Conferencia de consenso: tratamiento de la diabetes tipo 2 en el paciente anciano

El tratamiento de la diabetes tipo 2 en el anciano representa un importante reto tanto desde el punto de vista clínico como del de la salud pública. El envejecimiento poblacional está condicionando un marcado incremento de la pandemia de diabetes en las personas de edad avanzada. Sin embargo, existen pocas evidencias científicas que apoyen el tratamiento más adecuado de la diabetes en los ancianos. Dada la gran heterogeneidad de la población anciana, que incluye a sujetos con muy diferente capacidad funcional y cognitiva, diversa comorbilidad y con muy diferente expectativa de vida, resulta crucial realizar una valoración global del anciano desde una perspectiva biopsicosocial y abordar integralmente los factores de riesgo vascular, planteando unos objetivos personalizados de control glucémico. En ancianos frágiles o con corta expectativa de vida puede ser razonable mantener un objetivo de HbA1c de 7,6-8,5%. La estrategia terapéutica en el anciano con diabetes tipo 2 debe individualizarse y consensuarse con el paciente y sus cuidadores, en función del objetivo planteado. Mejorar la calidad de vida, preservar la seguridad del paciente y evitar los efectos adversos del tratamiento antidiabético deben ser objetivos básicos. Dada la mayor predisposición de los ancianos a las hipoglucemias y sus graves consecuencias en esta población, deberían priorizarse las terapias antidiabéticas que minimicen el riesgo de episodios hipoglucémicos

Differentiated Thyroid Cancer in Navarra (Spain): Historic Cohort Results (1987–2003)

Introduction. Navarra has the highest incidence of differentiated thyroid cancer in Spain. The aim of this study was to review its management carried out by the Navarra's multidisciplinary Thyroid Disease Unit, from 1987 to 2003. Material and Methods. 325 patients were studied to find the incidence, prevalence, and prognostic factors. Statistical analysis comprised univariate and multivariate Cox proportional hazards regression models for survival and tumor recurrence. Results. The average annual incidence was 3.6 per 100,000 inhabitants, with a final prevalence of 82.4 per 100,000. Regarding survival and recurrence, statistical significance was observed for stage IV, follicular carcinoma, capsular and prethyroid muscles invasion, and T4 group. Only survival was related to tumour size larger than 40 mm. Only recurrence was related to lymph node metastases and radioiodine dose higher than 100 mCi. Conclusions. Attendance of patients in a functional unit setting has allowed us to classify them into three risk groups

Factors associated with therapeutic response in acromegaly diagnosed in the elderly in Spain

ContextSome reports suggest that acromegaly in elderly patients has a more benign clinical behavior and could have a better response to first-generation long-acting somatostatin receptor ligands (SRL). However, there is no specific therapeutic protocol for this special subgroup of patients. ObjectiveThis study aimed at identifying predictors of response to SRL in elderly patients. DesignMulticentric retrospective nationwide study of patients diagnosed with acromegaly at or over the age of 65 years. ResultsOne-hundred and eighteen patients (34 men, 84 women, mean age at diagnosis 71.7 +/- 5.4 years old) were included. Basal insulin-like growth factor type 1 (IGF-1) above the upper limit of normal (ULN) and growth hormone (GH) levels (mean +/- SD) were 2.7 +/- 1.4 and 11.0 +/- 11.9 ng/ml, respectively. The mean maximal tumor diameter was 12.3 +/- 6.4 mm, and up to 68.6% were macroadenoma. Seventy-two out of 118 patients (61.0%) underwent surgery as primary treatment. One-third of patients required first-line medical treatment due to a rejection of surgical treatment or non-suitability because of high surgical risk. After first-line surgery, 45/72 (63.9%) were in disease remission, and 16/34 (46.7%) of those treated with SRL had controlled disease. Patients with basal GH at diagnosis <= 6 ng/ml had lower IGF-1 levels and had smaller tumors, and more patients in this group reached control with SRL (72.7% vs. 33.3%; p < 0.04) [OR: 21.3, IC: 95% (2.4-91.1)], while male patients had a worse response [OR: 0.09, IC 95% (0.01-0.75)]. The predictive model curve obtained for SRL response showed an AUC of 0.82 CI (0.71-0.94). ConclusionsThe most frequent phenotype in newly diagnosed acromegaly in the elderly includes small adenomas and moderately high IGF-1 levels. GH at diagnosis <= 6 ng/ml and female gender, but not age per se, were associated with a greater chance of response to SRL

Association between exposure to air pollution and blood lipids in the general population of Spain.

