Publications by authors named "Berta Soldevila"

31 Publications

Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated?

Rev Endocr Metab Disord 2021 Jul 31. Epub 2021 Jul 31.

Department of Endocrinology, Hospital Universitario de La Princesa, Instituto de Investigación de La Princesa, Universidad Autónoma de Madrid, Madrid, Spain.

Although SARS-CoV-2 viral attacks starts by the interaction of spike protein (S Protein) to ACE2 receptor located at the cell surface of respiratory tract and digestive system cells, different endocrine targets, endocrine organs and metabolic conditions are of fundamental relevance for understanding disease progression and special outcomes, in particular those of fatal consequences for the patient. During pandemic, moreover, a specific phenotype of COVID-19 metabolic patient has been described, characterized by being at particular risk of worse outcomes. In the present paper we describe the mechanism of viral interaction with endocrine organs, emphasizing the specific endocrine molecules of particular relevance explaining COVID-19 disease evolution and outcomes.
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http://dx.doi.org/10.1007/s11154-021-09678-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325622PMC
July 2021

Reference Intervals of Thyroid Function Tests Assessed by Immunoassay and Mass Spectrometry in Healthy Pregnant Women Living in Catalonia.

J Clin Med 2021 May 31;10(11). Epub 2021 May 31.

Endocrine, Thyroid & Obesity Research Group, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, s/n Camí de les Escoles, 08916 Badalona, Spain.

Background: Recent guidelines recommend establishing a local reference interval (RI) for thyroid function. We aimed to establish trimester-specific RIs for thyrotropin (TSH) and free thyroxine (FT4) in a cohort of healthy pregnant women in Catalonia (Spain).

Methods: A prospective observational study was conducted with 332 healthy pregnant women, from the first trimester (1T) to delivery. TSH was measured using an Architect immunoassay (Abbott) and FT4 by two immunoassays, Architect (Abbott) and Cobas (Roche), in the three trimesters. FT4 was also measured by liquid chromatography mass spectrometry (LC/MS/MS) in the 1T.

Results: TSH (µUI/mL) increased throughout pregnancy (1T: 0.03-3.78; 2T: 0.51-3.53; 3T: 0.50-4.32; < 0.0001) and FT4 (pmol/L) progressively decreased (Architect 1T: 10.42-15.96; 2T: 8.37-12.74; 3T: 8.24-12.49; < 0.0001; and Cobas: 1T: 11.46-19.05; 2T: 9.65-14.67; 3T: 8.88-14.54; < 0.0067). The FT4 RI during 1T determined LC/MS/MS was 8.75-18.27. Despite the 1T FT4 results measured by LC/MS/MS and with the two immunoassays being significantly correlated, the results obtained by the three methods were found to be non-interchangeable.

Conclusions: We established trimester-specific RIs for TSH and for FT4 with immunoassays in our population. We also validated the 1T FT4 using LC/MS/MS to confirm the results of FT4 lower than the 2.5th percentile or higher than the 97.5th percentile.
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http://dx.doi.org/10.3390/jcm10112444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198941PMC
May 2021

Impact of COVID-19 on nutritional status during the first wave of the pandemic.

Clin Nutr 2021 May 8. Epub 2021 May 8.

Endocrinology and Nutrition Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Autonomous University of Barcelona, Barcelona, Spain. Electronic address:

Background & Aims: Patients affected by COVID-19 may develop disease related malnutrition (DRM) due to the catabolic situation, symptoms that interfere with intake and prolonged hospital stay. This study aims to know the percentage of patients admitted for COVID-19 who required artificial nutrition (AN), their clinical characteristics, as well as the prevalence of DRM and the risk of sarcopenia at hospital discharge and after 6 months.

Material And Methods: Observational, prospective study, with successive inclusion of adult patients admitted for COVID-19 in whom institutional nutritional support (NS) care protocol was applied. Those who received AN underwent a nutritional screening by Short Nutritional Assessment Questionnaire (SNAQ) and an assessment by Subjective Global Assessment (SGA) at hospital discharge, as well as a screening for sarcopenia (SARC-F test) and SNAQ re-test 15 days and 6 months after by a phone call. Symptoms related to food intake, anthropometric and analytical data were also collected.

Results: We evaluated 936 patients with a mean age of 63.7 ± 15.3 years; predominantly male (59.7%), overweight 41%, obesity 40.4%; hypertension 52.9%; diabetes mellitus 26.6% and cancer 10.4%. The stay hospital length was 17.3 ± 13.8 days and 13.6% patients died during hospitalization. The modality of nutritional support was: 86.1% dietary adaptation + oral nutritional supplements (ONS); 12.4% enteral nutrition (EN) by nasogastric (NG) tube; 0.9% parenteral nutrition (PN) and 0.6% EN plus PN. Focusing on patients who received AN, follow-up post discharge was possible in 62 out of 87 who survived. Of these, at the time of hospital discharge, 96.7% presented nutritional risk by SNAQ and 100% malnutrition by SGA (20% B; 80% C). During admission, 82.3% presented intense anorexia and the mean weight loss was 10.9 ± 6 Kg (p < 0.001). Fifteen days after being discharged, 12.9% still had anorexia, while hyperphagia appeared in 85.5% of the patients and risk of sarcopenia by SARC-F was present in 87.1% of them. Six months after discharge, 6.8% still had anorexia and 3.4% hyperphagia, with a global weight gain of 4.03 ± 6.2 Kg (p=<0.0001). Risk of malnutrition was present in only 1.7% of the patients, although risk of sarcopenia persisted in 49.2%.

Conclusion: All patients admitted by COVID-19 for whom EN or PN were indicated following an institutional protocol still presented malnutrition at hospital discharge, and almost all showed risk of sarcopenia, that persisted in almost half of them at 6 months. These findings suggest that nutritional and functional problems persist in these patients after discharge, indicating that they require prolonged nutritional support and monitoring.
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http://dx.doi.org/10.1016/j.clnu.2021.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106234PMC
May 2021

Pasireotide in the Personalized Treatment of Acromegaly.

Front Endocrinol (Lausanne) 2021 16;12:648411. Epub 2021 Mar 16.

Endocrinology & Nutrition Service, La Princesa University Hospital, Madrid, Spain.

