valid cognitive assessment at baseline and during follow-up. The primary cognitive outcome is the occurrence of accelerated cognitive decline at the end of follow-up. The two treatment groups will be compared by using a logistic regression. Accelerated cognitive decline is defined as a rate of cognitive decline that falls at or below the 16th percentile of decline for the whole cohort on either the MMSE or a combined score of the trail making and verbal fluency test. Potential confounders are taken into account at an individual patient level, using a regression based index. Discussion Between December 2010 and December 2012, 6042 patients were randomised and treated with either linagliptin (5 mg) or glimepiride (1-4 mg) once daily in CAROLINA®. Cognitive tests were conducted in nearly 4500 participants at baseline and are scheduled for two subsequent assessments, after 160 weeks of follow-up and end of follow-up. This substudy of the ongoing CAROLINA® trial will establish if linagliptin is superior to glimepiride in the prevention of accelerated cognitive decline in patients with type 2 diabetes mellitus. Final results are expected in 2019. Trial registration ClinicalTrials.gov Identifier: NCT 01243424 .

Background Patients with type 2 diabetes have an increased risk of cognitive impairment which can lead to impaired diabetes self-management and an increased risk of diabetes-related complications. Routine screening for cognitive impairment in elderly patients with type 2 diabetes is therefore increasingly advocated. The aim of this study is to investigate whether people with type 2 diabetes and screen-detected cognitive impairment use acute health care services more often than patients not suspected of cognitive impairment. Methods People with type 2 diabetes ≥ 70 years were screened for cognitive impairment in primary care. Diagnoses in screen positives were established at a memory clinic. Information about acute health care use was collected for 2 years prior to and 2 years after screening and compared to screen negatives. Results 154 participants (38% female, mean age 76.7 ± 5.2 years, diabetes duration 8.7 ± 8.2 years) were included, 37 patients with cognitive impairment, 117 screen negatives. A higher percentage of participants with cognitive impairment compared to screen negative patients used acute health care services; this difference was significant for general practitioner’s out of hours services (56% versus 34% used this service over 4 years, p = 0.02). The mean number of acute health care visits was also higher in those with cognitive impairment than in screen negatives (2.2 ± 2.8 versus 1.4 ± 2.2 visits in 4 years, p < 0.05; 1.4 ± 2.2 versus 0.7 ± 1.5 visits in 2 years after screening, p = 0.03). Factors that could have played a role in this increased risk of acute health care services use were a low educational level, the presence of depressive symptoms (CES-D score ≥ 16), self-reported problems in self-care and self-reported problems in usual activities. Conclusions People with type 2 diabetes and screen-detected cognitive impairment use acute health care services more often.

We addressed the question whether chronic kidney disease (CKD) may contribute to cognitive decline in type 2 diabetes. Participants with type 2 diabetes with elevated cardiovascular risk or CKD from cognition substudies of two large trials were studied prospectively (CARMELINA: n = 2666, mean ± SD age 68.1 ± 8.7 years, CAROLINA: n = 4296; 64.7 ± 9.4 years). Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) at baseline were related to cognitive performance (Mini-Mental State Examination (MMSE) and attention and executive functioning score (A&E)) in linear regression analyses, adjusted for demographics, cardiovascular risk factors and treatment, at baseline and follow-up. CKD at baseline was more common in CARMELINA than CAROLINA (eGFR<60 in 72.6 % and 19.6 %, macroalbuminuria in 35.0 % and 4.1 %, respectively). Baseline eGFR was related to A&E in CARMELINA (b = 0.02 per 10 ml/min/1.73m2, 95%CI [0.01,0.03]). Baseline UACR was related to A&E in CAROLINA (b = −0.01 per doubling of UACR mg/g, 95%CI [−0.02,−0.002]). Baseline UACR predicted decline in A&E in CAROLINA (median 6.1 years follow-up; b = −0.01, 95%CI [−0.03,−0.0001] per doubling of UACR mg/g). eGFR and UACR were associated with A&E in two cohorts with type 2 diabetes, enriched for CKD and cardiovascular disease. The small effect size estimates indicate limited impact of kidney dysfunction on cognition in this setting. NCT01897532 NCT01243424 •Relations between chronic kidney disease and cognition in type 2 diabetes were studied.•Study cohorts were large and enriched for presence of chronic kidney disease.•Cognition was assessed longitudinally with multiple tests.•Effect sizes for relations between chronic kidney disease and cognition were small.•This indicates limited impact of chronic kidney disease on cognition in this setting.

To investigate the relationship between the diabetes-specific dementia risk score (DSDRS) and concurrent and future cognitive impairment (CI) in type 2 diabetes (T2D). DSDRS were calculated for participants with T2D aged ≥60 years from the CARMELINA-cognition substudy (ClinicalTrials.gov Identifier: NCT01897532). Cognitive assessment included Mini-Mental State Examination (MMSE) and a composite attention and executive functioning score (A&E). The relation between baseline DSDRS and probability of CI (MMSE < 24) and variation in cognitive performance was assessed at baseline (n = 2241) and after 2.5 years follow-up in patients without baseline CI (n = 1312). Higher DSDRS was associated with a higher probability of CI at baseline (OR = 1.17 per point, 95% CI 1.12–1.22) and follow-up (OR = 1.24 per point, 95% CI 1.14–1.35). Moreover, in patients without baseline CI, higher DSDRS was also associated with lower baseline cognitive performance (MMSE: F(1, 1930) = 47.07, p < .0001, R2 = 0.02); A&E z-score: (F(1, 1871) = 33.44 p < .0001, R2 = 0.02) and faster cognitive decline at follow-up (MMSE: F(3, 1279) = 38.41, p < .0001; A&E z-score: F(3, 1206) = 148.48, p < .0001). The DSDRS identifies patients with T2D at risk of concurrent as well as future CI. The DSDRS may thus be a supportive tool in screening strategies for cognitive dysfunction in patients with T2D. •The diabetes-specific dementia risk score (DSDRS) was developed to predict dementia.•Higher DSDRS are also associated with concurrent and future cognitive impairment.•The DSDRS was also shown to predict incident cognitive deficits short of dementia.•The DSDRS can advise which T2D patients to screen/monitor for cognitive problems.

