1,8-cineole ameliorates experimental diabetic angiopathy by inhibiting NLRP3 inflammasome-mediated pyroptosis in HUVECs via SIRT2.

Accumulating evidence strongly support the key role of NLRP3-mediated pyroptosis in the pathogenesis and progression of vascular endothelial dysfunction associated with diabetes mellitus. Various studies have demonstrated that the activation or upregulation of Silent Information Regulation 2 homolog 2 (SIRT2) exerts inhibitory effect on the expression of NLRP3. Although 1,8-cineole has been found to protect against endothelial dysfunction and cardiovascular diseases, its role and mechanism in diabetic angiopathy remain unknown. Therefore, the aim of this study was to investigate the ameliorative effect of 1,8-cineole through SIRT2 on pyroptosis associated with diabetic angiopathy in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanism. The findings revealed that 1,8-cineole exhibited a protective effect against vascular injury and ameliorated pathological alterations in the thoracic aorta of diabetic mice. Moreover, it effectively mitigated pyroptosis induced by palmitic acid-high glucose (PA-HG) in HUVECs. Treatment with 1,8-cineole effectively restored the reduced levels of SIRT2 and suppressed the elevated expression of pyroptosis-associated proteins. Additionally, our findings demonstrated the occurrence of NLRP3 deacetylation and the physical interaction between NLRP3 and SIRT2. The SIRT2 inhibitor AGK2 and siRNA-SIRT2 effectively attenuated the effect of 1,8-cineole on NLRP3 deacetylation in HUVECs and compromised its inhibitory effect against pyroptosis in HUVECs. However, overexpression of SIRT2 inhibited PA-HG-induced pyroptosis in HUVECs. 1,8-Cineole inhibited the deacetylation of NLRP3 by regulating SIRT2, thereby reducing pyroptosis in HUVECs. In conclusion, our findings suggest that PA-HG-induced pyroptosis in HUVECs plays a crucial role in the development of diabetic angiopathy, which can be mitigated by 1,8-cineole.

N6-methyladenosine demethylase fat mass and obesity-associated protein suppresses hyperglycemia-induced endothelial cell injury by inhibiting reactive oxygen species formation via autophagy promotion.

INTRODUCTION: Hyperglycemia-induced endothelial cell injury is one of the main causes of diabetic vasculopathy. Fat mass and obesity-associated protein (FTO) was the first RNA N6-methyladenosine (m6A) demethylase identified; it participates in the pathogenesis of diabetes. However, the role of FTO in hyperglycemia-induced vascular endothelial cell injury remains unclear. MATERIALS AND METHODS: The effects of FTO on cellular m6A, autophagy, oxidative stress, proliferation, and cytotoxicity were explored in human umbilical vein endothelial cells (HUVECs) treated with high glucose (33.3 mmol/mL) after overexpression or pharmacological inhibition of FTO. MeRIP-qPCR and RNA stability assays were used to explore the molecular mechanisms by which FTO regulates autophagy. RESULTS: High glucose treatment increased m6A levels and reduced FTO protein expression in HUVECs. Wild-type overexpression of FTO markedly inhibited reactive oxygen species generation by promoting autophagy, increasing endothelial cell proliferation, and decreasing the cytotoxicity of high glucose concentrations. The pharmacological inhibition of FTO showed the opposite results. Mechanistically, we identified Unc-51-like kinase 1 (ULK1), a gene responsible for autophagosome formation, as a downstream target of FTO-mediated m6A modification. FTO overexpression demethylated ULK1 mRNA and inhibited its degradation in an m6A-YTHDF2-dependent manner, leading to autophagy activation. CONCLUSIONS: Our study demonstrates the functional importance of FTO-mediated m6A modification in alleviating endothelial cell injury under high glucose conditions and indicates that FTO may be a novel therapeutic target for diabetic vascular complications.

Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway.

BACKGROUND: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. METHODS: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. RESULTS: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. CONCLUSION: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.

Ion channel Piezo1 activation aggravates the endothelial dysfunction under a high glucose environment.

BACKGROUND: Vasculopathy is the most common complication of diabetes. Endothelial cells located in the innermost layer of blood vessels are constantly affected by blood flow or vascular components; thus, their mechanosensitivity plays an important role in mediating vascular regulation. Endothelial damage, one of the main causes of hyperglycemic vascular complications, has been extensively studied. However, the role of mechanosensitive signaling in hyperglycemic endothelial damage remains unclear. METHODS: Vascular endothelial-specific Piezo1 knockout mice were generated to investigate the effects of Piezo1 on Streptozotocin-induced hyperglycemia and vascular endothelial injury. In vitro activation or knockdown of Piezo1 was performed to evaluate the effects on the proliferation, migration, and tubular function of human umbilical vein endothelial cells in high glucose. Reactive oxygen species production, mitochondrial membrane potential alternations, and oxidative stress-related products were used to assess the extent of oxidative stress damage caused by Piezo1 activation. RESULTS: Our study found that in VECreERT2;Piezo1flox/flox mice with Piezo1 conditional knockout in vascular endothelial cells, Piezo1 deficiency alleviated streptozotocin-induced hyperglycemia with reduced apoptosis and abscission of thoracic aortic endothelial cells, and decreased the inflammatory response of aortic tissue caused by high glucose. Moreover, the knockout of Piezo1 showed a thinner thoracic aortic wall, reduced tunica media damage, and increased endothelial nitric oxide synthase expression in transgenic mice, indicating the relief of endothelial damage caused by hyperglycemia. We also showed that Piezo1 activation aggravated oxidative stress injury and resulted in severe dysfunction through the Ca2+-induced CaMKII-Nrf2 axis in human umbilical vein endothelial cells. In Piezo1 conditional knockout mice, Piezo1 deficiency partially restored superoxide dismutase activity and reduced malondialdehyde content in the thoracic aorta. Mechanistically, Piezo1 deficiency decreased CaMKII phosphorylation and restored the expression of Nrf2 and its downstream molecules HO-1 and NQO1. CONCLUSION: In summary, our study revealed that Piezo1 is involved in high glucose-induced oxidative stress injury and aggravated endothelial dysfunction, which have great significance for alleviating endothelial damage caused by hyperglycemia.

