Metabolic and Clinical Outcomes in Type 1 Diabetes in the COVID-19 Pre- and Post-Vaccination Periods in Spain: The COVID-SED1 Study.

Aims: To evaluate the metabolic and clinical outcomes in the Spanish type 1 diabetes mellitus (T1D) population before and after COVID-19 vaccination. Methods: A retrospective observational study was carried out in Spanish public hospitals previously enrolled in the SED1 study. Adults and children with T1D were included and their clinical electronic records were reviewed. Clinical, laboratory, and glucometric parameters from continuous glucose monitoring (CGM) data corresponding to the periods before and after administering the first COVID-19 vaccination were analyzed. Results: A total of 26 centers and 228 patients participated in this new phase of the SED1 study and 187 were finally evaluable (mean age 37.5 ± 15.6 years, 56.7% women). Overall, 94.6% of the sample was vaccinated, and this percentage increased with higher levels of education (p-value = 0.027). In the pre- and post-vaccination periods, respectively, the number of patients with acute hyperglycemic decompensation was 6/161 (3.7%) and 7/161 (4.3%) (p = 1) and with acute hypoglycemic decompensation was 6/161 (3.7%) and 6/161 (3.7%) (p = 1). The HbA1c level was lower in the post-vaccination period(mean ± SD, mg/dL): pre-vaccination 7.4 ± 0.9; post-vaccination 7.2 ± 1.0, (-0.19; p-value = 0.0006). A total of 31.9% of patients (95% CI: 24.7-39.7) in the pre-vaccination period and 45.0% (IC95%: 37.1-53.1) in the post-vaccine period had HbA1c < 7% (p-value < 0.001). Glucometrics from CGM data also showed numerical improvements post-vaccination. Conclusions: The COVID-19 vaccination was highly accepted in the Spanish T1D population, with hesitancy about the COVID-19 vaccine being higher in those with lower educational levels. A mildly better glycemic control was observed in the post-vaccination period.

Association between exposure to air pollution and blood lipids in the general population of Spain.

BACKGROUND AND AIMS: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain. METHODS: We included 4647 adults (>18 years), participants in the national, cross-sectional, population-based di@bet.es study, conducted in 2008-2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1 H-NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter <10 µm (PM10 ), <2.5 µm (PM2.5 ) and nitrogen dioxide (NO2 ), corresponding to the health examination year, obtained by modelling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). RESULTS: In multivariate linear regression models, each IQR increase in PM10 , PM2.5 and NO2 was associated with 3.3%, 3.3% and 3% lower levels of HDL-c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL-p) concentrations (p < .001 for all associations). In multivariate logistic regression, there was a significant association between PM10 , PM2.5 and NO2 concentrations and the odds of presenting low HDL-c (<40 mg/dL), low HDL-p (

Ambient air pollution and thyroid function in Spanish adults. A nationwide population-based study (Di@bet.es study).

BACKGROUND: Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain. METHODS: The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5µm (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche). RESULTS: In multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM2.5 (4.86 µg/m3). There was no association between NO2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women. CONCLUSIONS: Exposures to PM2.5 in the general population were associated with mild alterations in thyroid function.

Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers.

