Addition of intermittently scanned continuous glucose monitoring to standard care in a cohort of pregnant women with type 1 diabetes: effect on glycaemic control and pregnancy outcomes.

AIMS/HYPOTHESIS: The aim of this study was to assess whether the addition of intermittently scanned continuous glucose monitoring (isCGM) to standard care (self-monitoring of blood glucose [SMBG] alone) improves glycaemic control and pregnancy outcomes in women with type 1 diabetes and multiple daily injections. METHODS: This was a multicentre observational cohort study of 300 pregnant women with type 1 diabetes in Spain, including 168 women using SMBG (standard care) and 132 women using isCGM in addition to standard care. In addition to HbA1c, the time in range (TIR), time below range (TBR) and time above range (TAR) with regard to the pregnancy glucose target range (3.5-7.8 mmol/l) were also evaluated in women using isCGM. Logistic regression models were performed for adverse pregnancy outcomes adjusted for baseline maternal characteristics and centre. RESULTS: The isCGM group had a lower median HbA1c in the second trimester than the SMBG group (41.0 [IQR 35.5-46.4] vs 43.2 [IQR 37.7-47.5] mmol/mol, 5.9% [IQR 5.4-6.4%] vs 6.1% [IQR 5.6-6.5%]; p=0.034), with no differences between the groups in the other trimesters (SMBG vs isCGM: first trimester 47.5 [IQR 42.1-54.1] vs 45.9 [IQR 39.9-51.9] mmol/mol, 6.5% [IQR 6.0-7.1%] vs 6.4% [IQR 5.8-6.9%]; third trimester 43.2 [IQR 39.9-47.5] vs 43.2 [IQR 39.9-47.5] mmol/mol, 6.1% [IQR 5.8-6.5%] vs 6.1% [IQR 5.7-6.5%]). The whole cohort showed a slight increase in HbA1c from the second to the third trimester, with a significantly higher rise in the isCGM group than in the SMBG group (median difference 2.2 vs 1.1 mmol/mol [0.2% vs 0.1%]; p=0.033). Regarding neonatal outcomes, newborns of women using isCGM were more likely to have neonatal hypoglycaemia than newborns of non-sensor users (27.4% vs 19.1%; ORadjusted 2.20 [95% CI 1.14, 4.30]), whereas there were no differences between the groups in large-for-gestational-age (LGA) infants (40.6% vs 45.1%; ORadjusted 0.73 [95% CI 0.42, 1.25]), Caesarean section (57.6% vs 48.8%; ORadjusted 1.33 [95% CI 0.78, 2.27]) or prematurity (27.3% vs 24.8%; ORadjusted 1.05 [95% CI 0.55, 1.99]) in the adjusted models. A sensitivity analysis in pregnancies without LGA infants or prematurity also showed that the use of isCGM was associated with a higher risk of neonatal hypoglycaemia (non-LGA: ORadjusted 2.63 [95% CI 1.01, 6.91]; non-prematurity: ORadjusted 2.52 [95% CI 1.12, 5.67]). For isCGM users, the risk of delivering an LGA infant was associated with TIR, TAR and TBR in the second trimester in the logistic regression analysis. CONCLUSIONS/INTERPRETATION: isCGM use provided an initial improvement in glycaemic control that was not sustained. Furthermore, offspring of isCGM users were more likely to have neonatal hypoglycaemia, with similar rates of macrosomia and prematurity to those of women receiving standard care.

Cost-effectiveness of multicomponent interventions in type 2 diabetes mellitus in a cluster randomised controlled trial: the INDICA study.