Association of the systemic immuno-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio with diabetic microvascular complications.

Background: The systemic immuno-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are widely used and have been shown to be predictive indicators of various diseases. Diabetic nephropathy (DN), retinopathy (DR), and peripheral neuropathy (DPN) are the most prominent and common microvascular complications, which have seriously negative impacts on patients, families, and society. Exploring the associations with these three indicators and diabetic microvascular complications are the main purpose. Methods: There were 1058 individuals with type 2 diabetes mellitus (T2DM) in this retrospective cross-sectional study. SII, NLR, and PLR were calculated. The diseases were diagnosed by endocrinologists. Logistic regression and subgroup analysis were applied to evaluate the association between SII, NLP, and PLR and diabetic microvascular complications. Results: SII, NLR, and PLR were significantly associated with the risk of DN [odds ratios (ORs): 1.52, 1.71, and 1.60, respectively] and DR [ORs: 1.57, 1.79, and 1.55, respectively] by multivariate logistic regression. When NLR ≥2.66, the OR was significantly higher for the risk of DPN (OR: 1.985, 95% confidence interval: 1.29-3.05). Subgroup analysis showed no significant positive associations across different demographics and comorbidities, including sex, age, hypertension, HbA1c (glycated hemoglobin), and dyslipidemia. Conclusion: This study found a positive relationship between NLR and DN, DR, and DPN. In contrast, SII and PLR were found to be only associated with DN and DR. Therefore, for the diagnosis of diabetic microvascular complications, SII, NLR and PLR are highly valuable.

BAG3 promotes proliferation and migration of arterial smooth muscle cells by regulating STAT3 phosphorylation in diabetic vascular remodeling.

BACKGROUND: Diabetic vascular remodeling is the most important pathological basis of diabetic cardiovascular complications. The accumulation of advanced glycation end products (AGEs) caused by elevated blood glucose promotes the proliferation and migration of vascular smooth muscle cells (VSMCs), leading to arterial wall thickening and ultimately vascular remodeling. Therefore, the excessive proliferation and migration of VSMCs is considered as an important therapeutic target for vascular remodeling in diabetes mellitus. However, due to the lack of breakthrough in experiments, there is currently no effective treatment for the excessive proliferation and migration of VSMCs in diabetic patients. Bcl-2-associated athanogene 3 (BAG3) protein is a multifunctional protein highly expressed in skeletal muscle and myocardium. Previous research has confirmed that BAG3 can not only regulate cell survival and apoptosis, but also affect cell proliferation and migration. Since the excessive proliferation and migration of VSMCs is an important pathogenesis of vascular remodeling in diabetes, the role of BAG3 in the excessive proliferation and migration of VSMCs and its molecular mechanism deserve further investigation. METHODS: In this study, BAG3 gene was manipulated in smooth muscle to acquire SM22αCre; BAG3FL/FL mice and streptozotocin (STZ) was used to simulate diabetes. Expression of proteins and aortic thickness of mice were detected by immunofluorescence, ultrasound and hematoxylin-eosin (HE) staining. Using human aorta smooth muscle cell line (HASMC), cell viability was measured by CCK-8 and proliferation was measured by colony formation experiment. Migration was detected by transwell, scratch experiments and Phalloidin staining. Western Blot was used to detect protein expression and Co-Immunoprecipitation (Co-IP) was used to detect protein interaction. RESULTS: In diabetic vascular remodeling, AGEs could promote the interaction between BAG3 and signal transducer and activator of transcription 3 (STAT3), leading to the enhanced interaction between STAT3 and Janus kinase 2 (JAK2) and reduced interaction between STAT3 and extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in accumulated p-STAT3(705) and reduced p-STAT3(727). Subsequently, the expression of matrix metallopeptidase 2 (MMP2) is upregulated, thus promoting the migration of VSMCs. CONCLUSIONS: BAG3 upregulates the expression of MMP2 by increasing p-STAT3(705) and decreasing p-STAT3(727) levels, thereby promoting vascular remodeling in diabetes. This provides a new orientation for the prevention and treatment of diabetic vascular remodeling.

l-thyroxine attenuates extracellular Hsp90α-induced vascular endothelial calcification in diabetes mellitus, as revealed by parallel metabolic profiles.

