A rare missense mutation in a type 2 diabetes patient decreases the transcriptional activity of human sterol regulatory element binding protein-1

11 pages, 3figures, 1 table.-PMID: 16429400 [PubMed]Sterol regulatory element binding protein 1 (SREBP-1) transcription factors play a key role in energy homeostasis by regulating genes involved in both carbohydrate and lipid metabolism, and in adipocyte differentiation. The 5' end of the mRNA-encoding SREBP-1 exists in two forms, designated 1a and 1c. The divergence results from the use of two transcription start sites that produce two separate 5' exons, each of which is spliced to a common exon 2. Mutations in the sterol regulatory element binding protein gene (SREBF)-1 may contribute to insulin resistance states. However, the variants described to date do not affect the SREBP function. In this study, we investigated the functional consequences of a novel missense mutation common to both SREBP-1 isoforms identified in a Spanish Type 2 diabetic patient (c.677C>T, SREBP-1a p.T226M; c.605C>T, SREBP-1c p.T202M). Using reporter gene analysis and electrophoretic mobility shift assays, we found that this variant impaires the transcriptional activity and reduces DNA binding ability despite its comparable protein stability to the wild-type SREBP-1. This decreased activity impaires the expression of known downstream targets, such as the LDL receptor and fatty acid synthase genes. Our findings suggest that the threonine residue and/or surrounding region play an important role in the SREBP-1 functionThis study was supported by grants from Instituto de Salud Carlos III, Red de Centros (RCMN) C03/08, and from Ministerio de Educación y Ciencia (SAF2003-01262). S.V. is supported by a fellowship from Consejo Superior de Investigaciones Científicas I3P-BPD2001-1.Peer reviewe

Validation of the Spanish version of the Problem Areas in Diabetes (PAID-SP) Scale

This study aimed to assess the psychometric properties of the Spanish version of the Problem Areas in Diabetes (PAID-SP) Scale. Data were collected from patients with type 1 and type 2 diabetes. The findings suggested that the PAID-SP is a reliable and valid measure of diabetes-specific emotional problems

Caries dental en diabéticos tipo 1: Influencia de factores sistémicos de la enfermedad en la instauración de la caries dental

Objetivos: La diabetes mellitus es una de las enfermedades crónicas más prevalentes en población general. Se presenta un estudio que pretende evaluar la presencia de caries en los pacientes diabéticos tipo 1. El objetivo específico era comprobar si había o no mayor incidencia de caries en diabéticos tipo 1 comparándolos con un grupo de individuos no diabéticos. También, se comprobó la relación con las tasas de flujo salival y con los factores propios de la enfermedad como el grado de control metabólico, el tiempo de evolución de la enfermedad y la existencia de complicaciones crónicas. Diseño del estudio: Se estudiaron 90 diabéticos tipo 1 de edades comprendidas entre los 18 y los 50 años de edad y un grupo de pacientes controles no diabéticos pareados por edad y sexo. Se realizó una exploración visual y táctil, en todos los dientes de los sujetos explorados. Se tuvo en cuenta el grado de la higiene oral mediante el índice de placa de O'Leary, y se estudiaron las tasas de saliva basal y estimulada en ambos grupos. En el grupo diabético se relaciono con el control de la enfermedad mediante la obtención de la media de la hemoglobina glicosilada (HbA1c) de los dos años previos a la exploración, así como la evolución de su enfermedad en años y la existencia de complicaciones como neuropatía diabética o retinopatía. Resultados: Bajo similares condiciones de higiene oral y de flujo salival, el grupo diabético resultó tener una incidencia de caries mayor que el grupo control (p<0.05). Asimismo, al estudiar específicamente al grupo diabético, ni el control metabólico de la enfermedad, ni la evolución de la enfermedad, ni la existencia de complicaciones de la diabetes tenían influencia en la instauración de caries dental. Conclusiones: Se sugiere que habría que estudiar factores cualitativos salivales que explicasen esta mayor incidencia de caries en los diabéticos.Objectives: Diabetes mellitus is one of the most common chronic diseases in the general population. A study is made of the presence of caries in type 1 diabetic patients. The specific aim was to determine whether such patients present a greater incidence of dental caries than non-diabetic individuals. An evaluation was also made of the relationship of caries to salivary flow and to factors inherent to the disease such as the degree of metabolic control, the duration of diabetes, and the existence of chronic complications. Study design: The study comprised 90 type 1 diabetics between 18 and 50 years of age, and a group of non-diabetic controls matched for age and sex. Visual and tactile exploration of the dentition was carried out in all cases. Oral hygiene was rated based on the O'Leary plaque index, and basal (unstimulated) and stimulated salivary flow were evaluated in both groups. In the diabetic group, correlations were established with disease control based on the mean glycosylated hemoglobin (HbA1c) value corresponding to the two years prior to examination; evolution of the disease in years; and the existence of complications such as diabetic neuropathy or retinopathy. Results: Under similar conditions of oral hygiene and salivary flow, the diabetic group showed a higher incidence of caries than the control group (p<0.05). Likewise, on specifically analyzing the diabetic group, metabolic control of the disease, the duration of diabetes, and the existence of complications of the disease exerted an influence upon the development of dental caries. Conclusions: Qualitative salivary studies are advised to better account for this increased incidence of caries in the diabetic population

