There are marked differences between countries with regard to reimbursement decision-making, yet few studies have tried to understand this process and its consequences by a detailed analysis of the local context and decision-making structure. This article describes reimbursement decision-making and subsequent prescribing patterns of new pharmaceuticals by means of a case study on glitazones in treatment of type 2 diabetes mellitus patients in Denmark. The study shows that institutional arrangements, providing the context in which evidence is used, are (...) highly important for understanding the reimbursement decision-making process. In particular the Danish Medicines Agency (DMA) has shaped the decision to reimburse glitazones on the basis of physician-mediated requests of individual patients. Relatively few patients have been prescribed glitazones since their introduction in 2000, suggesting that individual reimbursement may be an effective instrument in controlling overall expenditure of selected pharmaceuticals, although in the case of glitazones this has likely been achieved at the expense of equality in access to the products. The discussion focuses on the generalizability of the findings to both other pharmaceuticals in the individual reimbursement scheme in Denmark, and to other countries that are trying to balance the need to control overall pharmaceutical care expenditure with the need to secure equality in access to new drugs with therapeutic added value. (shrink)

ObjectiveType 2 diabetes mellitus (T2DM) is a high risk of cognitive decline and dementia, but the underlying mechanisms are not yet clearly understood. This study aimed to explore the functional connectivity (FC) and topological properties among whole brain networks and correlations with impaired cognition and distinguish T2DM from healthy controls (HC) to identify potential biomarkers for cognition abnormalities.MethodsA total of 80 T2DM and 55 well-matched HC were recruited in this study. Subjects’ clinical data, neuropsychological tests and resting-state functional (...) magnetic resonance imaging data were acquired. Whole-brain network FC were mapped, the topological characteristics were analyzed using a graph-theoretic approach, the FC and topological characteristics of the network were compared between T2DM and HC using a general linear model, and correlations between networks and clinical and cognitive characteristics were identified. The support vector machine (SVM) model was used to identify differences between T2DM and HC.ResultsIn patients with T2DM, FC was higher in two core regions [precuneus/posterior cingulated cortex (PCC)_1 and later prefrontal cortex_1] in the default mode network and lower in bilateral superior parietal lobes (within dorsal attention network), and decreased between the right medial frontal cortex and left auditory cortex. The FC of the right frontal medial-left auditory cortex was positively correlated with the Montreal Cognitive Assessment scales and negatively correlated with the blood glucose levels. Long-range connectivity between bilateral auditory cortex was missing in the T2DM. The nodal degree centrality and efficiency of PCC were higher in T2DM than in HC (P < 0.005). The nodal degree centrality in the PCC in the SVM model was 97.56% accurate in distinguishing T2DM patients from HC, demonstrating the reliability of the prediction model.ConclusionFunctional abnormalities in the auditory cortex in T2DM may be related to cognitive impairment, such as memory and attention, and nodal degree centrality in the PCC might serve as a potential neuroimaging biomarker to predict and identify T2DM. (shrink)

Type 2 diabetes mellitus is related to a variety of cognitive impairments that may even progress to dementia. Studies have found the angular gyrus is a cross-modal integration hub that is involved in a variety of cognitive processes. However, few studies have focused on the patterns of resting-state functional connections of the AG in patients with T2DM. This study explored the functional connection between the AG and the whole brain and the relationship between the FC and clinical/cognitive variables (...) in patients with T2DM. 44 patients with T2DM and 43 sex-, age-, and education-matched healthy controls underwent resting-state fMRI and received neuropsychological assessments. Compared with the control group, the T2DM group showed abnormal rsFCs between the AG and multiple brain regions. The FC between the left AG and the left medial temporal lobe in the T2DM group was positively correlated with scores on the Montreal Cognitive Assessment, after a Bonferroni correction. Collectively, patients with T2DM have abnormal FCs between the AG and extensive brain regions that may be related to various cognitive processes. (shrink)