OBJECTIVE: To analyse the cost-effectiveness of multicomponent interventions designed to improve outcomes in type 2 diabetes mellitus (T2DM) in primary care in the Canary Islands, Spain, within the INDICA randomised clinical trial, from the public health system perspective. DESIGN: An economic evaluation was conducted for the within-trial period (2 years) comparing the four arms of the INDICA study. SETTING: Primary care in the Canary Islands, Spain. PARTICIPANTS: 2334 patients with T2DM without complications were included. INTERVENTIONS: Interventions for patients (PTI), for primary care professionals (PFI), for both (combined intervention arm for patients and professionals, CBI) and usual care (UC) as a control group. OUTCOMES: The main outcome was the incremental cost per quality-adjusted life-years (QALY). Only the intervention and the healthcare costs were included. ANALYSIS: Multilevel models were used to estimate results, and to measure the size and significance of incremental changes. Missed values were treated by means of multiple imputations procedure. RESULTS: There were no differences between arms in terms of costs (p=0.093), while some differences were observed in terms of QALYs after 2 years of follow-up (p=0.028). PFI and CBI arms were dominated by the other two arms, PTI and UC. The differences between the PTI and the UC arms were very small in terms of QALYs, but significant in terms of healthcare costs (p=0.045). The total cost of the PTI arm (€2571, 95% CI €2317 to €2826) was lower than the cost in the UC arm (€2750, 95% CI €2506 to €2995), but this difference did not reach statistical significance. Base case estimates of the incremental cost per QALY indicate that the PTI strategy was the cost-effective option. CONCLUSIONS: The INDICA intervention designed for patients with T2DM and families is likely to be cost-effective from the public healthcare perspective. A cost-effectiveness model should explore this in the long term. TRIAL REGISTRATION NUMBER: NCT01657227.

Patient-reported outcome measures for knowledge transfer and behaviour modification interventions in type 2 diabetes-the INDICA study: a multiarm cluster randomised controlled trial.

OBJECTIVE: This study assesses the effectiveness of different interventions of knowledge transfer and behaviour modification to improve type 2 diabetes mellitus patients' (T2DM) reported outcomes measures (PROMs) in the long-term. Design: open, community-based pragmatic, multicentre, controlled trial with random allocation by clusters to usual care (UC) or to one of the three interventions. PARTICIPANTS: A total of 2334 patients with uncomplicated T2DM and 211 healthcare professionals were included of 32 primary care centres. SETTING: Primary Care Centers in Canary Islands (Spain). INTERVENTION: The intervention for patients (PTI) included an educational group programme, logs and a web-based platform for monitoring and automated short message service (SMS). The intervention for professionals (PFI) included an educational programme, a decision support tool embedded into the electronic clinical record and periodic feedback about patients' results. A third group received both PTI and PFI (combined intervention, CBI). OUTCOME MEASURE: Cognitive-attitudinal, behavioural, affective and health-related quality of life (HQoL) variables. RESULTS: Compared with UC at 24 months, the PTI group significantly improved knowledge (p=0.005), self-empowerment (p=0.002), adherence to dietary recommendations (p<0.001) and distress (p=0.01). The PFI group improved at 24 months in distress (p=0.03) and at 12 months there were improvements in depression (p=0.003), anxiety (p=0.05), HQoL (p=0.005) and self-empowerment (p<0.001). The CBI group improved at 24 months in self-empowerment (p=0.008) and adherence to dietary recommendations (p=0.004) and at 12 months in knowledge (p=0.008), depression (p=0.006), anxiety (p=0.003), distress (p=0.01), HQoL (p<0.001) and neuropathic symptoms (p=0.02). Statistically significant improvements were also observed at 24 months in the proportion of patients who quit smoking for PTI and CBI (41.5% in PTI and 42.3% in CBI vs 21.2% in the UC group). CONCLUSIONS: Assessed interventions to improve PROMs in T2DM attain effectiveness for knowledge, self-empowerment, distress, diet adherence and tobacco cessation. PTI produced the most lasting benefits. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01657227 (6 August 2012) https://clinicaltrials.gov/ct2/show/NCT01657227.

Prehabilitation for Bariatric Surgery: A Randomized, Controlled Trial Protocol and Pilot Study.