The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low and high expression of , low or mutated condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.
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http://dx.doi.org/10.3389/fendo.2021.648411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008639PMC
March 2021

Epithelial-Mesenchymal Transition in the Resistance to Somatostatin Receptor Ligands in Acromegaly.

Front Endocrinol (Lausanne) 2021 15;12:646210. Epub 2021 Mar 15.

Endocrine Tumours Lab, Program of Predictive and Personalized Medicine of Cancer (PMPPC), Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.

Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory and invasive capacities. EMT is involved in physiological processes, such as embryogenesis and wound healing, and in pathological processes such as cancer, playing a pivotal role in tumor progression and metastasis. Pituitary tumors, although typically benign, can be locally invasive. Different studies have shown the association of EMT with increased tumor size and invasion in pituitary tumors, and in particular with a poor response to Somatostatin Receptor Ligands (SRLs) treatment in GH-producing pituitary tumors, the main cause of acromegaly. This review will summarize the current knowledge regarding EMT and SRLs resistance in acromegaly and, based on this relation, will suggest new biomarkers and possible therapies to SRLs resistant tumors.
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http://dx.doi.org/10.3389/fendo.2021.646210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006574PMC
March 2021

Advanced lipoprotein profile in individuals with normal and impaired glucose metabolism.

Rev Esp Cardiol (Engl Ed) 2021 Mar 27. Epub 2021 Mar 27.

Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Servicio de Endocrinología y Nutrición, Hospital de la Santa Creu i Sant Pau e Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain; Facultad de Medicina, Universidad de Vic - Universidad Central de Cataluña (UVic/UCC), Vic, Barcelona, Spain.

Introduction And Objectives: Several types of lipoproteins beyond low-density lipoproteins (LDL) are causally related to cardiovascular disease. We aimed to analyze an advanced lipoprotein profile in individuals with normal and impaired glucose metabolism from different cohorts of a Mediterranean region.

Methods: Cross-sectional study in 929 participants (463 normoglycemia, 250 prediabetes, and 216 type 2 diabetes mellitus) with normal renal function, free from cardiovascular disease, and without lipid-lowering treatment. Conventional and advanced (nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analyzed.

Results: Compared with men, normoglycemic women showed lower serum triglyceride and LDL cholesterol concentrations, lower total LDL particles (P) as well as their subclasses and their cholesterol and triglyceride content, higher high-density lipoproteins (HDL)-P and all HDL-related variables (P≤ .05 for all comparisons). Compared with normoglycemic participants, diabetic participants showed higher large and small very LDL-P concentrations (P <.05) and lower total HDL-P and medium HDL-P concentrations (P <.05). Waist circumference and Fatty Liver Index were positively associated with a proatherogenic profile.

Conclusions: Women had a better advanced lipoprotein profile than did men. Adiposity indexes related to insulin-resistance were positively associated with a proatherogenic lipid profile. NMR revealed altered lipoprotein particles other than LDL in participants with diabetes, frequently associated with an increased cardiovascular risk. Our findings support the usefulness of extended lipoprotein analysis by NMR spectroscopy to uncover new therapeutic targets to prevent cardiovascular events in at-risk participants.
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http://dx.doi.org/10.1016/j.rec.2021.02.006DOI Listing
March 2021

Atherogenic dyslipidemia, but not hyperglycemia, is an independent factor associated with liver fibrosis in subjects with type 2 diabetes and NAFLD: a population-based study.

Eur J Endocrinol 2021 Apr;184(4):587-596

Department of Endocrinology and Nutrition, Hospital Germans Trias I Pujol, Badalona, Barcelona, Spain.

Objective: To investigate the prevalence and risks factors associated with the presence of liver fibrosis in subjects with nonalcoholic fatty liver disease (NAFLD) with and without type 2 diabetes mellitus (T2D).

Design And Methods: This study was part of a population-based study conducted in the Barcelona metropolitan area among subjects aged 18-75 years old. Secondary causes of steatosis were excluded. Moderate-to-advanced liver fibrosis was defined as a liver stiffness measurement (LSM) ≥ 8.0 kPa assessed by transient elastography.

Results: Among 930 subjects with NAFLD, the prevalence of moderate-to-advanced liver fibrosis was higher in subjects with T2D compared those without (30.8% vs 8.7%). By multivariable analysis, one of the main factors independently associated with increased LSM in subjects with NAFLD was atherogenic dyslipidemia but only in those with T2D. The percentage of subjects with LSM ≥ 8.0 kPa was higher in subjects with T2D and atherogenic dyslipidemia than in those with T2D without atherogenic dyslipidemia both for the cut-off point of LSM ≥8.0 kPa (45% vs 24% P = 0.002) and ≥13 kPa (13% vs 4% P = 0.020). No differences were observed in the prevalence of LSM ≥8.0 kPa regarding glycemic control among NAFLD-diabetic subjects.

Conclusions: Factors associated with moderate-to-advanced liver fibrosis in NAFLD are different in subjects with and without T2D. Atherogenic dyslipidemia was associated with the presence of moderate-to-advanced liver fibrosis in T2D with NAFLD but not in non-diabetic subjects. These findings highlight the need for an active search for liver fibrosis in subjects with T2D NAFLD and atherogenic dyslipidemia.
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http://dx.doi.org/10.1530/EJE-20-1240DOI Listing
April 2021

Estimation of the prevalence of thyroid dysfunction in Catalonia through two different registries: Pharmaceutical dispensing and diagnostic registration.

Endocrinol Diabetes Metab 2021 01 8;4(1):e00167. Epub 2020 Jul 8.

Endocrinology and Nutricion Department Hospital Germans Trias I Pujol Badalona Spain.

Background: Population studies on the prevalence of thyroid dysfunctions are costly. The pharmacy dispensing (PDR) and diagnosis (DR) registers allow us to study the epidemiology of these pathologies in a simpler way. Our aims: 1/Estimate the prevalence of thyroid dysfunction in Catalonia based on data from the PDR and the DR, 2/to evaluate the concordance of the results obtained by both strategies.

