- 174 G>C IL-6 polymorphism and primary iron overload in male patients.

Primary iron overload (IO) is commonly associated with mutations in the hereditary hemochromatosis gene (HFE). Nonetheless, other genetic variants may influence the development of IO beyond HFE mutations. There is a single nucleotide polymorphism (SNP) at - 174 G>C of the interleukin (IL)-6 gene which might be associated with primary IO. Our aim was to study the association between the SNP - 174 G>C gene promoter of IL-6 and primary IO in middle-aged male patients. We studied 37 men with primary IO diagnosed by liver histology. Controls were age-matched male volunteers (n = 37). HFE mutations and the SNP - 174 G>C gene promoter of IL-6 were evaluated by PCR-RFLP. Logistic regression was used to evaluate the association between primary IO and SNP - 174 G>C gene promoter of IL-6. Patients and control subjects were in Hardy-Weinberg equilibrium for the SNP - 174 G>C gene promoter of IL-6 (p = 0.17). Significantly different genotype frequencies were observed between patients (43% CC, 43% CG, and 14% GG) and control subjects (10% CC, 41% CG, and 49% GG) (OR = 4.09, 95% CI = 2.06-8.13; p < 0.0001). The multiple logistic regression analysis showed that IO was significantly associated with CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 (OR = 6.3, 95% CI = 1.9-21.4; p < 0.005) in a model adjusted by age and body mass index. In conclusion, CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 can be proposed as one of the gene variants influencing iron accumulation in male adults with HFE mutations. Studies in larger cohorts are warranted.

Markers of inflammation and cardiovascular disease in recently diagnosed celiac disease patients.

AIM: To evaluate novel risk factors and biomarkers of cardiovascular disease in celiac disease (CD) patients compared with healthy controls. METHODS: Twenty adult patients with recent diagnosis of CD and 20 sex, age and body mass index-matched healthy controls were recruited during a period of 12 mo. Indicators of carbohydrate metabolism, hematological parameters and high sensitive C reactive protein were determined. Moreover, lipoprotein metabolism was also explored through evaluation of the lipid profile and the activity of cholesteryl ester transfer protein and lipoprotein associated phospholipase A2, which is also considered a specific marker of vascular inflammation. The protocol was approved by the Ethic Committee from School of Pharmacy and Biochemistry, University of Buenos Aires and from Buenos Aires Italian Hospital, Buenos Aires, Argentina. RESULTS: Regarding the indicators of insulin resistance, CD patients showed higher plasma insulin levels [7.2 (5.0-11.3) mU/L vs 4.6 (2.6-6.7) mU/L, P < 0.05], increased Homeostasis Model Assessment-Insulin Resistance [1.45 (1.04-2.24) vs 1.00 (0.51-1.45), P < 0.05] and lower Quantitative Sensitive Check index [0.33 (0.28-0.40) vs 0.42 (0.34-0.65), P < 0.05] indexes. Folic acid concentration [5.4 (4.4-7.9) ng/mL vs 12.2 (8.0-14.2) ng/mL, P < 0.01] resulted to be lower and High-sensitivity C reactive protein levels higher (4.21 ± 6.47 mg/L vs 0.98 ± 1.13 mg/L, P < 0.01) in the patient group. With respect to the lipoprotein profile, CD patients showed lower high density lipoprotein-cholesterol (HDL-C) (45 ± 15 mg/dL vs 57 ± 17 mg/dL, P < 0.05) and apo A-I (130 ± 31 mg/dL vs 155 ± 29 mg/dL, P < 0.05) levels, as well as higher total cholesterol/HDL-C [4.19 (3.11-5.00) vs 3.52 (2.84-4.08), P < 0.05] and apo B/apo A-I (0.75 ± 0.25 vs 0.55 ± 0.16, P < 0.05) ratios in comparison with control subjects. No statistically significant differences were detected in lipoprotein-associated lipid transfer protein and enzymes. CONCLUSION: The presence and interaction of the detected alterations in patients with CD, would constitute a risk factor for the development of atherosclerotic cardiovascular disease.