Bariatric surgery is the most efficacious treatment for obesity, though it is not free from complications. Preoperative conditioning has proved beneficial in various clinical contexts, but the evidence is scarce on the role of prehabilitation in bariatric surgery. We describe the protocol and pilot study of a randomized (ratio 1:1), parallel, controlled trial assessing the effect of a physical conditioning and respiratory muscle training programme, added to a standard 8-week group intervention based on therapeutical education and cognitive-behavioural therapy, in patients awaiting bariatric surgery. The primary outcome is preoperative weight-loss. Secondary outcomes include associated comorbidity, eating behaviour, physical activity, quality of life, and short-term postoperative complications. A pilot sample of 15 participants has been randomized to the intervention or control groups and their baseline features and results are described. Only 5 patients completed the group programme and returned for assessment. Measures to improve adherence will be implemented and once the COVID-19 pandemic allows, the clinical trial will start. This is the first randomized, clinical trial assessing the effect of physical and respiratory prehabilitation, added to standard group education and cognitive-behavioural intervention in obese patients on the waiting list for bariatric surgery. Clinical Trial Registration: NCT0404636.

Ultrasonographic evaluation of adrenal gland size in two body weight categories of healthy adult cats.

OBJECTIVES: Adrenal gland size and its association with body weight have been rarely evaluated in cats. This study was undertaken to assess the association between feline body weight and adrenal gland thickness, and to propose reference intervals (RIs) for adrenal gland thickness in healthy cats. METHODS: This was a cross-sectional study in which 39 healthy cats were included. The cats were divided into two weight categories, classified as ⩽4.0 kg and >4-8 kg of ideal body weight (with 13 and 26 cats in each group, respectively), which took into consideration the body condition score of the cats. All cats underwent an ultrasound examination that was taken from a subcostal position. Maximum dorsoventral thicknesses of the left (MTL) and right (MTR) adrenal glands were measured in a sagittal plane. RIs were obtained for the maximum thickness (MT), which included the MTLs and MTRs of each cat. RIs with the 90% confidence intervals were calculated according to American Society for Veterinary Clinical Pathology guidelines on RIs. RESULTS: No statistical differences for adrenal gland thickness were observed between the left and right (P = 0.543) adrenal glands or between male and female cats (P = 0.943). Mean MT was significantly greater in the group of cats weighing >4-8 kg compared with the group of cats weighing ⩽4 kg (3.7 ± 0.6 vs 3.2 ± 0.4 mm; P <0.005). The lower limit of the RI for MT was 2.4 mm (range 2.2-2.6 mm) in the group weighing ⩽4 kg and 2.6 mm (range 2.4-2.8 mm) in the group weighing >4-8 kg. The upper limit of the RI for MT was 3.9 mm (range 3.7-4.1 mm) in the group of cats weighing ⩽4 kg and 4.8 mm (range 4.6-5.1 mm) in the group of cats weighing >4-8 kg. CONCLUSIONS AND RELEVANCE: The use of RIs based on two group sizes allows for a more accurate ultrasonographic evaluation of adrenal gland thickness in cats. The maximum normal adrenal gland thickness is lower in smaller cats (3.9 mm for those weighing ⩽4 kg and 4.8 mm for those weighing >4-8 kg).

Epidemiology of childhood-onset type 1 diabetes in Gran Canaria (2006-2018) / Epidemiología de la diabetes tipo 1 en la infancia en Gran Canaria (2006-2018)

AIMS: To study the incidence of type 1 diabetes (T1D) in children <14 years in the island of Gran Canaria (Canary Islands, Spain) during the 2006-2018 period and to evaluate its temporal trend, seasonality, age and sex distribution. Subjects and methods: We studied children <14 years of age living in Gran Canaria. We calculated the annual and overall incidence using recorded data from the Pediatric Endocrinology Department as the primary source and the local Diabetes Association and the hospital's pharmacy as secondary sources. The primary source is the only paediatric endocrine unit in the island. RESULTS: 453 new T1D cases were observed during the 13-year period. The overall incidence of T1D between 2006 and 2018 was 30.48/100,000 (95% CI: 27.74-33.42). Distribution among age groups was 24.8%, 38.2% and 36.9% for children between 0-4, 5-9 and 10-13.9 years old respectively. No significant temporal trend, seasonality or sex differences were found. CONCLUSIONS: Our study shows that the Island of Gran Canaria has one of the highest childhood incidences of T1D reported worldwide: among the highest rates in Europe, and higher than the rates published for the neighbouring African countries

