Interaction between haptoglobin genotype and glycemic variability on diabetic macroangiopathy: a population-based cross-sectional study.

PURPOSE: Haptoglobin (Hp) is a hemoglobin-binding protein that functions as an antioxidant in human plasma. It is reported that glycemic variability (GV) plays a key role in diabetes-related complications associated with impaired glucose metabolism and oxidative stress. Here we aim to investigate whether the effect of GV on diabetic macroangiopathy depends on Hp genotype in type 2 diabetes. METHODS: A number of 860 Chinese patients with type 2 diabetes was genotyped and assigned to two Hp subgroups (Hp 2-2 and Hp 1 carriers). Glycemic variability (GV) was assessed by using a retrospective continuous glucose monitoring system for three consecutive days, and it was measured using the glucose coefficient of variation (%CV), which is calculated as the ratio of glucose standard deviation to glucose mean. Clinical features, history of cardiac surgery, and vascular imaging tests were utilized to diagnose macroangiopathy. We evaluated the interaction between Hp genotypes and %CV on diabetic macroangiopathy. Furthermore, serum concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured using an enzyme-linked immunosorbent assay as a biomarker of oxidative stress. RESULTS: Serum 8-OHdG levels were positively correlated with %CV in Hp 1 carriers (r = 0.117; p = 0.021). Patients in the highest %CV tertile were associated with a higher prevalence of diabetic macroangiopathy than those in the lowest %CV tertile in Hp 1 carriers (OR = 2.461 [95% CI, 1.183-5.121], p = 0.016), but not in those with Hp 2-2 genotype (OR = 0.540 [95% CI, 0.245-1.191], p = 0.127). A significant interactive effect of Hp genotypes and %CV on diabetic macroangiopathy was found (p interaction = 0.008). CONCLUSION: Hp genotype modifies the effect of GV on diabetic macroangiopathy among Chinese patients with type 2 diabetes.

Clinical significance of skin autofluorescence for diabetic macroangiopathy and comparison with conventional markers of atherosclerosis: a cross-sectional and prospective study.

Background: Skin autofluorescence (SAF) is a marker for the accumulation of advanced glycation end products (AGEs), and is associated with diabetic macroangiopathy. However, whether SAF is superior to conventional markers of atherosclerosis such as carotid intima-media thickness (IMT) and pulse wave velocity (PWV) in detecting macroangiopathy remains unclear. Methods: We recruited 845 patients with type 2 diabetes enrolled in a community diabetes cohort (ViNA cohort) who had SAF, IMT, and PWV measured at baseline. The prevalence of macroangiopathy at baseline and new cardiovascular events during the 2-year follow-up period was investigated. SAF was measured using an AGE reader. Coronary artery calcification (CAC) was measured by computed tomography in 485 patients. Peripheral artery disease (PAD) was defined as the ankle-brachial blood pressure ratio of ≤ 0.9. Results: SAF, IMT, and PWV were significantly correlated with each other, and age, diabetes duration, and estimated glomerular filtration rate were their strong confounders. SAF was associated with baseline stroke and new stroke after adjusting for confounders, but not with coronary artery disease (CAD) or PAD. The nonsignificant relationship between SAF and CAD was consistent with the relationship between SAF and CAC. Multivariate analysis showed a significant association of SAF with baseline and new stroke independent of IMT and PWV. Maximum-IMT was significantly associated with baseline CAD, PAD, and stroke, but not with a new stroke, whereas PWV was associated with a new stroke. Conclusion: Among diabetic macroangiopathies, SAF is a good stroke biomarker, but not for CAD and PAD. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00608-8.

[Effect of Polygonati Rhizoma in improving pyroptosis injury of diabetic macroangiopathy via NLRP3/caspase-1/GSDMD pathway].

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1ß, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.

Effect of Polygonati Rhizoma in improving pyroptosis injury of diabetic macroangiopathy via NLRP3/caspase-1/GSDMD pathway / 中国中药杂志

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1β, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.

The effect of haptoglobin genotype on the association of asymmetric dimethylarginine and DDAH 1 polymorphism with diabetic macroangiopathy.