Guía de recomendaciones para el diagnóstico clínico, bioquímico y por imágenes de la acromegalia. Federación Argentina de Sociedades de Endocrinología (FASEN) - 2017 / Guidelines for the clinical, biochemical and imaging diagnosis of acromegaly. Federación Argentina de Sociedades de Endocrinología (FASEN) - 2017

RESUMEN Objetivo El objetivo de esta guía es formular pautas para el diagnóstico de acromegalia adecuadas a los parámetros internacionales y a los recursos disponibles en Argentina. Participantes El grupo de trabajo propuesto por la Federación Argentina de Sociedades de Endocrinología (FASEN) incluyó un equipo multidisciplinario compuesto por 5 médicos endocrinólogos (4 especialistas y una profesional joven), un neurocirujano y una bioquímica, expertos en el tema. Evidencia Esta guía basada en la evidencia se desarrolló utilizando la metodología AGREE para describir tanto las recomendaciones como la calidad de las pruebas. Los borradores de esta guía fueron revisados por un grupo multidisciplinario de especialistas reconocidos en acromegalia. Conclusiones Utilizando un enfoque basado en la evidencia, esta guía aborda la evaluación diagnóstica de la acromegalia en Argentina.

ABSTRACT Objective The aim is to formulate guidelines for the clinical, biochemical and imaging diagnosis of acromegaly in accordance with international criteria and resources available in Argentina. Participants The task force selected by FASEN included a multidisciplinary team of 5 endocrinologists (4 senior and 1 junior), a neurosurgeon and a biochemist, experts in the field. Evidence This evidence-based guidelines were developed using the AGREE methodology to describe both the recommendations and the quality of evidence. The draft of these guidelines was reviewed by endocrinologists, biochemists and neurosurgeons experts in the field. Conclusions Using an approach based on evidence, these guidelines address the diagnosis of acromegaly in Argentina.

Proatherogenic disturbances in lipoprotein profile, associated enzymes and transfer proteins in women with iron deficiency anaemia.

OBJECTIVE: To characterize the lipid-related atherogenic risk factors in iron deficiency anaemia (IDA) patients. DESIGN AND METHODS: Twenty IDA women were compared to healthy age-matched controls. Lipoprotein profile, cholesteryl ester transfer protein (CETP), paraoxonase (PON) 1 and lipoprotein-associated phospholipase A(2) (LpPLA(2)) activities and plasma levels of oxidized-LDL were evaluated. RESULTS: Triglycerides were higher (median [range]) (1.0 [0.5-1.9] vs. 0.7 [0.5-1.5] mmol/L, p<0.05) and HDL-C lower (mean + or - SD) (1.3 + or - 0.3 vs. 1.6 + or - 0.4 mmol/L, p<0.01) in the patients group. CETP (197 + or - 29% vs. 151 + or - 29% mL(-1) h(-1), p<0.001), PON 1 (122 + or - 17 vs. 140 + or - 33 micromol mL(-1) min(-1), p<0.05) and LpPLA(2) (9.6 + or - 2.0 vs. 8.1 + or - 1.7 micromol mL(-1) h(-1), p<0.05) activities were different in IDA women. No difference was observed in oxidized-LDL. Haemoglobin correlated negatively with triglycerides (r=-0.35, p<0.05), CETP (r=-0.62, p<0.001) and LpPLA(2) (r=-0.34, p<0.05), while ferritin was positively associated with HDL-C (r=0.39, p<0.05) and inversely with CETP (r=-0.49, p<0.005). CONCLUSION: The alterations in lipoprotein profile, CETP, PON 1 and LpPLA(2) activities described in the present study indicate that non-treated IDA might represent a proatherogenic state.

Biomarcadores de aterosclerosis e indicadores de resistencia insulínica en pacientes acromegálicos no diabéticos / Biomarkers of Atherosclerosis and Indicators of Insulin Resistance in Non-Diabetic Acromegalic Patients

