The effect of monomeric and oligomeric FLAVAnols in patients with type 2 diabetes and microalbuminuria (FLAVA-trial): A double-blind randomized controlled trial.

BACKGROUND & AIMS: Microalbuminuria is an early sign of vascular complications of type 2 diabetes and predicts cardiovascular disease and mortality. Monomeric and oligomeric flavanols (MOFs) are linked to improved vascular health. The aim of this study was to assess the effect of 3 months MOFs on albuminuria and endothelial function markers in patients with type 2 diabetes and microalbuminuria. METHODS: We conducted a double-blind, placebo-controlled trial among patients with type 2 diabetes and microalbuminuria. Patients with type 2 diabetes received either 200 mg MOFs or placebo daily on top of their habitual diet and medication. The primary endpoint was the between-group difference of the change in 24-h Albumin Excretion Rate (AER) over three months. Secondary endpoints were the between-group differences of the change in plasma levels of different markers of endothelial dysfunction. Mixed-modelling was applied for the longitudinal analyses. RESULTS: Participants (n = 97) were 63.0 ± 9.5 years old; diabetes-duration was 15.7 ± 8.5 years. Median baseline AER was 60 (IQR 20-120) mg/24 h. There was no within-group difference in median change of AER from baseline to 3 months in the intervention (0 (-35-21) mg/24 h, p = 0.41) or the control group (0 (-20-10) mg/24 h, p = 0.91). There was no between-group difference in the course of AER over three months (log-transformed data: ß = -0.02 (95%CI -0.23-0.20), p = 0.88), nor in the plasma levels of the endothelial dysfunction markers. CONCLUSION: Daily 200 mg MOFs for three months on top of habitual diet and usual care did not reduce AER and plasma markers of endothelial dysfunction compared to placebo, in patients with long-term type 2 diabetes and microalbuminuria. CLINICAL TRIALS REGISTRATION: NTR4669, www.trialregister.nl.

Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Microvascular disease in type 2 diabetes is a significant cause of end-stage renal disease, blindness and peripheral neuropathy. The strict control of known risk factors, e.g. lifestyle, hyperglycaemia, hypertension and dyslipidaemia, reduces the incidence of microvascular complications, but a residual risk remains. Lipoprotein (a) [Lp(a)] is a strong risk factor for macrovascular disease in the general population. We hypothesised that plasma Lp(a) levels and the LPA gene SNPs rs10455872 and rs3798220 are associated with the incident development of microvascular complications in type 2 diabetes. METHODS: Analyses were performed of data from the DiaGene study, a prospective study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886 individuals with type 2 diabetes, mean follow-up time = 6.97 years). To assess the relationship between plasma Lp(a) levels and the LPA SNPs with each newly developed microvascular complication (retinopathy n = 223, nephropathy n = 246, neuropathy n = 236), Cox proportional hazards models were applied and adjusted for risk factors for microvascular complications (age, sex, mean arterial pressure, non-HDL-cholesterol, HDL-cholesterol, BMI, duration of type 2 diabetes, HbA1c and smoking). RESULTS: No significant associations of Lp(a) plasma levels and the LPA SNPs rs10455872 and rs3798220 with prevalent or incident microvascular complications in type 2 diabetes were found. In line with previous observations the LPA SNPs rs10455872 and rs3798220 did influence the plasma Lp(a) levels. CONCLUSIONS/INTERPRETATION: Our data show no association between Lp(a) plasma levels and the LPA SNPs with known effect on Lp(a) plasma levels with the development of microvascular complications in type 2 diabetes. This indicates that Lp(a) does not play a major role in the development of microvascular complications. However, larger studies are needed to exclude minimal effects of Lp(a) on the development of microvascular complications.

