The mediating role of comorbid conditions in the association between type 2 diabetes and cognition: a cross-sectional observational study using the UK Biobank cohort

Aims: Using the UK Biobank cohort, a large sample of middle aged and older adults in the UK, the present study aimed to examine the cross-sectional association between type 2 diabetes and cognition and to assess the hypothesised mediating role of common comorbid conditions, whilst controlling for important demographic and lifestyle factors. Methods: Using regression models and general structural equation models, we examined the cross-sectional association between type 2 diabetes status and: fluid intelligence; reaction time; visual memory; digit span and prospective memory; and the hypothesised mediating role of common comorbid conditions: visceral obesity; sleep problems; macrovascular problems; respiratory problems,; cancer and depressive symptoms in 47,468 participants from the UK Biobank cohort, of whom 1,831 have type 2 diabetes. We controlled for ethnicity, sex, age, deprivation, smoking status, alcohol consumption, physical activity levels and use of diabetes medication. Results: Participants with type 2 diabetes had a significantly shorter digit span, b = -0.14, 99.2% CIs [-0.27, -0.11] than those without type 2 diabetes. Those with type 2 diabetes did not differ from those without type 2 diabetes on fluid intelligence, reaction time, visual memory and prospective memory. The associations that do exist between type 2 diabetes and cognition are consistently mediated via macrovascular problems, depressive symptoms, and to a lesser extent visceral obesity. Respiratory problems, sleep disturbances and cancer did not mediate the association between type 2 diabetes status and measures of cognition. Conclusions: Comorbid conditions explain some of the observed association between type 2 diabetes and cognitive deficits. This suggests that prevention, management or treatment of these comorbid conditions may be important to reduce the likelihood of cognitive decline. Treatment studies with long follow-ups are needed to examine this. Tweet: Comorbid conditions explain the association between type 2 diabetes and cognitive deficits. Prevention, management or treatment of these comorbid conditions may prevent or delay the onset of cognitive decline in people with type 2 diabetes

Kinetics and energetics of the translocation of maltose binding protein folding mutants

Protein translocation in Escherichia coli is mediated by the translocase that, in its minimal form, comprises a protein-conducting pore (SecYEG) and a motor protein (SecA). The SecYEG complex forms a narrow channel in the membrane that allows passage of secretory proteins (preproteins) in an unfolded state only. It has been suggested that the SecA requirement for translocation depends on the folding stability of the mature preprotein domain. Here we studied the effects of the signal sequence and SecB on the folding and translocation of folding stabilizing and destabilizing mutants of the mature maltose binding protein (MBP). Although the mutations affect the folding of the precursor form of MBP, these are drastically overruled by the combined unfolding stabilization of the signal sequence and SecB. Consequently, the translocation kinetics, the energetics and the SecA and SecB dependence of the folding mutants are indistinguishable from those of wild-type preMBP. These data indicate that unfolding of the mature domain of preMBP is likely not a rate-determining step in translocation when the protein is targeted to the translocase via SecB. (c) 2008 Elsevier Ltd. All rights reserved

Motivation: key to a healthy lifestyle in people with diabetes? Current and emerging knowledge and applications

Aim Motivation to take up and maintain a healthy lifestyle is key to diabetes prevention and management. Motivations are driven by factors on the psychological, biological and environmental levels, which have each been studied extensively in various lines of research over the past 25 years. Here, we analyse and reflect on current and emerging knowledge on motivation in relation to lifestyle behaviours, with a focus on people with diabetes or obesity. Structured according to psychological, (neuro‐)biological and broader environmental levels, we provide a scoping review of the literature and highlight frameworks used to structure motivational concepts. Results are then put in perspective of applicability in (clinical) practice. Results Over the past 25 years, research focusing on motivation has grown exponentially. Social–cognitive and self‐determination theories have driven research on the key motivational concepts ‘self‐efficacy’ and ‘self‐determination’. Neuro‐cognitive research has provided insights in the processes that are involved across various layers of a complex cortical network of motivation, reward and cognitive control. On an environmental – more upstream – level, motivations are influenced by characteristics in the built, social, economic and policy environments at various scales, which have provided entry points for environmental approaches influencing behaviour. Conclusions Current evidence shows that motivation is strongly related to a person's self‐efficacy and capability to initiate and maintain healthy choices, and to a health climate that supports autonomous choices. Some approaches targeting motivations have been shown to be promising, but more research is warranted to sustainably reduce the burden of diabetes in individuals and populations