Children diagnosed with type 1 diabetes mellitus (T1DM) are at risk for neurocognitive sequelae, including impaired attention functioning. The specific nature of the cognitive deficit varies; current literature underscores early age of diabetes diagnosis and increased disease duration as primary risk factors for this neurocognitive decline. Forty-three children with T1DM were evaluated for Attention Deficit/Hyperactivity Disorder (ADHD) symptomatology using the MOXO continuous performance test (MOXO-CPT) performed during a routine outpatient evaluation. The study cohort demonstrated a significant decline (...) in all four domains of attention functioning. The effect was most pronounced with early age at T1DM diagnosis, a longer disease duration and with poorer glycemic control (represented by higher HbA1c values). With increased disease duration (of 5 plus years), acute hyperglycemia was associated with inattention in the real-time setting. These findings highlight the need for routine screening of neurocognitive function in children with T1DM so that early intervention can be employed during this crucial period of cognitive development. (shrink)

We propose protein localization dependent signal activation (PLDSA) as a model to describe pre‐existing protein partitioning between the cytosol, and membrane surface, as a means to modulate signal activation, specificity, and robustness. We apply PLDSA to explain possible molecular links between type II diabetes mellitus (T2DM) and Alzheimer's disease (AD) by describing Ca+2‐mediated interactions between the Src non‐receptor tyrosine kinase and p52Shc adaptor protein. We suggest that these interactions may serve as a contributing factor to disease development and (...) progression. In particular, we propose that signaling response is regulated, in part, by Ca+2‐mediated partitioning of lipid‐bound and soluble forms of Src and p52shc. Thus, protein‐protein interactions that drive signaling in response to extracellular ligand binding are also mediated by partitioning of signaling proteins between membrane‐bound and soluble populations. We propose that PLDSA effects may explain, in part, the evolutionary basis of promiscuous protein interaction domains and their importance in cellular function. (shrink)

Type 2 diabetes mellitus is associated with cognitive impairment in many domains. There are several pieces of evidence that changes in neuronal neuropathies and metabolism have been observed in T2DM. Structural and functional MRI shows that abnormal connections and synchronization occur in T2DM brain circuits and related networks. Neuroplasticity and energy metabolism appear to be principal effector systems, which may be related to amyloid beta deposition, although there is no unified explanation that includes the complex etiology of T2DM (...) with cognitive impairment. Herein, we assume that cognitive impairment in diabetes may lead to abnormalities in neuroplasticity and energy metabolism in the brain, and those reflected to MRI structural connectivity and functional connectivity, respectively. (shrink)

BackgroundWomen with gestational diabetes mellitus have higher rates of perinatal depressive symptoms, compared to healthy pregnant women. In the general population, maternal depressive symptoms have been associated with infant sleep difficulties during the first year postpartum. However, there is lack of data on infants of mothers with gestational diabetes mellitus.MethodsThis study assessed the prospective associations between maternal perinatal depressive symptoms and infant sleep outcomes. The study population consisted of 95 Swiss women with gestational diabetes (...) class='Hi'>mellitus and their infants, enrolled in the control group of the MySweetheart trial. Perinatal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale at the first gestational diabetes mellitus visit during pregnancy, at 6–8 weeks postpartum, and 1 year postpartum. The Brief Infant Sleep Questionnaire was used to assess infant sleep at 1 year postpartum. Relevant maternal and infant measurements were collected or extracted from medical records as covariates.ResultsAntenatal maternal depressive symptoms at the first gestational diabetes mellitus visit were inversely associated with infant nocturnal sleep duration at 1 year postpartum. This association became marginally significant when covariates were added. Maternal depressive symptoms at 6–8 weeks postpartum were negatively and prospectively associated with infant nocturnal sleep duration, even when controlling for covariates. The association between maternal depressive symptoms and maternal perception of infant sleep as not a problem at all was significant at 1 year postpartum, although it became non-significant when controlling for appropriate covariates. No other significant associations were found.LimitationsThis study solely included measures derived from self-report validated questionnaires.ConclusionOur findings suggest it is of utmost importance to support women with gestational diabetes mellitus as a means to reduce the detrimental impact of maternal perinatal depressive symptoms on infant sleep, given its predictive role on infant metabolic health. (shrink)