Objective: The minimally invasive fine-needle aspiration cytology (FNAC) is the current gold standard for the diagnosis of thyroid nodule malignancy. However, the correct discrimination of follicular neoplasia often requires more invasive diagnostic techniques. The lack of suitable immunohistochemical markers to distinguish between follicular thyroid carcinoma and other types of follicular-derived lesions complicates diagnosis, and despite most of these tumours being surgically resected, only a small number will test positive for malignancy. As such, the development of new orthogonal diagnostic approaches may improve the accuracy of diagnosing thyroid nodules. Design: This study includes a retrospective, multi-centre training cohort including 54 fresh-frozen follicular-patterned thyroid samples and two independent, multi-centre validation cohorts of 103 snap-frozen biopsies and 33 FNAC samples, respectively. Methods: We performed a genome-wide genetic and epigenetic profiling of 54 fresh-frozen follicular-patterned thyroid samples using exome sequencing and the Illumina Human DNA Methylation EPIC platform. An extensive validation was performed using the bisulfite pyrosequencing technique. Results: Using a random forest approach, we developed a three-CpG marker-based diagnostic model that was subsequently validated using bisulfite pyrosequencing experiments. According to the validation cohort, this cost-effective method discriminates between benign and malignant nodules with a sensitivity and specificity of 97 and 88%, respectively (positive predictive value (PPV): 0.85, negative predictive value (NPV): 0.98). Conclusions: Our classification system based on a minimal set of epigenetic biomarkers can complement the potential of the diagnostic techniques currently available and would prioritize a considerable number of surgical interventions that are often performed due to uncertain cytology. Significance statement: In recent years, there has been a significant increase in the number of people diagnosed with thyroid nodules. The current challenge is their etiological diagnosis to discount malignancy without resorting to thyroidectomy. The method proposed here, based on DNA pyrosequencing assays, has high sensitivity (0.97) and specificity (0.88) for the identification of malignant thyroid nodules. This simple and cost-effective approach can complement expert pathologist evaluation to prioritize the classification of difficult-to-diagnose follicular-patterned thyroid lesions and track tumor evolution, including real-time monitoring of treatment efficacy, thereby stimulating adherence to health promotion programs.

Acromegaly disease activity according to ACRODAT®, a cross-sectional study in Spain: ACROVAL study.

OBJECTIVES: To evaluate disease activity status using the Acromegaly Disease Activity Tool (ACRODAT®) in a cohort of Spanish acromegaly patients, to assess the relationship between the level of disease activity according to both ACRODAT® and the physicians' clinical evaluation, and to study the potential discrepancies in the perception of symptoms between physicians and patients. DESIGN: Multicenter, observational, descriptive and cross-sectional study. METHODS: Disease activity was assessed in adult patients with acromegaly under pharmacological treatment during at least 6 months using ACRODAT®. RESULTS: According to ACRODAT®, 48.2%, 31.8% and 20.0% of a total of 111 patients were classified as having a stable disease (S), mild disease activity (M-DA) and significant disease activity (S-DA) respectively. ACRODAT® classification of disease activity significantly correlated with physicians' opinion, with a moderate inter-rater agreement and a specificity of 92.45% (PPV = 86.21%). No correlation was found between IGF-I levels and severity of symptoms or quality of life (QoL). A decision to take clinical action was significantly more frequent in S-DA and M-DA patients than S patients but no action was taken on 5 (22.7%) and 27 (77.1%) S-DA and M-DA patients, respectively CONCLUSIONS: ACRODAT® detected disease activity in 51.8% of patients. Interestingly, although M-DA and S-DA patients were likely to be in the process of being controlled, action was not always taken on these patients. ACRODAT® is a validated and highly specific tool that may be useful to routinely monitor acromegaly and to identify patients with non-obvious disease activity by incorporating "patient-centred" parameters like symptoms and QoL to the clinical evaluation of acromegaly.

Clinical characteristics and management of type 1 diabetes in Spain. The SED1 study.

