Cristina Maldonado-Araque

Aims: Cardiovascular disease (CVD) remains the leading cause of mortality. New biomarkers are needed to improve CVD risk prediction. Several studies have reported associations between surfactant protein D (SP‐D), an innate immune system component, and CVD; however, general population studies remain scarce. The main aim of this study was to investigate the association between SP‐D and CVD events incidence in the Spanish general adult population. Methods: Socio‐demographic, lifestyle (including smoking status) and clinical data from 1707 participants of the di@bet.es cohort without previous CVD events were collected and analysed. CVD events (including both morbidity and mortality) were reported at baseline and after 7.5 years of follow‐up. SP‐D serum levels were measured by ELISA and categorized in quartiles. Results: SP‐D categories are associated with CVD events incidence, independently from other strong risk factors such as cardiovascular risk scores (SCORE2 and SCORE2‐OP), BMI, hs‐CRP, or eGFR. Although SP‐D has been linked to smoking, SP‐D categories predicted CVD events incidence even among non‐smokers. The addition of SP‐D to multivariate models improved performance in the assessment, predicting 83% of the events with a specificity of 74% and a sensitivity of 84% in the overall population. Conclusions: SP‐D may be considered as a promising biomarker of CVD events in combination with other well established factors in clinical practice.

It is well known that environmental factors influence the risk of type 2 diabetes mellitus (T2DM). Several studies have linked the xenobiotics present in tobacco or air pollutants to T2DM development, although the underlying mechanisms remain unclear. Surfactant protein D (SP-D), an immune component released into the bloodstream after lung injury, has been associated with metabolic diseases. The aim of this study was to investigate whether SP-D mediates the effects of smoking or air pollution exposure on T2DM risk in the Spanish adult population. Socio-demographic, lifestyle (including smoking status) and clinical data from 2155 participants from the Di@bet.es cohort were analyzed. Annual concentrations of PM₁₀, PM_2.5, SO₂, CO and NO₂ according to participants’ residential address codes were used to study air pollution exposure. T2DM was diagnosed at baseline and after 7.5 years of follow-up. SP-D serum levels were measured by ELISA and categorized as above or below the 25th percentile. Our results revealed a higher percentage of smokers in the high SP-D category; however, no associations were observed between air pollutants (PM₁₀, PM_2.5, SO₂, CO) and SP-D categories. Both smoking and elevated SP-D levels were found to increase the risk of T2DM independently. Mediation analysis indicated that SP-D mediates 14% of the effect of smoking on T2DM incidence in the Spanish adult population.

Background/Objectives: Although evidence suggests that miR-484 and several fruit components are involved in glucose metabolism and insulin resistance metabolic pathways, the relationship between serum miR-484 levels and fruit consumption in relation to the risk of Type 2 diabetes (T2DM) remains elusive. The aim of this study was to evaluate the possible association between serum miR-484 levels and fruit intake frequency with the risk of T2DM in the Spanish adult population. Methods: 2234 subjects from the Di@bet.es cohort study without T2DM at baseline were studied. Socio-demographic, anthropometric and clinical data were recorded, as well as responses to a questionnaire on habits, including frequency of fruit consumption (daily vs. occasional). T2DM was diagnosed at baseline and after 7.5 years of follow-up. Baseline serum miR-484 levels were measured using real-time qPCR and categorized based on the 25th percentile. Association analyses were performed using logistic regression models adjusted for potential confounders. Interaction effects were evaluated on the multiplicative and additive scales. Results: There was no association between miR-484 levels and fruit intake frequency. Categorized miR-484 levels and fruit consumption were inversely and independently associated with the likelihood of incident T2DM. Analysis of the interaction effect suggests the presence of both positive multiplicative and additive interactions between miR-484 categories and fruit consumption frequency. Conclusions: Our study demonstrates a protective effect of daily fruit intake and high miR-484 levels regarding the risk of T2DM and supports the nutritional recommendations advocating daily fruit consumption. This study also suggests that the combined effect of low miR-484 levels and occasional fruit intake may increase the risk of T2DM beyond their independent effects.

Background/Objectives: Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) increases the risk of Type-2 Diabetes (T2DM). The Mediterranean diet (MD) has shown advantages in the management of MAFLD and preventing co-morbidities; however, its relationship with T2DM development in MAFLD has been less investigated. We aimed to evaluate the association of MD adherence with the risk of incident T2DM in the Spanish adult population with MAFLD and according to their weight gain at 7.5 years follow-up. Methods: A cohort of 714 participants (without weight increment: 377; with weight increment: 337) from the Di@bet.es cohort study with MAFLD and without T2DM at baseline were investigated. Anthropometric, sociodemographic, clinical data, and a survey on habits were recorded. OGTT and fasting blood biochemistry determinations were made. Baseline adherence to MD was estimated by the adapted 14-point MEDAS questionnaire and categorized as high and low adherence. Results: In total, 98 people developed T2DM at follow-up. The high adherence to MD was inversely associated with the development of T2DM in both the overall population (0.52 [0.31–0.87]) and subjects without weight gain at follow-up (0.35 [0.16–0.78]). Conclusions: Our results suggest the protective effect of high adherence to MD regarding the risk of T2DM in subjects with MAFLD, with this health benefit being more evident in men with the absence of weight gain. These results support the recommendations for MD use in these patients.

