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1.
Liraglutide Improves Forced Vital Capacity in Individuals With Type 2 Diabetes: Data From the Randomized Crossover LIRALUNG Study.
López-Cano, C, Ciudin, A, Sánchez, E, Tinahones, FJ, Barbé, F, Dalmases, M, García-Ramírez, M, Soto, A, Gaeta, AM, Pellitero, S, et al
Diabetes. 2022;(2):315-320
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Abstract
To evaluate the effect of liraglutide, a glucagon-like peptide 1 receptor agonist, on pulmonary function and serum levels of surfactant protein D (SP-D) in type 2 diabetes. A double-blind, randomized, crossover, placebo-controlled clinical trial comprising 76 patients with a baseline forced expiratory volume in 1 s <90% of that predicted. Liraglutide was administered for 7 weeks (2 weeks of titration plus 5 weeks at 1.8 mg daily). This short duration was intentional to minimize weight loss as a potential confounding factor. Serum level of SP-D was used as a biomarker of alveolar-capillary barrier integrity. Liraglutide exerted a positive impact on forced vital capacity (FVC) in comparison with placebo (ΔFVC 5.2% of predicted [from 0.8 to 9.6]; P = 0.009). No differences in the other pulmonary variables were observed. Participants under liraglutide treatment also experienced a decrease in serum SP-D (P = 0.038). The absolute change in FVC correlated with final serum SP-D in participants receiving liraglutide (r = -0.313, P = 0.036). Stepwise multivariate regression analysis showed that final serum SP-D independently predicted changes in FVC. In conclusion, liraglutide increased FVC in patients with type 2 diabetes. This effect was associated with a significant decrease of circulating SP-D, thus pointing to a beneficial effect in the alveolar-capillary function.
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Is There a Link between Obesity Indices and Skin Autofluorescence? A Response from the ILERVAS Project.
Sánchez, E, Sánchez, M, López-Cano, C, Bermúdez-López, M, Valdivielso, JM, Farràs-Sallés, C, Pamplona, R, Torres, G, Mauricio, D, Castro, E, et al
Nutrients. 2022;(1)
Abstract
There is controversial information about the accumulation of advanced glycation end-products (AGEs) in obesity. We assessed the impact of total and abdominal adiposity on AGE levels via a cross-sectional investigation with 4254 middle-aged subjects from the ILERVAS project. Skin autofluorescence (SAF), a non-invasive assessment of subcutaneous AGEs, was measured. Total adiposity indices (BMI and Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE)) and abdominal adiposity (waist circumference and body roundness index (BRI)) were assessed. Lean mass was estimated using the Hume index. The area under the receiver operating characteristic (ROC) curve was evaluated for each index. Different cardiovascular risk factors (smoking, prediabetes, hypertension and dyslipidemia) were evaluated. In the study population, 26.2% showed elevated SAF values. No differences in total body fat, visceral adiposity and lean body mass were detected between patients with normal and high SAF values. SAF levels showed a very slight but positive correlation with total body fat percentage (estimated by the CUN-BAE formula) and abdominal adiposity (estimated by the BRI). However, none of them had sufficient power to identify patients with high SAF levels (area under the ROC curve <0.52 in all cases). Finally, a progressive increase in SAF levels was observed in parallel with cardiovascular risk factors in the entire population and when patients with normal weight, overweight and obesity were evaluated separately. In conclusion, total obesity and visceral adiposity are not associated with a greater deposit of AGE. The elevation of AGE in obesity is related to the presence of cardiometabolic risk.
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Prediabetes Is Associated with Increased Prevalence of Sleep-Disordered Breathing.
Sánchez, E, Sapiña-Beltrán, E, Gavaldà, R, Barbé, F, Torres, G, Sauret, A, Dalmases, M, López-Cano, C, Gutiérrez-Carrasquilla, L, Bermúdez-López, M, et al
Journal of clinical medicine. 2022;(5)
Abstract
Type 2 diabetes leads to severe nocturnal hypoxemia, with an increase in apnea events and daytime sleepiness. Hence, we assessed sleep breathing parameters in the prediabetes stage. A cross-sectional study conducted on 966 middle-aged subjects without known pulmonary disease (311 patients with prediabetes and 655 controls with normal glucose metabolism) was conducted. Prediabetes was defined by glycated hemoglobin (HbA1c), and a nonattended overnight home sleep study was performed. Participants with prediabetes (n = 311) displayed a higher apnea−hypopnea index (AHI: 12.7 (6.1;24.3) vs. 9.5 (4.2;19.6) events/h, p < 0.001) and hypopnea index (HI: 8.4 (4.0;14.9) vs. 6.0 (2.7;12.6) events/h, p < 0.001) than controls, without differences in the apnea index. Altogether, the prevalence of obstructive sleep apnea was higher in subjects with prediabetes than in controls (78.1 vs. 69.9%, p = 0.007). Additionally, subjects with prediabetes presented impaired measurements of the median and minimum nocturnal oxygen saturation, the percentage of time spent with oxygen saturations below 90%, and the 4% oxygen desaturation index in comparison with individuals without prediabetes (p < 0.001 for all). After adjusting for age, sex, and the presence of obesity, HbA1c correlated with the HI in the entire population (r = 0.141, p < 0.001), and the presence of prediabetes was independently associated with the AHI (B = 2.20 (0.10 to 4.31), p = 0.040) as well as the HI (B = 1.87 (0.61 to 3.14), p = 0.004) in the multiple linear regression model. We conclude that prediabetes is an independent risk factor for an increased AHI after adjusting for age, sex, and obesity. The enhanced AHI is mainly associated with increments in the hypopnea events.