Since the 1990s, glycated haemoglobin (HbA1C) has been the gold standard for monitoring glycaemic control in people diagnosed as having either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Discussions are underway about diagnosing diabetes mellitus on the basis of HbA1C titres and using HbA1C tests to screen for T2DM. These discussions have focused on the relative benefits for individual patients, with some attention directed towards reduced costs to healthcare systems and (...) benefits to society. We argue that there are strong ethical reasons for adopting HbA1C-based diagnosis and T2DM screening that have not yet been articulated. The rationale includes the differential impact of HbA1C-based diabetic testing on disadvantaged groups, and what we are beginning to learn about HbA1C vis-à-vis population health. Although it is arguable that screening must primarily benefit the individual, using HbA1C to diagnose and screen for T2DM may promote a more just distribution of health resources and lead to advances in investigating, monitoring and tackling the social determinants of health. (shrink)

Cardiovascular disease is a major complication of type 2 diabetes mellitus. In addition to traditional risk factors, psychological determinants play an important role in CVD risk. This study applied Deep Neural Network to develop a CVD risk prediction model and explored the bio-psycho-social contributors to the CVD risk among patients with T2DM. From 2017 to 2020, 834 patients with T2DM were recruited from the Department of Endocrinology, Affiliated Hospital of Harbin Medical University, China. In this cross-sectional study, the (...) patients' bio-psycho-social information was collected through clinical examinations and questionnaires. The dataset was randomly split into a 75% train set and a 25% test set. DNN was implemented at the best performance on the train set and applied on the test set. The receiver operating characteristic curve analysis was used to evaluate the model performance. Of participants, 272 were diagnosed with CVD. The developed ensemble model for CVD risk achieved an area under curve score of 0.91, accuracy of 87.50%, sensitivity of 88.06%, and specificity of 87.23%. Among patients with T2DM, the top five predictors in the CVD risk model were body mass index, anxiety, depression, total cholesterol, and systolic blood pressure. In summary, machine learning models can provide an automated identification mechanism for patients at CVD risk. Integrated treatment measures should be taken in health management, including clinical care, mental health improvement, and health behavior promotion. (shrink)

BackgroundAging and type 2 diabetes mellitus are important risk factors for the development of cognitive deterioration and dementia. The objective of this research was to investigate the effects of an exercise intervention on cognitive function in older T2DM patients.MethodsEight literature databases were searched from inception to 20 January 2022. The researchers examined randomized controlled trials that evaluated the impact of exercise on the cognitive performance of older T2DM patients. The Cochrane risk-of-bias tool for RCTs was used to assess (...) each study. The quality of evidence was assessed using the GRADE approach. The mini-mental state examination, Modified MMSE, and Montreal cognitive assessment were used to evaluate the cognitive outcomes. We performed a subgroup analysis with stratification according to exercise intervention modality, duration, and cognitive impairment.ResultsFive trials were eligible, with a total of 738 T2DM patients. The combined findings revealed that exercise improved global cognitive function significantly. In the studies that were included, no relevant adverse events were reported.ConclusionExercise is beneficial in improving global cognitive function in older adults with T2DM. Studies with bigger sample sizes and higher quality are additionally expected to draw more definite conclusions.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42022296049]. (shrink)

Previous research has documented that type 2 diabetes mellitus is associated with cognitive impairment. Psychological variables were repeatedly investigated to understand why T2DM patients are poorly active, despite standards of medical care recommends performing aerobic and resistance exercise regularly and reducing the amount of time spent sitting. This exploratory study aims to investigate how affective variables as thoughts, feelings, and individuals’ stage of exercise adoption can modulate low cognitive performances during an experimental procedure based on exercise. The Exercise (...) Thoughts Questionnaire, Exercise-Induced Feeling Scale, and Physical Activity Stage of Change were administered to a sample of 12 T2DM patients. The Bivalent Shape Task alone, BST with exercise [control exercise recovery + BST], and BST with metaboreflex [post-exercise muscle ischemia + BST] were used as mental task, and response time to congruent, incongruent, and neutral stimuli was recorded. Concomitant cerebral oxygenation was evaluated by near-infrared spectroscopy. As expected, T2DM patients performed significantly better when the stimulus was presented in congruent trials. In the CER + BST session, T2DM patients showed longer reaction time to incongruent trials than in the PEMI + BST and BST alone sessions. Positive feelings toward exercise seem to modulate cognitive performances in high challenging task only if T2DM patients were conscious to play exercise. These results could provide some insights for health intervention targeting exercise for patients with T2DM in order to enhance cognitive performances. (shrink)

