Prevalencia del polimorfismo del nucleótido simple rs4704963 (T > C) del gen Early B-Cell Factor 1 en una población de pacientes diabéticos tipo 2 con obesidad / Prevalence of Early B-Cell Factor 1 Gene rs4704963 Single Nudeotide Polymorphism (T>C) in a Population of Type 2 Diabetic Patients with Obesity

RESUMEN Introducción: En estudios previos, se determinó para una población con agravamiento de la diabetes tipo 2 con obesidad (DBT+Ob) que sufría estrés una prevalencia del polimorfismo de nucleótido único (SNP) rs4704963 (T > C) del gen Early B-Cell Factor 1 (EBF1) del 16,5%. Objetivos: Determinar la prevalencia de este SNP en pacientes con DBT+ Ob que acuden al Hospital Ramos Mejía de la Ciudad Autónoma de Buenos .Aires y establecer si dicho polimorfismo se asocia con el estrés o la ocurrencia de eventos coronarios agudos. Material y métodos: Se llevó a cabo un estudio observacional, prospectivo, sobre prevalencia del polimorfismo en 53 pacientes con DBT+Ob e índice de masa corporal (IMC) entre 28 y 41, atendidos en el citado hospital en un período de 15 meses. A cada paciente se le computó una escala de estrés percibido, además de evaluarlo mediante la escala de acontecimientos vitales estresantes. Para el análisis estadístico, se realizaron las pruebas de Chi cuadrado y se calcularon los odds ratio (OR). Resultados: La población evaluada (53 pacientes) tuvo una media de edad de 60,2 ±9,77 años; 47,2% fueron hombres. De ellos, 8 individuos (15,1%) presentaron el SNP y todos fueron heterocigotas. Quince sujetos (28,3%) tuvieron síndrome isquémico agudo (SIA) y de estos solo uno (6,6%) tenía el SNP No se halló relación estadísticamente significativa entre la presencia del SNP y la aparición de SIA (p = 0,282). Catorce pacientes (26,4%) presentaron estrés crónico moderado o grave, y no hubo relación entre este hallazgo y la presencia del SNP (p = 0,979). Conclusiones: La prevalencia del SNP rs4704963 (T > C) del gen EBF1 en la población de DBT+Ob estudiada fue del 15,1% y no se halló relación estadísticamente significativa del SNP con el estrés ni con el SIA.

ABSTRACT Background: Previous studies established that in a population with exacerbation of type 2 diabetes with obesity (DBT+Ob) suffering from stress, the prevalence of early B-Cell Factor 1 (EBF1) gene rs4704963 single nucleotide polymorphism (SNP) (T>C) is 16.5%. Objectives: The aim of this study was to determine the prevalence of this SNP in patients with DBT+Ob attending Hospital Ramos Mejía of the Autonomous City of Buenos Aires and to ascertain whether this polymorphism is associated with stress or acute coronary events. Methods: An observational, prospective study on the prevalence of rs4704963 SNP was performed in 53 patients with DBT+Ob and body mass index between 28 and 41, seen in Hospital Ramos Mejía for a period of 15 months. Each patient was evaluated with a stressful life events scale and a perceived stress scale. The chisquare test and odds ratio (OR) were used for statistical analysis. Results: A total of 53 patients were included in the study. Mean population age was 60.2±9.77 years and 47.2% were men. Among these patients, 8 (15.1%) presented SNP and all were heterozygous. Fifteen patients (28.3%) had acute ischemic syndrome (AIS), and among these, only one (6.6%) had SNP No statistically significant relationship was found between the presence of SNP and AIS (p=0.282). Fourteen patients (26.4%) presented moderate or severe chronic stress, and there was no relationship between this finding and the presence of SNP (p=0.979). Conclusions: The prevalence of EBF1 gene rs4704963 SNP (T>C) in the DBT+Ob population was 15.1%. No statistically significant association was found between SNP and stress or AIS.

Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial.

BACKGROUND: The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events. METHODOLOGY/PRINCIPAL FINDINGS: Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent. CONCLUSIONS/SIGNIFICANCE: While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG. TRIAL REGISTRATION: ClinicalTrials.gov NCT00793754.

Urinary heparan sulphate is increased in normoalbuminuric diabetic patients

Forty-nine normoalbuminuric diabetic patients were studied: 22 males and 27 females, in whom urinary heparan sulphate (HS), albuminuria, creatininemia, creatininuria, creatinine clearance, HbA1c and arterial pressure (AP) were determined. Two groups were discerned: group 1, Type 1 DM, diabetic cases (n = 16); and group 2, Type 2 DM diabetic cases (n = 33). Patients were compared with 24 healthy controls: 12 men and 12 women, who showed a mean value + SD of 0.36 + 0.18 mg/24 h HS with significant differences between males and females (0.43 + 0.15 versus 0.28 + 0.17, respectively; p = 0.02). The total population of diabetic cases rendered a mean of 0.68 + 0.44 and comparison with controls proved highly significant (p < 0.001). Globally, male patients had a mean of 0.82 + 0.48 and females 0.54 + 0.35, with p < 0.02. Group 1 and 2 values of HS were not significantly different. HS levels falled to correlate either with age, body mass index (BM), time since onset of diabetes, albuminuria, creatininemia, creatininuria, creatinine clearance, HbA1c or arterial hypertension. To conclude: both normal and diabetic males eliminate a greater quantity of HS than females. Normoalbuminuric diabetic patients of both types eliminate a greater quantity of HS regardiess of arterial pressure and time since onset of diabetes.

Urinary heparan sulphate is increased in normoalbuminuric diabetic patients

Forty-nine normoalbuminuric diabetic patients were studied: 22 males and 27 females, in whom urinary heparan sulphate (HS), albuminuria, creatininemia, creatininuria, creatinine clearance, HbA1c and arterial pressure (AP) were determined. Two groups were discerned: group 1, Type 1 DM, diabetic cases (n = 16); and group 2, Type 2 DM diabetic cases (n = 33). Patients were compared with 24 healthy controls: 12 men and 12 women, who showed a mean value + SD of 0.36 + 0.18 mg/24 h HS with significant differences between males and females (0.43 + 0.15 versus 0.28 + 0.17, respectively; p = 0.02). The total population of diabetic cases rendered a mean of 0.68 + 0.44 and comparison with controls proved highly significant (p < 0.001). Globally, male patients had a mean of 0.82 + 0.48 and females 0.54 + 0.35, with p < 0.02. Group 1 and 2 values of HS were not significantly different. HS levels falled to correlate either with age, body mass index (BM), time since onset of diabetes, albuminuria, creatininemia, creatininuria, creatinine clearance, HbA1c or arterial hypertension. To conclude: both normal and diabetic males eliminate a greater quantity of HS than females. Normoalbuminuric diabetic patients of both types eliminate a greater quantity of HS regardiess of arterial pressure and time since onset of diabetes. (AU)