Does the advantage of transcutaneous oximetry measurements in diabetic foot ulcer apply equally to free flap reconstruction?

BACKGROUND: Transcutaneous oxygen pressure (TcpO2) is a precise method for determining oxygen perfusion in wounded tissues. The device uses either electrochemical or optical sensors. AIM: To evaluate the usefulness of TcpO2 measurements on free flaps (FFs) in diabetic foot ulcers (DFUs). METHODS: TcpO2 was measured in 17 patients with DFUs who underwent anterolateral thigh (ALT)-FF surgery and compared with 30 patients with DFU without FF surgery. RESULTS: Significant differences were observed in the ankle-brachial index; duration of diabetes; and haemoglobin, creatinine, and C-reactive protein levels between the two groups. TcpO2 values were similar between two groups except on postoperative days 30 and 60 when the values in the ALT-FF group remained < 30 mmHg and did not increase > 50 mmHg. CONCLUSION: Even if the flap is clinically stable, sympathectomy due to adventitia stripping during anastomosis and arteriovenous shunt progression due to diabetic polyneuropathy could lead to low TcpO2 values in the ALT-FF owing to its thick fat tissues, which is supported by the slow recovery of the sympathetic tone following FF. Therefore, TcpO2 measurements in patients with DFU who underwent FF reconstruction may be less accurate than in those who did not.

Association between PON1-rs662 Gene Polymorphism and Diabetic Retinopathy in Population of the Qom, Iran.

Background: Diabetic retinopathy is the most severe diabetic microvascular complication that causes changes in the vessel wall. One of the genes involved in this disease is PON1, which encodes paraoxanase1 protein in liver and kidney. It might regulate inflammatory and microvascular responses to the disease. The rs662 T>C is one of the single nucleotide polymorphisms of this gene that changes glutamine to arginine at position 192. Methods: In this study, 300 samples were collected, including 100 healthy and 100 diabetics without retinopathy, and 100 diabetics retinopathies were studied and their age range was from 30 to 80 years. Then 2.5 ml of blood was collected from all relevant individuals in tubes containing EDTANa2. This polymorphism was examined by tetra-ARMS PCR. Results: Results showed that there is no significant correlation between genotypes and alleles related to PON1 and Diabetes (CC genotype: p=0.609; C allele: p=0.228). On the other hand, an association was observed between PON1 and diabetic retinopathy (CT+CC genotype: p<0.001; CT allele: p<0.001). Considering that the Polyphen database examined the changes caused by replacing the amino acid arginine instead of glutamine at position 129 on the protein, it does not consider these changes dangerous and has introduced this polymorphism as benign. Conclusion: Based on the findings of this study, the rs662 locus could be considered as one of the molecular markers in future research.

Perfil clínico-metabólico de pacientes pé diabéticos frequentadores de uma Unidade Básica de Saúde de Altamira, Pará, Brasil / Clinical-metabolic profile of diabetic foot patients attendinga Basic Health Unit in Altamira, Pará, Brazil

Introdução: o pé diabético é de origem neuropática e representa uma das complicações do diabetes mellitus, abrange várias condições patológicas, que incluem neuropatia, doença arterial periférica, neuroartropatia de Charcot, ulceração do pé e, em alguns casos, amputação. Objetivo: descrever o perfil clínico-metabólico de pacientes pé diabéticos frequentadores de uma Unidade Básica de Saúde (UBS). Material e Método: trata-se de um estudo descritivo exploratório com abordagem quantitativa. Foram avaliados 15 pacientes portadores de úlceras do pé diabético atendidos em uma Unidade Básica de Saúde de Altamira, estado do Pará, Brasil. Os dados foram submetidos à análise de acordo com os indicadores dos perfis investigados. Resultados: todos os pacientes possuem diabetes tipo II, baixos níveis de renda familiar e escolaridade. O Índice de Massa Corpórea (IMC) foi de 92%, circunferência abdominal 93%, proteína C reativa ultrassensível, interleucina-6 e hemoglobina glicada estavam superiores ao normal em mais da metade dos doentes, assim como a vitamina D estava deficiente em mais da metade dos pacientes. Conclusões: há barreiras ao manejo adequado dos portadores de pé diabético na atenção básica da cidade de Altamira que podem contribuir para o desenvolvimento de complicações macro e microvasculares. Recomendações técnicas direcionadas aos gestores locais contribuem para a atenção básica na região.