OBJECTIVES: To determine the sociodemographic and clinical profile of a representative sample of people with type 1 diabetes mellitus (DM1) in Spain and identify factors associated with glycemic control. MATERIAL AND METHODS: A cross-sectional observational study was carried out in adults and children with DM1 treated in 75 Spanish public hospitals, geographically distributed in order to be representative of the Spanish population. Within each center, the patients were included on a consecutive basis as they visited the clinic. They were interviewed, and their clinical histories were reviewed. A descriptive statistical analysis was made, and factors associated with HbA1c were analysed using multivariate linear regression analysis. RESULTS: A total of 647 patients were included: 55.3% females, aged 36.6 ±â€¯14.4 years, 97.2% Caucasians, BMI 24.7 ±â€¯4.4 kg/m2 (12.1% ≥ 30 kg/m2), and 74.0% had secondary / university education. A total of 20.2% were active smokers. The mean time from the diagnosis of DM1 was 17.9 ±â€¯12.0 years. A total of 48.7% presented comorbidities: 19.3% retinopathy and 16.4% hypothyroidism. As regards treatment for DM1, 76.5% received basal-bolus insulin therapy and 20.7% continuous subcutaneous insulin infusion (CSII); 51.0% of the patients used an insulin/carbohydrate ratio (ICR), with 4.6 ±â€¯1.6 self-monitored capillary blood glucose (SMCBG) measurements a day, and 24.8% used continuous glucose monitoring (CGM). The mean HbA1c value was 7.6 ±â€¯1.1% (30% below 7%). Metabolic control improved (lower HbA1c) with more daily SMCBG (B = -0.053; p = 0.009), a higher educational level (B = 0.461; P < 0.001), greater number of hypoglycemia episodes (B = -0.253; P = 0.018) and carbohydrate counting (B = -0.190; P = 0.048), and worsened the longer the duration of the disease (B = 0.010; P = 0.010), higher total dose of insulin (B = 0.010; P < 0.0001), poorer adherence to diet (B = 0.650; P < 0.0001) and a family history of DM (B = -0.233; P = 0.007). CONCLUSIONS: The management of patients with DM1 in Spain, as well as the treatment they receive, is similar to that seen in other Western countries. Blood glucose control is associated with educational level, disease duration, and the characteristics of treatment and self-care.

Thyroid hormone resistance index and mortality in euthyroid subjects: Di@bet.es study.

OBJECTIVE: It has been proposed that a mild form of acquired resistance to thyroid hormone may occur in the general population. Its clinical significance remains largely unknown. The objective of the study was to explore whether a newly described thyroid hormone resistance index is associated with the risk of mortality in a sample of community-dwelling euthyroid subjects representative of the adult population of Spain. DESIGN: Longitudinal observational study including 3750 individuals, free of thyroid disease, TPO antibodies-negative (<50 IU/mL) and with TSH levels within the euthyroid range (≥0.5 and ≤5.0 mUI/mL) participating in the nationwide study Di@bet.es (2008-2010). METHODS: We used the Thyroid Feedback Quantile-based Index (TFQI) as a marker of resistance to thyroid hormone. The study population was grouped into categories according to their TFQI values at baseline. Fatal events were ascertained from the national death registry (end of follow-up December 2016). RESULTS: A total of 231 deaths were recorded during an average follow-up of 7.3 years. Compared with the category with the highest sensitivity to free thyroxine (TFQI ≤ p5) (reference), the relative risk of mortality in the categories with TFQI > p5 and ≤p25; >p25 and ≤p50; >p50 and ≤p75; >p75 and ≤p95 and >p95 were 1.01, (0.47-2.19), 1.42 (0.68-2.97), 1.54 (0.74-3.22), 1.47 (0.70-3.11) and 2.61 (1.16-5.89), respectively (P for trend 0.003). The association remained significant after multivariate adjustment of the data (P for trend 0.017). CONCLUSIONS: A thyroid hormone resistance index focused on deviations of the average pituitary response to thyroid hormones may be associated with all-cause mortality independently of other conventional risk factors and comorbidities.

Clinical characteristics and management of type 1 diabetes in Spain. The SED1 study. / Características clínicas y manejo de la diabetes tipo 1 en España. Estudio SED1.