Efect of periodontal disease and non surgical periodontal treatment on C-reactive protein. Evaluation of type 1 diabetic patient.

Objectives: The purpose of this study was to analyze how anti-infectious periodontal treatment affects C reactive protein (CRP) values in patients with type 1 diabetes, and correlate baseline CRP levels with periodontal disease severity. Study Design: A cohort of fifty three subjects with type 1 diabetes and moderate to severe periodontitis were recruited. Periodontal parameters were measured, and blood samples were obtained to evaluate high-sensitivity C-reactive protein (hs-CRP). Group 1 was treated with scaling, root planning, and systemic administration of doxycycline. Group 2 received only scaling and root planning. Results: Hs-CRP was reduced after periodontal treatment in group 1 (-0.22 mg/l) and 2 (-0.21 mg/l ) but this reduction was not statistically significant, even in the patients with the best response to periodontal treatment. However, significant correlation appeared between hs-CRP and mean probing pocket depth (PPD) (p=0, 01) and mean clinical attachment level (CAL) (p=0,03). Conclusions: Non-surgical periodontal treatment couldn¿t reduce hs-CRP values, however, it was found an asso- ciation between advanced periodontitis and elevated blood hs-CRP levels in patients with type 1 diabetes. It can be speculated that periodontal disease increases production of pro-inflammatory mediators in patients with type 1 diabetes, but other producing sources of these pro-inflammatory substances may exist

Type 1 diabetes mellitus and periodontal disease : relationship to different clinical variables

Objective: This study is designed to evaluate the frequency of periodontal disease in a group of patients with type 1 diabetes mellitus and how this relates with diabetes metabolic control, duration of diabetes, and presence of diabetic complications. Methods: A comparison was made of periodontal parameters (plaque index, bleeding index, pocket depth and attachment loss) in a group of diabetic patients (n=90) versus a group of non-diabetics (n=90). Logistic regression analysis was performed to evaluate relationship between periodontal parameters and degree of metabolic control, the duration of the disease, and the appearance of complications. Results: Diabetics had greater bleeding index (p<0.01), deeper periodontal pockets (p<0.01) and more periodontal attachment loss (p<0.01) than non-diabetics. Deficient metabolic control and presence of diabetic complication were associated with higher bleeding index and pocket depth (p?0.02). Conclusions: Patients with type 1 diabetes appear to show increased periodontal disease susceptibility, particularly those with poorer metabolic control or with diabetic complications