Background: Frailty is a common syndrome among older adults and patients with several comorbidities. Grip strength is a representative parameter of frailty because it is a valid indicator of current and long-term physical conditions in the general population and patients with severe mental illnesses. Physical and cognitive capacities of people with SMIs are usually impaired; however, their relationship with frailty or social functioning have not been studied to date. The current study aimed to determine if GS is a valid predictor (...) of changes in cognitive performance and social functioning in patients with type-2 diabetes mellitus and SMIs. Methods: Assessments of social functioning, cognitive performance, and GS were conducted in 30 outpatients with type 2 diabetes mellitus, 35 with major depressive disorder, 42 with bipolar disorder, 30 with schizophrenia, and 28 healthy controls, twice during 1-year, follow-up period. Descriptive analyses were conducted using a one-way analysis of variance for continuous variables and the chi-squared test for categorical variables. Differences between groups for the motor, cognitive, and social variables at T1 and T2 were assessed using a one-way analysis of covariance, with sex and age as co-variates. To test the predictive capacity of GS at baseline to explain the variance in cognitive performance and social functioning at T2, a linear regression analysis was performed. Results: Predictive relationships were found among GS when implicated with clinical, cognitive, and social variables. These relationships explained changes in cognitive performance after one year of follow-up; the variability percentage was 67.7%, in patients with type-2 diabetes mellitus and 89.1% in patients with schizophrenia. Baseline GS along with other variables, also predicted changes in social functioning in major depressive disorder, bipolar disorder, and schizophrenia, with variability percentages of 67.3, 36, and 59%, respectively. Conclusion: GS combined with other variables significantly predicted changes in cognitive performance and social functioning in people with SMIs or type-2 diabetes mellitus. Interventions aimed to improve the overall physical conditions of patients who have poor GS could be a therapeutic option that confers positive effects on cognitive performance and social functioning. (shrink)

The discovery of a novel polypeptide (Islet Amyloid Polypeptide: IAPP) isolated from human and cat islet amyloid and from amyloid of a human insulinoma is reviewed. Structurally, IAPP from the human and cat resembles calcitonin gene‐related peptide (CGRP). The structural similarities between the neuropeptide CGRP and IAPP support the premise that IAPP is hormonal in nature. Our immunohistochemical studies also indicate that normal islet B‐cells of several mammalian species (including man and cat) give strong immunoreactivity with antiserum directed to a (...) synthetic peptide segment of IAPP. The fact that IAPP is deposited as amyloid in the pancreatic islets of type 2 (noninsulin‐dependent) diabetics strongly supports an important but yet unknown link between IAPP and the development of this disease. (shrink)

Both glycemic control and handgrip strength affect microvascular function. Multiscale entropy of photoplethysmographic pulse amplitudes may differ by diabetes status and hand activity. Of a middle-to-old aged and right-handed cohort without clinical cardiovascular disease, we controlled age, sex, and weight to select the unaffected,the well-controlled diabetes, and the poorly controlled diabetes groups. MSEs were calculated from consecutive 1,500 PPG pulse amplitudes of bilateral index fingertips. Thesmall-, medium-,and large-scale MSEs were defined as the average of scale 1, scales (...) 2–4, and scales 5–10, respectively. Intra- and intergroups were compared by one- and two-samplet-tests, respectively. The dominant handMSE5–10was lower in the poorly controlled diabetes group than the well-controlled diabetes and the unaffected groups, whereas the nondominant handMSE5–10was lower in the well- and poorly controlled diabetes groups than the unaffected group. TheMSE1of dominant hand was higher than that of nondominant hand in the well-controlled diabetes. In conclusion, diabetes status and hand dominance may affect the MSE of PPG pulse amplitudes. (shrink)

