Real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes in Spain: The Dapa-ON multicenter retrospective study.

OBJECTIVE: To assess real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes mellitus (T1DM). METHODS: We conducted a multicenter retrospective study in Spain including data from 250 people living with T1DM receiving dapagliflozin as add-on therapy to insulin (80.8 % on-label use). The number of diabetic ketoacidosis (DKA) events was calculated over a 12-month follow-up (primary outcome). Changes in body weight, HbA1c, total daily insulin dose, and continuous glucose monitoring (CGM) metrics from baseline (at dapagliflozin prescription) to 12 months were also evaluated. RESULTS: A total of five DKA events (2.4 % [95 % CI 0.3;4.5] were reported in patients with a 12-month follow-up, n = 207): two events related to insulin pump malfunction, two events related to concomitant illnesses, and one event related to insulin dose omission. DKA events were more frequent among insulin pump users than among participants on multiple daily injections (7.7 % versus 1.2 %). Four of the reported DKA events occurred within the first six months after initiation of dapagliflozin. No deaths or persistent sequelae due to DKA were reported. No severe hypoglycemia episodes were reported. Significant reductions in mean body weight (-3.3 kg), HbA1c (-0.6 %), and total daily insulin dose (-8.6 %), P < 0.001, were observed 12 months after dapagliflozin prescription. Significant improvements in TIR (+9.3 %), TAR (-7.2 %), TBR (-2.5 %), and coefficient of variation (-5.1 %), P < 0.001, were also observed in the subgroup of patients with available CGM data. Finally, an improvement in urinary albumin-to-creatinine ratio (UACR) was found among participants with UACR ≥ 30 mg/g at baseline (median decrease of 99 mg/g in UACR, P = 0.001). CONCLUSION: The use of dapagliflozin in people living with T1DM has an appropriate safety profile after careful selection of participants and implementation of strategies to reduce the risk of DKA (i.e., prescribed according to the recommendations of the European Medicines Agency), and also leads to clinical improvements in this population.

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 (

Management of thyroid dysfunction and thyroid nodules in the ageing patient.

Thyroid dysfunction is a common endocrine disorder in the general population, with a reported prevalence of 10-15%. However, this rate is even higher in older adults, with an estimated prevalence of ≈25% in some populations. Since elderly patients usually present more comorbidities than younger individuals, thyroid dysfunction may carry a synergistic negative health impact, mainly due to increased cardiovascular disease risk. Moreover, thyroid dysfunction in the elderly can be more difficult to diagnose due to its subtle or even asymptomatic clinical presentation, and the interpretation of thyroid function tests may be affected by drugs that interfere with thyroid function or by the coexistence of several diseases. On the other hand, thyroid nodules are also a prevalent condition in older adults, and its incidence increases with age. The assessment and management of thyroid nodules in the ageing patient should take into account several factors, as risk stratification, thyroid cancer biology, patient´s overall health, comorbidities, treatment preferences, and goals of care. In this review article, we summarize the current knowledge on the pathophysiology, diagnosis, and therapeutic management of thyroid dysfunction in elderly patients and we also review how to identify and manage thyroid nodules in this population.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

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.

Serum vascular endothelial growth factor b and metabolic syndrome incidence in the population based cohort Di@bet.es study.

BACKGROUND/OBJECTIVES: Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up. SUBJECTS/METHODS: A total of 908 subjects from the Di@bet.es cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria. RESULTS: A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category. CONCLUSION: Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables.

Phase Angle and Handgrip Strength as a Predictor of Disease-Related Malnutrition in Admitted Patients: 12-Month Mortality.