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Dapagliflozin plus exenatide on patients with type 2 diabetes awaiting bariatric surgery in the DEXBASU study.
López-Cano, C, Santos, MD, Sánchez, E, Martí, R, Bueno, M, Gutiérrez-Carrasquilla, L, Lecube, A
Scientific reports. 2022;(1):3236
Abstract
The glucagon-like peptide-1 receptor agonist family together with the renal sodium/glucose cotransporter-2 inhibitors have garnered interest as potential therapeutic agents for subjects with type 2 diabetes and obesity. In these patients, bariatric surgery is indicated based in a BMI ≥ 35 kg/m2. A 24-week non-blinded, randomized pilot study to assess the efficacy of subcutaneous exenatide 2.0 mg once weekly plus oral dapagliflozin 10 mg once daily (Group A) compared to a control group (Group B) in 56 patients with type 2 diabetes awaiting bariatric surgery was conducted (EudraCTid.: 2017-001,454-33). Both groups received an energy-deficit low-fat diet. The primary endpoint was the proportion of patients running off the criteria for bariatric surgery at the end of the follow-up period (BMI ≤ 35.0 kg/m2 or a BMI ≤ 40.0 kg/m2 plus an HbA1c ≤ 6.0%). Changes in the BMI were also of interest. The proportion of patients who ran off the criteria for bariatric surgery was larger in Group A than in the control group (45.8% vs. 12.0%, p = 0.010). Participants in Group A exhibited an absolute decrease in body weight and BMI of 8.1 kg (95%IC: - 11.0 to - 5.2) and 3.3 kg/m2 (95%IC: - 4.5 to - 2.2), respectively (p < 0.001 for both in comparison with Group B). A higher percentage of participants in Group A reached a BMI < 35 kg/m2 (45.8 vs 12.0%) and lost > 10% of their initial body weight (20.8 vs 0%) compared to Group B. The combination of exenatide plus dapagliflozin appears as a strategic option to reduce the waiting list for bariatric surgery, especially in those patients with type 2 diabetes.
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Are Obesity Indices Useful for Detecting Subclinical Atheromatosis in a Middle-Aged Population?
Sánchez, E, Sánchez, M, Betriu, À, Rius, F, Torres, G, Purroy, F, Pamplona, R, Ortega, M, López-Cano, C, Hernández, M, et al
Obesity facts. 2020;(1):29-39
Abstract
OBJECTIVE There is a close relationship between excess adiposity and cardiovascular disease. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. Here, our objective was to assess the usefulness of these anthropometric indices to detect subclinical atheromatous disease. METHODS A cross-sectional study with 6,809 middle-aged subjects (mean age, 57 [53-63] years) with low to moderate cardiovascular risk from the ILERVAS project. Measures of total body fat (BMI, Clínica Universidad de Navarra - Body Adiposity Estimator [CUN-BAE], and Deurenberg's formula) and central adiposity (waist and neck circumferences, conicity index, waist-to-height ratio, Bonora's equation, the A body adiposity index, and body roundness index) were performed in all participants. Bilateral carotid and femoral ultrasound vascular studies allowed the identification of subjects with plaque. -Results: All measured indices were significantly higher in males with subclinical carotid or femoral plaques (p ≤ 0.021 for all). Also, a positive and significant correlation between all indices and the number of affected territories was found (p ≤ 0.013 for all). From the ROC analysis, all measurements identified patients with asymptomatic atheromatosis but none of them helped make clinical decisions. Regarding females, the results were less conclusive. CONCLUSION Obesity indices are related to subclinical atheromatosis, especially in men, in a large cohort of middle-aged subjects. However, the indices could not detect the presence of arterial plaque, so, when used in isolation, are unlikely to be decisive.
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Effects of Mediterranean Diet and Physical Activity on Pulmonary Function: A Cross-Sectional Analysis in the ILERVAS Project.
