Sensitive Zika biomarker detection assisted by quantum dot-modified electrochemical immunosensing platform.

We report the development of a new nanostructured electrochemical immunosensing platform for the detection of the Zika virus envelope protein (EP-ZIKV). For this, quantum dots (QDs) were explored in combination with screen-printed carbon electrodes (SPCEs) functionalized with a conductor polymeric film, formed from 2-(1H-pyrrol-1-yl)ethanamine (Pyam), and anti-EP DIII ZIKV antibodies. Carboxylated CdTe QDs were synthesized, characterized by optical and structural techniques, and covalently immobilized onto the SPCE/PPyam surface. Then, anti-EP ZIKV antibodies were also covalently conjugated to QDs. All stages of platform assembly were evaluated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The detection of EP-ZIKV was performed by differential pulse voltammetry (DPV). Results indicated that QDs were efficiently immobilized, and did not show oxidation, under the conditions evaluated, for at least 7 months. Anti-EP ZIKV antibodies were effectively immobilized on the PPyam/QDs surface, even after 2 months of electrode storage. The platform enabled the detection of EP-ZIKV with high sensitivity using minimal sample volumes (LOD = 0.1 ng mL-1 and LOQ = 0.4 ng mL-1). The platform was also able to detect EP-ZIKV in spiked serum samples. Moreover, the platform showed specificity, not detecting the EP-DENV 3 nor a mixture of four DENV serotypes antigens. Thus, the proposed combination favored the development of a sensitive immunosensing platform, promising for the detection of Zika in the viremic phase, which also holds potential for transposition to other arboviruses.

Fibrosis nonalcoholic steatohepatitis index validation and applicability considering glycaemic severity and T2D duration.

Nonalcoholic fatty liver disease (NAFLD) diagnosis without using invasive methods is extremely challenging, highlighting the need for simple indexes for this end. Recently, the fibrotic nonalcoholic steatohepatitis index (FNI) was developed and proposed as an affordable non-invasive score calculated with aspartate aminotransferase, high-density lipoprotein cholesterol and haemoglobin A1c. Herein, and given the link between NAFLD and diabetes, we aimed at validating FNI in a population with type 2 diabetes (T2D), also considering diabetes duration and glycaemic severity. The performance of FNI was higher than FIB-4 (AUROC = 0.89 vs 0.67, respectively). Additionally, using 0.1 as the rule-out cut-off of FNI, the sensitivity was 0.99 and the positive predictive value was 0.19. Both duration of diabetes and A1c did not impact FNI performance. In sum, FNI is a valuable score for predicting fibrotic nonalcoholic steatohepatitis not only for primary care units but also for diabetes specialized care.

Interpersonal Relationships in Diabetes: Views and Experience of People with Diabetes, Informal Carers, and Healthcare Professionals in Portugal.

INTRODUCTION: The increasing burden of diabetes poses a great challenge to healthcare systems and economy worldwide. Although modern therapeutic strategies for diabetes are widely available, most patients still fail to achieve optimal clinical targets and well-being. The primary objective of this study was to assess and explore potential drivers and successful management of diabetes among people with diabetes, family members and healthcare professionals in Portugal, by applying the protocol of the multinational study "Diabetes, Attitudes, Wishes and Needs (DAWN2)". MATERIAL AND METHODS: A total of 767 adults, including 417 people with diabetes, 123 family members and 227 healthcare professionals, participated in the study. Surveys assessed health-related quality of life, self-management, attitudes/beliefs, social support and priorities for improvement areas in diabetes care. RESULTS: Diabetes has a negative impact on the physical health and emotional well-being of patients in Portugal and is also a psychological burden for family members. Earlier diagnosis and treatment of diabetes were mentioned as a major area of improvement. Healthcare professionals indicated the need for diabetes self-management education. CONCLUSION: We have used for the first time in Portugal the DAWN2 protocol to address the wishes, needs, and attitudes of Portuguese diabetes patients, their relatives, and healthcare professionals regarding the disease.