Background: Phase Angle (PhA) value measured by bioelectrical impedance analysis (BIA) could be considered a good marker of the patient's cell mass and cellular damage. Various studies have shown that the value of PhA is associated with an increased nutritional risk in several pathologies. However, not many studies have focused on the use of PhA as a screening tool in admitted patients. The aim of this study is to evaluate the prognostic value of PhA to determine disease-related malnutrition (DRM) and the risk that this entails for mortality and length of stay (LOS). Methods: 570 patients admitted to the hospital for different causes were included in this retrospective observational study. Patients' nutritional risk was assessed by screening tests such as the Malnutrition Universal Screening tool (MUST) and Subjective Global Assessment (SGA), in addition to non-invasive functional techniques, such as BIA and handgrip strength (HGS), 24−48 h after admission. After performing an SGA as the gold standard to assess malnutrition, PhA and SPhA values were used to determine DRM. Furthermore, both samples: malnutrition status (MS) and non-malnutrition status (NMS) were compared, with SphA-Malnutrition corresponding to a diagnosis of malnutrition. Statistical analysis of the sample was conducted with JAMOVI version 2.2.2. Results: Patients with MS had lower PhA and SPhA than patients with NMS (p < 0.001). The ROC curve analysis (AUC = 0.81) showed a cut-off point for MS for PhA = 5.4° (sensitivity 77.51% and specificity 74.07%) and AUC = 0.776 with a cut-off point for SPhA = −0.3 (sensitivity 81.74% and specificity 63.53%). Handgrip strength (HGS) was also observed to be a good predictor in hospitalized patients. Carrying out a comparative analysis between MS and NMS, length of stay (LOS) was 9.0 days in MS vs. 5.0 days in NMS patients (OR 1.07 (1.04−1.09, p < 0.001)). A low SPhA-malnutrition value (SPhA < −0.3) was significantly associated with a higher mortality hazards ratio (HR 7.87, 95% CI 2.56−24.24, p < 0.001). Conclusion: PhA, SPhA and HGS are shown to be good prognostic markers of DRM, LOS and mortality and could therefore be useful screening tools to complement the nutritional assessment of admitted patients.

Association between long term exposure to particulate matter and incident hypertension in Spain.

Exposure to air particulate matter has been linked with hypertension and blood pressure levels. The metabolic risks of air pollution could vary according to the specific characteristics of each area, and has not been sufficiently evaluated in Spain. We analyzed 1103 individuals, participants in a Spanish nationwide population based cohort study (di@bet.es), who were free of hypertension at baseline (2008-2010) and completed a follow-up exam of the cohort (2016-2017). Cohort participants were assigned air pollution concentrations for particulate matter < 10 µm (PM10) and < 2.5 µm (PM2.5) during follow-up (2008-2016) obtained through modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). Mean and SD concentrations of PM10 and PM2.5 were 20.17 ± 3.91 µg/m3 and 10.83 ± 2.08 µg/m3 respectively. During follow-up 282 cases of incident hypertension were recorded. In the fully adjusted model, compared with the lowest quartile of PM10, the multivariate weighted ORs (95% CIs) for developing hypertension with increasing PM10 exposures were 0.82 (0.59-1.14), 1.28 (0.93-1.78) and 1.45 (1.05-2.01) in quartile 2, 3 and 4 respectively (p for a trend of 0.003). The corresponding weighted ORs according to PM2.5 exposures were 0.80 (0.57-1.13), 1.11 (0.80-1.53) and 1.48 (1.09-2.00) (p for trend 0.004). For each 5-µg/m3 increment in PM10 and PM2.5 concentrations, the odds for incident hypertension increased 1.22 (1.06-1.41) p = 0.007 and 1.39 (1.07-1.81) p = 0.02 respectively. In conclusion, our study contributes to assessing the impact of particulate pollution on the incidence of hypertension in Spain, reinforcing the need for improving air quality as much as possible in order to decrease the risk of cardiometabolic disease in the population.

Prevalence of diabetes mellitus in patients with home enteral nutrition / Prevalencia de diabetes mellitus en pacientes con nutrición enteral domiciliaria