Introduction: the diabetic foot is of neuropathic origin and represents one of the complications of diabetes mellitus, encompasses several pathological conditions, including neuropathy, peripheral arterial disease, Charcot neuroarthropathy, foot ulceration, osteomyelitis and, in some cases, amputation. Objective: to describe the clinical-metabolic profile of diabetic foot patients attending a Basic Health Unit (BHU). Material and Method: this is a descriptive exploratory study with a quantitative approach. Fifteen patients with diabetic foot ulcers treated at the Basic Health Unit in Altamira, state of Pará, Brazil, were evaluated. The data were submitted to analysis according to the indicators of the investigated profiles. Results: all patients have Type 2 Diabetes, low level of family income and education. The Body Mass Index (BMI) was 92%, abdominal circumference (93%), Ultrasensitive C-Reactive Protein, Interleukin-6 and glycated hemoglobin were higher than normal in more than half of the patients, as well as vitamin D was deficient in more of half of the patients. Conclusions: there are barriers to the proper management of patients with diabetic foot in primary care in the city of Altamira that can contribute to the development of macro and microvascular complications. Technical recommendations directed at local managers contribute to primary care in the region.

Ursolic acid enhances the effect of exercise training on vascular aging by reducing oxidative stress in aged type 2 diabetic rats.

Ursolic acid (UA) mediates the vasorelaxant activity via nitric oxide (NO) release, and upregulation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) in disease conditions with increased oxidative stress (OS). The present study aimed to reflect on the impact of 8 weeks of a combination of UA supplementation and resistance/endurance training in old male Wistar rats having a high-fat diet and/or low-dose streptozotocin-induced type 2 diabetes (HFD/STZ-induced T2D), with an emphasis on Sirtuin 1 (SIRT1)-endothelial nitric oxide synthase (eNOS) axis and OS indices in their aortic tissues. A total number of56 21-month-old male Wistar rats with HFD/STZ-induced T2D were randomized into seven groups (n = eight animals per group): (1) sedentary old nondiabetic (Control [C]); (2) sedentary HFD/STZ-induced T2D (Diabetic [D]); (3) sedentary HFD/STZ-induced T2D plus UA (Diabetic + Ursolic Acid [DU]); (4) endurance-trained HFD/STZ-induced T2D (Diabetic + Endurance Training [DE]); (5) resistance-trained HFD/STZ-induced T2D (Diabetic + Resistance Training [DR]); (6) endurance-trained HFD/STZ-induced T2D plus UA (Diabetic + Endurance Training + Ursolic Acid [DEU]); and (7) resistance-trained STZ-diabetic plus UA (Diabetic + Resistance Training + Ursolic Acid [DRU]) rats. The ladder-based resistance training group performed the ladder resistance training at 60% of the maximum voluntary carrying capacity (MVCC), 14-20 climbs in each session, with a one-min rest between each two trials, 5 days a week. The treadmill-based endurance exercise training protocol consisted of repeated bouts of high- and low-intensity training with 60-75% maximal running speed and 30%-40% maximal running speed in the course of 8 weeks, respectively. The animals in the supplement groups also took 500 mg of UA/kg of high-fat diet/day, resulting in a daily UA intake of approximately 250 mg UA per kg of body weight rat/day. The resistance/endurance training plus the UA consumption could partially reverse the levels of malondialdehyde (MDA), nitric oxide (NO), as well as total antioxidant capacity (TAC). It was concluded that oral 0.5% UA supplementation can prevent vascular aging biomarkers in a HFD/STZ-induced T2D model. Further studies are also required to clarify how chronic consumption of UA with/without training protocols reverses vascular aging process.

Molecular Mechanism of Naringenin Against High-Glucose-Induced Vascular Smooth Muscle Cells Proliferation and Migration Based on Network Pharmacology and Transcriptomic Analyses.

Although the protective effects of naringenin (Nar) on vascular smooth muscle cells (VSMCs) have been confirmed, whether it has anti-proliferation and anti-migration effects in high-glucose-induced VSMCs has remained unclear. This study aimed to clarify the potential targets and molecular mechanism of Nar when used to treat high-glucose-induced vasculopathy based on transcriptomics, network pharmacology, molecular docking, and in vivo and in vitro assays. We found that Nar has visible anti-proliferation and anti-migration effects both in vitro (high-glucose-induced VSMC proliferation and migration model) and in vivo (type 1 diabetes mouse model). Based on the results of network pharmacology and molecular docking, vascular endothelial growth factor A (VEGFA), the proto-oncogene tyrosine-protein kinase Src (Src) and the kinase insert domain receptor (KDR) are the core targets of Nar when used to treat diabetic angiopathies, according to the degree value and the docking score of the three core genes. Interestingly, not only the Biological Process (BP), Molecular Function (MF), and KEGG enrichment results from network pharmacology analysis but also transcriptomics showed that phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) is the most likely downstream pathway involved in the protective effects of Nar on VSMCs. Notably, according to the differentially expressed genes (DEGs) in the transcriptomic analysis, we found that cAMP-responsive element binding protein 5 (CREB5) is a downstream protein of the PI3K/Akt pathway that participates in VSMCs proliferation and migration. Furthermore, the results of molecular experiments in vitro were consistent with the bioinformatic analysis. Nar significantly inhibited the protein expression of the core targets (VEGFA, Src and KDR) and downregulated the PI3K/Akt/CREB5 pathway. Our results indicated that Nar exerted anti-proliferation and anti-migration effects on high-glucose-induced VSMCs through decreasing expression of the target protein VEGFA, and then downregulating the PI3K/Akt/CREB5 pathway, suggesting its potential for treating diabetic angiopathies.

