A comprehensive evaluation of omega-3 fatty acid supplementation in cystic fibrosis patients using lipidomics.

The evaluation of the benefits of omega-3 fatty acid supplementation in humans requires the identification and characterization of suitable biomarkers of its incorporation in the body. The reference method for the evaluation of omega-3, gas chromatography, is difficult to apply in clinical practice because of its low throughput and does not provide information about the incorporation of specific fatty acids in lipid species and the potential effects of supplementation on lipid classes. We used a quantitative lipidomic approach to follow the incorporation of omega-3 fatty acids into plasma lipids in cystic fibrosis patients (n=50) from a randomized controlled clinical trial after the supplementation of seaweed oil enriched with docosahexaenoic acid (DHA). Lipidomic analysis accurately showed the distribution of fatty acids in different lipid classes after omega-3 supplementation, and the performance in determining the compliance to supplementation was similar to that of gas chromatography coupled to mass spectrometry. Twelve months after fatty acid supplementation, DHA was predominantly incorporated into highly unsaturated cholesteryl esters (110.9±16.2 vs. 278.6±32.6 µM, mean±S.E.M.) and phosphatidylcholine (142.4±11.9 vs. 272.9±21.4 µM) and, to a lesser extent, into phosphatidylethanolamine (9.4±0.8 vs. 15.5±1.5 µM) and triglycerides (0.4±0.04 vs. 1.1±0.12 µM). In addition, a technique was developed for the fast measurement of the DHA/arachidonic acid ratio to simplify the follow-up of nutritional intervention with DHA-enriched foods. We conclude that lipidomics is a suitable approach for monitoring the incorporation of omega-3 fatty acids in nutritional studies.

Asociación entre el cambio relativo de peso e índice de masa corporal con la función pulmonar en adolescentes y adultos con fibrosis quística: influencia del género y la diabetes / Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes

FUNDAMENTO: El estado nutricional es un indicador pronóstico en la fibrosis quística (CF). La prevención del deterioro nutricional y de la pérdida de peso son objetivos clínicos principales, ya que están asociados con empeoramiento de la función pulmonar y aumento de la mortalidad. Objetivo: Identificar si existe una relación entre los parámetros clínicos de nutrición, y sus cambios relativos, con la función pulmonar (FEV1%) en una cohorte de pacientes adolescentes y adultos con CF. Métodos: Analizamos de forma retrospectiva una serie de 64 pacientes mayores de 14 años. Se recogieron datos del peso, talla e IMC, suplementos nutricionales, y la función pulmonar en fase de estabilidad tanto en el año de realización del primer test de sobrecarga oral de glucosa (OGTT) patológico como en el año previo. Se determinaron los cambios relativos de peso e IMC, y su relación con FEV1%, mediante regresión lineal y ANOVA, así como la influencia del género y la diabetes. Resultados: La media de edad de la serie fue de 26,8 años (28 mujeres y 36 varones). El 26,7% tenían una tolerancia normal a la glucosa (TGN) y el 18,3% tenían diabetes sin alteración de la glucosa en ayunas (CFRD sin FPG). La media del IMC fue de 20,32, con un peso medio de 53,53 kg. El 32,8% tenían un IMC < 18,5 y tan solo el 4,7% presentaban sobrepeso. De forma global, un cambio relativo de peso positivo (≥ 6%) se asociaba con un incremento del FEV1% (9,31%) respecto a los que presentaban una mayor pérdida de peso, de al menos un 2%, los cuales tenían una caída del FEV1 del 12,09%. Los pacientes con CFRD sin FPG presentaban peor función pulmonar si mostraban una pérdida relativa de peso superior al 2%, en comparación con TGN. Conclusiones: En los pacientes con CF, la ganancia relativa de peso tiene una asociación positiva con el FEV1%, mientras que una pérdida ≥ 2% tiene una repercusión significativa negativa en la función pulmonar