BACKGROUND AND AIMS: Diabetic atherosclerotic vascular disease is characterized by extensive vascular calcification. However, an elevated blood glucose level alone does not explain this pathogenesis. We investigated the metabolic markers underlying diabetic atherosclerosis and whether extracellular Hsp90α (eHsp90α) triggers vascular endothelial calcification in this particular metabolic environment. METHODS: A parallel human/animal model metabolomics approach was used. We analyzed 40 serum samples collected from 24 patients with atherosclerosis and from the STZ-induced ApoE-/- mouse model. A multivariate statistical analysis of the data was performed, and mouse aortic tissue was collected for the assessment of plaque formation. In vitro, the effects of eHsp90α on endothelial cell calcification were assessed by serum analysis, Western blotting and immunoelectron microscopy. RESULTS: Diabetic ApoE-/- mice showed more severe plaque lesions and calcification damage. Stearamide, oleamide, l-thyroxine, l-homocitrulline and l-citrulline are biomarkers of diabetic ASVD; l-thyroxine was downregulated in both groups, and the thyroid sensitivity index was correlated with serum Hsp90α concentration. In vitro studies showed that eHsp90α increased Runx2 expression in endothelial cells through the LRP1 receptor. l-thyroxine reduced the increase in Runx2 levels caused by eHsp90α and affected the distribution and expression of LRP1 through hydrogen bonding with glutamine at position 1054 in the extracellular segment of LRP1. CONCLUSIONS: This study provides a mechanistic link between characteristic serum metabolites and diabetic atherosclerosis and thus offers new insight into the role of extracellular Hsp90α in promoting vascular calcification.

Endothelial dysfunction in vascular complications of diabetes: a comprehensive review of mechanisms and implications.

Diabetic vascular complications are prevalent and severe among diabetic patients, profoundly affecting both their quality of life and long-term prospects. These complications can be classified into macrovascular and microvascular complications. Under the impact of risk factors such as elevated blood glucose, blood pressure, and cholesterol lipids, the vascular endothelium undergoes endothelial dysfunction, characterized by increased inflammation and oxidative stress, decreased NO biosynthesis, endothelial-mesenchymal transition, senescence, and even cell death. These processes will ultimately lead to macrovascular and microvascular diseases, with macrovascular diseases mainly characterized by atherosclerosis (AS) and microvascular diseases mainly characterized by thickening of the basement membrane. It further indicates a primary contributor to the elevated morbidity and mortality observed in individuals with diabetes. In this review, we will delve into the intricate mechanisms that drive endothelial dysfunction during diabetes progression and its associated vascular complications. Furthermore, we will outline various pharmacotherapies targeting diabetic endothelial dysfunction in the hope of accelerating effective therapeutic drug discovery for early control of diabetes and its vascular complications.

Clinacanthus nutans: Its potential against diabetic vascular diseases

Diabetes is an independent risk factor for the development of cardiovascular disease, with approximately 80% of cardiovascular mortality and morbidity linked to vascular complications such as atherosclerosis. It has been estimated that up to one-third of patients with diabetes mellitus use some form of complementary and/or alternative medicine. One plant that has received attention from diabetic patients for its perceived antidiabetic properties is Clinacanthus nutans, a member of the Acanthaceae family that is known as snake grass. Ethnomedical applications of this herb have been identified for the treatment of certain conditions, including fever, diabetes, skin rashes, and insect bites. This review aims to assess the potential of C. nutans to be used in the prevention and/or treatment of diabetic vasculopathy. Evidence for antidiabetic, anti-inflammatory, and dyslipidemic properties of C. nutans, as shown from experimental studies, is presented and discussed. Diabetes, inflammation, and hyperlipidemia are known to play significant roles in the initiation and severity of diabetic cardiovascular disease; thus, targeting these factors might be beneficial for preventing and/or treating diabetic vasculopathy.

Tratamiento y gestión del pie diabético / Treatment and management of diabetic foot

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Importancia médica del glucocáliz endotelial: Parte 2: su papel en enfermedades vasculares y complicaciones de la diabetes mellitus / Medical significance of endothelial glycocalyx: Part 2: Its role in vascular diseases and in diabetic complications

El glucocáliz endotelial es una capa constituida por glucosaminoglicanos, proteoglicanos y glucoproteínas que cubre al endotelio en su cara luminal. La participación del deterioro del glucocáliz endotelial parece esencial en los pasos iniciales de la fisiopatología de la aterosclerosis, de las complicaciones microangiopáticas de la diabetes mellitus y de la enfermedad venosa crónica. Los factores de riesgo de la aterosclerosis como la hipercolesterolemia, la hiperglucemia, la inflamación, el exceso de sodio y las fuerzas de tensión alteradas causan deterioro del glucocáliz. Esto provoca disfunción endotelial y permite la filtración de lipoproteínas (LDL) y de leucocitos al espacio subendotelial, iniciando la formación de la placa de ateroma. En la diabetes el glucocáliz adelgazado, principalmente por estrés oxidativo, posibilita la filtración de proteínas (albuminuria) y el trastorno endotelial de la microangiopatía. La hipertensión venosa crónica altera las fuerzas de tensión y daña el glucocáliz, lo que permite la filtración de leucocitos a las partes más profundas de la pared venosa, iniciando la inflamación y el deterioro morfológico y funcional de las venas que lleva a la enfermedad venosa crónica. El tratamiento con glucosaminoglicanos (sulodexida) logra prevenir o revertir el daño al glucocáliz endotelial y algunas de sus consecuencias; es eficaz en la enfermedad venosa crónica, especialmente con úlceras venosas. También ha sido útil en aterosclerosis obliterante de miembros inferiores y en la nefropatía diabética con albuminuria.