Methods: The population studied was the one registered with the public health system in Catalonia(Catsalut). In the PDR analysis, the information obtained through the Pharmaceutical Provision file (during 2012, 2013, 2014) was used regarding the number of patients under treatment (NPT) (levothyroxine and antithyroid medication). The DR analysis (2014) was performed by ICD-9 codes (hyperthyroidism 242 and hypothyroidism 243, 244).

Results: According to the NPT in the PDR analysis, the prevalence of treated hypothyroidism increased over 3 years: 2.81%(2012), 2.92%(2013) and 3.07%(2014) ( < .00001). The prevalence of hyperthyroidism in treatment was 0.14%(2012), 0.13%(2013) and 0.14%(2014). According to the DR analysis in 2014, the prevalence of hypothyroidism was 2.54% and 0.35% for hyperthyroidism. The PDR analysis estimated a higher hypothyroidism prevalence compared to that estimated by the DR ( < .0001) and vice versa in the case of hyperthyroidism.

Conclusion: Both PDR and DR prevalence estimations of thyroid dysfunction show some degree of discordance probably due to undercoding bias in the case of DR and the absence of subclinical pathology in the case of PDR. However, both approaches are valid and complementary for estimating the prevalence of thyroid dysfunction.
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http://dx.doi.org/10.1002/edm2.167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831201PMC
January 2021

Advanced lipoprotein profile disturbances in type 1 diabetes mellitus: a focus on LDL particles.

Cardiovasc Diabetol 2020 08 9;19(1):126. Epub 2020 Aug 9.

Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau & Institut d'Investigació Biomédica Sant Pau (IIB Sant Pau), Sant Quintí, 89, 08041, Barcelona, Spain.

Background: Lipoprotein disturbances have been associated with increased cardiovascular disease (CVD) risk in type 1 diabetes mellitus (T1DM). We assessed the advanced lipoprotein profile in T1DM individuals, and analysed differences with non-diabetic counterparts.

Methods: This cross-sectional study involved 508 adults with T1DM and 347 controls, recruited from institutions in a Mediterranean region of Spain. Conventional and advanced (assessed by nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analysed. Crude and adjusted (by age, sex, statin use, body mass index and leukocyte count) comparisons were performed.

Results: The median (interquartile range) age of the study participants was 45 (38-53) years, 48.2% were men. In the T1DM group, the median diabetes duration was 23 (16-31) years, and 8.1% and 40.2% of individuals had nephropathy and retinopathy, respectively. The proportion of participants with hypertension (29.5 vs. 9.2%), and statin use (45.7% vs. 8.1%) was higher in the T1DM vs. controls (p < 0.001). The T1DM group had a better conventional (all parameters, p < 0.001) and NMR-lipid profile than the control group. Thus, T1DM individuals showed lower concentrations of atherogenic lipoproteins (VLDL-particles and LDL-particles) and higher concentrations of anti-atherogenic lipoproteins (HDL-particles) vs. controls, even after adjusting for several confounders (p < 0.001 for all). While non-diabetic women had a more favourable lipid profile than non-diabetic men, women with T1DM had a similar concentration of LDL-particles compared to men with T1DM (1231 [1125-1383] vs. 1257 [1128-1383] nmol/L, p = 0.849), and a similar concentration of small-LDL-particles to non-diabetic women (672.8 [614.2-733.9] vs. 671.2 [593.5-761.4] nmol/L, respectively; p = 0.790). Finally, T1DM individuals showed higher discrepancies between NMR-LDL-particles and conventional LDL-cholesterol than non-diabetic subjects (prevalence of LDL-cholesterol < 100 mg/dL & LDL-particles > 1000 nmol/L: 38 vs. 21.2%; p < 0.001). All these differences were largely unchanged in participants without lipid-lowering drugs (T1DM, n = 275; controls, n = 317).

Conclusions: Overall, T1DM participants showed a more favourable conventional and NMR-lipid profile than controls. However, the NMR-assessment identified several lipoprotein derangements in LDL-particles among the T1DM population (higher discrepancies in NMR-LDL-particles vs. conventional LDL-cholesterol; a worse profile in T1DM women) that were overlooked in the conventional analysis. Further studies are needed to elucidate their role in the development of CVD in this population.
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http://dx.doi.org/10.1186/s12933-020-01099-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416413PMC
August 2020

The Circulating Fatty Acid Transporter Soluble CD36 Is Not Associated with Carotid Atherosclerosis in Subjects with Type 1 and Type 2 Diabetes Mellitus.

J Clin Med 2020 Jun 2;9(6). Epub 2020 Jun 2.

Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, 08041 Barcelona, Spain.

This study aimed to determine the association of fatty acid transporter plasma soluble cluster of differentiation 36 (sCD36) with subclinical carotid atherosclerosis (SCA). A cross-sectional study was conducted in 1023 subjects, 225 with type 1 diabetes (T1D), 276 with type 2 diabetes (T2D) and 522 who were nondiabetic. Carotid atherosclerotic plaque (CAP) presence was determined using B-mode carotid ultrasound imaging. sCD36 were analysed by ELISA, and CD36 surface receptor and mRNA expression were measured by flow cytometry and real-time PCR. Logistic regression models were used to evaluate sCD36 as a biomarker of SCA. Up to 376 (36.75%) participants had at least one CAP, 76 T1D, 164 T2D and 136 without diabetes, while the remaining 647 (63.25%) did not have any CAP. There were no differences in sCD36 between patients with and without CAP in T1D ( = 0.287) or T2D ( = 0.513). Although nondiabetic subjects with plaques had lower sCD36 levels than those without ( = 0.023), the multivariate models revealed no association of sCD36 with CAP in any of the three study groups. No differences were found in surface CD36 or CD36 mRNA expression between the patients with and without CAP. sCD36 is not associated with SCA in type 1 or type 2 diabetic or in nondiabetic subjects.
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http://dx.doi.org/10.3390/jcm9061700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355534PMC
June 2020

Distinct pattern of peripheral lymphocyte subsets in Graves' disease with persistency of anti-TSHR autoantibodies.

Autoimmunity 2019 Aug - Sep;52(5-6):220-227. Epub 2019 Jul 31.

Immunology Division, LCMN Germans Trias i Pujol University Hospital Badalona, Barcelona, Spain.

