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.

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.

Association between area- and individual-level socio-economic factors with glycated haemoglobin-Evidence from a Portuguese population-based study.

AIMS: This study aims to estimate the associations between area-level deprivation and individual-level socio-economic factors, as well as their interaction, with glycated haemoglobin (HbA1c ) levels. METHODS: We conducted a gamma multilevel regression analysis using individual-level data from the Portuguese National Health Examination Survey and a deprivation index built through factor analysis, at municipality level, with census variables. RESULTS: Living in a municipality with high material deprivation and having a low level of education were independently associated with an increase of 2.3% (95% confidence interval [CI] 0.6, 4.0) and of 1.6% (95% CI 0.6, 2.7) in the mean levels of HbA1c , respectively. The interaction between area material deprivation and individual-level education was not associated with the levels of HbA1c (0.5%, 95% CI -1.3, 2.3). CONCLUSIONS: Our findings support the collective resources model that argues that people in less deprived areas have better health because there are more collective resources. The results suggest that to reduce socio-economic inequalities associated with the levels of HbA1c and, consequently, with diabetes, will require attention to the area material deprivation and individual-level education. Upstream social determinants of health are thus highlighted.

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.

Prevalence, awareness, treatment and control of diabetes in Portugal: Results from the first National Health examination Survey (INSEF 2015).

AIMS: Diabetes Mellitus is a major public health threat worldwide and continues to increase in numbers and significance. Estimates of diabetes prevalence, awareness, treatment and control are essential to effectively monitor its trends, plan and evaluate interventions. METHODS: We conducted a nationwide health examination survey in the population residing in Portugal aged between 25 and 74 years old in 2015. It consisted in a cross sectional prevalence study which included the measurement of HbA1c, a physical examination and a general health interview of a probabilistic sample of 4911 individuals (Authorization n°9348/2010 of the National Committee for Data Protection). RESULTS: The overall prevalence of diabetes was 9.9% (95%CI: 8.4; 11.5). It was higher in males than in females (12.1% vs 7.8%). Diabetes was more prevalent among individuals of lower education and without any professional activity. The majority of persons with diabetes was aware of their condition (87.1%) and was taking antidiabetic medication (79.7%). Of these, 63.2% had glycated hemoglobin levels lower than 7.0% (53 mmol/mol), but the majority failed to comply with the LDL and blood pressure recommended clinical targets (71.9% and 59.0%). Similarly, the prevalence of prediabetes was 16%, higher among women than men (17.5% vs 14.4%). CONCLUSION: The prevalence of diabetes and prediabetes remains higher than the global and European estimates, although there is increasing awareness of this disorder.

Immunoglobulin M gene association with autoantibody reactivity and type 1 diabetes.

Several lines of evidence show that autoimmune responses evolving in type 1 diabetes (T1D) patients include the generation of multi-reactive autoantibody (AutoAb) repertoires, but their role in T1D pathogenesis remains elusive. We tested the hypothesis that variants at the immunoglobulin heavy chain (IGH) locus are genetic determinants of AutoAbs against pancreatic antigens and contribute to T1D susceptibility. With this aim, two independent study designs were used: a case-control study and a family-based cohort comprising a total of 240 T1D patients, 172 first-degree relatives (mother and/or father), and 130 unrelated healthy controls living in Portugal. We found that three SNPs in the IGH locus show suggestive association with T1D with the highest nominal association at rs1950942 (in the IGHM-IGHJ gene region) in both the case-control study (P = 9.35E-03) and the family-based cohort (P = 3.08E-03). These SNPs were also associated with IgG AutoAbs against pancreatic antigens and with AutoAb multi-reactivity in T1D patients. Notably, we found that the SNP with the highest association with T1D susceptibility and IgG autoantibody reactivity (rs1950942) was also associated with anti-GAD IgM reactivity in T1D patients (P = 5.98E-03) and in non-affected parents (P = 4.17E-03). This finding implies that IGH association with autoreactive IgM is detectable irrespective of disease status.These results suggest that genetic variants at the IgM gene region of the IGH locus contribute to antibody autoreactivity and are associated with T1D. We propose that the control of autoantibody generation by IGH polymorphisms is a component of the complex architecture of T1D genetic susceptibility.

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.

[The geography of diabetes mellitus in Portugal: how context influence the risk of dying]. / Geografias da diabetes mellitus em Portugal: como as condições do contexto influenciam o risco de morrer.