Endothelial glycocalyx is a layer composed by glycosaminoglycans, proteoglycans and glycoproteins attached to the vascular endothelial luminal surface. Shredding of glycocalyx appears as an essential initial step in the pathophysiology of atherosclerosis and microangiopathic complications of diabetes mellitus, as well as in chronic venous disease. Atherosclerosis risk factors, as hypercholesterolemia (LDL), hyperglycemia, inflammation, salt excess and altered shear stress can damage glycocalyx. This lead to endothelial dysfunction and allows LDL and leukocytes to filtrate to the subendothelial space initiating atheroma plaque formation. Degradation of glycocalyx in diabetes mellitus is mainly due to oxidative stress and enables protein filtration (albuminuria) and endothelial disorder of microangiopathy. Chronic venous hypertension brings to altered shears stress which results in shredded glycocalyx, this allows leukocytes to migrate into venous wall and initiate inflammation leading to morphologic and functional venous changes of the chronic venous disease. Treatment with glycosaminoglycans (sulodexide) prevents or recovers the damaged glycocalyx and several of its consequences. This drug improves chronic venous disease and promotes healing of chronic venous ulcers. It has also been useful in peripheral arterial obstructive disease and in diabetic nephropathy with albuminuria.

Efecto del sulodexide sobre la capacidad de relajación y alteraciones estructurales de la arteria aorta en ratas diabéticas por estreptozotocina / Effect of sulodexide on aortic vasodilation capacity and associated morphological changes in rats with streptozotocin-induced diabetes

La disfunción endotelial (DE) se presenta en pacientes con hipercolesterolemia, hipertensión arterial, obesidad y diabetes mellitus. Evidencias sugieren un papel de los glicosaminoglicanos en la DE. Evaluamos el efecto del sulodexide (SLD), un glicosaminoglicano utilizado en el tratamiento de la albuminuria y la enfermedad isquémica en pacientes diabéticos, sobre la relajación arterial y los cambios morfológicos en un modelo experimental de diabetes tipo 1. La diabetes se indujo a ratas Sprague Dawley administrando estreptozotocina (STZ), 60 mg/kg, i.v. Los animales fueron distribuidos en los siguientes grupos: I= control, II= diabéticas, III: control + sulodexide, IV= diabéticas + sulodexide (15 mg/kg/día s.c). A los 3 meses fueron sacrificados, las aortas extraídas para evaluar la relajación vascular inducida por acetilcolina (Ach) y nitroprusiato de sodio en anillos precontraídos con fenilefrina. Fueron evaluadas histológicamente mediante microscopía de luz y coloraciones diversas. El SLD in vitro no modificó la tensión basal de los anillos arteriales en reposo o precontraídos con fenilefrina. La diabetes disminuyó la capacidad de relajación arterial en respuesta a la Ach en un 28,8-35,1% vs control, efecto que fue prevenido por SLD. No se observó diferencia significativa en la relajación inducida por nitroprusiato sódico entre los grupos. El estudio histológico en los animales diabéticos mostró alteraciones estructurales, particularmente en la íntima y la adventicia, cambios que fueron prevenidos por el tratamiento con SLD. Nuestros resultados apoyan la potencial utilidad terapéutica del SLD en el tratamiento de la disfunción endotelial.

Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans(GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, iv. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.

Heterogeneidade clínica e coexistência das neuropatias diabéticas: diferenças e semelhanças entre diabetes melito tipos 1 e 2 / Clinical heterogeneity and coexistence of diabetic neuropathies: difference and similarities between types 1 and 2 diabetes mellitus

OBJETIVO: Estudar a heterogeneidade e a coexistência das neuropatias no diabetes melito tipos 1 (DMT1) e 2 (DMT2). MÉTODOS: Foram avaliados 74 DMT2 e 20 DMT1 em relação à idade (anos), tempo de diagnóstico do DM (TDDM, em anos), índice de massa corpórea (IMC, kg/m²), HbA1c e tipo de neuropatia (critérios da American Diabetes Association). RESULTADOS: DMT1 era mais jovem (32,7 ± 11 versus 56,9 ± 10,3; p = 0,0001), com maior TDDM (17,1 ± 9,7 versus 10,4 ± 6,8; p = 0,003) e menor IMC (23,6 ± 3,8 versus 28,4 ± 5,3; p = 0,0005). A neuropatia autonômica cardiovascular (NAC) (60 por cento versus 32,4 por cento; p = 0,02) e a coexistência desta com polineuropatia (PND) (62,5 por cento versus 33,3 por cento; p = 0,03) foram mais prevalentes no DMT1; a PND dolorosa crônica (PNDDC) (60,8 por cento versus 30,0 por cento; p = 0,009) o foi no DMT2. A HbA1c (p = 0,04) foi preditiva de PND em ambos os grupos. O TDDM (p = 0,03) e a PNDDC (p = 0,003) foram preditivos de NAC no DMT1. A idade (p = 0,0004) teve valor preditivo para PNDDC no DMT2. CONCLUSÕES: As neuropatias apresentam distribuição heterogênea no DMT1 e no DMT2. Com exceção do controle glicêmico, os fatores relacionados a essa complicação diferem de acordo com o tipo de diabetes.