Lower plasma levels of high-density lipoproteins in adolescents with type 2 diabetes have been associated with a higher pulse wave velocity, a marker of arterial stiffness. Evidence suggests that HDL proteins or particle subspecies are altered in T2D and these may drive these relationships. In this work, we set out to reveal any specific proteins and subspecies that are related to arterial stiffness in youth with T2D from proteomics data. Plasma and PWV measurements were previously acquired from lean and (...) T2D adolescents. Each plasma sample was separated into 18 fractions and evaluated by mass spectrometry. Then, we applied a validated network-based computational approach to reveal HDL subspecies associated with PWV. Among 68 detected phospholipid-associated proteins, we found that seven were negatively correlated with PWV, indicating that they may be atheroprotective. Conversely, nine proteins show positive correlation with PWV, suggesting that they may be related to arterial stiffness. Intriguingly, our results demonstrate that apoA-I and histidine-rich glycoprotein may reverse their protective roles and become antagonistic in the setting of T2D. Furthermore, we revealed two arterial stiffness-associated HDL subspecies, each of which contains multiple PWV-related proteins. Correlation and disease association analyses suggest that these HDL subspecies might link T2D to its cardiovascular-related complications. (shrink)

BackgroundComorbidity between diabetes mellitus and depression is highly prevalent. The risk of depression in a person with diabetes is approximately twice that of a person without this disease. Depression has a major impact on patient well-being and control of diabetes. However, despite the availability of effective and specific therapeutic interventions for the treatment of depression in people with diabetes, 50% of patients do not receive psychological treatment due to insufficient and difficult accessibility to psychological therapies (...) in health systems. The use of information and communication technologies has therefore been proposed as a useful tool for the delivery of psychological interventions, but it continues to be a field in which scientific evidence is recent and controversial. This systematic review aims to update the available information on the efficacy of psychological interventions delivered through ICTs to improve depressive symptomatology in patients with diabetes.MethodsA systematic review of the literature was performed following the PRISMA guidelines and using MEDLINE, Embase, PubMed, Web of Science, PsycINFO, Scopus, and Cochrane Library databases to search for randomized clinical trials of eHealth treatments for patients with diabetes and comorbid depression from 1995 through 2020. In addition, studies related to follow-up appointments were identified. Inclusion criteria were as follows: randomized clinical trials ; patients with type 1 and type 2 diabetes; adult population over 18 years of age; presence of depressive symptomatology assessed with standardized instruments; treatments for depression based on established psychotherapeutic techniques and principles; delivered through eHealth technologies. We did not limit severity of depressive symptomatology, delivery setting or comparison group. Two coauthors independently reviewed the publications identified for inclusion and extracted data from the included studies. A third reviewer was involved to discuss discrepancies found. The PEDro scale was used to assess the quality of the RCTs. No meta-analysis of the results was performed. The protocol used for this review is available in PROSPERO.ResultsThe initial search identified 427 relevant scientific publications. After removing duplicates and ineligible citations, a total of 201 articles were analyzed in full text. Ten articles met the criteria of this review and were included, obtaining very good scientific quality after evaluation with the PEDro scale. The main results show that the eHealth psychological intervention for depression in patients with diabetes showed beneficial effects both at the end of treatment and in the short and long term for the improvement of depressive symptomatology. The methodology used was very heterogeneous. However, all studies were based on cognitive-behavioral tools and used standardized assessment instruments to evaluate depressive symptomatology or diagnosis of MDD. Glycemic control was assessed by glycosylated hemoglobin, but no benefits were found in improving glycemic control. Only four studies included psychoeducational content on diabetes and depression, but none used tools to improve or enhance adherence to medical prescriptions or diabetes self-care.ConclusionsICT-based psychological interventions for the treatment of depression in people with diabetes appear to be effective in reducing depressive symptomatology but do not appear to provide significant results with regard to glycemic control. Nonetheless, the scientific evidence reported to date is still very limited and the methodology very diverse. In addition, no studies have implemented these systems in routine clinical practice, and no studies are available on the economic analysis of these interventions. Future research should focus on studying and including new tools to ensure improvements in diabetes outcomes and not only on psychological well-being in order to advance knowledge about these treatments. Economic evaluations should also be undertaken to analyze whether these treatment programs implemented using eHealth technologies are cost-effective. (shrink)