INTRODUCTION: Diabetes Mellitus is a public health problem that is on the increase throughout the world, including in Portugal. This paper aims to identify the changing geographic pattern of this cause of death in Portugal and its association with sociomaterial deprivation. MATERIAL AND METHODS: This is a transversal ecological study of the deaths by Diabetes Mellitus in Portuguese municipalities in three periods (1989-1993, 1999-2003 and 2006-2010). It uses a Bayesian hierarchical model in order to obtain a smooth standardized mortality ratio and the relative risk of death by Diabetes Mellitus associated to sociomaterial deprivation. RESULTS: In 1989-1993, the highest smooth standardized mortality ratio values were found in coastal urban municipalities (80% of municipalities with smooth standardized mortality ratio ≥ 161, of which 60% are urban); in 2006-2010, the opposite was found, with the highest smooth standardized mortality ratio values occurring in rural areas in southern inland regions (76.9% of municipalities with smooth standardized mortality ratio ≥ 161, of which 69.2% are rural), particularly the Alentejo. The relative risk of death by Diabetes Mellitus increases with vulnerability associated to social and economic conditions in the area of residence, and is significant in the last two periods (relative risk: 1.00; IC95%: 0.98-1.02). DISCUSSION: Diabetes Mellitus presents a geographic pattern marked by coastal-inland and urban-rural asymmetry. However, this has been altering over the last twenty years. 48% of the population reside in municipalities where the smooth standardized mortality ratio has increased in the last twenty years, particularly in the rural areas of inland Portugal. CONCLUSION: The highest smooth standardized mortality ratio are currently found in rural municipalities with the highest index of sociomaterial deprivation.

Introdução: A Diabetes Mellitus é um problema de saúde pública em crescimento em todo o mundo e também em Portugal. Pretendemos identificar a evolução do padrão geográfico desta causa de morte e a associação com a privação sociomaterial, em Portugal. Material e Métodos: Estudo ecológico transversal dos óbitos por Diabetes Mellitus ocorridos nos municípios portugueses em três períodos (1989-1993, 1999-2003 e 2006-2010). Aplicámos um modelo hierárquico bayesiano, de modo a obter a Razão Padronizada de Mortalidade Suavizada e o Risco Relativo, de mortalidade por diabetes associado à privação sociomaterial. Resultados: Observámos os valores da Razão Padronizada de Mortalidade Suavizada mais elevados, em 1989-1993, nos municípios urbanos do litoral (80% dos municípios com Razão Padronizada de Mortalidade Suavizada ≥ 161, sendo 60% urbanos); em 2006-2010 verificámos o oposto, destacando-se, pelos valores de Razão Padronizada de Mortalidade Suavizada elevados, as áreas rurais localizadas no interior sul do país (76,9% dos municípios com Razão Padronizada de Mortalidade Suavizada ≥ 161 sendo 69,2% rurais), principalmente no Alentejo. O Risco Relativo de mortalidade por Diabetes Mellitus aumenta com o aumento da vulnerabilidade associada às condições sociais e económicas da área de residência, principalmente nos dois últimos períodos (Risco Relativo: 1,00; IC95%: 0,98-1,02). Discussão: A Diabetes Mellitus apresenta um padrão geográfico marcado pela assimetria litoral-interior e urbano-rural, que tem vindo a alterar-se ao longo dos últimos vinte anos, verificando-se uma transição geográfica: 48% da população reside em municípios em que a Razão Padronizada de Mortalidade Suavizada aumentou nos últimos vinte anos, com destaque para as áreas rurais do interior de Portugal. Conclusão: As Razões Padronizadas de Mortalidade Suavizada mais elevadas verificam-se, actualmente, em municípios rurais, com índice de privação sociomaterial mais elevado. Palavras-chave: Demografia; Diabetes Mellitus/epidemiologia; Diabetes Mellitus/mortalidade; Factores Socioeconómicos; Portugal.

[Therapeutic patient education in diabetes management]. / Educação do doente terapêutico no tratamento da diabetes.

Late complications of type 1 and type 2 diabetes can also be effectively avoided or delayed using active intervention and available therapies. Despite these facts, the percentage of people with diabetes following the therapy proposed by health care professionals is quite low. People with diabetes or any other chronic disease have to be involved in their own treatment. Basic knowledge is very important for the patient but the reinforcement of appropriate attitudes and a continuous process of motivation is fundamental in changing habits and behaviour. We need to educate patients, giving them the tools and skills to manage their disease, allowing them to become autonomous, empowering them. In the Therapeutic Patient Education model the patient is no longer the object but instead one of the actors in the process. He becomes part of the team and part of the solution. Goals are agreed as a result of input of the patient's desires, details of his daily life, his perceptions and the HCP's biomedical objectives. The patient takes care of himself and will, step by step, become aware of the consequences of his actions, in collaboration with his health team.