OBJECTIVE: To evaluate the heterogeneity and the coexistence of diabetic neuropathy (DNP) in type 1 (T1DM) and 2 (T2DM) diabetes mellitus. METHODS: 74 T2DM and 20 T1DM patients were evaluated according to age (years), time from diagnosis of diabetes (TDD, years), body mass index (BMI, kg/m²), HbA1c and DNP type (American Diabetes Association criteria). RESULTS: T1DM was younger (32.7 ± 11.0 versus 56.9 ± 10.3; p = 0.0001), leaner (BMI: 23.6 ± 3.85 versus 28.4 ± 5.3; p = 0.0005) and they had longer TDD (17.1 ± 9.7 versus 10.4 ± 6.8; p = 0.003). Cardiovascular autonomic neuropathy (CAN) (60 percent versus 32.4 percent; p = 0.02) and its coexistence with polyneuropathy (PN) (62.5 percent versus 33.3 percent; p = 0.03) were more common in T1DM. Chronic painful polyneuropathy (CPP) was more prevalent in T2DM (60.8 percent versus 30.0 percent; p = 0.009). Logistic regression showed HbA1c as an independent variable related to PN (p = 0.04) in both groups. TDD (p = 0.03) and CPP (p = 0.003) were related to CAN in T1DM. Age (p = 0.0004) was related to CPP in T2DM. CONCLUSIONS: The DNP have shown a heterogeneity distribution in type 1 and type 2 diabetes mellitus. The related factors to different phenotypes of this complication, apart from hyperglycemia, may be variable between these two types of diabetes mellitus.

Doença arterial coronariana subclínica em pacientes com Diabetes Mellitus tipo 1 em hemodiálise / Enfermedad arterial coronaria subclínica en pacientes con Diabetes Mellitus tipo 1 en hemodiálisis / Subclinical coronary artery disease in patients with type 1 Diabetes Mellitus undergoing hemodialysis

FUNDAMENTO: A aterosclerose ocorre mais cedo em pacientes com diabetes mellitus tipo 1 (DM-1) e a doença arterial coronariana (DAC) constitui a mais importante causa de morte. OBJETIVO: Avaliar a prevalência e as características anatômicas da DAC em pacientes com DM-1 e insuficiência renal crônica, submetidos à diálise. MÉTODOS: Este é um estudo descritivo de 20 pacientes com DM-1 submetidos à diálise sem DAC conhecida. A DAC foi avaliada através de angiografia coronariana quantitativa (ACQ) e ultra-som intravascular (USIV). A ACQ foi realizada em todas as lesões >30 por cento, visualmente Todos os segmentos proximais de 18 mm das artérias coronárias foram analisados por USIV. Todos os outros segmentos coronarianos com estenose >30 por cento também foram analisados. RESULTADOS: A angiografia detectou 29 lesões >30 por cento em 15 pacientes (75 por cento). Onze (55 por cento) das lesões eram >50 por cento e 10 (50 por cento) >70 por cento. Treze pacientes tiveram as 3 principais artérias avaliadas pelo USIV. A aterosclerose estava presente em todos os pacientes e em todos os 51 segmentos proximais de 18 mm analisados. Esses segmentos significam que a medida do diâmetro dos vasos apresentava-se significantemente maior no USIV do que na ACQ, em todos os vasos. As imagens do ISIV de 25 (86,2 por cento) das 29 lesões >30 por cento foram obtidas. Placas fibróticas eram comuns (48 por cento) e 60 por cento apresentavam remodelamento intermediário de vasos. CONCLUSÃO: A DAC estava presente em todos os vasos de todos os pacientes com diabete tipo 1 submetidos a hemodiálise. Esses achados estão de acordo com outros estudos de autópsia, angiografia e USIV. Além disso, eles indicam a necessidade de estudos adicionais epidemiológicos e de imagem, para um melhor entendimento e tratamento de uma condição clínica complexa e grave que afeta jovens indivíduos.

BACKGROUND: In patients with type 1 diabetes mellitus, atherosclerosis occurs earlier in life and coronary artery disease (CAD) constitutes the major cause of death. OBJECTIVE: Evaluate the prevalence and anatomic characteristics of coronary artery disease (CAD) in type 1 diabetic patients with chronic renal failure undergoing hemodialysis. METHODS: This is a descriptive study of 20 patients with type 1 diabetes mellitus undergoing hemodialysis without known CAD. CAD was assessed by quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). QCA was performed in all lesions >30 percent, visually. All proximal 18-mm segments of the coronary arteries were analyzed by IVUS. All other coronary segments with stenosis >30 percent were also analyzed. RESULTS: Angiography detected 29 lesions >30 percent in 15 patients (75 percent). Eleven (55 percent) of the lesions were >50 percent and 10 (50 percent) >70 percent. Thirteen patients had all 3 major arteries interrogated by IVUS. Atherosclerosis was present in all patients and in all 51 proximal 18-mm segments analyzed. The mean vessel diameter of these segments was significantly larger at the IVUS than at the QCA, for all vessels. IVUS images of 25 (86.2 percent) of the 29 lesions >30 percent were obtained. Fibrotic plaques were common (48 percent) and 60 percent had intermediate vessel remodeling. CONCLUSION: CAD was present in all vessels of all type 1 diabetic patients undergoing hemodialysis. These findings are in agreement with other autopsy, angiography and IVUS studies. Additionally, they indicate the need for additional epidemiological and imaging studies to better understand and treat such a complex and serious clinical condition affecting young people.

