Blood glucose testing and primary prevention of diabetes mellitus type 2 - evaluation of the effect of evidence based patient information

<p>Abstract</p> <p>Background</p> <p>Evidence-based patient information (EBPI) has been recognised as important tool for informed choice in particular in the matter of preventive options. An objective, on the best scientific evidence-based consumer information about subthreshold elevated blood glucose levels (impaired fasting glucose and impaired glucose tolerance) and primary prevention of diabetes, is not available yet. Thus we developed a web-based EBPI and aim to evaluate its effects on informed decision making in people 50 years or older.</p> <p>Methods/Design</p> <p>We conduct a web-based randomised-controlled trial to evaluate the effect of information about elevated blood glucose levels and diabetes primary prevention on five specific outcomes: (i) knowledge of elevated blood glucose level-related issues (primary outcome); (ii) attitudes to a metabolic testing; (iii) intention to undergo a metabolic testing; (iv) decision conflict; (v) satisfaction with the information. The intervention group receives a specially developed EBPI about subthreshold elevated blood glucose levels and diabetes primary prevention, the control group information about this topic, available in the internet.</p> <p>The study population consists of people between 50 and 69 years of age without known diabetes. Participants will be recruited via the internet page of the cooperating health insurance company, Techniker Krankenkasse (TK), and the internet page of the German Diabetes Centre. Outcomes will be measured through online questionnaires. We expect better informed participants in the intervention group.</p> <p>Discussion</p> <p>The design of this study may be a prototype for other web-based prevention information and their evaluation.</p> <p>Trial registration</p> <p>Current Controlled Trial: ISRCTN22060616.</p

T cells at the site of autoimmune inflammation show increased potential for trogocytosis

CD4+ T cells acquire membrane fragments from antigen-presenting-cells via a process termed trogocytosis. Identifying which CD4+ T cells undergo trogocytosis in co-culture with Ag-loaded APC can enrich for antigen-reactive T cells without knowledge of their fine specificity or cytokine-production profiles. We sought to assess the suitability of this method to identify disease relevant effector and regulatory T cells during autoimmune inflammation. Trogocytosis efficiently identified MBP-reactive T cells in vitro and ex-vivo following immunization. However, Foxp3+ regulatory T cells constitutively displayed a higher rate of trogocytosis than their Foxp3- counterparts which limits the potential of trogocytosis to identify antigen-reactive Treg cells. During inflammation a locally elevated rate of trogocytosis (seen in both effector and regulatory T cells isolated from the inflamed CNS) precludes the use of trogocytosis as a measure of antigenic reactivity among cells taken from inflammatory sites. Our results indicate trogocytosis detection can enrich for Ag-reactive conventional T cells in the periphery but is limited in its ability to identify Ag-reactive Treg or T effector cells at sites of inflammation. Increased trogocytosis potential at inflammatory sites also draws into the question the biological significance of this phenomenon during inflammation, in Treg mediated suppression and for the maintenance of tolerance in health and disease

Detection of Ag-reactive T cells by membrane exchange after in vivo priming.

<p>(A–E) Tg4 CD4+ T cells were transferred to B10.PL hosts 1 day prior to immunisation with CFA-only or CFA+Ac1-9 4Tyr (control mice were left unimmunised). 5 days after immunisation DLN cells were removed CD4+ T cells were purified and co-cultured with biotinylated BMDC in the presence or absence of 4Tyr (A). (B) The proportion of Tg4 T cells in the DLN of immunised VS non-immunised mice (shown as percentage of CD4+). C) Membrane acquisition within the whole CD4+ population of cells co-cultured with BMDC in the presence or absence of 4Tyr. Membrane acquisition by host (D) and donor (E) CD4+ cells co-cultured with BMDC in the presence or absence of 4Tyr. Each data point represents cells from an individual mouse. *<i>p</i><0.05. ***, <i>p</i><0.001.</p

MBP-reactive T cells rapidly acquire plasma membrane fragments from APC upon activation.

<p>(A–E) Biotinylated B10.PL splenocytes (CD45.1−) were co-cultured with Tg4 T cells (CD45.1+) in the presence or absence of graded concentrations of Ac1-9(4Tyr) membrane transfer to CD45.1+ Tg4 T cells was detected by staining with SA-APC. (B) Acquisition of biotinylated membrane fragments by Tg4 T cells co-cultured in the absence (middle panel) or presence (right hand panel) of 1 µM 4Tyr for 1 h. (C) Acquisition of biotinylated membrane fragments by Tg4 T cells across a dose range of 4Tyr after overnight culture. (D) Detection of biotinylated membrane fragments and CD69 on Tg4T cells cultured in the presence or absence of 4Tyr. E) CD69 expression in SA+ Tg4 T cells in the presence or absence of Ag, error bars are SD, ***, <i>p</i><0.001.Data shown is from one experiment representative of 3 similar experiments.</p

An integrated psychosomatic treatment program for people with diabetes (psy-PAD)