BACKGROUND: There are few data available in the literature on the prevalence of diabetes mellitus (DM) in patients with home enteral nutrition (HEN) via tube feeding. The objective was to analyze the prevalence of DM in patients receiving HEN, as well as evaluating the complications, the prescribed antidiabetic treatments and the nutrition regimen selected. DESIGN: This was a retrospective, single-center, observational study reviewing clinical histories. The population consisted of patients over 18 years of age who started HEN by tube between January 2016 and January 2018. Sociodemographic variables were recorded, as well as variables related to HEN. Additional variables were recorded in patients with DM. RESULTS: In the 198 study patients, followed up for a median of 104 days, the prevalence of DM was 31.8%, and patients with DM were older (71.3±11.5 vs. 64.2±15.8; p = 0.002) than those without DM. There were no differences between patients with and without DM as regards the prescription of HEN, its route and form of administration, and its complications. One hundred and thirty-two patients (66.7%) died during follow-up. The presence of DM did not increase the risk of death during follow-up (after adjusting for age, gender, and diagnosis). More than 85% of patients with DM received a specific formula for diabetes, and 84.1% of these patients received drug treatment. CONCLUSION: The prevalence of DM was high in patients receiving HEN, most of whom were prescribed specific enteral nutrition formulas. The presence of DM was not associated with greater morbidity and mortality or with differences in HEN regimens or indications

INTRODUCCIÓN: Existen pocos datos en la literatura sobre la prevalencia de la diabetes mellitus (DM) en los pacientes con nutrición enteral domiciliaria (NED) por sonda. El objetivo es analizar la prevalencia de los pacientes con DM en NED, las complicaciones, el tratamiento antidiabético y las pautas nutricionales escogidas. DISEÑO: Estudio observacional retrospectivo unicéntrico con revisión de historias clínicas. Población: pacientes mayores de 18 años que iniciaron NED y ambulatoria mediante sonda desde enero de 2016 a enero de 2018. Se recogieron variables sociodemográficas y relacionadas con la NED. En personas con DM se recogieron otras variables adicionales. RESULTADOS: Ciento noventa y ocho pacientes con una mediana de seguimiento de 104 días. La prevalencia de la DM fue del 31,8%, con mayor edad (71,3±11,5 vs. 64,2±15,8; p = 0,002) que los no DM. No encontramos diferencias entre personas con DM y sin ella respecto a la indicación de la NED, vía y forma de administración ni complicaciones mecánicas o infecciosas. Fallecieron 132 pacientes (66,7%) durante el seguimiento. La presencia de diabetes no incrementó el riesgo de fallecer durante el seguimiento (ajustado por la edad, el género y el diagnóstico). Más del 85% de los pacientes con DM recibieron una fórmula específica para diabetes. El 84,1% de los pacientes con DM recibieron tratamiento farmacológico. CONCLUSIÓN: En pacientes con NED por sonda, la prevalencia de DM fue elevada, y los pacientes recibieron mayoritariamente fórmulas nutricionales específicas. La presencia de diabetes no se asoció con una mayor morbimortalidad o diferencias en las pautas o indicaciones de la NED

Prevalence of diabetes mellitus in patients with home enteral nutrition.

BACKGROUND: There are few data available in the literature on the prevalence of diabetes mellitus (DM) in patients with home enteral nutrition (HEN) via tube feeding. The objective was to analyze the prevalence of DM in patients receiving HEN, as well as evaluating the complications, the prescribed antidiabetic treatments and the nutrition regimen selected. DESIGN: This was a retrospective, single-center, observational study reviewing clinical histories. The population consisted of patients over 18 years of age who started HEN by tube between January 2016 and January 2018. Sociodemographic variables were recorded, as well as variables related to HEN. Additional variables were recorded in patients with DM. RESULTS: In the 198 study patients, followed up for a median of 104 days, the prevalence of DM was 31.8%, and patients with DM were older (71.3±11.5 vs. 64.2±15.8; p=0.002) than those without DM. There were no differences between patients with and without DM as regards the prescription of HEN, its route and form of administration, and its complications. One hundred and thirty-two patients (66.7%) died during follow-up. The presence of DM did not increase the risk of death during follow-up (after adjusting for age, gender, and diagnosis). More than 85% of patients with DM received a specific formula for diabetes, and 84.1% of these patients received drug treatment. CONCLUSION: The prevalence of DM was high in patients receiving HEN, most of whom were prescribed specific enteral nutrition formulas. The presence of DM was not associated with greater morbidity and mortality or with differences in HEN regimens or indications.

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.