Neoplasia mandibular y gastrostomía: a propósito de un caso nutricional

A case of a 47 year old male with mandibular squamous cell carcinoma is presented. Severe caloric malnutrition is diagnosed following the nutritional assessment of SENPE-SEDOM method. Severe mechanical dysphagia is developed due to surgery and oncological treatment. Dysphagia is diagnosed by the clinical exploration known as Volume-Viscosity Method (MECV-V). The patient requires dietary adaptations including texture and nutritional input and finally, the use of gastrostomy feeding tube and enteral nutrition. The aim of this nutritional treatment is to improve the nutritional status that in our case worsened as a consequence of oncological disease, aggressive treatments and inaccurate nutritional indications made by non-expert staff. Once oncological treatment is concluded, dysphagia ameliorates and nutritional progression from enteral to oral feeding is possible. To reach the nutritional recovery a new dietary texture adaptation is made and nutritional supplements are added. The gastrostomy feeding tube will remain until the status of free of oncological disease is achieved.Se expone el caso de un varón de 47 años con carcinoma epidermoide mandibular. Su evolución ocasiona la aparición de una desnutrición calórica severa que requiere una valoración nutricional completa con el método SENPE-SEDOM. Dicha situación se agrava con el tratamiento quirúrgico y oncológico, desarrollando una disfagia mecánica grave, valorada y diagnosticada con el Método de Exploración Clínica Volumen-Viscosidad (MECV-V). El paciente requiere progresivas adaptaciones dietéticas tanto de textura como de aporte nutricional, precisando el uso de sonda de alimentación por gastrostomía y de nutrición enteral a través de ella. La finalidad es mejorar el estado nutricional, que había empeorado como consecuencia de la enfermedad, de los tratamientos y de incorrectas indicaciones nutricionales por personal no experto en nutrición. Al finalizar el tratamiento oncológico, se produce una mejoría de la disfagia, y se modifica la intervención dietética y nutricional, por lo que se progresa de vía enteral a oral con nueva adaptación de textura y con suplementos dietético-nutricionales que permitan la recuperación del estado nutricional, manteniendo la sonda de alimentación por gastrostomía hasta que el paciente se encuentre libre de enfermedad

Dental caries in type 1 diabetics : influence of systemic factors of the disease upon the development of dental caries

Objectives: Diabetes mellitus is one of the most common chronic diseases in the general population. A study is made of the presence of caries in type 1 diabetic patients. The specific aim was to determine whether such patients present a greater incidence of dental caries than non-diabetic individuals. An evaluation was also made of the relationship of caries to salivary flow and to factors inherent to the disease such as the degree of metabolic control, the duration of diabetes, and the existence of chronic complications. Study design: The study comprised 90 type 1 diabetics between 18 and 50 years of age, and a group of non-diabetic controls matched for age and sex. Visual and tactile exploration of the dentition was carried out in all cases. Oral hygiene was rated based on the O?Leary plaque index, and basal (unstimulated) and stimulated salivary flow were evaluated in both groups. In the diabetic group, correlations were established with disease control based on the mean glycosylated hemoglobin (HbA1c) value corresponding to the two years prior to examination; evolution of the disease in years; and the existence of complications such as diabetic neuropathy or retinopathy. Results: Under similar conditions of oral hygiene and salivary flow, the diabetic group showed a higher incidence of caries than the control group (p<0.05). Likewise, on specifically analyzing the diabetic group, metabolic control of the disease, the duration of diabetes, and the existence of complications of the disease exerted an influence upon the development of dental caries. Conclusions: Qualitative salivary studies are advised to better account for this increased incidence of caries in the diabetic population

Atherogenic Ratios in Patients with Recurrent Acute Coronary Syndrome and Receiving Statin Therapy: Clinical Usefullness as Cardiovascular Predictors

Patients who have already suffered a vascular event require more and better control of cardiovascular risk factors. Different atherogenic indexes such as TC/HDLc, LDLc/HDLc, apoB/apoA-I, LDLc/apoB and non-HDLc/HDLc have been used to follow-up the patients because of their predictive capacity of the lipid profile. The aim of this study was to evaluate atherogenic ratios as a marker of the lipid residual risk in high-risk patients receiving statin therapy and to know the changes produced by previous lipid-lowering drugs treatment for a previous coronary event. The study including patients admitted to coronary care units of six Spanish tertiary hospitals for Acute Coronary Syndrome (ACS). A total of 633 ACS patients were included; of these, 478 (75.8%) had presented a myocardial infarction and 153 (24.2%) angina. A previous ACS had occurred in 43.1% of cases, and was the first episode in 56.9% of the studied patients. Among patients with known ischemic heart disease, 187 (52.2%) were receiving lipid-lowering drugs, mainlystatins (182 patients, 50.7%). Of those with a first ACS, 59 (21.7%) were on lipid-lowering drugs: 55 (20.1%) statins and 4 (1.7%) fibrates. Patients with recurrent ACS had similar triglyceride and HDLc levels, but significantly lower total cholesterol and LDLc concentrations compared with those presenting the first ACS. Patients with recurrent ACS had significantly lower non-HDLc levels, TC/HDLc and LDLc/HDLc, but higher HDLc/TC and HDLc/LDLc ratios compared with first ACS patients. In patients taking statins the lipid residual vascular risk was related with the persistence of cardiovascular risk factors, and related with lipid profile with dyslipemia no-LDL dependent. So, we can conclude that the correction of lipid profile by statin is not per se sufficient to control cardiovascular risk