Introdução: Os encargos crescentes com a diabetes representam um desafio para os sistemas de saúde e economia a nível mundial. Apesar de terapias modernas para a diabetes disponíveis, a maioria das pessoas continua privada de cuidados e bem-estar adequados. O objetivo primário deste estudo foi avaliar e explorar os fatores relevantes para o controlo ativo e eficaz da diabetes para as pessoas com diabetes, familiares e profissionais de saúde em Portugal, aplicando o protocolo do estudo multinacional "Diabetes, Attitudes, Wishes and Needs (DAWN2)". Material e Métodos: Participaram no estudo 767 adultos (417 pessoas com diabetes, 123 familiares e 227 profissionais de saúde). Foram avaliados a qualidade de vida associada à saúde, autogestão, atitudes/crenças, apoio social e prioridades em áreas de melhoria no tratamento da diabetes. Resultados: A diabetes tem um impacto negativo na saúde física e no bem-estar emocional das pessoas em Portugal, sendo também uma carga psicológica para os seus familiares. O diagnóstico e tratamento precoces da diabetes foram indicados como a principal área de melhoria. Profissionais de saúde indicaram a necessidade de educação para a autogestão da diabetes. Conclusão: Pela primeira vez em Portugal usámos o protocolo DAWN2 para ir ao encontro dos desejos, necessidades e atitudes dos doentes Portugueses com diabetes, os seus familiares e profissionais de saúde relativamente à doença.

Prediabetes blunts DPP4 genetic control of postprandial glycaemia and insulin secretion.

AIMS/HYPOTHESIS: Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven. METHODS: We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet. RESULTS: In individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10-7) and C-peptide release responses (rs2300757, p=6.86x10-5) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher association with the genetic control of insulin secretion was detected in later phases of the post-OGTT response, suggesting that the DPP4 gene directly senses glucose challenges. Accordingly, in mice fed a normal chow diet but not a high-fat diet, we found that, under OGTT, expression of Dpp4 is strongly downregulated at 30 min in the mouse liver. Strikingly, no genetic association was found in prediabetic individuals, indicating that post-OGTT control by DPP4 is abrogated in prediabetes. Furthermore, Dpp4 KO mice provided concordant evidence that Dpp4 modulates post-OGTT C-peptide release in normoglycaemic but not dysmetabolic states. CONCLUSIONS/INTERPRETATION: These results showed the DPP4 gene as a strong determinant of post-OGTT levels via glucose-sensing mechanisms that are abrogated in prediabetes. We propose that impairments in DPP4 control of post-OGTT insulin responses are part of molecular mechanisms underlying early metabolic disturbances associated with type 2 diabetes.

Increased Intake of Both Caffeine and Non-Caffeine Coffee Components Is Associated with Reduced NAFLD Severity in Subjects with Type 2 Diabetes.

Coffee may protect against non-alcoholic fatty liver disease (NAFLD), but the roles of the caffeine and non-caffeine components are unclear. Coffee intake by 156 overweight subjects (87% with Type-2-Diabetes, T2D) was assessed via a questionnaire, with 98 subjects (all T2D) also providing a 24 h urine sample for quantification of coffee metabolites by LC-MS/MS. NAFLD was characterized by the fatty liver index (FLI) and by Fibroscan® assessment of fibrosis. No associations were found between self-reported coffee intake and NAFLD parameters; however, total urine caffeine metabolites, defined as Σcaffeine (caffeine + paraxanthine + theophylline), and adjusted for fat-free body mass, were significantly higher for subjects with no liver fibrosis than for those with fibrosis. Total non-caffeine metabolites, defined as Σncm (trigonelline + caffeic acid + p-coumaric acid), showed a significant negative association with the FLI. Multiple regression analyses for overweight/obese T2D subjects (n = 89) showed that both Σcaffeine and Σncm were negatively associated with the FLI, after adjusting for age, sex, HbA1c, ethanol intake and glomerular filtration rate. The theophylline fraction of Σcaffeine was significantly increased with both fibrosis and the FLI, possibly reflecting elevated CYP2E1 activity-a hallmark of NAFLD worsening. Thus, for overweight/obese T2D patients, higher intake of both caffeine and non-caffeine coffee components is associated with less severe NAFLD. Caffeine metabolites represent novel markers of NAFLD progression.

Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits.