Measurement invariance testing of the patient health questionnaire-9 (PHQ-9) across people with and without diabetes mellitus from the NHANES, EHMS and UK Biobank datasets

Background: The prevalence of depression is higher among those with diabetes than in the general population. The Patient Health Questionnaire (PHQ-9) is commonly used to assess depression in people with diabetes, but measurement invariance of the PHQ-9 across groups of people with and without diabetes has not yet been investigated. Methods: Data from three independent cohorts from the USA (n=1,886 with diabetes, n=4,153 without diabetes), Quebec, Canada (n= 800 with diabetes, n= 2,411 without diabetes), and the UK (n=4,981 with diabetes, n=145,570 without diabetes), were used to examine measurement invariance between adults with and without diabetes. A series of multiple group confirmatory factor analyses were performed, with increasingly stringent model constraints applied to assess configural, equal thresholds, and equal thresholds and loadings invariance, respectively. One-factor and two-factor (somatic and cognitive-affective items) models were examined. Results: Results demonstrated that the most stringent models, testing equal loadings and thresholds, had satisfactory model fit in the three cohorts for one-factor models (RMSEA = .063 or below and CFI = .978 or above) and two-factor models (RMSEA = .042 or below and CFI = .989 or above). Limitations: Data were from Western countries only and we could not distinguish between type of diabetes. Conclusions: Results provide support for measurement invariance between groups of people with and without diabetes, using either a one-factor or a two-factor model. While the two-factor solution has a slightly better fit, the one-factor solution is more parsimonious. Depending on research or clinical needs, both factor structures can be used

Relationship between parental feeding practices and neural responses to food cues in adolescents

Social context, specifically within the family, influences adolescent eating behaviours and thus their health. Little is known about the specific mechanisms underlying the effects of parental feeding practices on eating. We explored relationships between parental feeding practices and adolescent eating habits and brain activity in response to viewing food images. Fifty- seven adolescents (15 with type 2 diabetes mellitus, 21 obese and 21 healthy weight controls) underwent fMRI scanning whilst viewing images of food or matched control images. Participants completed the Kids Child Feeding Questionnaire, the Childrens’ Dutch Eating Behaviour Questionnaire (DEBQ) and took part in an observed meal. Parents completed the Comprehensive Feeding Practices Questionniare and the DEBQ. We were particularly interested in brain activity in response to food cues that was modulated by different feeding and eating styles. Healthy-weight participants increased activation (compared to the other groups) to food in proportion to the level of parental restriction in visual areas of the brain such as right lateral occipital cortex (LOC), right temporal occipital cortex, left occipital fusiform gyrus, left lateral and superior LOC. Adolescents with type 2 diabetes mellitus had higher activation (compared to the other groups) with increased parental restrictive feeding in areas relating to emotional control, attention and decision-making, such as posterior cingulate, precuneus, frontal operculum and right middle frontal gyrus. Participants with type 2 diabetes mellitus also showed higher activation (compared to the other groups) in the left anterior intraparietal sulcus and angular gyrus when they also reported higher self restraint. Parental restriction did not modulate food responses in obese participants, but there was increased activity in visual (visual cortex, left LOC, left occipital fusiform gyrus) and reward related brain areas (thalamus and parietal operculum) in response to parental teaching and modelling of behaviour. Parental restrictive feeding and parental teaching and modelling affected neural responses to food cues in different ways, depending on motivations and diagnoses, illustrating a social influence on neural responses to food cues

Examining evidence for behavioural mimicry of parental eating by adolescent females. An observational study