OBJECTIVES: To determine the sociodemographic and clinical profile of a representative sample of people with type 1 diabetes mellitus (DM1) in Spain and identify factors associated with glycemic control. MATERIAL AND METHODS: A cross-sectional observational study was carried out in adults and children with DM1 treated in 75 Spanish public hospitals, geographically distributed in order to be representative of the Spanish population. Within each center, the patients were included on a consecutive basis as they visited the clinic. They were interviewed, and their clinical histories were reviewed. A descriptive statistical analysis was made, and factors associated with HbA1c were analyzed using multivariate linear regression analysis. RESULTS: A total of 647 patients were included: 55.3% females, aged 36.6±14.4 years, 97.2% Caucasians, BMI 24.7±4.4kg/m2 (12.1% ≥30kg/m2), and 74.0% had secondary / university education. A total of 20.2% were active smokers. The mean time from the diagnosis of DM1 was 17.9±12.0 years. A total of 48.7% presented comorbidities: 19.3% retinopathy and 16.4% hypothyroidism. As regards treatment for DM1, 76.5% received basal-bolus insulin therapy and 20.7% continuous subcutaneous insulin infusion (CSII); 51.0% of the patients used an insulin/carbohydrate ratio (ICR), with 4.6±1.6 self-monitored capillary blood glucose (SMCBG) measurements a day, and 24.8% used continuous glucose monitoring (CGM). The mean HbA1c value was 7.6±1.1% (30% below 7%). Metabolic control improved (lower HbA1c) with more daily SMCBG (B=-0.053; p=0.009), a higher educational level (B=0.461; P<0.001), greater number of hypoglycemia episodes (B=-0.253; P=0.018) and carbohydrate counting (B=-0.190; P=0.048), and worsened the longer the duration of the disease (B=0.010; P=0.010), higher total dose of insulin (B=0.010; P<0.0001), poorer adherence to diet (B=0.650; P<0.0001) and a family history of DM (B=-0.233; P=0.007). CONCLUSIONS: The management of patients with DM1 in Spain, as well as the treatment they receive, is similar to that seen in other Western countries. Blood glucose control is associated with educational level, disease duration, and the characteristics of treatment and self-care.

Iodine Deficiency and Mortality in Spanish Adults: Di@bet.es Study.

Background: Longitudinal data assessing the impact of iodine deficiency (ID) on mortality are scarce. We aimed to study the association between the state of iodine nutrition and the risk of total and cause-specific mortality in a representative sample of the Spanish adult population. Methods: We performed a longitudinal observational study to estimate mortality risk according to urinary iodine (UI) concentrations using a sample of 4370 subjects >18 years representative of the Spanish adult population participating in the nationwide study Di@bet.es (2008-2010). We used Cox regression to assess the association between UI at the start of the study (<50, 50-99, 100-199, 200-299, and ≥300 µg/L) and mortality during follow-up (National death registry-end of follow-up December 2016) in raw models, and adjusted for possible confounding variables: age, sex, educational level, hypertension, diabetes, obesity, chronic kidney disease, smoking, hypercholesterolemia, thyroid dysfunction, diagnosis of cardiovascular disease or cancer, area of residence, physical activity, adherence to Mediterranean diet, dairy and iodinated salt intake. Results: A total of 254 deaths were recorded during an average follow-up period of 7.3 years. The causes of death were cardiovascular 71 (28%); cancer 85 (33.5%); and other causes 98 (38.5%). Compared with the reference category with adequate iodine nutrition (UI 100-300 µg/L), the hazard ratios (HRs) of all-cause mortality in the category with UI ≥300 µg/L were 1.04 (95% confidence interval [CI 0.54-1.98]); however, in the categories with 50-99 UI and <50 µg/L, the HRs were 1.29 [CI 0.97-1.70] and 1.71 [1.18-2.48], respectively (p for trend 0.004). Multivariate adjustment did not significantly modify the results. Conclusions: Our data indicate an excess mortality in individuals with moderate-severe ID adjusted for other possible confounding factors.

Renal function and attributable risk of death and cardiovascular hospitalization in participants with diabetes from a registry-based cohort.