Diagnosis and treatment of diabetic retinopathy under the guidance of traditional Chinese and western medicine theory / 中国基层医药

Diabetic retinopathy is one of the serious microvascular diseases caused by diabetes. It is the leading cause of visual impairment among workers over 40 years old in developed countries. At present, western medicine methods for treating diabetic retinopathy include pan-retinal photocoagulation, vitrectomy, and intravitreal injection of anti-vascular endothelial growth factor and other methods. Traditional Chinese medicine treatment of diabetic retinopathy is mainly to treat patients using oral Chinese herb preparation based on syndrome differentiation and using certain external traditional Chinese medicine methods, such as auricular point therapy. This paper investigates the research progress of diabetic retinopathy treatment with traditional Chinese and western medicine and provides novel ideas for treating diabetic retinopathy with traditional Chinese combined with western medicine.

Correlations between macular microvascular parameters in patients with type 2 diabetes mellitus and urinary albumin creatinine ratio / 中华眼底病杂志

Objective:To observe and analyze the correlation between macular microvascular parameters and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM).Methods:A cross-sectional study. From October 2017 to April 2018, 100 eyes of 100 patients (T2DM) and 27 eyes of 27 healthy controls (the control group) were enrolled in Xuzhou First People’s Hospital. All subjects underwent anterior segment examination via slit-lamp biomicroscopy, dilated fundus examination, 7-field fundus photographs, OCT angiography (OCTA), the fasting glucose test, glycosylated hemoglobin (HbA1c), urinary albumin, urinary creatinine and UACR levels determination. Height and weight measurement were taken for calculating body mass index (BMI). Diabetic retinopathy was ruled out by fundoscopic examinations and 7-field fundus photographs in T2DM patients. According to the UACR, patients in the T2DM group were subdivided into A1 group (UACR< 30 mg/g), A2 group (UACR 30-300 mg/g), and A3 group (UACR>300 mg/g), with 38 cases and 38 eyes respectively , 40 cases with 40 eyes, 22 cases with 22 eyes. A 6 mm×6 mm scanning area centered on the macular fovea were scanned for right eye using a frequency domain OCTA instrument, which were divided into three concentric circles centered on the macular fovea by the software automatically. The foveal zone was defined as a circular area measuring 1 mm in diameter, the parafoveal zone was described as a middle circle area measuring 1-3 mm in diameter, and the perifoveal zone was an outer circle area measuring 3-6 mm in diameter. The vessel density of superficial capillary plexus (SCP) and deep capillary plexus (DCP), foveal avascular area (FAZ) and perimeter (PERIM), non-circularity index (AI) were measured. The correlation between the macular vessel density, FAZ and UACR was analyzed by Spearman correlation analysis.Results:A1 group, A2 group, A3 group, and normal control group. The macular area SCP and DCP ( F=13.722, 5.644), foveal area ( F=4.607, 4.719), parafoveal area ( H=23.142, F=2.904), the blood flow density of the area around the fovea ( F=12.292, H=10.946), the difference was statistically significant ( P<0.05); with the increase of UACR, the blood flow density of each area of SCP and DCP showed a downward trend. The results of correlation analysis showed that the blood flow density of the whole SCP, parafoveal area, and surrounding area of T2DM patients was negatively correlated with UACR ( r=-0.376, -0.240, -0.364,-0.347, P<0.05). There were no correlation among fasting plasma glucose, HbAlc and UACR ( r=0.179, 0.085, P>0.05). There were no correlation among blood flow density in BMI, SCP foveal area, DCP and UACR (| r|<0.3, P>0.05). Conclusion:The whole, parafovea and perifovea vessel density values of SCP in T2DM eyes without DR are negatively correlated with UACR.