Diabetes is a major public health issue that affects the nations of our time to a large extent and is described as a non-communicable epidemic. Diabetes mellitus is a common disease where there is too much sugar (glucose) floating around in your blood. This occurs because either the pancreas can’t produce enough insulin or the cells in body have become resistant to insulin. The concentration in this paper is on diagnosis diabetes by designing a proposed expert (...) system. The main goal of this expert system is to get the appropriate diagnosing of the illness, dealing with it quickly, and tips for permanent treatment whenever possible is given out. SL5 object expert system language was used for designing and implementing the proposed expert system. (shrink)

The concept of quality of life is the basis for a new paradigm of clinical medicine. Its assessment is considered to be an important instrument in determining disease severity and effectiveness of different treatment modalities. Our studies are devoted to the problem of diabetes complications especially anemia in patients with diabetic kidney disease. Anemia in subjects with diabetic nephropathy may result from various pathogenic factors including erythropoietin deficiency, iron deficiency, vitamin B12 and/or folate deficiencies, the effects of proinflammatory cytokines (...) etc. Diabetic patients with anemia are at increased risk of cardiovascular accidents and death. The aim of this study was to assess the influence of anemia on the quality of life of patients with early stages of diabetic nephropathy. We investigated 127 patients with type 2 diabetes mellitus and early diabetic nephropathy. Anemia was defined according to the World Health Organization criteria. Anemic patients were divided into three groups according to the stage of chronic kidney disease. Patients’ quality of life was assessed with SF-36 health survey. Anemic patients had lower scores of physical role functioning and emotional role functioning as compared to the patients with normal hemoglobin level, irrespective of the stage of chronic kidney disease. Patients with anemia and chronic kidney disease stage 3 had lower scores of general health perceptions, physical functioning, bodily pain, vitality and mental health than patients in the non-anemic group. Social role functioning was similar in anemic and non-anemic patients. The possible mechanisms and implications of the above mentioned findings are discussed with a medical and humanitarian perspective. The directions of further studies are proposed. (shrink)

Insulin‐dependent diabetes mellitus (IDDM) is an autoimmune disease whose etiology is complex. Both genetic susceptibility, which is polygenic, and environmental factors, including virus infections, appear to be involved in the development of IDDM. In this review, we have tried to balance the discussion of diabetes by examining both immunological and virological perspectives. Several mouse models, including viral and non‐viral models, have been used to study diabetes. For this review, we include lessons gleaned from the non‐obese diabetic (...) (NOD) mouse and from mouse models of coxsackievirus‐ and encephalomyocarditis‐virus‐induced diabetes. Finally, we present a multi‐stage model in which several viral infections, including the coxsackieviruses, are postulated to play a role in the autoimmune destruction of pancreatic beta cells. (shrink)

Insulin is synthesized in pancreatic B‐cells of islets of Langerhans. Understanding the mechanisms of action of B‐cytotoxins on pancreatic islets seems to be important for elucidating not only the causes of diabetes mellitus but also its prevention.

The aims of this study were to measure the readability of Australian based informed consent documents and determine whether informed consent readability guidelines have been established by Australian human research ethics committees (HRECs). A total of 20 informed consent documents, 10 HIV/AIDS and 10 type 2 diabetes, were measured for readability using the Simple Measure of Gobbledygook (SMOG) and Gunning Fog Index (Fog). Published guidelines and policy statements of the two local HREC who approved the 20 clinical trials under (...) study where examined to identify whether they had any formal policies/guidelines on the readability of informed consent documents. The two HRECs were contacted via e-mail to also determine whether they utilised any informal readability standards or “rules of thumb” that may not have been mentioned in the published documents. The HIV/AIDS and type 2 diabetes informed consent documents were, on average, written at a grade 13 reading level. Formal readability standards had not been established by the two local HRECs, however, they did verify the use of informal rules for assessing readability of informed consent documents. Based on Australian literacy data, the majority of informed consent documents were written well beyond the reading ability of many Australians. Unreadable informed consent documents may result in patients rejecting trial participation altogether or conversely may result in their participating in a trial with inadequate consent. Therefore, a step toward reducing the complexity of informed consent documents may be to implement objective readability assessments into the human research ethics application and review process. (shrink)