FUNDAMENTO: La aterosclerosis ocurre más temprano en pacientes con diabetes mellitus tipo 1 (DM-1) y la enfermedad arterial coronaria (EAC) constituye la más importante causa de muerte. OBJETIVO: Evaluar la prevalencia y las características anatómicas de la EAC en pacientes con DM-1 e insuficiencia renal crónica, sometidos a diálisis. MÉTODOS: Este es un estudio descriptivo de 20 pacientes con DM-1 sometidos a diálisis sin EAC conocida. La EAC se evaluó mediante angiografía coronaria cuantitativa (ACC) y ultrasonido intravascular (IVUS). La ACC se realizó en todas las lesiones >30 por ciento, se llevó a cabo el análisis visual por IVUS en todos los segmentos proximales de 18 mm de las arterias coronarias. También se analizaron todos los otros segmentos coronarios con estenosis >30 por ciento. RESULTADOS: La angiografía detectó 29 lesiones >30 por ciento en 15 pacientes (75 por ciento). Once (55 por ciento) de las lesiones eran >50 por ciento y 10 (50 por ciento) >70 por ciento. Trece pacientes tuvieron las tres arterias principales evaluadas por el IVUS. La aterosclerosis estaba presente en todos los pacientes y en todos los 51 segmentos proximales de 18 mm analizados. Esos segmentos significan que la medición del diámetro de los vasos resultaba significantemente mayor en el IVUS que en la ACC, en todos los vasos. De las imágenes del IVUS se obtuvieron 25 (86,2 por ciento) de las 29 lesiones >30 por ciento. Placas fibróticas eran comunes (48 por ciento) y el 60 por ciento presentaban remodelamiento intermediario de vasos. CONCLUSIÓN: La EAC estaba presente en todos los vasos de todos los pacientes con diabetes tipo 1 sometidos a hemodiálisis. Esos hallazgos están de acuerdo con otros estudios de autopsia, angiografía e IVUS. Además de ello, indican la necesidad de estudios adicionales epidemiológicos y de imagen, para una mejor comprensión y tratamiento de una condición clínica compleja y severa que afecta a jóvenes individuos.

Neuropatia autonômica: uma complicação de alto risco no diabetes melito tipo 1: [revisão] / Autonomic neuropathy: a high risk complication for type 1 diabetes mellitus: [review]

O acometimento patológico do sistema nervoso no diabetes melito é muito amplo e, freqüentemente, bastante grave. A prevalência de neuropatia diabética atinge níveis elevados com a evolução temporal do diabetes, chegando, geralmente, a freqüências acima de 50 por cento de lesão neurológica em diferentes grupos de pacientes analisados em nosso meio e no exterior. A lesão neurológica nesta situação patológica é extensa no organismo humano diabético, envolvendo amplamente todo o sistema nervoso periférico nos seus componentes sensitivo-motor e autonômico: com clínica característica e concordante com as hipóteses patogênicas de natureza metabólica e/ou microvascular. O sistema nervoso autonômico é o elemento fundamental na regulação da função da maior parte dos sistemas ou órgãos no organismo, portanto, a sua lesão pode trazer importantes alterações para as funções cardiovascular, respiratória, digestiva, urinária e genital, podendo influir na função vital de alguns desses órgãos ou sistemas. Este artigo aborda as alterações decorrentes da lesão do sistema nervoso autonômico, especialmente nos pacientes diabéticos tipo 1, procurando dimensionar o risco de morbimortalidade.

The pathological alteration of the nervous system in diabetic patients is extensive and frequently severe. The prevalence of the diabetic neuropathy reach high levels with the evolution of the diabetes, often showing frequencies higher than 50 percent in several groups of patients. The neurological lesion in this pathological situation is extensive in the diabetic patient, including widely the peripheral nervous system with its components sensory, motor and autonomic: with typical symptoms and in accordance with the pathogenesis of metabolic origin and/or microvascular disease. The autonomic nervous system is a main regulator of many systems in the human body. Then its lesion can promote significant alterations in the function of the cardiovascular, respiratory, gastrointestinal, urogenital system, that can be related to increased motality. This review anlyses the abnormalities related to lesion of the autonomic nervous system, particularly in type 1 diabetic patients, trying to characterize the risk of morbidity and mortality.