OBJETIVOS: Estudiar la incidencia de diabetes mellitus tipo 1 (DM1) en niños menores de 14 años en la isla de Gran Canaria (Islas Canarias, España) durante el período 2006-2018, así como evaluar su tendencia temporal, estacionalidad y distribución por sexo y edad. Sujetos y métodos: Los sujetos objeto de estudio fueron los niños menores de 14 años que habitan la isla de Gran Canaria. Calculamos la incidencia para todo el período, y la incidencia anual usando los datos recogidos en nuestra unidad de endocrinología pediátrica como fuente primaria y los datos de la asociación local de diabetes y la farmacia hospitalaria como fuentes secundarias. La fuente primaria es la única unidad de endocrinología pediátrica de la isla. RESULTADOS: Observamos un total de 453 nuevos casos de DM1 durante el período de estudio. La incidencia global para el período 2006-2018 fue de 30,48/100.000 (IC 95%: 27,74-33,42). La distribución por grupos de edad fue del 24,8, 38,2 y 36,9% para niños entre 0-4, 5-9 y 10-13,9 años de edad, respectivamente. No encontramos la aparición de ninguna tendencia temporal significativa. Tampoco encontramos la presencia de estacionalidad ni diferencias significativas en cuanto a la aparición de DM1 en base al sexo. CONCLUSIONES: Nuestro estudio muestra que la isla de Gran Canaria presenta una de las incidencias de DM1 más altas del mundo. Se encuentra entre las más altas de Europa, y es claramente superior a la publicada para los países vecinos africanos

Epidemiology of childhood-onset type 1 diabetes in Gran Canaria (2006-2018).

AIMS: To study the incidence of type 1 diabetes (T1D) in children <14 years in the island of Gran Canaria (Canary Islands, Spain) during the 2006-2018 period and to evaluate its temporal trend, seasonality, age and sex distribution. SUBJECTS AND METHODS: We studied children <14 years of age living in Gran Canaria. We calculated the annual and overall incidence using recorded data from the Pediatric Endocrinology Department as the primary source and the local Diabetes Association and the hospital's pharmacy as secondary sources. The primary source is the only paediatric endocrine unit in the island. RESULTS: 453 new T1D cases were observed during the 13-year period. The overall incidence of T1D between 2006 and 2018 was 30.48/100,000 (95% CI: 27.74-33.42). Distribution among age groups was 24.8%, 38.2% and 36.9% for children between 0-4, 5-9 and 10-13.9 years old respectively. No significant temporal trend, seasonality or sex differences were found. CONCLUSIONS: Our study shows that the Island of Gran Canaria has one of the highest childhood incidences of T1D reported worldwide: among the highest rates in Europe, and higher than the rates published for the neighbouring African countries.

Autosomal recessive hypercholesterolemia in Spain.

BACKGROUND AND AIMS: Autosomal recessive hypercholesterolemia (ARH) is a very rare disease, caused by mutations in LDL protein receptor adaptor 1 (LDLRAP1). It is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature cardiovascular disease. We aimed to characterize ARH in Spain. METHODS: Data were collected from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. A literature search was performed up to June 2017, and all diagnostic genetic studies for familial hypercholesterolemia of Spain were reviewed. RESULTS: Seven patients with ARH were identified, 6 true homozygous and one compound heterozygous with a novel mutation: c.[863C>T];p.[Ser288Leu]. High genetic heterogeneity was found in this cohort. True homozygous subjects for LDLRAP1 have more severe phenotypes than the compound heterozygous patient, but similar to patients with homozygous familial hypercholesterolemia (HoFH). Cardiovascular disease was present in 14% of the ARH patients. LDL-C under treatment was above 185 mg/dl and the response to PCSK9 inhibitors was heterogeneous. Finally, the estimated prevalence in Spain is very low, with just 1 case per 6.5 million people. CONCLUSIONS: ARH is a very rare disease in Spain, showing high genetic heterogeneity, similarly high LDL-C concentrations, but lower incidence of ASCVD than HoFH.