BACKGROUND: Nutritional status is a prognostic factor in cystic fibrosis. Prevention of nutritional impairment and weigh loss are major clinical objectives because they are associated with worsening of lung function and increased mortality. OBJECTIVE: To identify a potential relationship of clinical nutrition parameters, and their relative changes, with lung function (FEV1%) in a cohort of adolescent and adult patients with CF. METHODS: A retrospective analysis of 64 patients older than 14 years. Weight, height, BMI, and lung function data were collected at a period of disease stability, both in the year of the first abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative changes in weight and BMI, and their relationship with FEV1%, were determined by linear regression and ANOVA tests; influence of gender and diabetes was also assessed. RESULTS: Mean age of the series (28 females and 36 males) was 26.8 years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32, with a mean weight of 53.53 kg; 32.8% had BMI < 18.5, and only 4.7% were overweight. Overall, a positive relative change in weight (≥ 6%) was associated with an increase in FEV1% (9.31%), as compared to those with a greater weight loss (at least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had poorer lung function if they had a negative relative change in weight by at least 2% as compared to NGT. CONCLUSIONS: In patients with CF, a relative weight gain is positively associated to FEV1%, while a relative weight loss of at least 2% has a significant negative impact on lung function

Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes.

BACKGROUND: Nutritional status is a prognostic factor in cystic fibrosis. Prevention of nutritional impairment and weigh loss are major clinical objectives because they are associated with worsening of lung function and increased mortality. OBJECTIVE: To identify a potential relationship of clinical nutrition parameters, and their relative changes, with lung function (FEV1%) in a cohort of adolescent and adult patients with CF. METHODS: A retrospective analysis of 64 patients older than 14years. Weight, height, BMI, and lung function data were collected at a period of disease stability, both in the year of the first abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative changes in weight and BMI, and their relationship with FEV1%, were determined by linear regression and ANOVA tests; influence of gender and diabetes was also assessed. RESULTS: Mean age of the series (28 females and 36 males) was 26.8years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32, with a mean weight of 53.53kg; 32.8% had BMI<18.5, and only 4.7% were overweight. Overall, a positive relative change in weight (≥6%) was associated with an increase in FEV1% (9.31%), as compared to those with a greater weight loss (at least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had poorer lung function if they had a negative relative change in weight by at least 2% as compared to NGT. CONCLUSIONS: In patients with CF, a relative weight gain is positively associated to FEV1%, while a relative weight loss of at least 2% has a significant negative impact on lung function.

Resistencia insulínica, disfunción de la célula beta pancreática y diferencias en los puntos intermedios de las curvas de glucemia e insulina tras una sobrecarga oral estándar de glucosa en adultos con fibrosis quística / Insulin resistance, beta-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis

FUNDAMENTO: La diabetes se ha convertido en una comorbilidad prevalente que tiene un impacto negativo sobre el estado nutricional, la función pulmonar y la supervivencia en la fibrosis quística. OBJETIVO: Identificar alteraciones en los puntos intermedios del test de tolerancia oral a la glucosa de 2 h (OGTT), la disfunción de la célula β pancreática y la resistencia insulínica en la diabetes relacionada con la fibrosis quística. MÉTODOS: Analizamos de forma retrospectiva una serie de 64 pacientes mayores de 14 años, mediante los datos del primer OGTT patológico durante su seguimiento. Se determinaron la resistencia insulínica, usando el modelo HOMA-IR, la función de la célula β pancreática según Wareham, el tiempo en alcanzar la concentración máxima plasmática de insulina y glucosa y el área bajo la curva (AUC0-120). RESULTADOS: Se incluyeron 28 mujeres y 36 varones. La media de edad de la serie fue de 26,8 años. El 26,7% tenía una tolerancia normal (TGN), un 18,3% diabetes sin alteración de la glucosa en ayunas (CFRD sin FPG), el 10% una alteración indeterminada (INDET) y el 45% intolerancia hidrocarbonada (IGT). En los valores del HOMA-IR no se encontraron diferencias entre ningún grupo. Los casos con alguna alteración diagnóstica tenían una peor función de la célula β, con un retraso significativo en la secreción de insulina, aunque no hubo diferencias en su producción total (AUC0-120). El tiempo en alcanzar el pico máximo de glucosa era significativamente menor en los TGN frente al resto de categorías, siendo el AUC0-120 de glucosa mayor en las distintas categorías diagnósticas frente a TGN. CONCLUSIONES: En más de la mitad de los casos el pico máximo de glucemia en la OGTT se alcanza en puntos intermedios y no en el tiempo clásico de 120min. La secreción precoz de insulina está retrasada en los pacientes con fibrosis quística y alteraciones en el metabolismo de la glucosa, sin llegar a observarse diferencias en la producción total de la misma. La ausencia de alteraciones significativas en el HOMA-IR sugiere que la disfunción de la célula β es el principal mecanismo patogénico

BACKGROUND: diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. OBJECTIVE: To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic β-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. METHODS: It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic β-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. RESULTS: Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse β cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. CONCLUSIONS: In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that β-cell dysfunction is the main pathogenetic mechanism

Insulin resistance, ß-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis.