BACKGROUND: Dimethylarginine dimethylaminohydrolase (DDAH) 1 maintains the bioavailability of nitric oxide by degrading asymmetric dimethylarginine (ADMA). Here, we aimed to investigate the effect of haptoglobin (Hp) genotype on the association of ADMA and DDAH 1 polymorphism with diabetic macroangiopathy. METHODS: In stage 1, 90 Chinese participants with type 2 diabetes were enrolled to measure a panel of targeted metabolites, including ADMA, using tandem mass spectrometry (BIOCRATES AbsoluteIDQ™ p180 kit). In stage 2, an independent cohort of 2965 Chinese patients with type 2 diabetes was recruited to analyze the effect of Hp genotype on the association between DDAH 1 rs233109 and diabetic macroangiopathy. Hp genotypes were detected using a validated assay based on the TaqMan method. DDAH 1 rs233109 was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using the MassARRAY platform. RESULTS: In stage 1, serum ADMA levels correlated with common Hp genotypes (ß ± SE = - 0.049 ± 0.023, P = 0.035), but not with diabetic macroangiopathy (P = 0.316). In stage 2, the distribution of DDAH 1 rs233109 genotype frequencies was 15% (CC), 47% (TC), and 38% (TT), which was in Hardy-Weinberg equilibrium (P = 0.948). A significant Hp genotype by rs 233109 genotype interaction effect on diabetic macroangiopathy was found (P = 0.017). After adjusting for confounders, patients homozygous for rs233109 CC were more likely to develop diabetic macroangiopathy than those carrying TT homozygotes in the Hp 2-2 subgroup [odds ratio = 1.750 (95% confidence interval, 1.101-2.783), P = 0.018]. CONCLUSION: Hp genotype affects the association between DDAH 1 rs233109 and diabetic macroangiopathy in Chinese patients with type 2 diabetes.

Macro and microangiopathy related to retinopathy and choroidopathy in type 2 diabetes.

PURPOSE: To describe the relationship between diabetic retinopathy (DR) and choroidal thickness (CT), and systemic macro and microangiopathy in patients with type 2 diabetes (T2D). METHODS: Cross-sectional study enrolling 200 eyes (100 T2D naïve patients) without macular edema. DR was graded and swept-source optical coherence tomography Triton DRI (Topcon) was used to measure CT, which gave automatic measurements in ETDRS grid. An endocrinologist examined all the patients and searched in their medical records for data about macro and microangiopathy: ischemic cardiopathy (IC), cerebrovascular accident (CVA), peripheral artery disease (PAD), nephropathy, and peripheral polyneuropathy (PPN). RESULTS: Mean age was 67.38 ± 8.15 years, mean axial length was 23.26 ± 0.09 mm, and mean IOP was 16.75 ± 3.06 mmHg. Sixty eyes had no DR, 46 had mild, 64 had moderate, 20 had severe, and 10 had proliferative DR. IC was correlated with horizontal choroidal zones (p < 0.05 and η between 0.16 and 0.21) but not with DR (p = 0.16). CVA was neither correlated with CT (p > 0.05) nor with DR (p = 0.39). PAD was not correlated with CT (p > 0.05) but it was with DR (p = 0.03). The type of nephropathy was correlated both with CT in vertical sectors (p < 0.05 and η between 0.15 and 0.27) and DR (p = 0.01, τ = 0.24). PPN was not correlated with CT (p > 0.05) but it was with DR (p = 0.03). CONCLUSIONS: DR is correlated with microangiopathy (nephropathy and PPN) but not with macroangiopathy (IC, CVA, and PAD). CT is mildly correlated with nephropathy and IC. Some choroidal regions are more sensitive than others to each diabetic macro and microvascular manifestation.

Pathogenesis and Treatment of Diabetic Macroangiopathy Based on Theory of Hidden Pathogen Damaging Collaterals / 中国实验方剂学杂志

The basic pathological change of diabetic macroangiopathy is atherosclerosis， and the metabolism legacy effect of hyperglycemia will cause continuous damage to the large vessels. Oxidative stress is a common mechanism for diabetes and its chronic complications and it is also the basis of the metabolism legacy effect which keeps damaging the large vessels. Anti-oxidant therapy can delay the course of diabetic macroangiopathy. According to the theory of traditional Chinese medicine （TCM）， the pathogenicity of hidden pathogen is concealing， lingering， and refractory. On the basis of the syndrome and treatment of collateral diseases， vessel-collateral theory， and hidden pathogen theory of TCM， the pathological changes of diabetic macroangiopathy are summarized as pathogen concealment-accumulation of sugar and lipids leading to phlegm and blood stasis-accumulation of toxins-damage to vessels and collaterals-hardening vessels. The core pathogenesis is the hidden pathogen damaging the collaterals， and the basic pathological change is vessel hardening. The toxins of sugar， lipid， phlegm， and stasis are the pathological products and the key to be treated. According to this theory， the medicinal materials with the functions of activating blood to dredging collaterals， resolving phlegm to clearing collaterals， Promoting qi to unblocking collaterals and removing toxins to shunting collaterals can be selected for prescription. These medicinal materials can inhibit the generation of reactive oxygen species， affect the oxidase activity， and enhance the antioxidant capacity， thereby regulating the oxidative stress response， protecting the vascular endothelial function， reducing the damage of the large blood vessels， and slowing down the progression of the disease. Such therapy is of great significance in clinical practice and research， providing a new idea for the prevention and treatment of diabetic macroangiopathy.