Onset of Graves' disease during pregnancy in a woman with established hypothyroidism.

BACKGROUND: Pregnancy strongly influences the thyroid gland and its function. Thyroid guidelines recommend a 30 to 50% increase of the preconceptional levothyroxine dose in women with hypothyroidism, when pregnancy is diagnosed. CASE: A 33 year-old, 8-week pregnant woman with hypothyroidism, presents with a 2-week history of palpitations, sweating, nervousness and fatigue. Physical examination shows tachycardia (108 bpm), distal tremors and diffuse goiter. After biochemical confirmation of hyperthyroidism, her levothyroxine dose is reduced and finally interrupted. Propylthiouracil is started and maintained until after the delivery of a healthy baby at week 40. Two weeks postpartum, hyperthyroidism worsens and propylthiouracil is replaced by methimazole. Eighteen months after delivery 7.5 mCi 131Iodine was given. Two months later, hypothyroidism developed and levothyroxine was initiated. CONCLUSION: Although conversion of Hashimoto's hypothyroidism into Graves' disease is exceptional in pregnancy, pregnant women with autoimmune hypothyroidism should ideally have their TSH concentrations measured before empirically increasing their levothyroxine dose.

Study of the pathogenesis and treatment of diabetes mellitus through animal models / Estudio de la patogénesis y tratamiento de la diabetes mellitus a través de modelos animales

Most research in diabetes mellitus (DM) has been conducted in animals, and their replacement is currently a chimera. As compared to when they started to be used by modern science in the 17th century, a very high number of animal models of diabetes is now available, and they provide new insights into almost every aspect of diabetes. Approaches combining human, in vitro, and animal studies are probably the best strategy to improve our understanding of the underlying mechanisms of diabetes, and the choice of the best model to achieve such objective is crucial. Traditionally classified based on pathogenesis as spontaneous or induced models, each has its own advantages and disadvantages. The most common animal models of diabetes are described, and in addition to non-obese diabetic mice, biobreeding diabetes-prone (BB-DP) rats, streptozotocin-induced models, or high-fat diet-induced diabetic C57Bl/6J mice, new valuable models, such as dogs and cats with spontaneous diabetes, are described (AU)

La mayoría de la investigación desarrollada en diabetes ha sido realizada mediante el uso de modelos animales, siendo su reemplazo todavía una quimera. Comparado con los primeros usos de estos modelos por la ciencia moderna, a partir del siglo XVII, el número de modelos animales disponible en la actualidad es muy elevado, ofreciendo nuevas perspectivas dentro de casi todos los aspectos de la enfermedad. Los abordajes que combinen estudios en humanos, in vitro y modelos animales son probablemente la mejor estrategia para mejorar el entendimiento de los mecanismos de la enfermedad aún subyacentes y, en este sentido, la elección del modelo que más se ajuste a dichos objetivos es determinante. Clasificados tradicionalmente en función de su patogénesis, en espontáneos o inducidos, cada modelo ofrece sus propias ventajas y desventajas. Se describen aquí los modelos de diabetes más comunes y, aparte del ratón Non-obese-Diabetic, la rata BioBreeding Diabetes-Prone, u otros modelos inducidos por estreptozotocina o dieta con alto contenido graso, se describen otros valiosos modelos de diabetes, como son el perro y el gato con diabetes espontáneas tipo 1 y tipo 2 (AU)

Study of the pathogenesis and treatment of diabetes mellitus through animal models.