Graves' disease (GD) is characterized by the production of autoantibodies against the TSHR (TRAbs). With long-term treatment, serum concentrations of TRAbs decline but in some patients, despite being clinically stable, TRAbs persist for many years. To investigate whether GD patients with persistence of TRAbs constitute a subset of patients that could be identified by phenotypic analysis of circulating lymphocytes, suggesting disease heterogeneity. Peripheral blood lymphocytes (including naïve, memory and effector T and B cells, Th17, regulatory T cells (Treg), recent thymic emigrants (RTEs) and double positive CD4CD8 (DP) cells) were analysed by flow cytometry in a cross-sectional study in 25 clinically stable GD patients, five patients at onset of GD disease and 40 healthy donors (HDs). GD patients with persistence of TRAbs showed a lower percentage of Treg and lower absolute numbers of central and effector memory CD8 T cells than HD. No differences in RTEs were found in peripheral blood from GD patients compared to HD. Stable GD patients had higher percentage of DP cells of effector phenotype than HD. Using extensive phenotypic analysis of lymphocyte subpopulations, it is possible to detect changes that help to identify patients with persistent TSHR antibodies and may contribute to understand why the autoimmune response is maintained.
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http://dx.doi.org/10.1080/08916934.2019.1646253DOI Listing
July 2020

Subclinical atherosclerosis burden predicts cardiovascular events in individuals with diabetes and chronic kidney disease.

Cardiovasc Diabetol 2019 07 19;18(1):93. Epub 2019 Jul 19.

Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain.

Background: Individuals with diabetes have remarkably high rates of cardiovascular morbidity and mortality. However, the incremental cardiovascular risk in diabetes is heterogeneous and has often been related to renal involvement. The purpose of this study was to analyse the prognostic value of subclinical atherosclerosis in determining the incidence of first cardiovascular events (CVEs) in individuals with diabetes and chronic kidney disease (CKD) compared to CKD individuals without diabetes.

Methods: We included data from individuals with CKD with and without diabetes, free from pre-existing cardiovascular disease, from the NEFRONA cohort. Participants underwent baseline carotid and femoral ultrasound and were followed up for 4 years. All CVEs during follow-up were registered. Bivariate analysis and Fine-Gray competing risk models were used to perform the statistical analysis.

Results: During the mean follow-up time of 48 months, a total of 203 CVE was registered. 107 CVE occurred among participants without diabetes (19.58 per 1000 person-years) and 96 CVE occurred among participants with diabetes (44.44 per 1000 person-years). Following the competing risk analysis, the variables predicting CVEs in CKD individuals without diabetes were the number of territories with plaque at baseline (HR 1.862, 95% CI [1.432;2.240]), age (HR 1.026, 95% CI [1.003;1.049]) and serum concentrations of 25-OH vitamin D (HR 0.963, 95% CI [0.933;0.094]). The only variable predicting CVEs among CKD participants with diabetes was the number of territories with plaque at baseline (HR 1.782, 95% CI [1.393, 2.278]). For both models, concordance (C) index yielded was over 0.7.

Conclusions: The burden of subclinical atherosclerosis is the strongest predictor of future CVEs in diabetic individuals with CKD. Early detection of subclinical atherosclerotic burden by multiterritorial vascular ultrasound could improve CVE prediction in this population.
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http://dx.doi.org/10.1186/s12933-019-0897-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639953PMC
July 2019

Ultrasound Tissue Characterization of Carotid Plaques Differs Between Patients with Type 1 Diabetes and Subjects without Diabetes.

J Clin Med 2019 Mar 28;8(4). Epub 2019 Mar 28.

Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, 08907 Barcelona, Spain.

The aim of the study was to investigate ultrasound tissue characterization of carotid plaques in subjects with and without diabetes type 1 (T1D). B-mode carotid ultrasound was performed to assess the presence and type of plaque in a group of 340 subjects with and 304 without T1D, all of them without cardiovascular disease. One hundred and seven patients with T1D (49.5% women; age 54 ± 9.8 years) and 67 control subjects without diabetes who had at least one carotid plaque were included in the study. The proportion of subjects who had only echolucent plaques was reduced in the group of patients with T1D (48.6% vs. 73.1%). In contrast, the proportion with only echogenic (25.2% vs. 7.5%) and calcified plaques (9.4% vs. 1.5%) was increased compared with subjects without diabetes. Moreover, having at least one echogenic plaque was more frequent in T1D patients compared with subjects without diabetes (49.5% vs. 26.9% = 0.005). In addition to diabetes (OR 2.28; = 0.026), age (OR 1.06, = 0.002) was the other variable associated with echogenic plaque existence in multiple regression analysis. Patients with T1D exhibit a differential pattern of carotid plaque type compared with subjects without diabetes, with an increased frequency of echogenic and extensively calcified plaques.
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http://dx.doi.org/10.3390/jcm8040424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518191PMC
March 2019

Prevalence and progression of subclinical atherosclerosis in patients with chronic kidney disease and diabetes.

Atherosclerosis 2018 09 19;276:50-57. Epub 2018 Jul 19.

Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain; Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain; Department of Endocrinology and Nutrition, University Hospital de la Santa Creu i Sant Pau & Institut d'Investigació Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain. Electronic address:

Background And Aims: Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD) and diabetes. Traditional cardiovascular risk factors fail to fully account for the increase in cardiovascular risk in these patients. This study aims to analyse the prevalence and progression of subclinical atherosclerosis in CKD patients with and without diabetes.

Methods: We included data from CKD patients with and without diabetes free from previous cardiovascular events from the NEFRONA cohort. Patients underwent baseline and 24-month follow-up carotid and femoral ultrasound examinations. Multivariable models were used to assess the contribution of diabetes to the presence and plaque progression.

Results: A total of 419 patients with diabetes and 1129 without diabetes were included. Diabetic patients were older, had higher BMIs, more hypertension and dyslipidaemia. At baseline, the proportion of patients with plaque was higher among diabetic patients (81.4% vs. 64.1%, p < 0.001). Diabetic patients more frequently had more than two vascular territories with plaque (64.4% vs. 48.4%, p < 0.001). Multivariable analysis indicated that plaque at baseline was significantly associated with age, gender, smoking and renal replacement therapy (RRT) in the non-diabetic patients, but only with age and male gender in diabetic patients. Plaque progression was significantly associated with age, number of territories with basal plaque, smoking and RRT in both groups.