Influence of Endothelial Dysfunction on Diabetic Macroangiopathy： A Perspective from Theory of "Restraining Excessiveness to Acquire Harmony" / 中国实验方剂学杂志

The normal function of vascular endothelial cells is an important foundation for maintaining vascular permeability， restricting inflammatory activities of the vascular wall， and balancing the coagulation and fibrinolytic system. Endothelial dysfunction caused by persistent damage from pathological factors is considered as an early and prominent event of diabetic macroangiopathy. In traditional Chinese medicine， the classical theory of "restraining excessiveness to acquire harmony" was originally a condensed generalization of the rule of generation， restriction， replacement and evolution in the natural world， revealing the internal regulation mechanism of the stable operation of things. Then it gradually evolved into an important rule to explain the physiological phenomena and pathological mechanism of human body and guide the treatment. Corresponding to the nature， the body homeostasis also requires to achieve a state of strong viscera function and inexhaustible Qi and blood generation under the rule of restriction and generation. The pathogenesis of diabetic macroangiopathy is the process of "the predominant one failing to restrict and the hyperactive one becoming harmful". The loss of restriction and generation of the five organs leads to powerless Qi transformation and， as a result， the Qi， blood and body fluid cannot be dispersed. Therefore， the Qi， blood and body fluid turn into phlegm and blood stasis， such as glucose and lipid metabolism disorder， oxidative stress， inflammatory response and high blood viscosity， and finally block the veins. Excessive phlegm and blood stasis cannot be resolved， instead they become harmful and invade the blood vessel， causing endothelial dysfunction and further resulting in diabetic macroangiopathy. Under the guidance of the theory of "restraining excessiveness to acquire harmony"， the method of "harmonizing viscera， eliminating pathogen and removing turbidity" can effectively regulate the function of vascular endothelial cells， thus playing a positive role in preventing and treating diabetic macroangiopathy. The mechanism may be related to reducing oxidative stress， inhibiting inflammation， limiting vascular smooth muscle proliferation， and reducing platelet adhesion.

Profilin-1 is involved in macroangiopathy induced by advanced glycation end products via vascular remodeling and inflammation.

BACKGROUND: The accumulation of advanced glycation end products (AGEs) have been implicated in the development and progression of diabetic vasculopathy. However, the role of profilin-1 as a multifunctional actin-binding protein in AGEs-induced atherosclerosis (AS) is largely unknown. AIM: To explore the potential role of profilin-1 in the pathogenesis of AS induced by AGEs, particularly in relation to the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) signaling pathway. METHODS: Eighty-nine individuals undergoing coronary angiography were enrolled in the study. Plasma cytokine levels were detected using ELISA kits. Rat aortic vascular smooth muscle cells (RASMCs) were incubated with different compounds for different times. Cell proliferation was determined by performing the MTT assay and EdU staining. An AGEs-induced vascular remodeling model was established in rats and histological and immunohistochemical analyses were performed. The mRNA and protein levels were detected using real-time PCR and Western blot analysis, respectively. In vivo, shRNA transfection was performed to verify the role of profilin-1 in AGEs-induced proatherogenic mediator release and aortic remodeling. Statistical analyses were performed using SPSS 22.0 software. RESULTS: Compared with the control group, plasma levels of profilin-1 and receptor for AGEs (RAGE) were significantly increased in patients with coronary artery disease, especially in those complicated with diabetes mellitus (P < 0.01). The levels of profilin-1 were positively correlated with the levels of RAGE (P < 0.01); additionally, the levels of both molecules were positively associated with the degree of coronary artery stenosis (P < 0.01). In vivo, tail vein injections of AGEs induced the release of proatherogenic mediators, such as asymmetric dimethylarginine, intercellular adhesion molecule-1, and the N-terminus of procollagen III peptide, concomitant with apparent aortic morphological changes and significantly upregulated expression of the profilin-1 mRNA and protein in the thoracic aorta (P < 0.05 or P < 0.01). Downregulation of profilin-1 expression with an shRNA significantly attenuated AGEs-induced proatherogenic mediator release (P < 0.05) and aortic remodeling. In vitro, incubation of vascular smooth muscle cells (VSMCs) with AGEs significantly promoted cell proliferation and upregulated the expression of the profilin-1 mRNA and protein (P < 0.05). AGEs (200 µg/mL, 24 h) significantly upregulated the expression of the STAT3 mRNA and protein and JAK2 protein, which was blocked by a JAK2 inhibitor (T3042-1) and/or STAT3 inhibitor (T6308-1) (P < 0.05). In addition, pretreatment with T3042-1 or T6308-1 significantly inhibited AGEs-induced RASMC proliferation (P < 0.05). CONCLUSION: AGEs induce proatherogenic events such as VSMC proliferation, proatherogenic mediator release, and vascular remodeling, changes that can be attenuated by silencing profilin-1 expression. These results suggest a crucial role for profilin-1 in AGEs-induced vasculopathy.