BACKGROUND: diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. OBJECTIVE: To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic ß-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. METHODS: It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic ß-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. RESULTS: Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse ß cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. CONCLUSIONS: In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that ß-cell dysfunction is the main pathogenetic mechanism.

Tolerabilidad de la inhalación de dos soluciones salinas hipertónicas en pacientes con fibrosis quística / Tolerance of two inhaled hypertonic saline solutions in patients with cystic fibrosis

Fundamento y objetivo: El propósito del trabajo fue estudiar la tolerabilidad de dos soluciones salinas hipertónicas (SSH) en pacientes con fibrosis quística (FQ).Pacientes y método: Se estudiaron 81 pacientes con FQ (44 varones, edad media 23,63 años). Los pacientes inhalaron 5ml de una SSH al 7%. Los que no la toleraron inhalaron, al menos 24 horas después, 5ml de una SSH al 7% con ácido hialurónico al 0,1%.Resultados: Veintiún pacientes (26%) no toleraron la SSH inmediatamente tras su inhalación. La tos fue la causa más frecuente de no tolerancia. Los mayores de 18 años y los que tenían peor función pulmonar toleraron la SSH peor. El 81% de los pacientes que no toleraron la SSH toleraron bien la SSH con hialurónico. Conclusiones: Bastantes pacientes con FQ no toleran la inhalación de la SSH inmediatamente tras su nebulización. Los mayores de 18 años y los que tienen peor función pulmonar la toleraron peor. El ácido hialurónico añadido a la SSH minimiza los efectos secundarios de ésta (AU)

Background and objective: The aim of our study was to evaluate the tolerance of two inhaled hypertonic saline solutions (HS) in patients with cystic fibrosis. Patients and method: Eighty one cystic fibrosis (CF) patients (44 males; mean age 23.63years) inhaled 5ml of 7% inhaled HS solution and, in those patients who did not tolerate HS, we evaluated the tolerance of a 7% HS (at dose of 5ml) added to 0.1% hyaluronic acid at least twenty-four hours later. Results: Twenty one (26%) patients did not tolerate the HS solution immediately after its inhalation. Cough was the most common symptom. Patients over 18years of age showed worse tolerance to HS than patients younger than 18years of age. Those patients that did not tolerate HS had a worse lung function that the ones that showed good tolerance. Eighty-one percent of patients who did not tolerate the HS alone tolerated well the HS with hyaluronic acid. Conclusions: CF patients cannot tolerate inhaled HS immediately after nebulisation. Patients over 18years and those with worse lung function tolerate HS worst. Hyaluronate acid added to 7% HS solution improves the tolerability (AU)

[Tolerance of two inhaled hypertonic saline solutions in patients with cystic fibrosis]. / Tolerabilidad de la inhalación de dos soluciones salinas hipertónicas en pacientes con fibrosis quística.

BACKGROUND AND OBJECTIVE: The aim of our study was to evaluate the tolerance of two inhaled hypertonic saline solutions (HS) in patients with cystic fibrosis. PATIENTS AND METHOD: Eighty one cystic fibrosis (CF) patients (44 males; mean age 23.63 years) inhaled 5 ml of 7% inhaled HS solution and, in those patients who did not tolerate HS, we evaluated the tolerance of a 7% HS (at dose of 5 ml) added to 0.1% hyaluronic acid at least twenty-four hours later. RESULTS: Twenty one (26%) patients did not tolerate the HS solution immediately after its inhalation. Cough was the most common symptom. Patients over 18 years of age showed worse tolerance to HS than patients younger than 18 years of age. Those patients that did not tolerate HS had a worse lung function that the ones that showed good tolerance. Eighty-one percent of patients who did not tolerate the HS alone tolerated well the HS with hyaluronic acid. CONCLUSIONS: CF patients cannot tolerate inhaled HS immediately after nebulisation. Patients over 18 years and those with worse lung function tolerate HS worst. Hyaluronate acid added to 7% HS solution improves the tolerability.