Systemic insulin availability is determined by a balance between beta-cell secretion capacity and insulin clearance (IC). Insulin-degrading enzyme (IDE) is involved in the intracellular mechanisms underlying IC. The liver is a major player in IC control yet the role of hepatic IDE in glucose and lipid homeostasis remains unexplored. We hypothesized that IDE governs postprandial IC and hepatic IDE dysfunction amplifies dysmetabolic responses and prediabetes traits such as hepatic steatosis. In a European/Portuguese population-based cohort, IDE SNPs were strongly associated with postprandial IC in normoglycemic men but to a considerably lesser extent in women or in subjects with prediabetes. Liver-specific knockout-mice (LS-IDE KO) under normal chow diet (NCD), showed reduced postprandial IC with glucose intolerance and under high fat diet (HFD) were more susceptible to hepatic steatosis than control mice. This suggests that regulation of IC by IDE contributes to liver metabolic resilience. In agreement, LS-IDE KO hepatocytes revealed reduction of Glut2 expression levels with consequent impairment of glucose uptake and upregulation of CD36, a major hepatic free fatty acid transporter. Together these findings provide strong evidence that dysfunctional IC due to abnormal IDE regulation directly impairs postprandial hepatic glucose disposal and increases susceptibility to dysmetabolic conditions in the setting of Western diet/lifestyle.

Effects of Meal Fructose/Glucose Composition on Postprandial Glucose Appearance and Hepatic Glycogen Synthesis in Healthy Subjects.

Dietary fructose overshadows glucose in promoting metabolic complications. Intestinal fructose metabolism (IFM) protects against these effects in rodents, by favoring gluconeogenesis, but the extent of IFM in humans is not known. We therefore aimed to infer the extent of IFM by comparing the contribution of dietary fructose to systemic glucose and hepatic glycogen appearance postprandially. Twelve fasting healthy subjects ingested two protein meals in random order, one supplemented with 50 g 5/95 fructose/glucose (LF) and the other with 50 g 55/45 fructose/glucose (HF). Sources of postprandial plasma glucose appearance and hepatic glycogen synthesis were determined with deuterated water. Plasma glucose excursions, as well as pre- and post-meal insulin, c-peptide, and triglyceride levels were nearly identical for both meals. The total gluconeogenic contribution to plasma glucose appearance was significantly higher for HF versus LF (65 ± 2% vs. 34 ± 3%, p < 0.001). For HF, Krebs cycle anaplerosis accounted for two-thirds of total gluconeogenesis (43 ± 2%) with one-third from Triose-P sources (22 ± 1%). With LF, three-quarters of the total gluconeogenic contribution originated via Krebs cycle anaplerosis (26 ± 2%) with one-quarter from Triose-P sources (9 ± 2%). HF and LF gave similar direct and indirect pathway contributions to hepatic glycogen synthesis. Increasing the fructose/glucose ratio had significant effects on glucose appearance sources but no effects on hepatic glycogen synthesis sources, consistent with extensive IFM. The majority of fructose carbons were converted to glucose via the Krebs cycle.

Development of an Interactive Lifestyle Programme for Adolescents at Risk of Developing Type 2 Diabetes: PRE-STARt.

BACKGROUND: Type 2 diabetes (T2D) is increasing in young people. Reporting on the processes used when developing prevention interventions is needed. We present the development of a family-based interactive lifestyle intervention for adolescents with risk factors for T2D in the future. METHOD: A multidisciplinary team in the UK site led the intervention development process with sites in Portugal, Greece, Germany and Spain. Potential programme topics and underpinning theory were gathered from literature and stakeholders. A theoretical framework based on self-efficacy theory and the COM-B (capability, opportunity, motivation, behaviour) model was developed. Sessions and supporting resources were developed and refined via two iterative cycles of session and resource piloting, feedback, reflection and refinement. Decision on delivery and content were made by stakeholders (young people, teachers, parents, paediatricians) and all sites. Materials were translated to local languages. Site-specific adaptations to the language, content and supporting resources were made. RESULTS: The "PRE-STARt" programme is eight 90-min interactive sessions with supporting curriculum and resources. Iterative development work provided valuable feedback on programme content and delivery. CONCLUSION: Reporting on the intervention development process, which includes stakeholder input, could yield a flexible approach for use in this emerging 'at risk' groups and their families.

Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia.