Pesquisa de enfermedad arterial periférica de miembros inferiores en personas mayores de 50 años / Investigation of lower limb peripheral artery disease in people over the age of 50

Introducción: La enfermedad arterial periférica de miembros inferiores se considera un problema de salud por presentar elevadas tasas de morbi-mortalidad y de amputaciones no traumáticas. En ocasiones se desconoce su presencia en los adultos de la población general. Objetivo: Evaluar mediante pesquiza la presencia de la enfermedad arterial periférica de miembros inferiores en personas mayores de 50 años de la población. Métodos: Estudio descriptivo y analítico en 235 personas mayores de 50 años de diferentes municipios de la capital. El diagnóstico de la enfermedad arterial se realizó por examen físico y estudio hemodinámico. Se analizaron variables sociodemográficas y algunos factores de riego cardiovasculares. Se trabajó con un nivel de confiabilidad del 95 por ciento. Resultados: Predominaron el sexo femenino (68,1 por ciento), la piel blanca (53,2 por ciento) y el grupo etáreo entre 50 y 69 años (68,1 por ciento). Hubo mayor frecuencia de la enfermedad en el sexo masculino (70,5 por ciento). El 55,7 por ciento presentó macroangiopatía diabética. Las prevalencias encontradas para la enfermedad arterial periférica y para los factores de riesgo fueron de 51,9 por ciento y de 91,5 por ciento, respectivamente. El 64,7 por ciento de las personas presentaban tres o más factores. La hipertensión (χ 2 = 23,66; p = 0,0000; OR: 3,88) y la obesidad (χ 2 = 8,74; p < 0,001; OR: 1,38) estuvieron asociadas con la enfermedad arterial periférica. Conclusiones: Las personas mayores de 50 años de edad, del sexo masculino y con más de tres factores de riesgo tienen un riesgo elevado de presentar una enfermedad arterial periférica de miembros inferiores(AU)

Introduction: Lower limb peripheral artery disease is considered a health problem because it has high rates of morbidity-mortality and non-traumatic amputations. Its presence in adults in the general population is sometimes unknown. Objective: Assess by investigation the presence of peripheral artery disease of lower limbs in people of the population over 50 years. Methods: Descriptive and analytical study in 235 people over 50 years from different municipalities of the capital. The diagnosis of arterial disease was made by physical examination and hemodynamic study. Sociodemographic variables and some cardiovascular risk factors were analyzed. The reliability level was of 95 percent. Results: Female sex (68.1 percent), white skin (53.2 percent) and the age group between 50 and 69 years (68.1 percent) predominated. There was a higher frequency of the disease in the male sex (70.5 percent). 55.7 percent had diabetic macroangiopathy. The prevalences found for peripheral artery disease and risk factors were 51.9 percent and 91.5 percent, respectively. 64.7 percent of people had three or more factors. Hypertension (χ 2 = 23.66; p = 0.0000; OR: 3.88) and obesity (χ 2 = 8,74; p < 0,001; OR: 1,38) were associated with peripheral artery disease. Conclusions: People over 50 years of age, males and with more than three risk factors have a high risk of developing peripheral lower limb artery disease(AU)

Correlation analysis of epicardial adipose tissue thickness, C-reactive protein, interleukin-6, visfatin, juxtaposed with another zinc finger protein 1, and type 2 diabetic macroangiopathy.