Prevalence of impacted mandibular third molars and its association with distal caries in mandibular second molars using cone beam computed tomography / Prevalencia de terceros molares mandibulares impactados y su asociación con caries distales en segundos molares mandibulares mediante tomografía computarizada de haz cónico

This study evaluated the prevalence and eruption's pattern of impacted mandibular third molars (IMTM) and the influence of their eruption status on the distal caries of mandibular second molars (MSM) using cone-beam computed tomography (CBCT). Material and methods: CBCT images taken for different purposes in private dental practices were analyzed retrospectively. Radiographic assessment included: prevalence of IMTM, degree of angulation, level of impaction and type of IMTM. Furthermore, the distance between the cement-enamel junctions (CEJ) of second and third molars and the occurrence of caries lesion on the distal surface of MSM was also evaluated. Data were analyzed by chi square test and logistic regression was used to find the association between distal caries of MSM and eruption status of IMTM. Results: Three hundred and eight CBCTs were screened, the prevalence of IMTM was 36.88% and their angulation degree were mostly less than 90º (mesioangular). Amongst those with impaction, 58 subjects (43%) had distal caries on MSM, 29.6% in females and 30.4% in the age group 19-27 years. Caries on the distal side of MSM were significantly associated with age, level and type of impaction, angulation degree and CEJ distances (p<0.05). Conclusions: The prevalence of IMTM is high (36.88%) and there are significant relationships between angulation degree, level and type of impaction, and CEJ distances with caries on the distal side of MSM.

Introducción: Este estudio evaluó la prevalencia y el patrón de erupción de terceros molares mandibulares impactados (TMMI), y la influencia de su estado de erupción en la caries distal de los segundos molares mandibulares (SMM) mediante tomografía computarizada de haz cónico (TCHC). Material y métodos: se analizaron retrospectivamente las imágenes de TCHC tomadas para diferentes fines en prácticas dentales privadas. La evaluación radiográfica incluyó: prevalencia de TMMI, grado de angulación, nivel de impacto y tipo de TMMI. Además, también se evaluó la distancia entre la unión amelocementaria (UAC) de los segundos y terceros molares y la aparición de lesión de caries en la superficie distal de SMM. Los datos se analizaron mediante la prueba de chi cuadrado y se usó la regresión logística para evaluar asociaciones entre la caries distal de SMM y el estado de erupción de TMMI. Resultados: Se examinaron 308 TCHC, la prevalencia de TMMI fue de 36.88% y su grado de angulación fue mayoritariamente menor a 90º (mesioangular). Entre aquellos con impacto, 58 sujetos (43%) tenían caries distales en los SMM, 29.6% eran mujeres y 30.4% pertenecieron al grupo de edad de 19-27 años. Las caries en el lado distal de MSM se asociaron significativamente con la edad, el nivel y el tipo de impactación, el grado de angulación y las distancias UAC (p<0.05). Conclusiones: la prevalencia de TMMI es alta (36.88%) y existen relaciones significativas entre el grado de angulación, el nivel y el tipo de impacto, y las distancias UAC con presencia de caries en el lado distal de los SMM.

Use of monomeric and oligomeric flavanols in the dietary management of patients with type 2 diabetes mellitus and microalbuminuria (FLAVA trial): study protocol for a randomized controlled trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2D) are prone to micro- and macro-vascular complications. Monomeric and oligomeric flavanols (MOF) isolated from grape seeds (Vitis vinifera) have been linked to improved endothelial function and vascular health. The aim of this study is to determine the effect of a daily supplementation of 200 mg MOF on renal endothelial function of patients with T2D and microalbuminuria. METHODS/DESIGN: For this double-blind, placebo-controlled, randomized, multicenter trial 96 individuals (ages 40-85 years) with T2D and microalbuminuria will be recruited. Participants will be randomly assigned to the intervention group, receiving 200 mg of MOF daily for 3 months, or to the control group, receiving a placebo. The primary endpoint is the evolution over time in albumin excretion rate (AER) until 3 months of intervention as compared with placebo. Secondary endpoints are the evolution over time in established plasma markers of renal endothelial function-asymmetric dimethylarginine (ADMA), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and von Willebrand Factor (vWF)-until 3 months of intervention as compared with placebo. Mixed modeling will be applied for the statistical analysis of the data. DISCUSSION: We hypothesize that T2D patients with microalbuminuria have a medically determined requirement for MOF and that fulfilling this requirement will result in a decrease in AER and related endothelial biomarkers. If confirmed, this may lead to new insights in the dietary management of patients with T2D. TRIAL REGISTRATION: Nederlands Trial Register, NTR4669 , registered on 7 July 2014.