Coexistence of mastoid, frontal and vertebral hemangiomas in a patient with diabetic neuropathy: Possible correlation between diabetic angiopathy and intraosseous neoangiogenesis.

Bony hemangiomas are benign vascular lesions with an expansive growth; usually they tend to obliterate the entire bony cavity. They are typical lesion of the spinal bones, but they can rarely arise within other bones of the neurocranium. Diabetic microangiopathy is a condition characterized by the development of aberrant vessel tangles anastomosed to each other due to dysregulated neoangiogenesis. We report the case of a 56-year-old woman, suffering from type 2 diabetes mellitus, admitted to the neurology department due to a reported worsening of paresthesias and dysesthesias of the upper and lower limbs. She performed a contrast-enhanced brain CT scan that showed the presence, at the level of the right mastoid process, of an hypervascular angioma. A subsequent MRI study of the brain and spine showed the presence of multiple bone angiomas, at the level of the right frontal theca and C7, Th3, and Th7 vertebral bodies. Due to the absence of further symptoms and clinical and radiological signs of intracranial compression, the patient did not perform surgery. A radiological follow-up was advised. Although possible pathophysiological correlations between diabetes and vertebral hemangiomas are mentioned in literature, vascular lesions of this type involving vertebrae and skull base simultaneously can be discovered in a patient with chronic diabetic disease. As long as these lesions remain asymptomatic, surgical treatment is not indicated, and the patient is followed over time with radiological follow-up.

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy.

As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people's health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic ß-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.

Roles of Sirt1 and its modulators in diabetic microangiopathy: A review.

Diabetic vascular complications include diabetic macroangiopathy and diabetic microangiopathy. Diabetic microangiopathy is characterised by impaired microvascular endothelial function, basement membrane thickening, and microthrombosis, which may promote renal, ocular, cardiac, and peripheral system damage in diabetic patients. Therefore, new preventive and therapeutic strategies are urgently required. Sirt1, a member of the nicotinamide adenine dinucleotide-dependent histone deacetylase class III family, regulates different organ growth and development, oxidative stress, mitochondrial function, metabolism, inflammation, and aging. Sirt1 is downregulated in vascular injury and microangiopathy. Moreover, its expression and distribution in different organs correlate with age and play critical regulatory roles in oxidative stress and inflammation. This review introduces the background of diabetic microangiopathy and the main functions of Sirt1. Then, the relationship between Sirt1 and different diabetic microangiopathies and the regulatory roles mediated by different cells are described. Finally, we summarize the modulators that target Sirt1 to ameliorate diabetic microangiopathy as an essential preventive and therapeutic measure for diabetic microangiopathy. In conclusion, targeting Sirt1 may be a new therapeutic strategy for diabetic microangiopathy.

Evaluation of bi-directional causal association between obstructive sleep apnoea syndrome and diabetic microangiopathy: a Mendelian randomization study.

Background: The relationship between obstructive sleep apnea syndrome (OSAS) and diabetic microangiopathy remains controversial. Objective: This study aimed to use bidirectional two-sample Mendelian Randomization (MR) to assess the causal relationship between OSAS and diabetic microangiopathy. Methods: First, we used the Linkage Disequilibrium Score Regression(LDSC) analysis to assess the genetic correlation. Then, the bidirectional two-sample MR study was conducted in two stages: OSAS and lung function-related indicators (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) were investigated as exposures, with diabetic microangiopathy as the outcome in the first stage, and genetic tools were used as proxy variables for OSAS and lung function-related measures in the second step. Genome-wide association study data came from the open GWAS database. We used Inverse-Variance Weighted (IVW), MR-Egger regression, Weighted median, Simple mode, and Weighted mode for effect estimation and pleiotropy testing. We also performed sensitivity analyses to test the robustness of the results. Furthermore, we performed multivariate and mediation MR analyses. Results: In the LDSC analysis, We found a genetic correlation between OSAS, FVC, FEV 1, and diabetic microangiopathy. In the MR analysis, based on IVW analysis, genetically predicted OSAS was positively correlated with the incidence of diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). In the subgroup analysis of DR, there was a significant causal relationship between OSAS and background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). The reverse MR did not show a correlation between the incidence of diabetic microangiopathy and OSAS. Reduced FVC had a potential causal relationship with increased incidence of DR and PDR. Reduced FEV1 had a potential causal relationship with the increased incidence of BDR, PDR, and DKD. Multivariate MR analysis showed that the association between OSAS and diabetic microangiopathy remained significant after adjusting for confounding factors. However, we did not find the significant mediating factors. Conclusion: Our results suggest that OSAS may be a cause of the development of diabetic microangiopathy, and OSAS may also be associated with a high risk of diabetic microangiopathy, providing a reference for a better understanding of the prevention of diabetic microangiopathy.