Type 2 diabetes (T2D) heterogeneity is a major determinant of complications risk and treatment response. Using cluster analysis, we aimed to stratify glycemia within metabolic multidimensionality and extract pathophysiological insights out of metabolic profiling. We performed a cluster analysis to stratify 974 subjects (PREVADIAB2 cohort) with normoglycemia, prediabetes, or non-treated diabetes. The algorithm was informed by age, anthropometry, and metabolic milieu (glucose, insulin, C-peptide, and free fatty acid (FFA) levels during the oral glucose tolerance test OGTT). For cluster profiling, we additionally used indexes of metabolism mechanisms (e.g., tissue-specific insulin resistance, insulin clearance, and insulin secretion), non-alcoholic fatty liver disease (NAFLD), and glomerular filtration rate (GFR). We found prominent heterogeneity within two optimal clusters, mainly representing normometabolism (Cluster-I) or insulin resistance and NAFLD (Cluster-II), at higher granularity. This was illustrated by sub-clusters showing similar NAFLD prevalence but differentiated by glycemia, FFA, and GFR (Cluster-II). Sub-clusters with similar glycemia and FFA showed dissimilar insulin clearance and secretion (Cluster-I). This work reveals that T2D heterogeneity can be captured by a thorough metabolic milieu and mechanisms profiling-metabolic footprint. It is expected that deeper phenotyping and increased pathophysiology knowledge will allow to identify subject's multidimensional profile, predict their progression, and treat them towards precision medicine.

Insights from qualitative research on NAFLD awareness with a cohort of T2DM patients: time to go public with insulin resistance?

BACKGROUND: It is estimated that around 70% of Type 2 Diabetes Mellitus patients (T2DM) have Non-Alcoholic Fatty Liver Disease (NAFLD). Awareness and education are amongst the major shortcomings of the public health response to the increasing threat of NAFLD. Characterizing the specific NAFLD-related information needs of particular high-risk metabolic communities, for instance, T2DM patients, might aid in the development of evidence-based health promotion strategies, ultimately promoting NAFLD-awareness, treatment adherence and therapeutic success rates. METHODS: Semi-structured interviews with T2DM patients were conducted to gain insight into their awareness of NAFLD, including its relationship with insulin resistance and T2DM. RESULTS: Awareness of NAFLD as a disease entity, as well as its progression to end-stage liver disease or its relationship with other metabolic conditions, including insulin resistance and T2DM was low. Surveillance behaviours were also suboptimal and perceptions on the self-management knowledge and praxis regarding lifestyle intervention components of T2DM treatment seemed detached from those of NAFLD. CONCLUSIONS: Our findings could inform the integration of NAFLD-related content in T2DM health promotion strategies. Rising awareness on NAFLD progression and its relationship with T2DM using culturally and community-relevant constructs might facilitate the development of primary and secondary prevention programmes to promote the adherence to lifestyle interventions by influencing NAFLD threat perceptions.

Association between glycated albumin, fructosamine, and HbA1c with neonatal outcomes in a prospective cohort of women with gestational diabetes mellitus.

OBJECTIVE: To investigate whether glycated albumin, fructosamine, and hemoglobin A1c (HbA1c) are associated with neonatal complications in newborns of pregnant women with gestational diabetes mellitus (GDM). METHODS: Between November 2016 and September 2017, women with a singleton pregnancy and GDM were enrolled in a prospective study in an obstetric Portuguese referral center. Glycemic markers were compared between mothers of newborns with and without complications. Multivariable logistic regression models and corresponding areas under the receiver operating characteristic curve (AUC) were used. RESULTS: A total of 85 women participated in the study. Raised levels of glycated albumin and fructosamine were associated with at least one neonatal complication (OR- [odds ratio] estimate: 1.33, P=0.015; OR: 1.24, P=0.027, respectively) and with respiratory disorders at birth (OR 1.41, P=0.004; OR 1.26, P=0.014, respectively). HbA1c was not associated with these outcomes. All biomarkers were associated with large-for-gestational age (LGA) status (OR 1.61, P<0.001; OR 1.45, P<0.001; OR 3.62, P=0.032 for glycated albumin, fructosamine, and HbA1c, respectively). All had similar AUC for at least one neonatal complication (0.82; 0.81; 0.79, respectively). For newborn respiratory disorders, AUCs were 0.83, 0.81, and 0.76, respectively, and for LGA status were 0.81, 0.79, and 0.71, respectively. CONCLUSION: Raised values of glycated albumin and fructosamine were associated with particular perinatal complications in newborns of mothers with GDM, better discriminating mothers of newborns with and without complications than HbA1c.