BACKGROUND: To investigate the correlation between the thickness of epicardial adipose tissue (EAT), C-reactive protein (CRP), interleukin (IL) -6, visfatin, juxtaposed with another zinc finger protein 1 (JAZF1) and type 2 diabetic mellitus (T2DM) macroangiopathy. METHODS: The study enrolled 82 patients with T2DM with macroangiopathy (the Complication Group), and 85 patients with T2DM (the Diabetes Group) who were admitted to Shandong Provincial Third Hospital from February 2018 to February 2020. In addition, 90 healthy people who underwent physical examination at the same hospital during the same period were enrolled (the Healthy Control Group). Age, gender, height, weight, waist circumference (WC), hip circumference (HC), diabetic course and therapeutic drugs, waist hip ratio (WHR), and body mass index (BMI) were recorded and calculated. RESULTS: The baseline characteristics of the three groups were comparable, and the diabetic course of the Complication Group and the Diabetes Group was not significantly different (P > 0.05). The WHR of the Complication Group was higher than that of the Diabetes Group and the Healthy Control Group, with statistical significance (P < 0.05). The FPG, 2hPG, HbA1C, CRP, IL-6, Visfatin, JAZF1, HOMA-IR, EAT thickness, and baPWV of the Complication Group were all higher than those of the Diabetes Group and the Healthy Control Group (P < 0.05, respectively). The JAZF1 and FIns of the Complication Group and Diabetes Group were lower than those of the Healthy Control Group, and JAZF1 of the Complication Group was lower than the Diabetes Group with statistical significance (P<0.05, respectively). Pearson correlation analysis showed that the EAT thickness was positively correlated with CRP, IL-6, visfatin, and JAZF1 (r = 0.387, 0.451, 0.283, 0.301, respectively, all P<0.001). Pearson correlation analysis showed that baPWV was positively correlated with EAT thickness, CRP, IL-6, visfatin, and JAZF1 (r = 0.293, 0.382, 0.473, 0.286, respectively, all P < 0.001). Multivariate stepwise regression analysis showed that FPG, 2hPG, HbA1C, CRP, IL-6, visfatin, JAZF1, and EAT thickness were independent risk factors that affected T2DM macroangiopathy. CONCLUSIONS: Clinical monitoring and treatment of T2DM macroangiopathy can use CRP, IL-6, Visfatin, JAZF1, and EAT thickness as new targets to delay the progression of the disease. Further research on the relationship between the above factors and the pathogenesis of T2DM macroangiopathy may be helpful provide new treatment strategies.

Radix pseudostellariae of Danzhi Jiangtang capsule relieves oxidative stress of vascular endothelium in diabetic macroangiopathy.

AIM: Medicinal plants act as an alternative source of anti-diabetic agents. Recently, Danzhi Jiangtang capsule (DJC) has been clinically used for treatment of diabetes, but the effect of DJC on diabetic macroangiopathy remained unclear. The present study investigates the therapeutic role of DJC in diabetic macroangiopathy and elucidates the underlying mechanisms. METHODS: Diabetes patients were treated with DJC for 20 weeks. Blood glucose and serum parameters (insulin, FFA, SOD, GSH-Px, MDA, NO) were determined before and after treatment. Streptozotocin -induced diabetic rat model and human HUVECs cells were applied to assess the anti-oxidative capacity of DJC and its bioactive constituents. The expression levels of eNOS, JNK, GRP78, CHOP, Bcl2, and BAX were measured by qPCR and/or immunoblotting. RESULTS: Diabetic macroangiopathy were ameliorated by DJC administration. Radix pseudostellariae (RP) mediated the anti-oxidative stress capacity of DJC, which improved insulin resistance (p < 0.01) and relieved oxidative stress (p < 0.01) of vascular endothelium through oxidative stress signaling and apoptosis pathway. The ability of DJC to ameliorate diabetic macroangiopathy and relieve oxidative stress was mainly mediated by its bioactive constituent RP. CONCLUSION: This study would provide experimental evidence for DJC in the prevention and treatment of diabetes and diabetic macroangiopathy.

Allicin alleviates inflammation of diabetic macroangiopathy via the Nrf2 and NF-kB pathway.

As diabetic macroangiopathy is becoming increasingly prevalent, it is urgent to explore preventive and therapeutic drugs and study the mechanism. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ)for five consecutive days. Diabetic mice were divided into diabetic and allicin groups. After sacrifice, frozen aortic root sections were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2) and inflammation cytokine-tumor necrosis factor α (TNF-α), and the remaining aortic tissues were analyzed by Western blot for the expression of proinflammation genes. In vitro, Nrf2 and inflammatory relative protein expression levels in Human Umbilical Vein Endothelial Cells (HUVECs) were examined. HUVECs proliferation and apoptosis were measured. TNF-α expression was increased in diabetic group compared to that in control group; this effect was alleviated in allicin-treated mice. Inflammation relative protein expression of Vascular Cell Adhesion Molecule 1(VCAM-1), Matrix metalloproteinase 2 (MMP-2), Inducible Nitric Oxide Synthase (iNOS), and monocyte chemotactic protein 1 (MCP-1) was higher in the diabetic group than in the control group; however, allicin treatment inhibited these diabetes-induced increase. In vitro, allicin treatment reversed the hyperglycemia-induced reduction in proliferation, and decreased the apoptosis induced by high glucose. Inflammation relative protein expression was consistent with that in vivo. Additionally, the expression of nuclear factor kappa-B (NF-κB)and Nrf2 was increased in both DM mice and HUVECs; allicin treatment induced a significant reduction in NF-κB level and improvement in Nrf2 level. Allicin alleviates inflammation caused by diabetic macroangiopathy, and the mechanism may occur via increasing Nrf2 and decreasing NF-κB.

Comments from the Editor of the Special Issue "Clinical Research on Diabetic Complications".