Alterações das propriedades funcionais e estruturais de grandes artérias no diabetes mellitus / Modifications of structural and functional properties of large arteries in diabetes mellitus

Alterações funcionais e estruturais das grandes artérias exercem um importante papel na patogênese das doenças cardiovasculares. O diabetes mellitus, ao lado da hipertensão arterial e do envelhecimento, pode induzir essas alterações em diferentes territórios arteriais, e assim levar ao desenvolvimento de aterosclerose e suas conseqüências cardiovasculares. A principal alteração da função das grandes artérias é o aumento da rigidez, enquanto que a principal alteração estrutural é o maior espessamento da camada intima-media da artéria carótida, encontradas em ambos os tipos 1 e 2 de diabetes. Os mecanismos destas alterações estruturais e funcionais arteriais no diabetes incluem a resistência à insulina, o acúmulo de colágeno devido à glicação enzimática inadequada, disfunção endotelial e do sistema nervoso autônomo. O aumento de rigidez arterial é um marcador de risco cardiovascular em pacientes diabéticos, e o tratamento tanto do diabetes per se quanto de dislipidemia e hipertensão arterial associadas pode modificar beneficamente essas alterações arteriais.

Functional and structural modifications in large arteries play an important role in the pathogenesis of cardiovascular diseases. The diabetes mellitus besides arterial hypertension and ageing can induce these alterations in different arterial sites, and so leading to the development of atherosclerosis and its cardiovascular consequences. The main functional change of large arteries is an increase of stiffness, while the main structural modification is an increase of the intima-media thickness of carotid artery, and both changes have been recognized in both type 1 and type 2 diabetes. The mechanisms of these structural and functional arterial modifications in diabetes include insulin resistance, collagen increase due to inadequate enzymatic glycation, endothelial and autonomic dysfunction. The increase of arterial stiffness is an independent cardiovascular risk marker in diabetic patients, and the treatment of diabetes per se and even of associated dyslipidemia and arterial hypertension can favorably modify these arterial changes.

El endotelio: una encrucijada en las complicaciones vasculares de la diabetes en el anciano / The endothelium: an intersection in the vascular complications of diabetes in the elderly

Objetivo. Ofrecer una visión global de la relación existente entre la diabetes mellitus y la disfunción endotelial en ancianos, y cómo ésta es la base de las complicaciones vasculares. Desarrollo. La diabetes es una enfermedad de base endocrina pero con consecuencias y manifestaciones vasculares; en su producción y desarrollo concurren una serie de elementos implicados que podemos dividir en dos grupos: los tradicionales factores de riesgo asociados a la diabetes, entre los que debe incluirse el envejecimiento, y los que se deben a mecanismos fisiopatológicos de la enfermedad. El envejecimiento, proceso fisiológico, supone alteraciones importantes en la estructura y la función de las células endoteliales que crearán un entorno propicio para el inicio o la progresión de enfermedades vasculares. Sobre este terreno actuarán los principales mecanismos fisiopatológicos propios de la diabetes, entre los que cabe destacar la glicosilación no enzimática de proteínas, la vía de los radicales libres, la vía del sorbitol y el mioinositol y la vía de la proteincinasa C. De la interrelación de ambos factores (que comparten mecanismos de daño endotelial), junto con la coexistencia de otros factores de riesgo cardiovascular cuya consideración queda fuera del propósito de esta revisión, surgirá la disfunción endotelial, que producirá a lo largo del tiempo el daño vascular que se manifestará clínicamente. Conclusiones. La diabetes y el envejecimiento asocian factores que conducen a la disfunción endotelial, lo que suscita la cuestión del efecto de su coexistencia: si todo el daño ya está hecho como consecuencia del envejecimiento, la presencia de diabetes mellitus no añadirá nada. Si, a la inversa, los mecanismos de defensa están agotados por la senescencia, la agresión que supone la diabetes mellitus producirá un cuantioso daño vascular

AIMS. To offer a global vision of the relation that exists between diabetes mellitus and endothelial dysfunction in the elderly, and to show how this is the underlying cause accounting for the vascular complications that are observed. DEVELOPMENT. Diabetes is an endocrine-based diseased but with consequences and manifestations in the vascular system; its production and development involve a series of elements that can be divided into two groups: the traditional risk factors associated to diabetes, which must include aging, and those that are due to pathophysiological mechanisms of the disease. Aging, a physiological process, entails important alterations in the structure and function of endothelial cells that will create an environment that favours the onset or progression of vascular diseases. The main pathophysiological mechanisms typically found in diabetes, including the non-enzymatic glycosylation of proteins, the free-radical pathway, the sorbitol and myoinositol pathway, and the protein kinase C pathway, will act in this medium. The interaction of the two factors (which share endothelial damage mechanisms), together with the coexistence of other cardiovascular risk factors that fall beyond the scope of this review, will give rise to endothelial dysfunction, which, as time goes by, will produce vascular damage that will later become clinically apparent. CONCLUSIONS. Diabetes and aging associate factors that lead to endothelial dysfunction, which raises the question of the effect of their coexistence, that is, if all the damage is already done as a consequence of aging, the presence of diabetes mellitus will not add anything new. If, in contrast, the defence mechanisms are exhausted due to senescence, then diabetes mellitus will be a hard blow on the organism and produce extensive vascular damage

Correlación clínica, bioquímica e histopatológica en pacientes periodontales diabéticos / Clinical, biochemical and histopatological correlación in diabetic patients with periodontal disease