Association between glycated haemoglobin, glycated albumin and fructosamine with neonatal birthweight and large-for-date status infants in gestational diabetes mellitus: a prospective cohort study.

This study aims to investigate associations between glycated haemoglobin (HbA1c), glycated albumin (GA) and fructosamine with neonatal birthweight in gestational diabetes mellitus (GDM). The prospective cohort consisted of 82 women with GDM and their newborns, enrolled between November 2016 and September 2017. Considering neonatal birthweight and birthweights ≥90th percentile for gestational age as outcomes, linear and logistic regression models were used, respectively. Fructosamine (R2=0.62) and GA (R2=0.61) performed very similarly between them and best than HbA1c (R2=0.58). The added value of GA or fructosamine to HbA1c resulted in increase in models' performances. GA attained the best discriminative ability regarding large-for-date status babies (AUC = 0.80, OR-estimate 1.58, p=.001) followed by fructosamine (AUC = 0.78, OR-estimate 1.42, p=.001) and HbA1c (AUC = 0.69, OR-estimate 3.09, p=.070). GA and fructosamine, besides from providing additional information to HbA1c, when used separately perform better than the traditional biomarker in predicting neonatal birthweight and large-for-date babies in pregnant women with GDM. Impact statement What is already known on this subject? HbA1c is the standard glycaemic indicator used in GDM. Its association with birthweight and large-for-date status has been previously reported. However, it has become increasingly questionable whether it is a suitable glycaemic marker in pregnancy. There is a growing interest in other non-traditional shorter-term glycaemic indicators, such as GA and fructosamine. Nevertheless, few studies exist and almost all are retrospective and with ethnically homogeneous study populations composed by pregnant women not only with GDM but also type 1 and type 2 diabetes mellitus. What do the results of this study add? Our prospective multi-ethnic cohort composed solely on pregnant women with GDM and their infants show that even though all of the aforementioned biomarkers are associated with birthweight and large-for-date status in GDM when used separately, GA and fructosamine seem to perform better than HbA1c. When used with HbA1c, they improve the predicting performance of the traditional marker. What are the implications of these findings for future clinical practice and/or further research? These findings suggest that GA and fructosamine can provide important additional or substitute information to HbA1c in GDM, namely in predicting birthweight and large-for-date status babies. Larger studies are needed to confirm if this non-traditional biomarkers can change clinical practice.

Effects of combined training with different intensities on vascular health in patients with type 2 diabetes: a 1-year randomized controlled trial.

BACKGROUND: Exercise, when performed on a regular basis, is a well-accepted strategy to improve vascular function in patients with type 2 diabetes. However, the exercise intensity that yields maximal adaptations on structural and functional indices in patients with type 2 diabetes remains uncertain. Our objective was to analyze the impact of a 1-year randomized controlled trial of combined high-intensity interval training (HIIT) with resistance training (RT) vs. a combined moderate continuous training (MCT) with RT on structural and functional arterial indices in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes (n = 80) were randomized into an exercise intervention with three groups: control, combined HIIT with RT and combined MCT with RT. The 1-year intervention had 3 weekly exercise sessions. High-resolution ultrasonography of the common carotid artery and central and peripheral applanation tonometry were used to assess the changes in structural and functional arterial indices. Generalized estimating equations were used to model the corresponding outcomes. RESULTS: After adjusting the models for sex, baseline moderate-to-vigorous physical activity, and mean arterial pressure changes, while using the intention-to-treat analysis, a significant interaction was observed on the carotid intima-media thickness (cIMT) for both the MCT (ß = - 4.25, p < 0.01) and HIIT group (ß = - 3.61, p < 0.01). However, only the HIIT observed favorable changes from baseline to 1-year on peripheral arterial stiffness indices such as carotid radial arterial pulse wave velocity (ß = - 0.10, p = 0.044), carotid to distal posterior tibial artery pulse wave velocity (ß = - 0.14, p < 0.01), and on the distensibility coefficient (ß = - 0.00, p < 0.01). No effect was found for hemodynamic variables after the intervention. CONCLUSIONS: Following a 1-year intervention in patients with type 2 diabetes, both the MCT and HIIT group reduced their cIMT, whereas only the HIIT group improved their peripheral arterial stiffness indices and distensibility coefficient. Taken together, HIIT may be a meaningful tool to improve long-term vascular complications in type 2 diabetes. Trial registration clinicaltrials.gov ID: NCT03144505.