With this Editorial, we are hereby presenting to the reader the Special Issue on "Clinical Research on Diabetic Complications". Chronic complications of diabetes mellitus have a major impact on the life of subjects with the disease, resulting in decreased quality of life and increased morbidity and mortality. This Special Issue includes contributions addressing different clinical aspects of the natural history, prevention and prediction, and characterization and management of diabetes-related complications.

Efectividad de la cirugía arterial en pacientes diabéticos en un período de cinco años / Effectiveness of arterial surgery in diabetic patients over a period of five years

Introducción: La macroangiopatía diabética constituye un serio problema para los pacientes que la portan y la cirugía revascularizadora constituye una alternativa de tratamiento. Objetivo: Demostrar la efectividad de las cirugías arteriales realizadas en pacientes diabéticos en un período de cinco años. Métodos: Estudio descriptivo, retrospectivo, en 71 historias clínicas de pacientes portadores de macroangiopatía diabética que recibieron cirugía arterial en el Instituto Nacional de Angiología y Cirugía Vascular (enero/2011- diciembre/2015). Se analizaron las variables: edad, género, color de la piel, supervivencia de la extremidad, estado de permeabilidad de los injertos y frecuencia de fallecimientos, que en su conjunto medirán la efectividad de la cirugía. Resultados: Hubo un incremento lineal de las cirugías revascularizadoras. La edad media fue de 64,5 ± 9,7 años, con un 67,6 por ciento de mayores de 60 años y más del 60 por ciento eran hombres. El 52,9 por ciento tenía piel blanca, el 80,3 por ciento tuvo grado 4 según Fontaine y el 66,2 por ciento tenía oclusión arterial severa. En más del 90 por ciento se realizó cirugía derivativa o endarterectomía, el 87,3 por ciento tuvo afectado el sector infrainguinal y en el 64,8 por ciento sobrevivió la extremidad. No se registraron muertes perioperatorias ni fallecidos a los seis meses. El 63 por ciento de las cirugías fueron permeables a los seis meses. Conclusiones: Las cirugías arteriales son efectivas pues la mayoría de los pacientes mantienen la extremidad afectada y no se registran fallecimientos perioperatorios ni a los seis meses de evaluación, además, la mayor cantidad de injertos resultaron ser permeables en ese tiempo(AU)

Introduction: Diabetic macroangiopathy is a serious problem for patients who suffer it; and revascularization surgery is an alternative to its treatment. Objective: To show the effectiveness of arterial surgeries performed in diabetic patients over a period of five years. Methods: Descriptive, retrospective study in 71 clinical records of patients with diabetic macroangiopathy who received arterial surgery at the National Institute of Angiology and Vascular Surgery (January / 2011- December / 2015). The variables analyzed were: age, gender, skin color, survival of the limb, state of permeability of the grafts and frequency of deaths, which as a whole will measure the effectiveness of the surgery. Results: There was a linear increase in revascularization surgeries. The mean age was 64.5 ± 9.7 years, with 67. 6 percent of people over 60 years old, and more than 60 percent were men. 52.9 percent had white skin, 80.3 percent had grade 4 according to Fontaine and 66.2 percent had severe arterial occlusion. In more than 90 percent, derivative surgery or endarterectomy was performed; 87.3 percent had affectations in the infrainguinal sector and in 64.8 percent the limb survived. There were no perioperative deaths or deaths at six months. 63 percent of the surgeries were permeable at six months. Conclusions: Arterial surgeries were effective because the majority of patients maintained the affected limb and there were no perioperative deaths neither at the six months evaluation; in addition, most of the grafts were permeable in that time(AU)

[Diabetic macroangiopathy].

Diabetes mellitus represents a significant medico - social problem for health care around the world. The main reason for an invalidism and a mortality of patients with diabetes mellitus are the lesions of heart and vessels united in the concept "diabetic macroangiopathty". This complication is often taped already at the time of diagnosis of a diabetes mellitus and demands active treatment.

The Associations between Paraoxonase 1 L55M/Q192R Genetic Polymorphisms and the Susceptibilities of Diabetic Macroangiopathy and Diabetic Microangiopathy: A Meta-Analysis.