Most research in diabetes mellitus (DM) has been conducted in animals, and their replacement is currently a chimera. As compared to when they started to be used by modern science in the 17th century, a very high number of animal models of diabetes is now available, and they provide new insights into almost every aspect of diabetes. Approaches combining human, in vitro, and animal studies are probably the best strategy to improve our understanding of the underlying mechanisms of diabetes, and the choice of the best model to achieve such objective is crucial. Traditionally classified based on pathogenesis as spontaneous or induced models, each has its own advantages and disadvantages. The most common animal models of diabetes are described, and in addition to non-obese diabetic mice, biobreeding diabetes-prone (BB-DP) rats, streptozotocin-induced models, or high-fat diet-induced diabetic C57Bl/6J mice, new valuable models, such as dogs and cats with spontaneous diabetes, are described.

Effect of liraglutide on physical performance in type 2 diabetes (LIPER2): A randomised, double-blind, controlled trial.

Preclinical studies and small clinical trials suggest that glucagon-like peptide 1 (GLP1) may have a positive effect on ventricular function. Liraglutide is a GLP1-analogue used in the treatment of type 2 diabetes. LIPER2 is a phase IV, randomised, double-blind, placebo-controlled, parallel-design trial, assessing the effect of 6 months' liraglutide 1.8 mg/d on measures of cardiac function and physical performance in patients with type 2 diabetes. A total of 30 patients with type 2 diabetes will be included, if their HbA1c is between 7 and 10% while on oral agents (including metformin if tolerated and not contraindicated), a maximum of 2 intermediate or long-acting insulin injections per day or a combination of both. After their baseline examinations, patients are randomised to receive a daily subcutaneous liraglutide or placebo injection (titrated to 1.8 mg/d if tolerated) for 6 months. The primary end-point is the maximal oxygen consumption during cycle ergometry at the end of the study period. Other end-points include distance covered during a 6-min walk test, left ventricular ejection fraction and other measures of ventricular systolic and diastolic functions assessed by echocardiography, heart rate, blood pressure, pro-brain natriuretic peptide, C-reactive protein, HbA1c, lipids, apolipoprotein B, body weight and waist girth. Safety end-points include adverse event reporting, blood count, kidney and liver function, amylase, lipase, electrolytes, calcitonin, CA19.9 and pregnancy test for fertile women. At the time of this report, recruitment is still ongoing. Results are expected to be reported in December 2016.

Quality of life and type 1 diabetes: a study assessing patients' perceptions and self-management needs.

PURPOSE: The main objective of this study was to assess quality of life (QoL) and treatment satisfaction in a group of patients with type 1 diabetes (T1D) and explore their needs regarding and their perception of QoL living with diabetes. MATERIALS AND METHODS: Patients with type 1 diabetes attending the outpatient endocrinology clinics of a reference hospital were invited to participate in a cross-sectional study. Clinical and sociodemographic data were obtained (interview and clinical records), and diabetes-related QoL was assessed using a standardized questionnaire. In 67 participants, satisfaction with treatment was also assessed, and an open interview was performed, assessing the impact of diabetes, long-term worries, flexibility, restrictions, and self-perception of QoL. Descriptive statistical analysis, bivariate analysis, and multivariate analysis were performed in order to find factors associated with QoL. Interviews were analyzed and summarized questionwise. RESULTS: Mean patient age was 31.4±11.6 years, diabetes duration 14.2±9.3 years, and glycated hemoglobin (HbA1c) 8.5%±1.9% (69±20.8 mmol/mol International Federation of Clinical Chemistry [IFCC]). The questionnaires showed good average QoL scores (94.6+22.9) and treatment satisfaction scores (25.7±6.7). QoL worsened with increasing HbA1c, female sex, severity of complications, and lower education (r (2)=0.283, P<0.005). In the open interview, 68.5% of the patients reported that diabetes had changed their lives, 83.5% identified complications as their most important long-term concern, and 59.7% said that they needed more training to manage the disease. CONCLUSION: Poor glycemic control, lower education, complications, and female sex are associated with worse QoL. Semi-structured interviews identified aspects not included in the standardized questionnaires.