Conclusions: Subclinical atherosclerosis is more prevalent, carries a higher plaque burden and is more rapidly progressive in renal patients with diabetes. In these patients, diabetes outweighs other described risk factors associated with the presence of subclinical atherosclerosis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2018.07.018DOI Listing
September 2018

Impact of TSH during the first trimester of pregnancy on obstetric and foetal complications: Usefulness of 2.5 mIU/L cut-off value.

Clin Endocrinol (Oxf) 2018 05 9;88(5):728-734. Epub 2018 Mar 9.

Endocrinology and Nutrition Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

Objective: An association of pregnancy outcomes with subclinical hypothyroidism has been reported; however, there still exists a strong controversy regarding whether subclinical hypothyroidism ought to be dealt with or not. The objective of the study was to evaluate the association of foetal-maternal complications with first trimester maternal Thyrotropin (TSH) values.

Design: A retrospective study in a single tertiary care hospital was performed.

Patients: A total of 1981 pregnant women were studied during 2012.

Measurements: Thyrotropin (TSH) universal screening was performed between 9 and 12 weeks of gestation. Outcomes included foetal-maternal complications and newborn health parameters.

Results: Median TSH was 1.72 (0.99-2.61) mIU/L. The incidence of perinatal loss, miscarriage and stillbirth was 7.2%, 5.9% and 1.1%, respectively. Median TSH of women with and without miscarriage was 1.97 (1.29-3.28) vs 1.71 (0.96-2.58) mIU/L (P = .009). Incidence of pre-eclampsia was 3.2%; TSH in these women was 2.10 (1.40-2.74) vs 1.71 (0.98-2.59) mIU/L in those without (P = .027). TSH in women with dystocia in labour was 1.76 (1.00-2.53) vs 1.68 (0.94-2.59) mIU/L in those who gave birth with normal progression (P = .044). Women with TSH 2.5-5.1 mIU/L had a higher risk of perinatal loss [OR 1.589 (1.085-2.329)], miscarriage [OR 1.702 (1.126-2.572)] and premature birth [OR 1.39 (1.013-1.876)], adjusted by mother's age. There was no association with the other outcomes analysed.

Conclusions: There is a positive association between maternal TSH in the first trimester of pregnancy and the incidence of perinatal loss and miscarriage. The TSH cut-off value of 2.5 mIU/L identified women with higher adverse pregnancy outcomes.
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http://dx.doi.org/10.1111/cen.13575DOI Listing
May 2018

Hypothyroidism during pregnancy and its association to perinatal and obstetric morbidity: a review.

Endocrinol Diabetes Nutr (Engl Ed) 2018 Feb;65(2):107-113

Germans Trias i Pujol Research Institute, Badalona, Spain; Medicine Department, Autonomous University of Barcelona, Spain; Endocrinology and Nutrition Department, Hospital Universitar Germans Trias i Pujol, Badalona, Spain. Electronic address:

There is currently no consensus among the different scientific societies on screening for thyroid dysfunction in the first trimester of pregnancy. Indeed, diagnosis and treatment of subclinical hypothyroidism during pregnancy are controversial, as no cut-off value for thyrotropin (TSH) is universally accepted. TSH measurement may be influenced by different factors throughout pregnancy, but especially during the first trimester. The association between overt hypothyroidism during pregnancy and obstetric and perinatal complications is well established. It is also accepted that thyroid hormones are important for neurodevelopment of the offspring. However, there is no scientific evidence available about the impact of subclinical hypothyroidism and its treatment during the first trimester of pregnancy on children's neurodevelopment. In recent years, studies conducted in the offspring of mothers with subclinical hypothyroidism have reported new biochemical parameters which may eventually serve as biomarkers of offspring neurodevelopment and which are more reproducible and are measured at an earlier time than the conventional clinical tests.
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http://dx.doi.org/10.1016/j.endinu.2017.11.009DOI Listing
February 2018

Insulin use and Excess Fracture Risk in Patients with Type 2 Diabetes: A Propensity-Matched cohort analysis.

Sci Rep 2017 06 19;7(1):3781. Epub 2017 Jun 19.

Musculoskeletal Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Despite normal to high bone mineral density, patients with type 2 diabetes (T2DM) have an increased fracture risk. T2DM medications could partially account for this excess risk. The aim of this study was to assess the association between insulin use and bone fracture risk in T2DM patients. A population-based matched cohort study based on a primary care records database validated for research use (Catalonia, Spain) was performed. Propensity score (PS) for insulin use was calculated using logistic regression including predefined predictors of fractures. A total of 2,979 insulin users and 14,895 non-users were observed for a median of 1.42 and 4.58 years respectively. Major fracture rates were 11.2/1,000 person-years for insulin users, compared with 8.3/1,000 among non-users. Matched models confirmed a significant association, with an adjusted subhazard ratio (adj SHR) of 1.38 [95% CI 1.06 to 1.80] for major fractures. No differences between types of insulin or different regimens were found. Estimated number needed to harm (fracture) was 82 (95% CI 32 to 416). Insulin use appears to be associated with a 38% excess fracture risk among T2DM patients in the early stages of the disease. Fracture risk should be included among the considerations to initiate insulin treatment.
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http://dx.doi.org/10.1038/s41598-017-03748-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476619PMC
June 2017

Relationship of YKL-40 and adiponectin and subclinical atherosclerosis in asymptomatic patients with type 1 diabetes mellitus from a European Mediterranean population.

Cardiovasc Diabetol 2015 Sep 18;14:121. Epub 2015 Sep 18.

Endocrinology and Nutrition Unit, Department of Medicine, Institute Research and Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Crta. Canyet s/n, 08916, Badalona, Barcelona, Spain.

Background: The glycoprotein YKL-40 is a new marker of early inflammation and endothelial dysfunction. Adiponectin is a collagen-like protein with anti-atherogenic and anti-inflammatory effects. Increased concentrations of both markers have been reported in patients with type 1 diabetes (T1D).