INTRODUCTION: Plenty of studies have focused on the associations of paraoxonase 1 Q192R and L55M genetic polymorphisms with diabetic macroangiopathy and microangiopathy susceptibility, but these associations remain controversial. Therefore, this meta-analysis was conducted to demonstrate these relationships. METHODS: Relevant studies published in English or Chinese were identified in PubMed, Embase, Wanfang Database, and CNKI by applying specific inclusion and exclusion criteria. Statistical analyses were performed using the STATA 12.0 statistical software. RESULTS: 25 Case-control studies were included in the meta-analyses: six on the association between paraoxonase 1 L55M genetic polymorphism and diabetic macroangiopathy risk, nine on the association between L55M and diabetic microangiopathy risk, 12 on the association between Q192R and diabetic macroangiopathy risk, and 12 on the association between Q192R and diabetic microangiopathy risk. Paraoxonase 1 L55M genetic polymorphism was significantly associated with diabetic microangiopathy susceptibility in the dominant model [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.33-0.83, P = 0.006], the homozygous model (OR 0.37, 95% CI 0.16-0.86, P = 0.021), the allelic contrast model (OR 0.62, 95% CI 0.43-0.90, P = 0.011), the recessive model (OR 12.04, 95% CI 8.02-18.06, P = 0.000), and the heterozygous model (OR 0.57, 95% CI 0.38-0.85, P = 0.006), but L55M was not significantly associated with macroangiopathy susceptibility. Paraoxonase 1 Q192R genetic polymorphism was significantly associated with diabetic macroangiopathy susceptibility in the homozygous model (OR 1.88, 95% CI 1.06-3.32, P = 0.030), the allelic contrast model (OR 1.31, 95% CI 1.02-1.69, P = 0.038), and the recessive model (OR 1.55, 95% CI 1.11-2.16, P = 0.010), but not in the dominant and heterozygous models. Meanwhile, there was no significant association between paraoxonase 1 Q192R genetic polymorphism and diabetic microangiopathy susceptibility. CONCLUSION: Paraoxonase 1 L55M and Q192R genetic polymorphisms play important roles in diabetic macroangiopathy and microangiopathy susceptibility. Further well-designed studies based on large samples are needed to confirm these results.

Enfermedades vasculares periféricas y niveles de calidad de vida en el municipio Diez de Octubre / Peripheral vascular diseases and levels of quality of life in 10 of October municipality

Objetivo: Determinar la prevalencia de las enfermedades vasculares periféricas y los niveles de calidad de vida en el municipio "Diez de Octubre". Métodos: Estudio descriptivo en una muestra aleatorizada (n= 200) de los 201 586 habitantes del municipio. El diagnóstico de las enfermedades vasculares periféricas se realizó por examen físico-vascular confirmado por estudios hemodinámico, ultrasonográfico, y ecográfico. Se aplicó el cuestionario de "Calidad de vida" SF-36 a los mayores de 18 años sin discapacidad mental. Resultados: La tasa de enfermedades vasculares periféricas fue de 66 por 100 000 habitantes debida a las flebopatías (59,5 por ciento), la macroangiopatia diabética (13,9 por ciento), la enfermedad arterial periférica (8,4 por ciento) y la cerebrovascular (6,4 por ciento). Los factores de riesgo más frecuentes fueron: obesidad (48,5 por ciento), hipertensión arterial (37,5 por ciento) y tabaquismo (33,5 por ciento). Hubo un incremento de enfermedades vasculares periféricas a partir de los 50 años con la presencia de dos o más enfermedades en el 37,3 por ciento. De las personas. En aquellas con enfermedad vascular se encontró una disminución (p < 0,05) en todas las escalas de la calidad de vida con un deterioro en la medida sumaria "salud física", la que se encontró asociada a su presencia (χ2 = 27,11; p = 0,001). Conclusiones: En el municipio Diez de Octubre, hay una elevada tasa de enfermedades vasculares periféricas con un deterioro importante en los niveles de calidad de vida de las personas que la padecen(AU)

Objective: To determine the prevalence of peripheral vascular diseases and the levels of quality of life in 10 of October municipality. Methods: A descriptive study was conducted on a random sample (n=200) from 201 586 inhabitants of the municipality. The diagnosis of peripheral vascular diseases was performed by physical-vascular examination confirmed by hemodynamic, ultrasound, and echo-Doppler studies. The "Quality of life" questionnaire SF-36 was applied to people older than 18 years without mental disabilities. Results: The rate of peripheral vascular disease was 66 per 100 000 inhabitants due to phlebopathies (59.5 percent), diabetic macroangiopathy (13.9 percent), peripheral arterial disease (8.4 percent) and cerebrovascular disease (6.4percent). The most frequent risk factors were obesity (48.5 percent), hypertension (37.5 percent) and smoking (33.5 percent). There was an increase in peripheral vascular diseases after the age of 50 years with two or more types of diseases in 37.3 percent of the population. A decrease (p <0.05) in all the quality of life scales, with deterioration in the disease-related summary measure "physical health", was found in people with vascular disorders (χ2= 27.11; p= 0.001). Conclusions: In 10 of October municipality, there is a high rate of peripheral vascular diseases with a significant deterioration of the quality of life of people who suffer them(AU)

Resultados y reacciones adversas en pacientes tratados con Heberprot-P® en la comunidad / Results and adverse reactions observed in patients treated with Heberprot-P in the community setting