Design, construction, and implementation of an online platform for patients with type 1 diabetes: EncoDiab.

PURPOSE: The purpose of this study was to develop, build, and implement a virtual platform equipped with practical tools, relevant contents, and communication rooms, with the aim of facilitating patients' self-management of type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: The design of the platform was based on the suggestions of T1DM patients who were being managed at two reference hospitals. Patients' needs and preferences were identified in group discussion sessions. Before having access to the platform, patients underwent a baseline assessment, which included physical examination and the administration of validated questionnaires for evaluation of clinical background, quality of life, treatment satisfaction, and well-being. RESULTS: A total of 33 patients were included in the study; 54.5% of them were men, their median age was 34 (18-50) years, the median duration of diabetes was 15 (1-38) years, and the median A1C was 7.4% (6%-12.6%). Based on their suggestions and requests, the online platform EncoDiab was built and organized into four domains: a personal domain, two domains shared by the patients and the staff of each of the two participating hospitals, and one domain that was accessible to all participants. The platform included practical tools (a body mass index calculator, a carbohydrate counting tool, and an insulin-dose calculator), a library with relevant information (documents on prevention and treatment of acute complications, nutrition, exercise, etc), and a chat room. CONCLUSION: Although the study is still ongoing, our current results demonstrate the feasibility of building and implementing an online platform for helping T1DM patients in the self-management of their disease in the public health setting.

Effectiveness and cost-effectiveness of knowledge transfer and behavior modification interventions in type 2 diabetes mellitus patients--the INDICA study: a cluster randomized controlled trial.

BACKGROUND: Type 2 diabetes mellitus is a chronic disease whose health outcomes are related to patients and healthcare professionals' decision-making. The Diabetes Intervention study in the Canary Islands (INDICA study) aims to evaluate the effectiveness and cost-effectiveness of educational interventions supported by new technology decision tools for type 2 diabetes patients and primary care professionals in the Canary Islands. METHODS/DESIGN: The INDICA study is an open, community-based, multicenter, clinical controlled trial with random allocation by clusters to one of three interventions or to usual care. The setting is primary care where physicians and nurses are invited to participate. Patients with diabetes diagnosis, 18-65 years of age, and regular users of mobile phone were randomly selected. Patients with severe comorbidities were excluded. The clusters are primary healthcare practices with enough professionals and available places to provide the intervention. The calculated sample size was 2,300 patients. Patients in group 1 are receiving an educational group program of eight sessions every 3 months led by trained nurses and monitored by means of logs and a web-based platform and tailored semi-automated SMS for continuous support. Primary care professionals in group 2 are receiving a short educational program to update their diabetes knowledge, which includes a decision support tool embedded into the electronic clinical record and a monthly feedback report of patients' results. Group 3 is receiving a combination of the interventions for patients and professionals. The primary endpoint is the change in HbA1c in 2 years. Secondary endpoints are cardiovascular risk factors, macrovascular and microvascular diabetes complications, quality of life, psychological outcomes, diabetes knowledge, and healthcare utilization. Data is being collected from interviews, questionnaires, clinical examinations, and records. Generalized linear mixed models with repeated time measurements will be used to analyze changes in outcomes. The cost-effectiveness analysis, from the healthcare services perspective, involves direct medical costs per quality-adjusted life year gained and two periods, a 'within-trial' period and a lifetime Markov model. Deterministic and probabilistic sensitivity analyses are planned. DISCUSSION: This ongoing trial aims to set up the implementation of evidence-based programs in the clinical setting for chronic patients. TRIAL REGISTRATION: Clinical Trial.gov NCT01657227.

Effect of statin and fibrate treatment on inflammation in type 2 diabetes. A randomized, cross-over study.