Introducción - El objetivo de este trabajo fue estudiar la correlación clínica, histológica y Bioquímica por efecto del raspaje y alisado radicular en pacientes diabéticos con enfermedad periodontal. Materiales y Métodos.- Se seleccionó una población total de 80 pacientes de ambos sexos (edad 25-60 años), 40 diabéticos 1 y 2, Y 40 no diabéticos. Se eligieron los s~etos compensados, según examen médico. Se examinó el terreno periodontal, seleccionándose pacientes con bolsas reales iguales o menores a 5 mm. Criterio de laboratorio: se consideraron diabéticos sujetos con glucemia igualo mayor a 140 mg.'dl, y HbAIC igual o mayor a 8 %. No diabéticos, los de glucemias inferiores a 115 mg.'dl, y HbAIC menor a 8 %. Previa administración de 2 g. de amoxicilina, se tomaron biopsias de encía libre e insertada a todos los pacientes,. Se realizó raspaje y alisado de todos los elementos dentarios, y se colocó protector periodontal. Se realizaron sesiones de higiene supervisada semanalmente. A los 40 Y 120 días se aplicaron nuevamente los criterios de selección clínicos y bioquímicos. Se tomaron biopsias, las que fueron analizadas microscópicamente. Se aplicaron las coloraciones HjE, PAS, y Tricrómico de Masson. Resultados.- Al tiempo 40, y principalmente 120 se encontró que en el 90 % de los pacientes seleccionados disminuyeron los valores de glucemia. En un 70 % de los casos estudiados se estabilizaron los valores de HbAIC, y se revirtieron los signos clínicos de enfermedad periodontal en un 80 % de los pacientes. El análisis histológico al tiempo demostró infiltrado mononuclear, congestión y proliferación de la capa media de los vasos, cuando se comparó con los controles no diabéticos. Al tiempo 40 y al 120, disminución del infiltrado y de los depósitos sensibles a Pas en las paredes de los pequeños vasos. Conclusión.- Se propone que el raspaje y alisado es un método eficaz para revertir los valores de glucemia, HbA 1 C, las microangiopatías gingivales y los signos clínicos en pacientes periodontales diabéticos.

Introduction - The aim of this paper was to study the clinical, biochemical and histopathological correlation caused by scaling and root planning in diabetic patients with periodonta1 disease. Material and Methods.- The study was conducted on 80 patients, both males and females, (age 25-60 years). Fourty patients had type 1 and type 2 diabetes, while 40 were non-diabetic patients. According to the medical examination, the subjects including in the study were well compensated. After studying the periodontal field, patients with real pockets measuring 5 mm or less were selected. Laboratory Criteria.- The subjects were considered to be diabetic when their basal…

Correlación clínica, bioquímica e histopatológica en pacientes periodontales diabéticos / Clinical, biochemical and histopatological correlación in diabetic patients with periodontal disease

Introducción - El objetivo de este trabajo fue estudiar la correlación clínica, histológica y Bioquímica por efecto del raspaje y alisado radicular en pacientes diabéticos con enfermedad periodontal. Materiales y Métodos.- Se seleccionó una población total de 80 pacientes de ambos sexos (edad 25-60 años), 40 diabéticos 1 y 2, Y 40 no diabéticos. Se eligieron los s~etos compensados, según examen médico. Se examinó el terreno periodontal, seleccionándose pacientes con bolsas reales iguales o menores a 5 mm. Criterio de laboratorio: se consideraron diabéticos sujetos con glucemia igualo mayor a 140 mg.dl, y HbAIC igual o mayor a 8 %. No diabéticos, los de glucemias inferiores a 115 mg.dl, y HbAIC menor a 8 %. Previa administración de 2 g. de amoxicilina, se tomaron biopsias de encía libre e insertada a todos los pacientes,. Se realizó raspaje y alisado de todos los elementos dentarios, y se colocó protector periodontal. Se realizaron sesiones de higiene supervisada semanalmente. A los 40 Y 120 días se aplicaron nuevamente los criterios de selección clínicos y bioquímicos. Se tomaron biopsias, las que fueron analizadas microscópicamente. Se aplicaron las coloraciones HjE, PAS, y Tricrómico de Masson. Resultados.- Al tiempo 40, y principalmente 120 se encontró que en el 90 % de los pacientes seleccionados disminuyeron los valores de glucemia. En un 70 % de los casos estudiados se estabilizaron los valores de HbAIC, y se revirtieron los signos clínicos de enfermedad periodontal en un 80 % de los pacientes. El análisis histológico al tiempo demostró infiltrado mononuclear, congestión y proliferación de la capa media de los vasos, cuando se comparó con los controles no diabéticos. Al tiempo 40 y al 120, disminución del infiltrado y de los depósitos sensibles a Pas en las paredes de los pequeños vasos. Conclusión.- Se propone que el raspaje y alisado es un método eficaz para revertir los valores de glucemia, HbA 1 C, las microangiopatías gingivales y los signos clínicos en pacientes periodontales diabéticos.(AU)

Introduction - The aim of this paper was to study the clinical, biochemical and histopathological correlation caused by scaling and root planning in diabetic patients with periodonta1 disease. Material and Methods.- The study was conducted on 80 patients, both males and females, (age 25-60 years). Fourty patients had type 1 and type 2 diabetes, while 40 were non-diabetic patients. According to the medical examination, the subjects including in the study were well compensated. After studying the periodontal field, patients with real pockets measuring 5 mm or less were selected. Laboratory Criteria.- The subjects were considered to be diabetic when their basalO(AU)