Aim: To assess the possible role of YKL-40 and adiponectin as a marker of subclinical cardiovascular disease in asymptomatic patients with type 1 diabetes with no history of ischemic or macrovascular heart disease and its relationship with other classic inflammatory biomarkers.

Methods: Concentrations of YKL-40, adiponectin, IL-6, IL-1β, TNF-α, hsCRP and homocysteine were determined in 150 T1D patients (58% men, age: 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution, BMI: 25.1 ± 3.6 kg/m(2); HbA1c 8.1 ± 2.3%, 4% smokers; 26% retinopathy, microalbuminuria 9%) and 50 controls age, sex and smoke condition matched. Subclinical atherosclerosis was assessed by a carotid ultrasonography and a computed tomography for evaluation of calcium artery calcification score (CACS).

Results: 82% of T1D patients and 92% of controls had a calcium score of 0. T1D patients showed a significantly higher mean common carotid artery intima media thickness (CIMT) compared to controls (0.55 ± 0.14 vs 0.48 ± 0.14 mm, p = 0.01). Concentrations of YKL-40 and adiponectin were significantly higher in T1D [42.6 (10.4-195.0) vs ±28.7 (11.0-51.2) ng/ml, p = 0.001 and 15.8 ± 9.1 vs. 12.4 ± 5.3 mg/ml, p = 0.008], with no differences when compared to other inflammatory parameters. In T1D patients no association was found between YKL-40 and adiponectin and screening test for subclinical arterial disease (neither CACS nor CIMT). A positive correlation was found between levels of YKL-40 and age and duration of disease (r = 0.28, p = 0.003; r = 0.35, p = 0.001). There were no differences in the YKL-40 in relation to the presence or absence of retinopathy or nephropathy. Levels of adiponectin were higher in patients with nephropathy (21.84 ± 8.15 vs. 14.88 ± 8.27 mg/ml, p = 0.008).

Conclusions: Type 1 diabetes patients from a Mediterranean area with a longer disease evolution, although a lower degree of subclinical disease, showed significatively higher concentrations of YKL-40 and adiponectin compared with the controls. Therefore, we conclude that YKL-40 and adiponectin are early inflammatory markers in diabetic subjects even in the presence of a low atherosclerotic background.
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http://dx.doi.org/10.1186/s12933-015-0287-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574547PMC
September 2015

High prevalence of vitamin D deficiency and lack of association with subclinical atherosclerosis in asymptomatic patients with Type 1 Diabetes Mellitus from a Mediterranean area.

Acta Diabetol 2015 Aug 10;52(4):773-9. Epub 2015 Jan 10.

Endocrinology and Nutrition Unit, Department of Medicine, Institute of Research and Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain,

Aims: Several studies linked vitamin D deficiency with coronary artery disease (CAD). The aim of this study was to evaluate the relationship between the concentrations of 25-hydroxyvitamin D (25OHD) and the presence of early atherosclerosis in asymptomatic Type 1 Diabetes (T1D) patients with no previous history of ischemic heart disease.

Methods: One hundred and forty-five patients with T1D (age 37.8 ± 8 years, 57 % male, all Caucasian, disease duration 20.6 ± 8.3 years, HbA1c 7.6 ± 1.4 % (60.2 ± 11.1 mmol/mol), body mass index (BMI) 25.2 ± 3.5 kg/m2, 52.4 % smokers, 23 % retinopathy, 10 % nephropathy) and 48 controls matched for age, sex, BMI and smoking habit were studied. 25OHD deficiency was defined for values ≤20 ng/mL. A sun exposure questionnaire, carotid ultrasonography to determine carotid intima-media thickness (CIMT) and the presence of atheroma plaques and cardiac computed tomography for evaluation of calcium artery calcification (CACS) were performed.

Results: T1D subjects showed a high proportion of 25OHD deficiency (43.2 % vs. 21.7 %, p = 0.032). Of all, 82 % of T1D patients and 92 % of controls had a calcium score of 0. CIMT was greater in patients with T1D (0.55 ± 0.14 mm vs 0.48 ± 0.15, p = 0.01) compared with controls. T1D subjects showed no differences in the results of CACS or CIMT according to the vitamin D concentrations.

Conclusions: T1D patients have lower concentrations and twice more prevalence of 25OHD deficiency than controls. There was no association between 25OHD concentrations and subclinical CAD.
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http://dx.doi.org/10.1007/s00592-014-0699-3DOI Listing
August 2015

[Safety and tolerability of GLP-1 receptor agonists].

Med Clin (Barc) 2014 Sep 15;143 Suppl 2:35-40. Epub 2014 Oct 15.

Servicio de Endocrinología y Nutrición. Hospital e Instituto de Investigación Germans Trias i Pujol. Universitat Autònoma de Barcelona. Campus de can Ruti, Badalona, Barcelona, España. Electronic address:

Glucagon-like peptide-1 receptor agonists (GLP-1ra) are a new group of drugs with a glucose-lowering action due to their incretin effect. The GLP-1 receptor is expressed in various human tissues, which could be related to the pleiotropic effects of human GLP-1, as well as to the adverse effects described in patients treated with GLP-1ra. The risk of hypoglycaemia is low, which is one of the main considerations in the safety of this family of compounds and is also important to patients with diabetes. The most frequent adverse effect is nausea, which usually occurs at the start of treatment and is transient in 20-60% of affected patients. This article also reviews the information available on antibody formation, the potential effect on the thyroid gland, and the controversial association between this group of drugs with pancreatitis and cancer.
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http://dx.doi.org/10.1016/S0025-7753(14)70107-1DOI Listing
September 2014

[Safety and tolerability of GLP-1 receptor agonists].