BACKGROUND: Many people with diabetes have permanently elevated blood sugar concentrations and a high level of diabetes-related psychological stress, also called “diabetes distress.” In clinical practice, diabetes distress is often an impediment to successful self-management. psy-PAD is a psychodynamically oriented short-term therapy program whose goal is to reduce diabetes distress and improve glycemic control. METHODS: A randomized controlled trial was conducted with 143 patients with either type 1 or type 2 diabetes who were being treated in eleven specialized diabetological practices. psy-PAD in the intervention group (eight sessions) was compared with optimized standard care as the control condition. The inclusion criteria were HbA1c ≥ 7.5% combined with diabetes distress (PAID >35, or doctor’s determination). The primary endpoint was the HbA1c at six months (t(1)). Diabetes-related distress (PAID), depressive symptoms (HADS-D, PHQ-9), anxiety symptoms (HADS-A), health-related quality of life (SF-36), panic (short form of the PHQ-D), body mass index (BMI), and triglyceride levels were secondary endpoints. Follow-ups were conducted at six (t(1)) and 12 months (t(2)) (trial registration: DRKS00003247). RESULTS: The intergroup comparison at t(1) revealed a significant, clinically relevant reduction of HbA1c by -0.53 percentage points (95% confidence interval [-0.89; -0.16], p = 0.005). The secondary analyses revealed relevant differences in the point estimators for diabetes distress at t(1) and t(2), depressive symptoms at t(2) and BMI at t(1). CONCLUSION: For people with diabetes and diabetes distress who do not achieve satisfactory glycemic control despite intensive treatment in specialized diabetological practices, integrated psychosomatic-psychotherapeutic treatment can lower blood sugar levels over the intermediate term and also reduce diabetes distress and depressive symptoms over a one-year period

Risk for high depressive symptoms in diagnosed and previously undetected diabetes: 5-year follow-up results of the Heinz Nixdorf Recall study.

OBJECTIVE: The objective of this study was to determine the risk for the development of high depressive symptoms in study participants with diagnosed and previously undetected diabetes mellitus compared to those without diabetes in a prospective population-based cohort study in Germany. METHODS: We estimated the 5-year cumulative incidence of high depressive symptoms in participants without high depressive symptoms at baseline (n = 3,633, 51.4% men, mean age (SD) 59.1 (7.6) years, 7.0% diagnosed diabetes, 5.3% previously undetected diabetes) from the population-based Heinz Nixdorf Recall study. Diabetes was assessed by self-report, medication, and blood glucose. High depressive symptoms were assessed using CES-D. We calculated odds ratios and their corresponding 95% confidence interval, using multiple logistic regression analyses. RESULT: Cumulative 5-year incidences (95% CI) of high depressive symptoms in participants with diagnosed, undetected, and without diabetes were 7.1 (4.2-10.9), 4.1 (1.8-8.0), and 6.5 (5.6-7.4), respectively. The age-sex-adjusted OR for developing high depressive symptoms was 1.22 (0.74-2.03) in participants with diagnosed compared to those without diabetes, and 1.00 (0.59-1.68) after adjustment for BMI, physical activity, education, stroke, and myocardial infarction. The age-sex adjusted OR for developing high depressive symptoms in participants with previously undetected diabetes compared to those without diabetes was 0.72; 0.35-1.48; and fully adjusted 0.62; 0.30-1.30. CONCLUSION: We found no significant associations, maybe due to low power. However, our results are in line with a recent meta-analysis suggesting that risk of developing high depressive symptoms in patients with diagnosed diabetes may be moderately higher than in those without diabetes, and that comorbidity may explain in part this association. In participants with previously undetected diabetes, this first longitudinal study indicates that the risk is not increased or may even be decreased. These results support the hypothesis that high depressive symptoms develop due to diabetes-related burden and comorbidity and not due to hyperglycemia or hyperinsulinaemia

Risk for High Depressive Symptoms in Diagnosed and Previously Undetected Diabetes: 5-Year Follow-Up Results of the Heinz Nixdorf Recall Study

Objective The objective of this study was to determine the risk for the development of high depressive symptoms in study participants with diagnosed and previously undetected diabetes mellitus compared to those without diabetes in a prospective population-based cohort study in Germany. Methods We estimated the 5-year cumulative incidence of high depressive symptoms in participants without high depressive symptoms at baseline (n = 3,633, 51.4% men, mean age (SD) 59.1 (7.6) years, 7.0% diagnosed diabetes, 5.3% previously undetected diabetes) from the population-based Heinz Nixdorf Recall study. Diabetes was assessed by self-report, medication, and blood glucose. High depressive symptoms were assessed using CES-D. We calculated odds ratios and their corresponding 95% confidence interval, using multiple logistic regression analyses. Result Cumulative 5-year incidences (95% CI) of high depressive symptoms in participants with diagnosed, undetected, and without diabetes were 7.1 (4.2–10.9), 4.1 (1.8–8.0), and 6.5 (5.6–7.4), respectively. The age-sex-adjusted OR for developing high depressive symptoms was 1.22 (0.74–2.03) in participants with diagnosed compared to those without diabetes, and 1.00 (0.59–1.68) after adjustment for BMI, physical activity, education, stroke, and myocardial infarction. The age-sex adjusted OR for developing high depressive symptoms in participants with previously undetected diabetes compared to those without diabetes was 0.72; 0.35–1.48; and fully adjusted 0.62; 0.30–1.30. Conclusion We found no significant associations, maybe due to low power. However, our results are in line with a recent meta-analysis suggesting that risk of developing high depressive symptoms in patients with diagnosed diabetes may be moderately higher than in those without diabetes, and that comorbidity may explain in part this association. In participants with previously undetected diabetes, this first longitudinal study indicates that the risk is not increased or may even be decreased. These results support the hypothesis that high depressive symptoms develop due to diabetes-related burden and comorbidity and not due to hyperglycemia or hyperinsulinaemia

Baseline participant characteristics, stratified by diabetes status.

1<p>at baseline: ever diagnosed by a physician.</p

Multiple logistic regression models analyzing the relationship between diagnosed and undetected diabetes and the development of high depressive symptoms.

1<p>Separate logistic regression models on different subpopulations.</p><p>²Baseline assessment: ever diagnosed by a physician, few missings (19 resp. 32 overall, cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056300#pone-0056300-t001" target="_blank">table 1</a>) defined as “no”.</p