Background and Aims: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain.Methods: We included 4647 adults (>18 years), participants in the national, cross- sectional, population- based [email protected] study, conducted in 2008– 2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1H- NMR lipoprotein test (Liposcale®). Participants were assigned air pollution con-centrations for particulate matter <10 μm (PM10), <2.5 μm (PM2.5) and nitrogen dioxide (NO2), corresponding to the health examination year, obtained by mod-elling combined with measurements taken at air quality stations (CHIMERE chemistry- transport model).Results: In multivariate linear regression models, each IQR increase in PM10, PM2.5 and NO2 was associated with 3.3%, 3.3% and 3% lower levels of HDL- c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL- p) concentrations (p< .001 for all associations). In multivariate logistic regression, there was a significant associa-tion between PM10, PM2.5 and NO2 concentrations and the odds of presenting low HDL- c (<40 mg/dL), low HDL- p (<p25) and higher LDL particle (LDL- p) concentrations (≥p75). In subgroup analyses there were stronger associations be-tween PM10 and NO2 and low HDL- p in men (p for interaction .008 and .034), and between NO2 and low HDL- p in individuals with obesity (p for interaction .015).Conclusions: Our study shows an association between the exposure to air pol-lutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosisFunding for open access charge: Universidad de Málaga / CBU

Ambient air pollution and thyroid function in Spanish adults. A nationwide population-based study ([email protected] study)

Background Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain. Methods The [email protected] study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5 mu m (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche). Results In multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM2.5 (4.86 mu g/m(3)). There was no association between NO2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women. Conclusions Exposures to PM2.5 in the general population were associated with mild alterations in thyroid function.CIBERDEM (Ministerio de Economia, Industria y Competitividad-ISCIII), Ministerio de Sanidad, Servicios Sociales e Igualdad-ISCIII, Instituto de Salud Carlos III (PI17/02136, PI20/01322), Consejeria de Salud y familias (PI-0144-2018), European Regional Development Fund (ERDF) "A way to build Europe". GRM belongs to the regional Nicolas Monardes research program of the Consejeria de Salud (RC-0006-2016; Junta de Andalucia, Spain). CMA is recipient of a "Rio Hortega" research contract (CM19/00186, Instituto de Salud Carlos III). VKDG is recipient of a "Rio Hortega" research contract (CM21/00214, Instituto de Salud Carlos III)

Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers

[Objective]: The minimally invasive fine-needle aspiration cytology (FNAC) is the current gold standard for the diagnosis of thyroid nodule malignancy. However, the correct discrimination of follicular neoplasia often requires more invasive diagnostic techniques. The lack of suitable immunohistochemical markers to distinguish between follicular thyroid carcinoma and other types of follicular-derived lesions complicates diagnosis, and despite most of these tumours being surgically resected, only a small number will test positive for malignancy. As such, the development of new orthogonal diagnostic approaches may improve the accuracy of diagnosing thyroid nodules.[Design]: This study includes a retrospective, multi-centre training cohort including 54 fresh-frozen follicular-patterned thyroid samples and two independent, multi-centre validation cohorts of 103 snap-frozen biopsies and 33 FNAC samples, respectively.[Methods]: We performed a genome-wide genetic and epigenetic profiling of 54 fresh-frozen follicular-patterned thyroid samples using exome sequencing and the Illumina Human DNA Methylation EPIC platform. An extensive validation was performed using the bisulfite pyrosequencing technique.[Results]: Using a random forest approach, we developed a three-CpG marker-based diagnostic model that was subsequently validated using bisulfite pyrosequencing experiments. According to the validation cohort, this cost-effective method discriminates between benign and malignant nodules with a sensitivity and specificity of 97 and 88%, respectively (positive predictive value (PPV): 0.85, negative predictive value (NPV): 0.98).[Conclusions]: Our classification system based on a minimal set of epigenetic biomarkers can complement the potential of the diagnostic techniques currently available and would prioritize a considerable number of surgical interventions that are often performed due to uncertain cytology.[Significance statement]: In recent years, there has been a significant increase in the number of people diagnosed with thyroid nodules. The current challenge is their etiological diagnosis to discount malignancy without resorting to thyroidectomy. The method proposed here, based on DNA pyrosequencing assays, has high sensitivity (0.97) and specificity (0.88) for the identification of malignant thyroid nodules. This simple and cost-effective approach can complement expert pathologist evaluation to prioritize the classification of difficult-to-diagnose follicular-patterned thyroid lesions and track tumor evolution, including real-time monitoring of treatment efficacy, thereby stimulating adherence to health promotion programs.Peer reviewe