Pancreatic β‐cells in the islet of Langerhans produce the hormone insulin, which maintains blood glucose homeostasis. Perturbations in β‐cell function may lead to impairment of insulin production and secretion and the onset of diabetes mellitus. Several essential β‐cell factors have been identified that are required for normal β‐cell function, including six genes that when mutated give rise to inherited forms of diabetes known as Maturity Onset Diabetes of the Young (MODY). However, the intracellular signaling pathways that (...) control expression of MODY and other factors continue to be revealed. Post‐transplant diabetes mellitus in patients taking the calcineurin inhibitors tacrolimus (FK506) or cyclosporin A indicates that calcineurin and its substrate the Nuclear Factor of Activated T‐cells (NFAT) may be required for β‐cell function. Here recent advances in our understanding of calcineurin and NFAT signaling in the β‐cell are reviewed. Novel therapeutic approaches for the treatment of diabetes are also discussed. BioEssays 29:1011–1021, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

BackgroundThe transplantation of porcine islet cells provides a new potential therapy to treat patients with type 1 diabetes mellitus (T1DM). Compared to other biomedical technologies, xenotransplantation stands out in terms of its involvement of animals as graft sources, as well as the possible transmission of infectious diseases. As these aspects are especially relevant for potential xenotransplantation recipients, it is important to assess their opinion regarding this technology, in particular in terms of the requirements that should be met in (...) the informed consent process for xenotransplantation.MethodsWe conducted qualitative interviews with seven T1DM patients to assess their information needs prior to xenotransplantation. Before the interview, the participants received a model informed consent form for a clinical trial with porcine islet cells transplantation. The interviews were transcribed and analysed using qualitative content analysis.ResultsIn the interviews, we identified several requirements that are crucial for patients with T1DM in order to consider xenotransplantation as a potential treatment option: therapy-related requirements, professional care and supervision, successful behaviour and attitude management, improving quality of life, and managing control/self-determination challenges. Regarding the informed consent form, several of the participants’ questions remained open and should be addressed in more detail. The interviewees stressed the importance of personal consultations.ConclusionsTo become a sustainable therapeutic option, patients especially expected an improved diabetes control and a reduction of diabetes-related burdens. Health-related aspects prove to be pivotal for diabetic patients when considering porcine islet cell transplantation. The use of pigs as source for organ retrievals was not considered as problematic. (shrink)

The nonobese diabetic (NOD) mouse spontaneously develops an autoimmune diabetes that shares many immunogenetic features with human insulin-dependent diabetes mellitus (IDDM), type 1 diabetes. The mononuclear cell infiltrates in the islet, which results in the development of insulitis (a prerequisite step for the development of diabetes) are primarily composed of T cells. It is now well accepted that these T cells play important roles in initiating and propagating an autoimmune process, which in turn destroys insulin-producing (...) islet β cells in the pancreas. T cells are subdivided into CD4+ helper T cells and CD8+ cytotoxic T cells. CD4+ T cells are further subdivided into Th1 and Th2 cells based on profiles of cytokine production, and these two T-cell populations counterregulate each other. Because many autoimmune diseases are Th1 T-cell mediated, current studies have focused on manipulating the Th1/Th2 imbalance to suppress the autoimmune process in the NOD model. Furthermore, the incidence of disease is much higher in females than that in males, suggesting an involvement of sex-steroid hormones in the development of diabetes. Understanding insights of the mechanism of immune-mediated islet cell destruction and the interaction between the immune and the neuroendocrine system may, therefore, provide new therapeutic means of preventing this chronic debilitating disease. BioEssays 20:750–757, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In Mexico, diabetes mellitus is the main cause of end − stage kidney disease, and some patients may be transplant candidates. Organ supply is limited because of cultural issues. And, there is a lack of standardized clinical guidelines regarding organ donation. These issues highlight the tension surrounding the fact that living donors are being selected despite being prediabetic. This article presents, examines and discusses using the principles of non-maleficience, autonomy, justice and the constitutionally guaranteed right to health, the (...) ethical considerations that arise from considering a prediabetic person as a potential kidney donor. (shrink)