AIMS: To estimate the attributable risk of renal function on all-cause mortality and cardiovascular hospitalization in patients with diabetes. METHODS: A prospective cohort study in 19,469 adults with diabetes, free of cardiovascular disease, attending primary care in Spain (2008-2011). The estimated glomerular filtration rate (eGFR) and other variables were collected and patients were followed to the first hospitalization for coronary or stroke event, or death, until the end of 2012. The cumulative incidence of the study endpoints by eGFR categories was graphically displayed and adjusted population attributable risks (PARs) for low eGFR was calculated. RESULTS: Mean follow-up was 3.2 years and 506 deaths and 1720 hospitalizations were recorded. The cumulative risk for the individual events increased as eGFR levels decreased. The PAR associated with having an eGFR of 60mL/min/1.73m2 or less was 11.4% (95% CI 4.8-18.3) for all-cause mortality, 9.2% (95% CI 5.3-13.4) for coronary heart disease, and 2.6% (95% CI -1.8 to 7.4) for stroke. CONCLUSIONS: Reduced eGFR levels were associated with a larger proportion of avoidable deaths and cardiovascular hospitalizations in people with diabetes compared to previously reported results in people with other cardiovascular risk factors.

Diagnosis, treatment, and management of gestational hypothyroidism. The TIROGEST study / Diagnóstico, tratamiento y manejo del hipotiroidismo gestacional. Estudio TIROGEST

Introduction: There is no agreement on the procedures to be used for diagnosis and treatment of gestational thyroid dysfunction. Controversy still exists on the normal range of thyroid-stimulating hormone (TSH) levels and use of gestational hypothyroidism (GH) screening. The aim of this study was to assess diagnosis and treatment of thyroid dysfunction during pregnancy in a group of Spanish hospitals. Study design: This was a retrospective, multicenter study in pregnant females with GH attending Spanish healthcare centers from March 2013 to July 2014. Variables analyzed included diagnosis criteria for GH (availability of universal screening for gestational thyroid disorders and TSH reference values (RVs) by trimester of pregnancy): risk factors for GH, iodine intake from food or supplementation, gestational age (at diagnosis/treatment) and l-thyroxine treatment. Results: Fourteen centers participated in the study. Universal screening was performed in only half of the centers, and only 14% had their own TSH RVs. Overall, 257 pregnant women were enrolled, 53.7% with hypothyroidism (HT) diagnosed before pregnancy (pre-GH) and 46.3% with HT diagnosed during pregnancy (intra-GH). A comparison of intra-GH and pre-GH women showed that intra-GH women made their first visit later (59.7% vs. 75.4% respectively before week 12, p = 0.007) and had more frequently high TSH levels (>2.5 μIU/ml) during the first trimester (94.4% vs. 67.0% respectively, p < 0.001). Conclusions: Our results suggest that GH may be underdiagnosed or inadequately diagnosed in most healthcare centers. These findings suggest the need of improving the current practice in Spain

Introducción: Los procedimientos a seguir para el diagnóstico y tratamiento de la disfunción tiroidea en la gestación no están del todo consensuados. Aún se discute el rango de normalidad de los valores de la hormona estimulante del tiroides (TSH) y el uso de screening para detectar hipotiroidismo gestacional (HG). El objetivo de este estudio es evaluar la forma de diagnóstico y tratamiento de la disfunción tiroidea durante la gestación en un grupo de hospitales de España. Diseño del estudio: Estudio retrospectivo, multicéntrico en mujeres embarazadas con HG atendidas en instituciones sanitarias españolas entre marzo de 2013 y julio de 2014. Las variables analizadas incluyeron criterios diagnósticos de HG (disponibilidad de screening universal para trastornos tiroideos gestacionales y valores de referencia de TSH según el trimestre gestacional); factores de riesgo de HG, ingesta de yodo mediante alimentos o suplementos, edad gestacional (al diagnóstico/tratamiento) y tratamiento con L-tiroxina. Resultados: Participaron un total de 14 centros. Únicamente la mitad de los centros empleaba el screening universal, y solo el 14% tenía valores de referencia de TSH propios. Se incluyeron un total de 257 embarazadas, 53,7% con diagnóstico de hipotiroidismo previo al embarazo (pre-HG) y 46,3% con hipotiroidismo diagnosticado durante el embarazo (intra-HG). Comparando los casos de pre-HG e intra-HG, las mujeres con intra-HG realizaban la primera visita más tarde (antes de la semana 12; 59,7% vs. 75,4% respectivamente, p = 0,007) y tenían más frecuentemente valores elevados de TSH (> 2,5 μUI/ml) durante el primer trimestre (94,4% vs. 67,0% respectivamente, p < 0,001). Conclusiones: Nuestros resultados sugieren que el HG puede estar infradiagnosticado o diagnosticado indebidamente en la mayoría de los centros sanitarios. Estos hallazgos sugieren la necesidad de mejorar la práctica actual en España