Gutiérrez-Carrasquilla, L, Sánchez, E, Hernández, M, Polanco, D, Salas-Salvadó, J, Betriu, À, Gaeta, AM, Carmona, P, Purroy, F, Pamplona, R, et al
Nutrients. 2019;11(2)
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Plain language summary
The Mediterranean diet is characterised by an abundant consumption of extra-virgin olive oil, fruits, vegetables, nuts, and legumes, a moderate consumption of fish and seafood, poultry, fermented dairy products, and red wine with meals, and low intakes of sweetened beverages, red meat and ready meals. The aim of the study was to evaluate the association between adherence to a Mediterranean diet and physical activity on pulmonary function in a large middle-aged population at low-to-moderate cardiovascular risk. The study is an ongoing study that between 2015 and 2017 enrolled a total of 3020 subjects – women aged between 50 to 70 years and men aged between 45 to 65 years – with the presence of at least one cardiovascular risk factor. Results indicate that a low adherence to the Mediterranean diet was linked with impaired breathing patterns and higher prevalence of abnormal lung function when compared to participants with a higher adherence to this dietary pattern. Additionally, vigorous physical activity was accompanied by better results in lung function than that observed in inactive subjects. The study provides initial clinical evidence about the independent and deleterious effect of both low adherence to the Mediterranean diet and low physical activity practice on lung function in participants without known pulmonary disease.
Abstract
A few studies showed that both adherence to Mediterranean diet (MedDiet) and physical activity practice have a positive impact on pulmonary function in subjects with lung disease. These associations are not well studied in subjects free from lung disease. In a cross-sectional study conducted in 3020 middle-aged subjects free of lung disease, adherence to the MedDiet using the Mediterranean Diet Adherence Screener, and physical activity practice using the International Physical Activity Questionnaire short form were recorded. Respiratory function was assessed using forced spirometry and the results were evaluated according to the Global initiative for Chronic Obstructive Lung Disease. Logistic regression models were used to analyze the associations between adherence to the MedDiet and physical activity practice with the presence of ventilatory defects. Participants with a high adherence to MedDiet, in comparison to those with low adherence, had both higher forced vital capacity (FVC; 100 (87⁻109) vs. 94 (82⁻105) % of predicted, p = 0.003) and forced expired volume in the first second (FEV1; 100 (89⁻112) vs. 93 (80⁻107) % of predicted, p < 0.001). According to their degree of physical activity, those subjects with a high adherence also had both higher FVC (100 (88⁻107) vs. 94 (83⁻105) % of predicted, p = 0.027) and FEV1 (100 (89⁻110) vs. 95 (84⁻108) % of predicted, p = 0.047) in comparison with those with low adherence. The multivariable logistic regression models showed a significant and independent association between both low adherence to MedDiet and low physical activity practice, and the presence of altered pulmonary patterns, with differences between men and women. However, no joint effect between adherence to MedDiet and physical activity practice on respiratory function values was observed. Low adherence to MedDiet and low physical activity practice were independently associated with pulmonary impairment. Therefore, the lung mechanics seem to benefit from heart-healthy lifestyle behaviors.
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The influence of sleep apnea syndrome and intermittent hypoxia in carotid adventitial vasa vasorum.
López-Cano, C, Rius, F, Sánchez, E, Gaeta, AM, Betriu, À, Fernández, E, Yeramian, A, Hernández, M, Bueno, M, Gutiérrez-Carrasquilla, L, et al
PloS one. 2019;(2):e0211742
Abstract
Subjects with sleep apnea-hypopnea syndrome (SAHS) show an increased carotid intima-media thickness. However, no data exist about earlier markers of atheromatous disease, such as the proliferation and expansion of the adventitial vasa vasorum (VV) to the avascular intima in this setting. Our aim was to assess carotid VV density and its relationship with sleep parameters in a cohort of obese patients without prior vascular events. A total of 55 subjects evaluated for bariatric surgery were prospectively recruited. A non-attended respiratory polygraphy was performed. The apnea-hypopnea index (AHI) and the cumulative percentage of time spent with oxygen saturation below 90% (CT90) were assessed. Serum concentrations of soluble intercellular adhesion molecule 1, P-selectin, lipocalin-2 and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. Contrast-enhanced carotid ultrasound was used to assess the VV density. Patients with SAHS (80%) showed a higher adventitial VV density (0.801±0.125 vs. 0.697±0.082, p = 0.005) and higher levels of sVCAM-1 (745.2±137.8 vs. 643.3±122.7 ng/ml, p = 0.035) than subjects with an AHI lower than 10 events/hour. In addition, a positive association exist between mean VV density and AHI (r = 0.445, p = 0.001) and CT90 (r = 0.399, p = 0.005). Finally, in the multiple linear regression analysis, female sex, fasting plasma glucose and AHI (but not CT90) were the only variables independently associated with the mean adventitial VV density (R2 = 0.327). In conclusion, a high VV density is present in obese subjects with SAHS, and chronic intermittent hypoxia is pointed as an independent risk factor for the development of this early step of atheromatous disease.
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Characteristics of atheromatosis in the prediabetes stage: a cross-sectional investigation of the ILERVAS project.
Sánchez, E, Betriu, À, López-Cano, C, Hernández, M, Fernández, E, Purroy, F, Bermúdez-López, M, Farràs-Sallés, C, Barril, S, Pamplona, R, et al
Cardiovascular diabetology. 2019;(1):154
Abstract
BACKGROUND Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage. METHODS Atheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines. RESULTS Prediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects. CONCLUSIONS The prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner. Trial registration NCT03228459 (clinicaltrials.gov).