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 ¹H‐NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter 10), 2.5) 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, PM_2.5 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, PM_2.5 and NO₂ concentrations and the odds of presenting low HDL‐c (10 and NO₂ and low HDL‐p in men (p for interaction .008 and .034), and between NO₂ and low HDL‐p in individuals with obesity (p for interaction .015).Conclusions: Our study shows an association between the exposure to air pollutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosis.

Background: Muscle ultrasonography of the quadriceps rectus femoris (QRF) is a technique on the rise in the assessment of muscle mass in application of nutritional assessment. The aim of the present study is to assess the usefulness of muscle ultrasonography in patients with cystic fibrosis, comparing the results with other body composition techniques such as anthropometry, bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and handgrip strength (HGS). At the same time, we intend to assess the possible association with the nutritional and respiratory status. Methods: This was a prospective observational study in adult patients with cystic fibrosis in a clinically stable situation. Muscle ultrasonography of the QRF was performed, and the results were compared with other measures of body composition: anthropometry, BIA, and DXA. HGS was used to assess muscle function. Respiratory parameters were collected, and nutritional status was assessed using Global Leadership Initiative on Malnutrition (GLIM) criteria. Results: A total of 48 patients were included, with a mean age of 34.1 ± 8.8 years. In total, 24 patients were men, and 24 patients were women. Mean BMI was 22.5 ± 3.8 kg/m². Mean muscular area rectus anterior (MARA) was 4.09 ± 1.5 cm², and mean muscular circumference rectus was 8.86 ± 1.61 cm. A positive correlation was observed between the MARA and fat-free mass index (FFMI) determined by anthropometry (r = 0.747; p < 0.001), BIA (r = 0.780; p < 0.001), and DXA (r = 0.678; p < 0.001), as well as muscle function (HGS: r = 0.790; p < 0.001) and respiratory parameters (FEV1; r = 0.445, p = 0.005; FVC: r = 0.376, p = 0.02; FEV1/FVC: r = 0.344, p = 0.037). A total of 25 patients (52.1%) were diagnosed with malnutrition according to GLIM criteria. Differences were observed when comparing the MARA based on the diagnosis of malnutrition (4.75 ± 1.65 cm² in normo-nourished vs. 3.37 ± 1.04 in malnourished; p = 0.014). Conclusions: In adults with cystic fibrosis, the measurements collected by muscle ultrasound of the QRF correlate adequately with body composition techniques such as anthropometry, BIA, DXA, and handgrip strength. Muscle ultrasound measurements, particularly the MARA, are related to the nutritional status and respiratory function of these patients.

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.

Objective: To analyze the reference range of thyroid‐stimulating hormone (TSH) in different BMI categories and its impact on the classification of hypothyroidism.Methods: The study included 3,928 individuals free of thyroid disease (without previous thyroid disease, no interfering medications, TSH 2), 0.6 to 5.5 µUI/mL in the normal‐weight category (BMI 20‐24.9 kg/m²), 0.6 to 5.5 µUI/mL in the overweight category (BMI 25‐29.9 kg/m²), 0.5 to 5.9 µUI/mL in the obesity category (BMI 30‐39.9 kg/m²), and 0.7 to 7.5 µUI/mL in the morbid obesity category (BMI ≥40). By using the reference criteria for the normal‐weight population, the prevalence of high TSH levels increased threefold in the morbid obesity category (P < 0.01).Conclusions: Persons with morbid obesity might be inappropriately classified if the standard ranges of normality of TSH for the normal‐weight population are applied to them.

Background: The aim of this study was to investigate the national prevalence of thyroid dysfunction in Spain and its association with various clinical, environmental, and demographic variables. Methods: The study included 4554 subjects (42.4% men) with a mean age of 50 years (range 18–93 years), who were participants in a national, cross-sectional, population-based survey conducted in 2009–2010. Data gathered included clinical and demographic characteristics, physical examination, and blood sampling. Thyrotropin, free thyroxine, free triiodothyronine, and thyroid peroxidase antibody (TPOAb) concentrations were analyzed by electrochemiluminescence. Urinary iodine (UI) levels were measured in an isolated urine sample. Results: The prevalence of treated hypothyroidism, untreated subclinical hypothyroidism, and untreated clinical hypothyroidism was 4.2% [confidence interval (CI) 3.6–4.9%], 4.6% [CI 4.0–5.2%], and 0.3% [CI 0.1–0.5%], respectively. The prevalence of total hypothyroidism (including all fractions) was 9.1% [CI 8.2–10.0%]. The prevalence of total hyperthyroidism was 0.8% [CI 0.6–1.1]. A total of 7.5% [CI 6.7–8.3%] of the population tested positive for TPOAbs (≥50 IU/mL). In multivariate logistic regression models, TPOAbs were strongly associated with both hypothyroidism ( p < 0.001) and hyperthyroidism ( p = 0.005), whereas high UI levels (>200 μg/g creatinine) were associated with hypothyroidism ( p < 0.001). The positive association between UI and hypothyroidism remained for both treated ( p < 0.001) and untreated ( p < 0.05) hypothyroidism, whereas it was especially significant for non-autoimmune (TPOAbs negative) forms ( p < 0.001). At UI levels ≥200 μg/g, there was a positive correlation between UI and thyrotropin levels (β = 0.152, p < 0.001) and a negative correlation between UI and free triiodothyronine levels (β = −0.134, p = 0.001). Conclusion: According to the data, a large proportion (10%) of the Spanish population has some evidence of thyroid dysfunction. High TPOAb concentrations were associated with both hypo- and hyperthyroidism, whereas high UI concentrations were associated with hypothyroidism.