Diagnosis, treatment, and management of gestational hypothyroidism. The TIROGEST study.

INTRODUCTION: There is no agreement on the procedures to be used for diagnosis and treatment of gestational thyroid dysfunction. Controversy still exists on the normal range of thyroid-stimulating hormone (TSH) levels and use of gestational hypothyroidism (GH) screening. The aim of this study was to assess diagnosis and treatment of thyroid dysfunction during pregnancy in a group of Spanish hospitals. STUDY DESIGN: This was a retrospective, multicenter study in pregnant females with GH attending Spanish healthcare centers from March 2013 to July 2014. Variables analyzed included diagnosis criteria for GH (availability of universal screening for gestational thyroid disorders and TSH reference values (RVs) by trimester of pregnancy): risk factors for GH, iodine intake from food or supplementation, gestational age (at diagnosis/treatment) and l-thyroxine treatment. RESULTS: Fourteen centers participated in the study. Universal screening was performed in only half of the centers, and only 14% had their own TSH RVs. Overall, 257 pregnant women were enrolled, 53.7% with hypothyroidism (HT) diagnosed before pregnancy (pre-GH) and 46.3% with HT diagnosed during pregnancy (intra-GH). A comparison of intra-GH and pre-GH women showed that intra-GH women made their first visit later (59.7% vs. 75.4% respectively before week 12, p=0.007) and had more frequently high TSH levels (>2.5µIU/ml) during the first trimester (94.4% vs. 67.0% respectively, p<0.001). CONCLUSIONS: Our results suggest that GH may be underdiagnosed or inadequately diagnosed in most healthcare centers. These findings suggest the need of improving the current practice in Spain.

Efficacy of sodium glucose cotransporter 2 inhibitors as an adjunct treatment for patients with diabetes type 2 / Eficacia de los inhibidores del cotransportador sodio glucosa tipo 2 como tratamiento adyuvante en pacientes con diabetes tipo 2 tratados con insulina

Objective: To analyze the effect of sodium glucose cotransporter 2 (SGLT2) inhibitors in a group of insulin-dependent type 2 diabetes mellitus (T2D) patients. Patients and methods: One hundred and five insulin treated T2D patients were enrolled. Primary endpoints were: fasting plasma glucose, HbA1c, weight, total insulin doses (TDI), total basal insulin (TDB) and total rapid insulin (TDR). Secondary variables were: total cholesterol, LDL cholesterol (cLDL), HDL cholesterol (cHDL), triglycerides and systolic (SBP) and diastolic (DBP) blood pressure. Safety and tolerance were evaluated through the appearance of severe hypoglycemia, ketoacidosis and infections. Results: After 4 months follow-up, a 0.7 (1.0)% HbA1c reduction was found, accompanied by a −2.8 (11.5) UI/day TDI decrease. Weight dropped for 73.7% of patients, with an average −2.0 (2.7) kg reduction. A global cHDL increase was noted after treatment, while no differences were observed for total cholesterol, triglycerides or cLDL. SBP dropped significantly, but no change in DBP was observed. Conclusion: The use of SGLT2 inhibitors in insulin treated T2D patients resulted in reduction of HbA1c, which was associated to weight loss, cHDL increase and SBP decrease