DNA Methylomes and Epigenetic Age Acceleration Associations with Poor Metabolic Control in T1D

© 2020 by the authors.Type 1 diabetes (T1D) is an autoimmune disease that leads to insulin deficiency and hyperglycemia. Little is known about how this metabolic dysfunction, which substantially alters the internal environment, forces cells to adapt through epigenetic mechanisms. Consequently, the purpose of this work was to study what changes occur in the epigenome of T1D patients after the onset of disease and in the context of poor metabolic control. We performed a genome-wide analysis of DNA methylation patterns in blood samples from 18 T1D patients with varying levels of metabolic control. We identified T1D-associated DNA methylation differences on more than 100 genes when compared with healthy controls. Interestingly, only T1D patients displaying poor glycemic control showed epigenetic age acceleration compared to healthy controls. The epigenetic alterations identified in this work make a valuable contribution to improving our understanding of T1D and to ensuring the appropriate management of the disease in relation to maintaining healthy aging.This work was financially supported by: The Plan Nacional de I+D+I co-funding FEDER (PI18/01527); the Government of the Principality of Asturias PCTI-Plan de Ciencia, Tecnología e Innovación de Asturias co-funding 2018-2022/FEDER (IDI/2018/146); AECC (PROYE18061FERN); FGCSIC (0348_CIE_6_E); the Spanish Society of Diabetes (Programme/Funding for Young Researchers to JLFM), and IUOPA-ISPA-FINBA (the IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain); A.F.F is supported by a Miguel Servet II fellowship (contract CPII16/00007); R.F.P. is supported by the Severo Ochoa programme (BP17-114, Government of the Principality of Asturias).Peer reviewe

Reclassification of type 2 diabetes to type 1 diabetes in Asturias (Spain) between 2011 and 2020

Abstract Background Differentiating between type 1 diabetes (T1D) and type 2 diabetes (T2D) can be difficult in adults. The aim of this study was to determine the frequency of diagnostic reclassification from T2D to T1D, the characteristics of the patients and the impact on the management of the disease. Methods Observational and descriptive study including patients diagnosed with T1D in Asturias (Spain) between 2011 and 2020 who had been considered as T2D for at least 12 months. Results A total of 205 patients were included, representing 45.3% of those diagnosed with T1D over 30 years of age. Median time of evolution as T2D was 7,8 years. The age was 59.1 ± 12.9 years. BMI was > 25 kg/m2 in 46.8% of patients. HbA1c was 9.1 ± 2.1%, 77 ± 22 mmol/mol, and 56.5% were using insulin. Pancreatic antibodies were present in 95.5%, the most frequent being GAD, 82.6%. At 6 months, basal insulin use increased from 46.9 to 86.3%, and HbA1c decreased, 9.2 ± 2.0%vs7.7 ± 1.2%, 77 ± 22vs60 ± 13 mmol/mol; p < 0.0001. Conclusions Diagnosis as T2D in patients with T1D in adults is common. Age, BMI, insulin use and other clinical features are not definitely discriminatory. GAD is the antibody of choice in case of diagnostic suspect. Reclassification has important implications for metabolic control