Dermatomicosis en las extremidades inferiores de pacientes diabéticos seguidos en una consulta de podología / Dermatomycosis in lower limbs of diabetic patients followed by podiatry consultation

Antecedentes. Los pacientes diabéticos son especialmente vulnerables a las micosis debido a las modificaciones inducidas por la enfermedad en su sistema inmunitario. Estas modificaciones comprometen los sistemas de defensa naturales, como la piel y las uñas, sobre todo en las extremidades inferiores. Objetivos. Evaluar la presencia de dermatomicosis en los miembros inferiores de pacientes diabéticos portugueses seguidos en consultas de podología y determinar los posibles factores predisponentes y las especies de hongos más frecuentes asociadas a los casos incluidos en el estudio. Métodos. Se realizó un estudio prospectivo de seis meses de duración en 163 pacientes diabéticos con signos y síntomas de dermatomicosis, atendidos por el servicio de podología de la Asociación Portuguesa de Diabetes en Lisboa. Se obtuvieron muestras de piel y/o de uñas de las extremidades inferiores y se registraron los datos demográficos y clínicos de los pacientes. Resultados. Trichophyton rubrum fue el dermatofito más frecuentemente aislado (12,1%), seguido por Trichophyton mentagrophytes (7,7%) y Trichophyton tonsurans (4,4%). En el presente estudio ha quedado demostrada la asociación entre la diabetes de tipo 2 y la presencia de dermatomicosis en la población estudiada (p=0,013); y así mismo entre la incidencia de dermatomicosis y la localización de la lesión corporal (p=0,000). Para ningún otro factor predisponente analizado se identificó una asociación positiva con la infección (p > 0,05). Conclusiones. En Portugal apenas se dispone de datos sobre micosis superficiales en pacientes diabéticos. El presente estudio proporciona información sobre la caracterización de las dermatomicosis en miembros inferiores de estos pacientes(AU)

Background. Diabetic patients are particularly susceptible to fungal infections due to modifications that occur in their immunological system. These modifications compromise natural defences, such as skin and nails, especially from lower limbs. Aims. Assessing the presence of dermatomycosis in lower limbs of Portuguese diabetic patients followed on Podiatry consultation. Determination of possible predisposing factors and the most frequent fungal species associated with the cases are included in the study. Methods. A six-month prospective study was carried out in 163 diabetic patients with signs and symptoms of dermatomycosis followed by Podiatry at the Portuguese Diabetes Association in Lisbon. Samples from the skin and/or nails of the lower limbs were collected and demographic and clinical data of those patients were recorded. Results. Trichophyton rubrum was the most frequently isolated dermatophyte (12.1%), followed by Trichophyton mentagrophytes (7.7%) and Trichophyton tonsurans (4.4%). Our study showed positive associations between type 2 diabetes and the presence of dermatomycosis in the studied population (p=0.013); this association was also shown between the occurrence of dermatomycosis and the localization of the body lesion (p=0.000). No other predisposing factor tested was positively associated with infection (p>0.05). Conclusions. Data on superficial fungal infections in diabetic patients are scarce in Portugal. This study provides information on the characterization of dermatomycosis in lower limbs of diabetic patients(AU)

Dermatomycosis in lower limbs of diabetic patients followed by podiatry consultation.

BACKGROUND: Diabetic patients are particularly susceptible to fungal infections due to modifications that occur in their immunological system. These modifications compromise natural defences, such as skin and nails, especially from lower limbs. AIMS: Assessing the presence of dermatomycosis in lower limbs of Portuguese diabetic patients followed on Podiatry consultation. Determination of possible predisposing factors and the most frequent fungal species associated with the cases are included in the study. METHODS: A six-month prospective study was carried out in 163 diabetic patients with signs and symptoms of dermatomycosis followed by Podiatry at the Portuguese Diabetes Association in Lisbon. Samples from the skin and/or nails of the lower limbs were collected and demographic and clinical data of those patients were recorded. RESULTS: Trichophyton rubrum was the most frequently isolated dermatophyte (12.1%), followed by Trichophyton mentagrophytes (7.7%) and Trichophyton tonsurans (4.4%). Our study showed positive associations between type 2 diabetes and the presence of dermatomycosis in the studied population (p=0.013); this association was also shown between the occurrence of dermatomycosis and the localization of the body lesion (p=0.000). No other predisposing factor tested was positively associated with infection (p>0.05). CONCLUSIONS: Data on superficial fungal infections in diabetic patients are scarce in Portugal. This study provides information on the characterization of dermatomycosis in lower limbs of diabetic patients.

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.