Objetivo: Analizar el efecto de los inhibidores del cotransportador sodio glucosa tipo 2 (iSGLT2) en u grupo de pacientes con diabetes mellitus tipo 2 (DM2) tratados con insulina. Pacientes y métodos: Seleccionamos ciento cinco pacientes con diabetes tipo 2 tratados con insulina. Los objetivos primarios: glucosa plasmática ayunas, HbA1c, peso, dosis total de insulina (DTI), dosis de insulina basal (DTB), dosis de insulina rápida (DTR). Como secundarios: Colesterol total, LDL colesterol (cLDL), HDL colesterol (cHDL), triglicéridos and tensión sistólica (TAS) and diastólica (TAD). La seguridad y tolerancia se valoró como hipoglucemia, cetoacidosis o infecciones. Resultados: Tras 4 meses, la HbA1c se redujo en 0,7 (1,0)% acompañado de una disminución en DTI de −2,8 (11,5) UI/día. El 73,7% de los pacientes perdieron peso, con un descenso medio de −2,0 (2,7) kg. El cHDL aumentó, mientras que no observamos diferencias en el colesterol total, triglicéridos o cLDL. TAS disminuyó significativamente sin observar cambios en TAD. Conclusión: El uso de iSGLT2 en pacientes con DM2 tratados con insulina reduce la HbA1c asociando pérdida de peso, aumento enl cHDL y descenso en TAS

Ambient temperature and prevalence of diabetes and insulin resistance in the Spanish population: Di@bet.es study.

Objective The activity of brown adipose tissue is sensitive to changes in ambient temperature. A lower exposure to cold could result in an increased risk of developing diabetes at population level, although this factor has not yet been sufficiently studied. Design We studied 5072 subjects, participants in a national, cross-sectional population-based study representative of the Spanish adult population (Di@bet.es study). All subjects underwent a clinical, demographic and lifestyle survey, a physical examination and blood sampling (75 g oral glucose tolerance test). Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). The mean annual temperature (°C) in each individual municipality was collected from the Spanish National Meteorology Agency. Results Linear regression analysis showed a significant positive association between mean annual temperature and fasting plasma glucose (ß: 0.087, P < 0.001), 2 h plasma glucose (ß: 0.049, P = 0.008) and HOMA-IR (ß: 0.046, P = 0.008) in multivariate adjusted models. Logistic regression analyses controlled by multiple socio-demographic variables, lifestyle, adiposity (BMI) and geographical elevation showed increasing odds ratios for prediabetes (WHO 1999), ORs 1, 1.26 (0.95-1.66), 1.08 (0.81-1.44) and 1.37 (1.01-1.85) P for trend = 0.086, diabetes (WHO 1999) ORs 1, 1.05 (0.79-1.39), 1.20 (0.91-1.59) and 1.39 (1.02-1.90) P = 0.037, and insulin resistance (HOMA-IR ≥75th percentile of the non-diabetic population): ORs 1, 1.03 (0.82-1.30), 1.22 (0.96-1.55), 1.26 (0.98-1.63) (P for trend = 0.046) as the mean annual temperature (into quartiles) rose. Conclusions Our study reports an association between ambient temperature and the prevalence of dysglycemia and insulin resistance in Spanish adults, consistent with the hypothesis that a lower exposure to cold could be associated with a higher risk of metabolic derangements.

Dairy Product Consumption and Metabolic Diseases in the Di@bet.es Study.

To date it is not clear what the role of dairy products is in metabolic diseases like diabetes, obesity, and hypertension. Therefore, the aim of this study is to test the association between dairy product consumption and those pathologies. A cross-sectional study was conducted with 5081 adults included in the di@bet.es study, from 100 health centers around Spain. Food frequency questionnaires were carried out concerning consumption habits, which included dairy product consumption. Logistic regression models were used for the association analyses between the variables controlling confounding variables. Women had a higher consumption of milk, cheese, or yogurt than men (p < 0.0001), but men consumed more sugar dairy products (p < 0.001). People who live in the North of Spain consume more dairy products than those who live in the East. Dairy product consumption was inversely associated with the presence of hypertension regardless of age, sex, geographical region, and body mass index (BMI) (Odds Ratio (OR) 0.743; p = 0.022). The presence of obesity was inversely associated with dairy consumption regardless of age, sex, and geographical region (OR 0.61; p < 0.001). Milk consumption was not associated with diabetes. Our results show that consuming dairy products is associated with a better metabolic profile in the Spanish population.

