Autoimmune Diabetes From Childhood to Adulthood: The Role of Pancreatic Autoantibodies and HLA-DRB1 Genotype.

CONTEXT: Autoimmune diabetes can develop at any age, but unlike early-onset diabetes, adult onset is less well documented. We aimed to compare, over a wide age range, the most reliable predictive biomarkers for this pathology: pancreatic-autoantibodies and HLA-DRB1 genotype. METHODS: A retrospective study of 802 patients with diabetes (aged 11 months to 66 years) was conducted. Pancreatic autoantibodies at diagnosis: insulin autoantibodies (IAA), glutamate decarboxylase autoantibodies (GADA), islet tyrosine phosphatase 2 autoantibodies (IA2A), and zinc transporter-8 autoantibodies (ZnT8A) and HLA-DRB1 genotype were analyzed. RESULTS: Compared with early-onset patients, adults had a lower frequency of multiple autoantibodies, with GADA being the most common. At early onset, IAA was the most frequent in those younger than 6 years and correlated inversely with age; GADA and ZnT8A correlated directly and IA2A remained stable.The absence of HLA-DRB1 risk genotype was associated with higher age at diabetes onset (27.5 years; interquartile range [IQR], 14.3-35.7), whereas the high-risk HLA-DR3/DR4 was significantly more common at lower age (11.9 years; IQR, 7.1-21.6). ZnT8A was associated with DR4/non-DR3 (odds ratio [OR], 1.91; 95% CI, 1.15-3.17), GADA with DR3/non-DR4 (OR, 2.97; 95% CI, 1.55-5.71), and IA2A with DR4/non-DR3 and DR3/DR4 (OR, 3.89; 95% CI, 2.28-6.64, and OR, 3.08; 95% CI, 1.83-5.18, respectively). No association of IAA with HLA-DRB1 was found. CONCLUSION: Autoimmunity and HLA-DRB1 genotype are age-dependent biomarkers. Adult-onset autoimmune diabetes is associated with lower genetic risk and lower immune response to pancreatic islet cells compared with early-onset diabetes.

Erythrocyte Membrane Nanomechanical Rigidity Is Decreased in Obese Patients.

This work intends to describe the physical properties of red blood cell (RBC) membranes in obese adults. The hypothesis driving this research is that obesity, in addition to increasing the amount of body fat, will also modify the lipid composition of membranes in cells other than adipocytes. Forty-nine control volunteers (16 male, 33 female, BMI 21.8 ± 5.6 and 21.5 ± 4.2 kg/m2, respectively) and 52 obese subjects (16 male and 36 female, BMI 38.2± 11.0 and 40.7 ± 8.7 kg/m2, respectively) were examined. The two physical techniques applied were atomic force microscopy (AFM) in the force spectroscopy mode, which allows the micromechanical measurement of penetration forces, and fluorescence anisotropy of trimethylammonium diphenylhexatriene (TMA-DPH), which provides information on lipid order at the membrane polar-nonpolar interface. These techniques, in combination with lipidomic studies, revealed a decreased rigidity in the interfacial region of the RBC membranes of obese as compared to control patients, related to parallel changes in lipid composition. Lipidomic data show an increase in the cholesterol/phospholipid mole ratio and a decrease in sphingomyelin contents in obese membranes. ω-3 fatty acids (e.g., docosahexaenoic acid) appear to be less prevalent in obese patient RBCs, and this is the case for both the global fatty acid distribution and for the individual major lipids in the membrane phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). Moreover, some ω-6 fatty acids (e.g., arachidonic acid) are increased in obese patient RBCs. The switch from ω-3 to ω-6 lipids in obese subjects could be a major factor explaining the higher interfacial fluidity in obese patient RBC membranes.

Incidence of diabetes mellitus and associated risk factors in the adult population of the Basque country, Spain.