Índice trabecular óseo y niveles de 25-hidroxivitamina D en las complicaciones microvasculares de la diabetes mellitus tipo 2 / Trabecular bone score and 25-hydroxyvitamin D levels in microvascular complications of type 2 diabetes mellitus

Antecedentes y objetivo:La enfermedad microvascular (EMV) diabética ha sido asociada con una fragilidad ósea incrementada. El objetivo fue analizar la relación entre la EMV y la microestructura trabecular -evaluada mediante el índice trabecular óseo (trabecular bone score, TBS)- en pacientes diabéticos tipo 2 (DM2). Adicionalmente, conocer la relación entre la vitamina D y la EMV.Pacientes y métodos:Diseño transversal analítico, que incluyó varones > 50 años y mujeres postmenopáusicas con DM2, participantes en una cohorte poblacional. Se clasificó como EMV+ la presencia de nefropatía, neuropatía y/o retinopatía. Fueron analizadas variables clínicas, de laboratorio, el TBS, la 25-hidroxivitamina D [25(OH)D] y la densidad mineral ósea (DMO). Se realizaron análisis bivariable y multivariable.Resultados:Fueron evaluados 361 pacientes (51,1% mujeres), de 63,8 (9) años. De ellos, 92 tenían EMV, con un peor control metabólico, mayor duración de la DM2, menor TBS (1,235 [0,1] vs. 1,287 [0,1]; p=0,003) y menores niveles de 25(OH)D (18,3 [7] vs. 21,6 [8] ng/mL; p=0,0001). No hubo diferencias entre EMV+ y EMV- en la DMO ni en los marcadores P1NP y β-CTX. Tras ajustar por confusores, incluyendo HbA1c y duración de la DM2, el TBS en EMV+ fue 1,252 (IC 95% 1,230-1,274) vs. 1,281 (IC 95% 1,267-1,295) en EMV- (p=0,034). La EMV se asoció a un nivel de 25(OH)D < 20 ng/mL con una OR ajustada=1,88 (IC 95% 1,06-3,31; p=0,028).Conclusiones:Los pacientes con EMV presentaron un TBS significativamente menor, tras ajustar por confusores. El análisis multivariable mostró asimismo una asociación significativa entre un nivel bajo de 25(OH)D y la EMV prevalente. (AU)

Background and objective:Diabetic microvascular disease (MVD) has been associated with increased bone fragility. The objective was to analyse the relationship between MVD and trabecular microstructure -assessed by the trabecular bone score (TBS)- in type 2 diabetic (T2D) patients. A second aim was to know the relationship between vitamin D and MVD.Patients and methods:Cross-sectional study, which included men >50 years and postmenopausal women participating in a population-based cohort, diagnosed with T2D. The presence of nephropathy, neuropathy and/or retinopathy was classified as MVD+. Clinical and laboratory variables, TBS, 25(OH)D and BMD by DXA, were evaluated. Bivariate and multivariate analysis were performed.Results:We evaluated 361 patients (51.1% women), 63.8 (9) years old. Of them, 92 were MVD+ and presented poorer metabolic control, longer duration of T2D, lower TBS [1.235 (.1) vs. 1.287 (.1); p=.007] and lower levels of 25(OH)D [18.3 (7) vs. 21.6 (8) ng/ml; p=.0001). There were no differences between MVD+ and MVD- with regard to BMD or P1NP and β-CTX markers. After adjusting for confounders, including HbA1c and duration of T2D, the TBS value in MVD+ was 1.252 (95% CI 1.230-1.274) vs. 1.281 (95% CI 1.267-1.295) in MVD- (p=.034). MVD was associated with a 25(OH)D level <20 ng ml with an adjusted OR of 1.88 (95% CI 1.06-3.31; p=.028).Conclusions:The MVD+ patients presented a significantly lower TBS, after adjusting for confounders. Furthermore, multivariable analysis showed a significant relationship between a low 25(OH)D level and a prevalent MVD. (AU)