Behavioural mimicry is a potential mechanism explaining why adolescents appear to be influenced by their parents' eating behaviour. In the current study we examined whether there is evidence that adolescent females mimic their parents when eating. Videos of thirty-eight parent and female adolescent dyads eating a lunchtime meal together were examined. We tested whether a parent placing a food item into their mouth was associated with an increased likelihood that their adolescent child would place any food item (non-specific mimicry) or the same item (specific mimicry) in their mouth at three different time frames, namely, during the same second or within the next fifteen seconds (+15), five seconds (+5) or two second (+2) period. Parents and adolescents' overall food intake was positively correlated, whereby a parent eating a larger amount of food was associated with the adolescent eating a larger meal. Across all of the three time frames adolescents were more likely to place a food item in their mouth if their parent had recently placed that same food item in their mouth (specific food item mimicry); however, there was no evidence of non-specific mimicry. This observational study suggests that when eating in a social context there is evidence that adolescent females may mimic their parental eating behaviour, selecting and eating more of a food item if their parent has just started to eat that food

Microstructural abnormalities in white and gray matter in obese adolescents with and without type 2 diabetes

Aims/hypotheses: In adults, type 2 diabetes and obesity have been associated with structural brain changes, even in the absence of dementia. Some evidence suggested similar changes in adolescents with type 2 diabetes but comparisons with a non-obese control group have been lacking. The aim of the current study was to examine differences in microstructure of gray and white matter between adolescents with type 2 diabetes, obese adolescents and healthy weight adolescents. Methods: Magnetic resonance imaging data were collected from 15 adolescents with type 2 diabetes, 21 obese adolescents and 22 healthy weight controls. Volumetric differences in the gray matter between the three groups were examined using voxel based morphology, while tract based spatial statistics was used to examine differences in the microstructure of the white matter. Results: Adolescents with type 2 diabetes and obese adolescents had reduced gray matter volume in the right hippocampus, left putamen and caudate, bilateral amygdala and left thalamus compared to healthy weight controls. Type 2 diabetes was also associated with significant regional changes in fractional anisotropy within the corpus callosum, fornix, left inferior fronto-occipital fasciculus, left uncinate, left internal and external capsule. Fractional anisotropy reductions within these tracts were explained by increased radial diffusivity, which may suggest demyelination of white matter tracts. Mean diffusivity and axial diffusivity did not differ between the groups. Conclusion/interpretation: Our data shows that adolescent obesity alone results in reduced gray matter volume and that adolescent type 2 diabetes is associated with both white and gray matter abnormalities

Self-Monitoring of Blood Pressure in Hypertension: A UK Primary Care Survey

This study aimed to determine the prevalence of Self-Monitoring Blood Pressure amongst people with hypertension using a cross-sectional survey. Of the 955 who replied (53%), 293 (31%) reported that they self-monitored blood pressure. Nearly 60% (198/331) self-monitored at least monthly. Diabetic patients monitoring their blood glucose were five times more likely than those not monitoring to monitor their blood pressure. Self-monitoring is less common in the UK than internationally, but is practiced by enough people to warrant greater integration into clinical practice

F1F0 ATP synthase subunit c is a substrate of the novel YidC pathway for membrane protein biogenesis

The Escherichia coli YidC protein belongs to the Oxa1 family of membrane proteins that have been suggested to facilitate the insertion and assembly of membrane proteins either in cooperation with the Sec translocase or as a separate entity. Recently, we have shown that depletion of YidC causes a specific defect in the functional assembly of F(1)F(0) ATP synthase and cytochrome o oxidase. We now demonstrate that the insertion of in vitro–synthesized F(1)F(0) ATP synthase subunit c (F(0)c) into inner membrane vesicles requires YidC. Insertion is independent of the proton motive force, and proteoliposomes containing only YidC catalyze the membrane insertion of F(0)c in its native transmembrane topology whereupon it assembles into large oligomers. Co-reconstituted SecYEG has no significant effect on the insertion efficiency. Remarkably, signal recognition particle and its membrane-bound receptor FtsY are not required for the membrane insertion of F(0)c. In conclusion, a novel membrane protein insertion pathway in E. coli is described in which YidC plays an exclusive role

Comment on Young-Hyman et al. Psychosocial care for people with diabetes: A position statement of the American Diabetes Association. Diabetes Care 2016;39:2126–2140

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