The aim of this study was to estimate the incidence of diabetes mellitus in the Basque Country and the risk factors involved in the disease by reassessing an adult population after 7 years of follow-up. In the previous prevalence study, 847 people older than 18 years were randomly selected from all over the Basque Country and were invited to answer a medical questionnaire, followed by a physical examination and an oral glucose tolerance test. In the reassessment, the same variables were collected and the resulting cohort comprised 517 individuals of whom 43 had diabetes at baseline. The cumulative incidence of diabetes was 4.64% in 7 years and the raw incidence rate was 6.56 cases/1000 person-years (95%CI: 4.11-9.93). Among the incident cases, 59% were undiagnosed. The most strongly associated markers by univariate analyses were age > 60 years, dyslipidaemia, prediabetes and insulin resistance. We also found association with hypertension, obesity, family history of diabetes and low education level. Multivariate analysis adjusted for age and sex showed that a set of risk factors assessed together (dyslipidaemia, waist-to-hip-ratio and family history of diabetes) had great predictive value (AUC-ROC = 0.899, 95%CI: 0.846-0.953, p = 0.942), which suggests the need for early intervention before the onset of prediabetes.

Altered intragenic DNA methylation of HOOK2 gene in adipose tissue from individuals with obesity and type 2 diabetes.

AIMS/HYPOTHESIS: Failure in glucose response to insulin is a common pathology associated with obesity. In this study, we analyzed the genome wide DNA methylation profile of visceral adipose tissue (VAT) samples in a population of individuals with obesity and assessed whether differential methylation profiles are associated with the presence of type 2 diabetes (T2D). METHODS: More than 485,000 CpG genome sites from VAT samples from women with obesity undergoing gastric bypass (n = 18), and classified as suffering from type 2 diabetes (T2D) or not (no type 2 diabetes, NT2D), were analyzed using DNA methylation arrays. RESULTS: We found significant differential methylation between T2D and NT2D samples in 24 CpGs that map with sixteen genes, one of which, HOOK2, demonstrated a significant correlation between differentially hypermethylated regions on the gene body and the presence of type 2 diabetes. This was validated by pyrosequencing in a population of 91 samples from both males and females with obesity. Furthermore, when these results were analyzed by gender, female T2D samples were found hypermethylated at the cg04657146-region and the cg 11738485-region of HOOK2 gene, whilst, interestingly, male samples were found hypomethylated in this latter region. CONCLUSION: The differential methylation profile of the HOOK2 gene in individuals with T2D and obesity might be related to the attendant T2D, but further studies are required to identify the potential role of HOOK2 gene in T2D disease. The finding of gender differences in T2D methylation of HOOK2 also warrants further investigation.

Epigenetic modulators of thyroid cancer.

There are some well known factors involved in the etiology of thyroid cancer, including iodine deficiency, radiation exposure at early ages, or some genetic changes. However, epigenetic modulators that may contribute to development of these tumors and be helpful to for both their diagnosis and treatment have recently been discovered. The currently known changes in DNA methylation, histone modifications, and non-coding RNAs in each type of thyroid carcinoma are reviewed here.

Gestational Diabetes Mellitus (GDM): Relationship Between Higher Cutoff Values for 100 g Oral Glucose Tolerance Test (OGTT) and Insulin Requirement During Pregnancy.

Objectives To study if there is any relationship about higher cutoff values for 100 g oral glucose tolerance test and the need for insulin in women diagnosed with gestational diabetes. Materials and Methods This is a retrospective population-based study of 201 women diagnosed with Gestational Diabetes Mellitus (GDM) between January 2012 and June 2014 in the area of Oviedo, Asturias, Spain. According to diagnostic criteria recommended by GEDE, NDDG, gestational diabetes is diagnosed if two or more plasma glucose levels meet or exceed the following threshold: fasting glucose of 105 mg/dl, 1-h 190 mg/dl, 2-h 165 mg/dl, or 3-h 145 mg/dl. We aim to know if there is any relationship between higher cutoffs and insulin requirement. Results 36 out of 201 patients (17.91%) needed insulin to achieve the targets of blood glucose control. There were no differences in mean maternal age and birthweights. Fasting blood glucose levels were significantly higher in women with further need for insulin than those who only needed diet and exercise (p < 0.001). Also, blood glucose levels 2 h after the oral glucose intake were statistically different between the two groups (p 0.032). AUC for fasting glucose value was the highest according to ROC curve. Conclusions Fasting cutoff vales for 100 g oral glucose tolerance test are consistently higher in women diagnosed with Gestational Diabetes that further needed insulin to achieve adequate blood glucose control. The positive predictive value of fasting glucose value 105 mg/dl on OGTT was 81.1%, whereas for the cut-off 95 mg/dl it was 54.0%.