Efficacy of sodium glucose cotransporter 2 inhibitors as an adjunct treatment for patients with diabetes type 2.

OBJECTIVE: To analyze the effect of sodium glucose cotransporter 2 (SGLT2) inhibitors in a group of insulin-dependent type 2 diabetes mellitus (T2D) patients. PATIENTS AND METHODS: One hundred and five insulin treated T2D patients were enrolled. Primary endpoints were: fasting plasma glucose, HbA1c, weight, total insulin doses (TDI), total basal insulin (TDB) and total rapid insulin (TDR). Secondary variables were: total cholesterol, LDL cholesterol (cLDL), HDL cholesterol (cHDL), triglycerides and systolic (SBP) and diastolic (DBP) blood pressure. Safety and tolerance were evaluated through the appearance of severe hypoglycemia, ketoacidosis and infections. RESULTS: After 4 months follow-up, a 0.7 (1.0)% HbA1c reduction was found, accompanied by a -2.8 (11.5) UI/day TDI decrease. Weight dropped for 73.7% of patients, with an average -2.0 (2.7) kg reduction. A global cHDL increase was noted after treatment, while no differences were observed for total cholesterol, triglycerides or cLDL. SBP dropped significantly, but no change in DBP was observed. CONCLUSION: The use of SGLT2 inhibitors in insulin treated T2D patients resulted in reduction of HbA1c, which was associated to weight loss, cHDL increase and SBP decrease.

Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: Di@bet.es study.

Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30-100, 15-30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia (FT4 < 12.0 pmol/L p5): OR 1.5 [1.1-2.2] p = 0.024, and hypotriiodothyroninemia (FT3 < 3.9 pmol/L p5): OR 1.8 [1.3-2.6] p = 0.001 than the reference category with ferritin ≥30 µg/L. There was no significant heterogeneity of the results between men, pre-menopausal and post-menopausal women or according to the iodine nutrition status. Our results confirm an association between ID and hypothyroxinemia and hypotriiodothyroninemia in the general adult population without changes in TSH.

Platelet-Derived Mitochondria Display Embryonic Stem Cell Markers and Improve Pancreatic Islet ß-cell Function in Humans.

Diabetes is a major global health issue and the number of individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) increases annually across multiple populations. Research to develop a cure must overcome multiple immune dysfunctions and the shortage of pancreatic islet ß cells, but these challenges have proven intractable despite intensive research effort more than the past decades. Stem Cell Educator (SCE) therapy-which uses only autologous blood immune cells that are externally exposed to cord blood stem cells adhering to the SCE device, has previously been proven safe and effective in Chinese and Spanish subjects for the improvement of T1D, T2D, and other autoimmune diseases. Here, 4-year follow-up studies demonstrated the long-term safety and clinical efficacy of SCE therapy for the treatment of T1D and T2D. Mechanistic studies found that the nature of platelets was modulated in diabetic subjects after receiving SCE therapy. Platelets and their released mitochondria display immune tolerance-associated markers that can modulate the proliferation and function of immune cells. Notably, platelets also expressed embryonic stem cell- and pancreatic islet ß-cell-associated markers that are encoded by mitochondrial DNA. Using freshly-isolated human pancreatic islets, ex vivo studies established that platelet-releasing mitochondria can migrate to pancreatic islets and be taken up by islet ß cells, leading to the proliferation and enhancement of islet ß-cell functions. These findings reveal new mechanisms underlying SCE therapy and open up new avenues to improve the treatment of diabetes in clinics. Stem Cells Translational Medicine 2017;6:1684-1697.