A randomized, crossover study compared the effects of atorvastatin, gemfibrozil and their combination on inflammatory markers in type 2 diabetes. C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2), secretory phospholipase A2 (sPLA2), interleukin 8 (IL8), monocyte chemotactic protein 1 (MCP1) and tumor necrosis factor α (TNFα) were measured. Both lipid-lowering drugs had positive, complementary and additive effects on inflammatory markers, which were closely related to baseline inflammatory status.

Electronegative low-density lipoprotein subfraction from type 2 diabetic subjects is proatherogenic and unrelated to glycemic control.

BACKGROUND: The physicochemical and biological characteristics of electronegative low-density lipoprotein (LDL) (LDL(-)) from type 2 diabetic patients (DM2), before and after insulin therapy, were studied. METHODS: Total LDL was subfractionated in LDL(+) (native LDL) and LDL(-) by anion-exchange chromatography. RESULTS: The proportion of LDL(-) was increased in plasma from DM2 patients compared to control subjects (13.8 +/- 4.6% versus 6.1 +/- 2.5, P < 0.05) and was not modified after glycemic optimization (14.0 +/- 5.9%). LDL(-) from DM2 patients presented similar differential characteristics versus LDL(+) than LDL(-) from controls; that is, decreased apoB and oxidizability, and increased triglyceride, nonesterified fatty acids (NEFA), apoE, apoC-III, platelet-activating factor (PAF) acetylhydrolase activity and aggregability. No difference in particle size, antioxidants, malondialdehyde (MDA), fructosamine or glycated low-density lipoprotein (gLDL) was observed between LDL subfractions. Concerning differences between LDL subfractions isolated from DM2 and from control subjects, the former showed increased MDA, fructosamine and gLDL proportion and decreased LDL size and antioxidant content. The only effect of glycemic optimization was a decrease in fructosamine and gLDL in LDL(+) from DM2 subjects. LDL(-) from DM2 patients presented low binding affinity to the low-density lipoprotein receptor (LDLr) in cultured fibroblasts compared to LDL(+) and two- to threefold increased ability to release interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells. CONCLUSION: These results suggest that, although nonenzymatic glycosylation and oxidation are increased in type 2 diabetes, these features would not be directly involved in the generation of LDL(-). Moreover, LDL(-) properties suggest that the high proportion observed in plasma could promote accelerated atherosclerosis in DM2 patients through increased residence time in plasma and induction of inflammatory responses in artery wall cells.

Postprandial thrombin activatable fibrinolysis inhibitor and markers of endothelial dysfunction in type 2 diabetic patients.

The aim of this study was to assess postprandial changes in thrombin activatable fibrinolysis inhibitor (TAFI) antigen, a thrombin-dependent fibrinolysis inhibitor with anti-inflammatory properties, and soluble markers of endothelial dysfunction in normotriglyceridemic type 2 diabetic patients. Fasting and postprandial TAFI antigen, thrombomodulin, tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor 1 were assessed in 12 normotriglyceridemic type 2 diabetic patients treated with diet (hemoglobin A1c, 6.80% +/- 0.67%) and 14 controls. Fasting low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, free fatty acids and apolipoprotein B, and fasting and postprandial triglyceride, glucose, and insulin were also measured. Fasting TAFI was higher in the control group (102% +/- 16.9% vs 72.9% +/- 15.9%; P < .0005) and was inversely correlated with glycemic control. It decreased 4 hours after the meal (31.8% reduction [P < .005] for controls and 12.6% [P < .05] for diabetic patients) and returned to fasting levels after 8 hours. This decrement was correlated with fasting TAFI, glucose and hemoglobin A1c, and the area under the curve of glucose. Thrombomodulin, TFPI, and plasminogen activator inhibitor 1 were similar in both groups, with thrombomodulin and TFPI showing a transient postprandial increase. A fat-rich meal produces a transient increase in markers of endothelial dysfunction and a temporary reduction in TAFI, an anti-inflammatory molecule whose concentration is low in type 2 diabetes mellitus.