Screening diabetes mellitus 2 based on electronic health records using temporal features.

The prevalence of type 2 diabetes mellitus is increasing worldwide. Current methods of treating diabetes remain inadequate, and therefore, prevention with screening methods is the most appropriate process to reduce the burden of diabetes and its complications. We propose a new prognostic approach for type 2 diabetes mellitus based on electronic health records without using the current invasive techniques that are related to the disease (e.g. glucose level or glycated hemoglobin (HbA1c)). Our methodology is based on machine learning frameworks with data enrichment using temporal features. As as result our predictive model achieved an area under the receiver operating characteristics curve with a random forest classifier of 84.22 percent when including data information from 2009 to 2011 to predict diabetic patients in 2012, 83.19 percent when including temporal features, and 83.72 percent after applying temporal features and feature selection. We conclude that he pathology prediction is possible and efficient using the patient's progression information over the years and without using the invasive techniques that are currently used for type 2 diabetes mellitus classification.

Use of Electronic Health Records and Geographic Information Systems in Public Health Surveillance of Type 2 Diabetes: A Feasibility Study.

BACKGROUND: Data routinely collected in electronic health records (EHRs) offer a unique opportunity to monitor chronic health conditions in real-time. Geographic information systems (GIS) may be an important complement in the analysis of those data. OBJECTIVE: The aim of this study was to explore the feasibility of using primary care EHRs and GIS for population care management and public health surveillance of chronic conditions, in Portugal. Specifically, type 2 diabetes was chosen as a case study, and we aimed to map its prevalence and the presence of comorbidities, as well as to identify possible populations at risk for cardiovascular complications. METHODS: Cross-sectional study using individual-level data from 514 primary care centers, collected from three different types of EHRs. Data were obtained on adult patients with type 2 diabetes (identified by the International Classification of Primary Care [ICPC-2] code, T90, in the problems list). GISs were used for mapping the prevalence of diabetes and comorbidities (hypertension, dyslipidemia, and obesity) by parish, in the region of Lisbon and Tagus Valley. Descriptive statistics and multivariate logistic regression were used for data analysis. RESULTS: We identified 205,068 individuals with the diagnosis of type 2 diabetes, corresponding to a prevalence of 5.6% (205,068/3,659,868) in the study population. The mean age of these patients was 67.5 years, and hypertension was present in 71% (144,938/205,068) of all individuals. There was considerable variation in diagnosed comorbidities across parishes. Diabetes patients with concomitant hypertension or dyslipidemia showed higher odds of having been diagnosed with cardiovascular complications, when adjusting for age and gender (hypertension odds ratio [OR] 2.16, confidence interval [CI] 2.10-2.22; dyslipidemia OR 1.57, CI 1.54-1.60). CONCLUSIONS: Individual-level data from EHRs may play an important role in chronic disease surveillance, namely through the use of GIS. Promoting the quality and comprehensiveness of data, namely through patient involvement in their medical records, is crucial to enhance the feasibility and usefulness of this approach.

Facilitators, barriers and expectations in the self-management of type 2 diabetes--a qualitative study from Portugal.

BACKGROUND: Patients with type 2 diabetes mellitus (DM) have a central role in managing their disease, but the effective adoption of self-management behaviours is often challenging. OBJECTIVES: The main objective of this study was to assess the facilitators, barriers and expectations in the self-management of type 2 DM, as perceived by patients. METHODS: Patients with type 2 DM were recruited at the Portuguese Diabetes Association outpatient clinic, using a convenient sampling technique. Qualitative data was obtained using video-recorded focus groups. Each session had a moderator and an observer, and followed a pre-tested questioning route. Two independent researchers transcribed and analysed the focus groups. RESULTS: Three major themes were identified: diet, physical exercise, and glycaemic control. Difficulties in changing dietary habits were grouped in four main categories: decisional, food quality, food quantity, and dietary schedule. Barriers related to physical exercise also included decisional aspects, as well as fatigue, muscle and joint pain, and other co-morbidities. Information and knowledge translation, as well as family and social ties, were commonly explored aspects across the three themes and were regarded as facilitators in some situations and as barriers in others. CONCLUSION: This study provided new insight on the barriers, facilitators and expectations in type 2 DM self-management, pointing out the importance of tailored guidance. Future research should explore interventions designed to promote and facilitate behaviour change in this population.