Epigenetic modulators of thyroid cancer / Moduladores epigenéticos del cancer de tiroides

There are some well known factors involved in the etiology of thyroid cancer, including iodine deficiency, radiation exposure at early ages, or some genetic changes. However, epigenetic modulators that may contribute to development of these tumors and be helpful to for both their diagnosis and treatment have recently been discovered. The currently known changes in DNA methylation, histone modifications, and non-coding RNAs in each type of thyroid carcinoma are reviewed here (AU)

Son conocidos algunos factores implicados en la etiología del cáncer de tiroides como el déficit de yodo o la exposición a radiación en edades tempranas o algunas alteraciones genéticas. Sin embargo, en los últimos años se han descubierto moduladores epigenéticos que puedan contribuir al desarrollo de estos tumores y podrían tener una utilidad tanto en el diagnóstico como en el tratamiento. En esta revisión se repasan las alteraciones conocidas hasta ahora tanto en la metilación del ADN como en las modificaciones de las histonas y los ARN no codificantes en cada uno de los tipos de carcinomas de tiroides (AU)

MEN 2A con doble mutación en gen RET: carcinoma medular de tiroides secretor de ACTH / MEN 2A with double mutation in RET gene: ectopic ACTH production in medullary thyroid carcinoma

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Ascitis quilosa postlaparoscopia abdominal; revisión y descripción de un caso / Chylous asctites post abdominal laparotomy; revision and report of a case

Describimos el caso de un varón de 23 años operado mediante laparoscopia de una masa residual secundaria a un carcinoma embrionario testicular. 15 días después acude al servicio de Urgencias por distensión abdominal y drenaje de líquido lechoso por las dos incisiones de la cirugía laparoscópica. Tras el análisis bioquímico del líquido que reflejaba un aumento de triglicéridos se llegó al diagnóstico de ascitis quilosa. Aunque es infrecuente, se describe que existe mayor probabilidad de ascitis quilosa después de cirugías oncológicas si se lleva a cabo la disección de ganglios linfáticos retroperitoneales. Se decide tratamiento conservador inicialmente con modificaciones dietéticas y posteriormente con nutrición parenteral, con resolución total de la ascitis (AU)

We describe the case of a 23 year old man who had undergone laparoscopic surgery in order to remove a residual mass secondary to a testicular embryonal carcinoma. 15 days after he attended the emergency department complaining about abdominal bloating and copious drainage via the two laparoscopic surgery incisions. Biochemical analysis was consistent with chylous ascites. Although this is uncommon, it is well known that there is more likely to develop chylous ascites after oncologic surgery if retroperitoneal lymph nodes dissection is performed. We decide to start with conservative treatment (dietary modifications) but, as it is not enough, then we decide stop any oral intake and treat him with parenteral nutrition, achieving then total resolution of the ascites (AU)

[Chylous asctites post abdominal laparotomy; revision and report of a case]. / Ascitis quilosa postlaparoscopia abdominal; revisión y descripción de un caso.

We describe the case of a 23 year old man who had undergone laparoscopic surgery in order to remove a residual mass secondary to a testicular embryonal carcinoma. 15 days after he attended the emergency department complaining about abdominal bloating and copious drainage via the two laparoscopic surgery incisions. Biochemical analysis was consistent with chylous ascites. Although this is uncommon, it is well known that there is more likely to develop chylous ascites after oncologic surgery if retroperitoneal lymph nodes dissection is performed1. We decide to start with conservative treatment (dietary modifications) but, as it is not enough, then we decide stop any oral intake and treat him with parenteral nutrition, achieving then total resolution of the ascites.

Describimos el caso de un varón de 23 años operado mediante laparoscopia de una masa residual secundaria a un carcinoma embrionario testicular. 15 días después acude al servicio de Urgencias por distensión abdominal y drenaje de líquido lechoso por las dos incisiones de la cirugía laparoscópica. Tras el análisis bioquímico del líquido que reflejaba un aumento de triglicéridos se llegó al diagnóstico de ascitis quilosa. Aunque es infrecuente, se describe que existe mayor probabilidad de ascitis quilosa después de cirugías oncológicas si se lleva a cabo la disección de ganglios linfáticos retroperitoneales1. Se decide tratamiento conservador inicialmente con modificaciones dietéticas y posteriormente con nutrición parenteral, con resolución total de la ascitis.