Summary Phytoextraction has been reported as an economically and ecologically sound alternative for the remediation of metal‐contaminated soils. Willow is a metal phytoextractor of interest because it allows to combine a gradual contaminant removal with production of biomass that can be valorized in different ways. In this work two willow clones growing on a metal‐contaminated site were selected: ‘Belgisch Rood’ (BR) with a moderate metal extraction capacity and ‘Tora’ (TO) with a twice as high metal accumulation. All cultivable bacteria associated with both willow clones were isolated and identified using 16SrDNA ARDRA analysis followed by 16SrDNA sequencing. Further all isolated bacteria were investigated for characteristics that might promote plant growth (production of siderophores, organic acids and indol acetic acid) and for their metal resistance. The genotypic and phenotypic characterization of the isolated bacteria showed that the TO endophytic bacterial population is more diverse and contains a higher percentage of metal‐resistant plant growth promoting bacteria than the endophytic population associated with BR. We hypothesize that the difference in the metal accumulation capacity between BR and TO clones might be at least partly related to differences in characteristics of their associated bacterial population. In this work, the bacterial population associated with the willow clone ‘Belgisch Rood’ (BR), with a moderate metal extraction capacity, was compared with the bacteria associated with ‘Tora’ (TO), a willow clone with a twice as high metal accumulation. The genotypic and phenotypic bacterial characterization showed that the TO‐associated endophytes are more diverse and contain a higher percentage of metal‐resistant plant growth promoting bacteria than the endophytic population associated with BR.

ObjectivesTo assess changes in depressive symptoms and health-related quality of life (HRQOL) after screening for cognitive impairment in people with type 2 diabetes.DesignA prospective cohort study, part of the Cognitive Impairment in Diabetes (Cog-ID) study.SettingParticipants were screened for cognitive impairment in primary care. People suspected of cognitive impairment (screen positives) received a standardised evaluation at a memory clinic.ParticipantsParticipants ≥70 years with type 2 diabetes were included in Cog-ID between August 2012 and September 2014, the current study includes 179 patients; 39 screen positives with cognitive impairment, 56 screen positives without cognitive impairment and 84 participants not suspected of cognitive impairment during screening (screen negatives).Outcome measuresDepressive symptoms and HRQOL assessed with the Center for Epidemiologic Studies Depression Scale (CES-D), 36-Item Short-Form Health Survey, European Quality of Life-5 Dimensions questionnaire and the EuroQol Visual Analogue Scale. Outcomes were assessed before the screening, and 6 and 24 months after screening. An analysis of covariance model was fitted to assess differences in score changes among people diagnosed with cognitive impairment, screen negatives and screen positives without cognitive impairment using a factor group and baseline score as a covariate.ResultsOf all participants, 60.3% was male, mean age was 76.3±5.0 years, mean diabetes duration 13.0±8.5 years. At screening, participants diagnosed with cognitive impairment had significantly more depressive symptoms and a worse HRQOL than screen negatives. Scores of both groups remained stable over time. Screen positives without cognitive impairment scored between the other two groups at screening, but their depressive symptoms decreased significantly during follow-up (mean CES-D: −3.1 after 6 and −2.1 after 24 months); their HRQOL also tended to improve.ConclusionsDepressive symptoms are common in older people with type 2 diabetes. Screening for and a subsequent diagnosis of cognitive impairment will not increase depressive symptoms.

Purpose The purpose of this study was to investigate if bacteria with beneficial properties that were isolated from willow growing on a metal-contaminated site can be further equipped with genes coding for a specific degradation pathway to finally obtain transconjugants that can be inoculated in willow to improve phytoremediation efficiency of mixed contaminations. Materials and methods Cultivable rhizosphere bacteria and root endophytes were isolated from willow (cv. Tora) growing on a metal-contaminated soil. All isolated strains were tested for their metal resistance and potential to promote plant growth. The two most promising strains were selected and were equipped with the pTOM plasmid coding for toluene degradation. Both transconjugants were inoculated separately and combined in willow cuttings exposed to mixed Cd–toluene contamination, and their effect on phytotoxicity, Cd uptake, and toluene evapotranspiration was evaluated. Results and discussion Many of the isolated strains tested positive for the production of siderophores, organic acids, and indole acetic acid (IAA) and showed increased Cd resistance. The Cd-resistant, siderophore-producing rhizosphere strain Burkholderia sp. HU001 and the Cd-resistant root endophyte Pseudomonas sp. HU002, able to produce siderophores, organic acids, and IAA, were selected as receptors for conjugation with the toluene-degrading Burkholderia vietnamiensis BU61 as a donor of the pTOM-TCE plasmid. Although inoculation with the individual transconjugant strains had no effect on plant growth and negatively affected Cd uptake, their combined inoculation resulted in an increased shoot biomass upon Cd–toluene exposure did not affect Cd uptake and strongly reduced evapotranspiration of toluene to the atmosphere. Conclusions In this study, inoculation of willow with a consortium of plant-associated bacteria equipped with the appropriate characteristics resulted in an improved phytoremediation of a mixed Cd–toluene contamination: the degradation of toluene was improved leading to a decreased toxicity and evapotranspiration, while Cd uptake and translocation were not affected.