Med Clin (Barc) 2014 ;143 Suppl 2:35-40

Servicio de Endocrinología y Nutrición. Hospital e Instituto de Investigación Germans Trias i Pujol. Universitat Autònoma de Barcelona. Campus de can Ruti, Badalona, Barcelona, España. Electronic address:

Glucagon-like peptide-1 receptor agonists (GLP-1ra) are a new group of drugs with a glucose-lowering action due to their incretin effect. The GLP-1 receptor is expressed in various human tissues, which could be related to the pleiotropic effects of human GLP-1, as well as to the adverse effects described in patients treated with GLP-1ra. The risk of hypoglycaemia is low, which is one of the main considerations in the safety of this family of compounds and is also important to patients with diabetes. The most frequent adverse effect is nausea, which usually occurs at the start of treatment and is transient in 20-60% of affected patients. This article also reviews the information available on antibody formation, the potential effect on the thyroid gland, and the controversial association between this group of drugs with pancreatitis and cancer.
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http://dx.doi.org/10.1016/S0025-7753(14)70107-1DOI Listing
January 2018

Thyroid hormone upregulates zinc-α2-glycoprotein production in the liver but not in adipose tissue.

PLoS One 2014 21;9(1):e85753. Epub 2014 Jan 21.

Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain.

Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not related to weight loss in hyperthyroidism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085753PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897515PMC
October 2014

Low prevalence of subclinical atherosclerosis in asymptomatic patients with type 1 diabetes in a European Mediterranean population.

Diabetes Care 2014 17;37(3):814-20. Epub 2013 Oct 17.

Endocrinology and Nutrition Unit, Department of Medicine, Institute of Research and Hospital Universitari Germans Trias i Pujol, Universitat Aut `onoma de Barcelona, Badalona, Spain.

Objective: To evaluate the presence of early carotid and coronary atherosclerosis in asymptomatic patients with type 1 diabetes with no history of ischemic heart disease.

Research Design And Methods: One hundred and fifty patients with type 1 diabetes (58% males; 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution; HbA1c 8.1 ± 2.3%; 52% nonsmokers; 26% retinopathy; 9% microalbuminuria) and 50 nondiabetic control subjects age and sex matched were studied. Carotid ultrasonography to determine common carotid artery intima-media thickness (c-IMT) and the presence of atheroma plaques and cardiac computed tomography for calcium analysis and quantification (coronary artery calcium score [CACS]) were performed.

Results: Most patients with type 1 diabetes and control subjects displayed a CACS of 0 (82 vs. 92%). Patients with type 1 diabetes with CACS ≥1 were older and had higher HbA1c (44.5 ± 5.1 vs. 36.7 ± 8.1 years [P < 0.001] and 8.5 ± 1.1 vs. 7.8 ± 1.0% [P < 0.003], respectively) and longer evolution of diabetes (25.4 ± 9.2 vs. 19.3 ± 7.4 years, P < 0.005) and mean c-IMT (0.67 ± 0.18 vs. 0.53 ± 0.11 mm, P < 0.001) compared with patients with CACS of 0. Smoking (P < 0.02), nephropathy (P < 0.05), retinopathy (P < 0.05), and male sex (P < 0.03) were significantly and positively associated with CACS ≥1. Mean c-IMT was significantly higher in patients with type 1 diabetes (0.55 ± 0.14 vs. 0.48 ± 0.14 mm, P < 0.01), and 11% of them presented atheroma plaques (8% of control subjects). Multivariant logistic regression analysis showed that c-IMT was related to CACS (β = 6.87, P < 0.001).

Conclusions: A small percentage of patients with type 1 diabetes showed data suggestive of subclinical atherosclerosis. Universal screening of coronary disease in this population is not justified. Carotid ultrasonography may be useful for screening in the subset of patients with cardiovascular risk factors and long disease evolution.
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http://dx.doi.org/10.2337/dc13-1453DOI Listing
August 2015

Controversies in endocrinology: On the need for universal thyroid screening in pregnant women.

Eur J Endocrinol 2014 Jan 29;170(1):R17-30. Epub 2013 Nov 29.

Department of Endocrinology and Nutrition, Hospital de Sant Joan Despí Moisès Broggi, Barcelona, Spain.

There is a well-known controversy among scientific societies regarding the recommendation to screen for thyroid dysfunction (TD) during pregnancy. Although several studies have shown an association between maternal subclinical hypothyroidism and/or hypothyroxinemia with obstetric problems and/or neurocognitive impairment in the offspring, there is only limited evidence on the possible positive effects of thyroxine (T4) treatment in such cases. Despite the scarcity of this evidence, there is a widespread agreement among clinicians on the need for treatment of clinical hypothyroidism during pregnancy and the risks that could arise due to therapeutic abstention. As maternal TD is a quite prevalent condition, easily diagnosed and for which an effective and safe treatment is available, some scientific societies have proposed to assess thyroid function during the first trimester of pregnancy and ideally before week 10 of gestational age. Given the physiologic changes of thyroid function during pregnancy, hormone assessment should be performed using trimester-specific reference values ideally based on locally generated data as geographic variations have been detected. Screening of TD should be based on an initial determination of TSH performed early during the first trimester and only if abnormal should it be followed by either a free or total T4 measurement. Furthermore, adequate iodine supplementation during pregnancy is critical and if feasible it should be initiated before the woman attempts to conceive.
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http://dx.doi.org/10.1530/EJE-13-0561DOI Listing
January 2014

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.

Clin Endocrinol (Oxf) 2013 Apr;78(4):621-8

Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, spain.

Context: One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined.

Objective: Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT.

Design, Patients And Methods: From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT).

Results: Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001).

Conclusions: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT.
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http://dx.doi.org/10.1111/cen.12036DOI Listing
April 2013

A prospective study of lymphocyte subpopulations and regulatory T cells in patients with chronic hepatitis C virus infection developing interferon-induced thyroiditis.

Clin Endocrinol (Oxf) 2011 Oct;75(4):535-43

Department of Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.

Objective: One of the side effects of interferon-alpha (IFN-α) therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4(+) CD25(+) CD127low/-FoxP3(+) regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT.

Design, Patients And Methods: From 120 patients with chronic HCV who started antiviral treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-HCV). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment (PT) and at appearance of IIT (TT).

Results: Eleven patients developed IIT: three Hashimoto's thyroiditis, one Graves'disease, one positive antithyroidal antibodies, one nonautoimmune hypothyroidism and five destructive thyroiditis. During antiviral treatment, an increase in CD8(+) and in Tregs was observed in both groups. A decrease in CD3(+) , CD19(+) and NKT lymphocyte subpopulations was also observed (all P < 0·05). However, no changes were observed in the percentage of CD4(+) , CD3(+) γδ(+) and iNKT lymphocytes, Th1/Th2 balance and Bcl2 expression on B cells when BT was compared with ET. At the appearance of IIT (TT), IIT patients had a higher Th1 response (CCR5(+) CCR7(-) ) (P < 0·01) and a higher Tregs percentage (P < 0·05) than Co-HCV.