Exploiting the therapeutic potential of 8-ß-d-glucopyranosylgenistein: synthesis, antidiabetic activity, and molecular interaction with islet amyloid polypeptide and amyloid ß-peptide (1-42).

8-ß-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of excessive postprandial glucose excursions and and increasing ß-cell sensitivity, insulin secretion, and circulating insulin within 7 days at a dose of 4 (mg/kg bw)/day. Suppression of islet amyloid polypeptide (IAPP) fibril formation by compound 1 was demonstrated by thioflavin T fluorescence and atomic force microscopy. Molecular recognition studies with IAPP and Aß1-42 employing saturation transfer difference (STD) confirmed the same binding mode for both amyloid peptides as suggested by their deduced epitope. Insights into the preferred conformation in the bound state and conformers' geometry resulting from interaction with Aß1-42 were also given by STD, trNOESY, and MM calculations. These studies strongly support 8-ß-d-glucopyranosylgenistein as a promising molecular entity for intervention in amyloid events of both diabetes and the frequently associated Alzheimer's disease.

Dermic diffusion and stratum corneum: a state of the art review of mathematical models.

Transdermal biotechnologies are an ever increasing field of interest, due to the medical and pharmaceutical applications that they underlie. There are several mathematical models at use that permit a more inclusive vision of pure experimental data and even allow practical extrapolation for new dermal diffusion methodologies. However, they grasp a complex variety of theories and assumptions that allocate their use for specific situations. Models based on Fick's First Law found better use in contexts where scaled particle theory Models would be extensive in time-span but the reciprocal is also true, as context of transdermal diffusion of particular active compounds changes. This article reviews extensively the various theoretical methodologies for studying dermic diffusion in the rate limiting dermic barrier, the stratum corneum, and systematizes its characteristics, their proper context of application, advantages and limitations, as well as future perspectives.

Risk of postprandial insulin resistance: the liver/vagus rapport.

Ingestion of a meal is the greatest challenge faced by glucose homeostasis. The surge of nutrients has to be disposed quickly, as high concentrations in the bloodstream may have pathophysiological effects, and also properly, as misplaced reserves may induce problems in affected tissues. Thus, loss of the ability to adequately dispose of ingested nutrients can be expected to lead to glucose intolerance, and favor the development of pathologies. Achieving interplay of several organs is of upmost importance to maintain effectively postprandial glucose clearance, with the liver being responsible of orchestrating global glycemic control. This dogmatic role of the liver in postprandial insulin sensitivity is tightly associated with the vagus nerve. Herein, we uncover the behaviour of metabolic pathways determined by hepatic parasympathetic function status, in physiology and in pathophysiology. Likewise, the inquiry expands to address the impact of a modern lifestyle, especially one's feeding habits, on the hepatic parasympathetic nerve control of glucose metabolism.

Postprandial but not fasting insulin resistance is an early identifier of dysmetabolism in overweight subjects.

The dynamic response to insulin is highly potentiated after meal ingestion, and this meal-induced insulin sensitization (MIS) in healthy subjects is dependent on cholinergic mechanisms. The main objective of this study was to test the hypothesis that the reduced response to insulin observed in moderately overweight subjects, in comparison with control lean subjects, is due to MIS impairment and not to a reduction in the direct hypoglycemic action of insulin. Both lean and overweight male subjects were recruited. Insulin sensitivity (IS) was assessed by the rapid insulin sensitivity test (RIST) performed after a 24 h fast, as well as after a standardized meal. Fasting glucose disposal was similar between lean and overweight subjects. Following the meal, glucose disposal increased more extensively in lean than overweight subjects. The insulin profiles, in both fasted and fed states, were superimposable, suggesting that the absence of a factor other than insulin is responsible for the decreased postprandial insulin sensitivity observed in overweight subjects. Our data suggest that in overweight subjects, MIS contribution is decreased, which is responsible for the postprandial impaired IS observed and is suggested to be the cause, not effect, of mild adiposity.