Introducción: La diabetes mellitus es considerada una epidemia en estos momentos a nivel mundial. Al aumentar la prevalencia de esta enfermedad aumenta la de pie diabético con sus respectivas lesiones. Objetivos: Determinar los resultados y reacciones adversas en pacientes tratados Heberprot-P® en la comunidad. Método: Estudio prospectivo en 17 pacientes con distintas lesiones de pie diabético atendidos en un área de salud entre enero de 2012 y abril de 2013. A todos se les aplicó, de forma ambulatoria, Heberprot-P® (factor de crecimiento epidérmico recombinante humano) hasta la granulación total de las lesiones. Resultados: El 52,94 por ciento de los pacientes tenían pie diabético grado 4 según la clasificación de Wagner. El 100 por ciento de los enfermos mostraron resultados satisfactorios. Las reacciones adversas se presentaron en seis ocasiones y en tres pacientes. Conclusiones: Se alcanzaron buenos resultados con el uso del Heberprot-P® considerados por las pocas reacciones adversas y la ausencia de amputación sobre todo en los pacientes diabéticos con úlceras del pie grado 4 de Wagner. El Heberprot-P® constituye un medicamento a tener en cuenta en la curación de las úlceras del pie diabético con la ventaja de que puede utilizarse de forma ambulatoria(AU)

Introduction: Diabetes mellitus is currently considered as an epidemic worldwide. With the rise of the prevalence of this disease, that of the diabetic foot with its different lesions increases too. Objectives: To determine the results and the adverse reactions in patients treated with Heberprot-P® in the community setting. Method: Prospective study of 17 patients with various diabetic foot lesions, who were seen in a health area from January 2012 to April 2013. They all received an outpatient treatment with Heberprot-P® (human recombinant epidermal growth factor) until complete granulation of lesions. Results: In the group, 52.94 percent of patients had grade 4 diabetic feet according to Wagner´s classification scale. All the treated patients showed satisfactory results and adverse reactions occurred six times in three patients. Conclusions: Good results are achieved with the use of Heberprot-P® due to few adverse reactions and absence of amputation, mainly in diabetics with grade 4-foot ulcers in Wagner´s classification scale. This is a drug to be taken into consideration for curing diabetic foot ulcers since it can also be used in outpatient treatment(AU)

Resultados y reacciones adversas en pacientes tratados con Heberprot-P® en la comunidad / Results and adverse reactions observed in patients treated with Heberprot-P in the community setting

Introducción: La diabetes mellitus es considerada una epidemia en estos momentos a nivel mundial. Al aumentar la prevalencia de esta enfermedad aumenta la de pie diabético con sus respectivas lesiones.Objetivos: Determinar los resultados y reacciones adversas en pacientes tratados Heberprot-P® en la comunidad.Método: Estudio prospectivo en 17 pacientes con distintas lesiones de pie diabético atendidos en un área de salud entre enero de 2012 y abril de 2013. A todos se les aplicó, de forma ambulatoria, Heberprot-P® (factor de crecimiento epidérmico recombinante humano) hasta la granulación total de las lesiones.Resultados: El 52,94 por ciento de los pacientes tenían pie diabético grado 4 según la clasificación de Wagner. El 100 por ciento de los enfermos mostraron resultados satisfactorios. Las reacciones adversas se presentaron en seis ocasiones y en tres pacientes.Conclusiones: Se alcanzaron buenos resultados con el uso del Heberprot-P® considerados por las pocas reacciones adversas y la ausencia de amputación sobre todo en los pacientes diabéticos con úlceras del pie grado 4 de Wagner. El Heberprot-P® constituye un medicamento a tener en cuenta en la curación de las úlceras del pie diabético con la ventaja de que puede utilizarse de forma ambulatoria(AU)

Introduction: Diabetes mellitus is currently considered as an epidemic worldwide. With the rise of the prevalence of this disease, that of the diabetic foot with its different lesions increases too.Objectives: To determine the results and the adverse reactions in patients treated with Heberprot-P® in the community setting.Method: Prospective study of 17 patients with various diabetic foot lesions, who were seen in a health area from January 2012 to April 2013. They all received an outpatient treatment with Heberprot-P® (human recombinant epidermal growth factor) until complete granulation of lesions.Results: In the group, 52.94 percent of patients had grade 4 diabetic feet according to Wagner´s classification scale. All the treated patients showed satisfactory results and adverse reactions occurred six times in three patients.Conclusions: Good results are achieved with the use of Heberprot-P® due to few adverse reactions and absence of amputation, mainly in diabetics with grade 4-foot ulcers in Wagner´s classification scale. This is a drug to be taken into consideration for curing diabetic foot ulcers since it can also be used in outpatient treatment(AU)