Introducción En la acromegalia, las comorbilidades cardiovasculares, respiratorias y metabólicas contribuyen a un aumento significativo de la mortalidad de los pacientes afectados. Asimismo, una proporción elevada de estos pacientes presentan diabetes mellitus. Pese a que el hallazgo de un perfil lipídico y lipoproteico anormal en pacientes acromegálicos suele ser habitual, cuando se intenta identificar y/o establecer el grado de modificaciones de parámetros específicos, los resultados son controversiales. Objetivos Evaluar la presencia de biomarcadores de aterosclerosis en pacientes con acromegalia activa no diabéticos y su asociación con la hormona del crecimiento (GH) y el factor de crecimiento similar a la insulina tipo 1 (IGF-1). Material y métodos Se estudiaron 14 pacientes y 14 controles sanos pareados por sexo y edad. Se midieron las concentraciones de GH e IGF-1 por inmunoensayos. Se evaluaron indicadores de resistencia insulínica (glucosa, insulina y HOMA), perfil lipoproteico, niveles plasmáticos de lipoproteínas de baja densidad oxidadas (LDLox), moléculas de adhesión celular vascular 1 (VCAM-1), endotelina-1 y actividad de fosfolipasa A2 asociada con lipoproteínas (LpPLA2). Resultados En comparación con los controles, los pacientes presentaron aumentos de GH (p < 0,05) e IGF-1 (p < 0,001), de los indicadores de resistencia insulínica (insulina p < 0,001; HOMA p < 0,001), triglicéridos (p < 0,05), apo B (p < 0,001), LDLox (117 ± 20 versus 89 ± 23 U/ L; p < 0,05) y endotelina-1 (0,9 ± 0,2 versus 0,7 ± 0,2 pg/ml; p < 0,05). Más aún, la GH y el IGF-1 se asociaron positivamente con (r; p <) insulina (0,40; 0,05 y 0,73; 0,001), HOMA (0,39; 0,05 y 0,74; 0,001), triglicéridos (0,57; 0,05 y 0,64; 0,001), colesterol de lipoproteínas de muy baja densidad (C-VLDL) (0,54; 0,05 y 0,47; 0,05), apo B (0,40; 0,05 y 0,54; 0,05), LDLox (0,59; 0,05 y 0,66; 0,05) y endotelina-1 (0,55; 0,05 y 0,51; 0,05). Conclusiones Los pacientes con acromegalia activa no diabéticos presentaron un estado de resistencia insulínica, así como modificaciones sutiles en el perfil lipoproteico y concentraciones elevadas de LDLox y endotelina-1. Las alteraciones descriptas podrían contribuir a un estado de mayor propensión al desarrollo de enfermedad cardiovascular aterosclerótica, la cual se sumaría a la miocardiopatía específica de la acromegalia.

Background Cardiovascular, respiratory and metabolic comorbidities associated with acromegaly contribute to a significant increase in the mortality of this disease. Many of these patients are also diabetic. Although it is frequent to find abnormal lipid and lipoprotein profiles in patients with acromegaly, controversial outcomes arise in an attempt to identify and/or establish the degree of the modifications of specific parameters. Objectives To assess the presence of biomarkers of atherosclerosis in non-diabetic patients with active acromegaly and its association with growth hormone (GH) and with insulin-like growth factor type 1 (IGF-1). Material and Methods The study included 14 patients and 14 healthy controls, pared by sex and age. Serum concentration of GH and IGF- 1 were determined by immunoassays. Indicators of insulin resistance (glucose, insulin and HOMA) were measured, as well as lipoprotein profile, plasmatic levels of oxidized LDL (oxLDL), vascular cell adhesion molecule 1 (VCAM-1), endothelin-1 and lipoprotein-associated phospholipase A2 activity (LpPLA2). Results Compared to controls, non-diabetic acromegalic patients had increased levels of GH (p<0.05) and IGF-1 (p<0.001), of indicators of insulin resistance (insulin p<0.001; HOMA p<0.001), triglycerides (p<0.05), apo B (p<0.001), oxLDL (117±20 versus 89±23 U/L; p<0.05) and endothelin-1 (0.9±0.2 versus 0.7±0.2 pg/ml; p<0.05). In addition, GH and IGF-1 were positively associated with (r; p <) insulin (0.40; 0.05 and 0.73; 0.001), HOMA (0.39; 0.05 and 0.74; 0.001), triglycerides (0.57; 0.05 and 0.64; 0.001), very low density lipoprotein-cholesterol (VLDL-C) (0.54; 0.05 and 0.47; 0.05), apo B (0.40; 0.05 and 0.54; 0.05), oxLDL (0.59; 0.05 and 0.66; 0.05) and endothelin-1 (0.55; 0.05 and 0.51; 0.05). Conclusions Non-diabetic patients with active acromegaly presented an insulin-resistant status, as well as subtle modifications of lipid profile and increased levels of oxLDL and endothelin- 1. These alterations could explain why these patients are more likely to develop atherosclerotic cardiovascular disease in addition to acromegalic cardiomyopathy.