Conclusions: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Th1 response and Tregs in patients with HCV who developed IIT.
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http://dx.doi.org/10.1111/j.1365-2265.2011.04112.xDOI Listing
October 2011

Bone mineral density and bone fracture in male patients receiving long-term suppressive levothyroxine treatment for differentiated thyroid carcinoma.

Endocrine 2010 Jun 16;37(3):467-72. Epub 2010 Apr 16.

Department of Endocrinology and Nutrition, Germans Trias i Pujol University Hospital, Via Canyet s/n, 08916 Badalona, Barcelona, Spain.

Studies on the effect of exogenous subclinical thyrotoxicosis on bone mineral density (BMD) in male patients treated with suppressive doses of levothyroxine for differentiated thyroid carcinoma (DTC) are not conclusive. In order to evaluate BMD (in femoral neck, lumbar spine, and distal radius) and bone fractures in men under long-term suppressive treatment with levothyroxine for DTC, we conducted a cross-sectional, retrospective study in 33 Caucasian men (mean ± SD age: 56 ± 14 years) under treatment for DTC. The control group comprised 33 healthy age- and body mass index-matched male volunteers. BMD was assessed by dual-energy X-ray absorptiometry (DXA). Bone turnover biomarkers (calcium, phosphate, alkaline phosphatase, PTH, vitamin D, urinary calcium, and N-Telopeptide/creatinine index) and testosterone were determined. Previous bone fractures were evaluated with a questionnaire and X-ray images of thoracic and lumbar vertebrae. Patients were treated for a mean duration of 15 ± 5 years. No differences were found between patients and controls in bone turnover biomarkers or areal BMD, T-scores or Z-scores in all sites evaluated. No earlier fractures or pain episodes were registered in either group and the incidence of asymptomatic vertebral fractures did not differ significantly between patient (18.8%) and control groups (16.7%), (P = 0.9). In conclusion, long-term suppressive treatment with levothyroxine in men with DTC does not appear to exert deleterious effects on bone mineral density or increase the prevalence of fracture.
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http://dx.doi.org/10.1007/s12020-010-9339-zDOI Listing
June 2010

Regulatory T cells in diabetes and gastritis.

Autoimmun Rev 2009 Jul 12;8(8):659-62. Epub 2009 Feb 12.

Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

Patients with Type 1 diabetes mellitus (T1D) have an increased prevalence of associated organ-specific autoimmune diseases such as pernicious anemia whose histological substrate is a chronic atrophic gastritis (CAG). Latent pernicious anemia precedes clinically-manifest pernicious anemia and may be difficult to detect solely on simple analytical grounds. We recently described an increased prevalence of clinically-latent pernicious anemia in T1D using low concentrations of pepsinogen I, a zymogen of pepsin present in gastric mucosa, as a useful additional diagnostic marker, besides parietal cell antibodies, for screening latent pernicious anemia in T1D. The failure of peripheral tolerance mechanisms such as regulatory T cells (Treg) might be involved in CAG development in T1D patients. Indeed, functional defects in Tregs have been described in T1D patients. To this end, the percentage of Tregs in peripheral blood of T1D-CAG patients was analyzed and compared with those of a group of T1D without associated autoantibodies and a healthy control group. Tregs levels were also analyzed in gastric biopsies of T1D-CAG patients. The results obtained have led to new questions regarding the pathogenic mechanisms implicated in the development of associated autoimmune diseases in T1D.
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http://dx.doi.org/10.1016/j.autrev.2009.02.014DOI Listing
July 2009

Regulatory T cells in type 1 diabetic patients with autoimmune chronic atrophic gastritis.

Endocrine 2009 Jun 17;35(3):420-8. Epub 2009 Mar 17.

Department of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Ctra Canyet s/n, Badalona, 08916 Barcelona, Spain.

Type A chronic atrophic gastritis (CAG) is increased in type 1 diabetic patients (DM1). To address this issue, we determined and analyzed the number of peripheral blood regulatory T cells (Tregs) in 15 DM1-CAG patients, 15 DM1 patients without associated autoantibodies (DM1) and 15 healthy controls by flow cytometry and compared gastric Tregs expression (CD4+Foxp3+/CD4+) in DM1-CAG patients with that observed in 10 control Helicobacter pylori CAG-infected biopsies. The percentage of peripheral Tregs was higher in DM1-CAG patients compared to DM1 and controls (CD4+Foxp3+: 7.67 +/- 1.91% vs. 5.38 +/- 1.57% and 5.65 +/- 1.76%, P < 0.001, respectively), with no differences between DM1 and controls. Gastric mucosal Tregs were higher in H. pylori CAG than in DM1-CAG patients (31.31 +/- 5.52% vs. 7.68 +/- 3.70%; P < 0.001). Data suggest that Tregs are stimulated in patients with more than one autoimmune disease (DM1 + CAG) in an ineffectual attempt to control autoimmune response and that the number of Tregs in gastric mucosa implicated in the chronification of gastritis differs according to the etiology.
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http://dx.doi.org/10.1007/s12020-009-9166-2DOI Listing
June 2009

Hypercalcemic encephalopathy in a patient with hepatocellular carcinoma.

Dig Dis Sci 2007 Nov 11;52(11):3296-7. Epub 2007 Apr 11.

Unitat de Curta Estada, Emergency Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.

Cirrhotic patients with hepatocellular carcinoma (HCC) frequently develop hepatic encephalopathy. Metabolic etiology of encephalopathy is less often considered in these patients. Although paraneoplastic hypercalcemia may be associated with several malignant tumors, it has also been described in HCC [1-4], and may cause neurologic disturbances. We present a case of hypercalcemic encephalopathy in a patient with hepatic cirrhosis and underlying HCC in whom first diagnostic was hepatic encephalopathy.
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http://dx.doi.org/10.1007/s10620-006-9159-4DOI Listing
November 2007
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