Study on retinal neurodegeneration and microvascular lesions in diabetic patients / 中华眼底病杂志

Objective:To observe the changes in the structure and function of the retina in diabetic patients, and preliminarily explore the changes in the characteristics of neuropathy and microvascular damage in different degrees of diabetic retinopathy (DR).Methods:A prospective controlled study. From May to December 2020, 63 eyes of 63 patients with type 2 diabetes who were recruited from the Department of Ophthalmology of Shandong Provincial Hospital and 40 healthy volunteers with age and sex matching in the same period (control group) were included in the study. All subjects underwent optical coherence tomography angiography (OCTA) and portable non-mydriatic visual electrophysiological diagnosis system RETeval. OCTA was used to measure the thickness of the retinal nerve fiber layer (pRNFL) around the optic disc, the blood flow density of theradial peripapillary capillary (RPC) around the optic disc, and the thickness of the macular ganglion cell complex (GCC). The "DR evaluation plan" mode of the RETeval device was used to perform flash electroretinogram examination, and the "DR evaluation score" measured by the system was recorded. According to the DR grading standard established in the early treatment of DR research, DR was classified. Diabetic patients were divided into non-DR (non-DR) group, mild to moderate non-proliferative DR (mNPDR) group, and severe non-proliferative DR (sNPDR) group, Proliferative DR (PDR) group, with 12, 16, 18, and 17 eyes respectively. The comparison of pRNFL thickness, GCC thickness, RPC blood flow density and "DR assessment score" between groups was performed by one-way analysis of variance; the correlation between pRNFL thickness and RPC blood flow density was analyzed by Pearson correlation analysis.Results:Compared with the control group, the overall, upper and lower thickness of the macular GCC of the affected eyes in different degrees of DR groups were significantly thinner, and the difference was statistically significant ( F=13.560, 15.840, 5.480; P<0.05). Compared with the control group, the overall pRNFL ( F=6.120), upper part ( F=6.310), lower part ( F=5.330), upper nose ( F=7.350), lower nose ( F=2.690), the upper nasal side ( F=4.780), the upper temporal side ( F=3.710), and the lower temporal side ( F=3.750) became thinner, the difference was statistically significant ( P<0.05). Correlation analysis results showed that the whole optic disc, upper part, lower part, upper nose, upper nasal side, lower nasal side, and lower temporal RPC blood flow density were positively correlated with pRNFL thickness ( r=0.260, 0.256, 0.275, 0.489, 0.444, 0.542, 0.261; P<0.01). The "DR evaluation scores" of the eyes in the control group, non-DR group, mNPDR group, sNPDR group, and PDR group were 12.71±5.62, 22.18±3.77, 24.68±2.41, 24.98±2.78, 29.17±7.98 points; the DR lesions were more severe, the evaluation score were higher, and the difference was statistically significant ( F=1.535, P<0.01). Conclusion:Compared with the control group, the macular GCC, pRNFL thickness and RPC blood flow density of diabetic patients are significantly reduced; the "DR evaluation score" is increased, and it is related to the severity of DR.

Association of Combined TCF7L2 and KCNQ1 Gene Polymorphisms with Diabetic Micro- and Macrovascular Complications in Type 2 Diabetes Mellitus.

BACKGROUND: Vascular complications are the major morbid consequences of type 2 diabetes mellitus (T2DM). The transcription factor 7-like 2 (TCF7L2), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and inwardly-rectifying potassium channel, subfamily J, member 11 gene (KCNJ11) are common T2DM susceptibility genes in various populations. However, the associations between polymorphisms in these genes and diabetic complications are controversial. This study aimed to investigate the effects of combined gene-polymorphisms within TCF7L2, KCNQ1, and KCNJ11 on vascular complications in Thai subjects with T2DM. METHODS: We conducted a case-control study comprising 960 T2DM patients and 740 non-diabetes controls. Single nucleotide polymorphisms in TCF7L2, KCNQ1, and KCNJ11 were genotyped and evaluated for their association with diabetic vascular complications. RESULTS: The gene variants TCF7L2 rs290487-T, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-C were associated with increased risk of T2DM. TCF7L2 rs7903146-C, TCF7L2 rs290487-C, KCNQ1 rs2237892-T, and KCNQ1 rs2237897-T revealed an association with hypertension. The specific combination of risk-alleles that have effects on T2DM and hypertension, TCF7L2 rs7903146-C, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-T, as genetic risk score (GRS), pronounced significant association with coronary artery disease (CAD), cumulative nephropathy and CAD, and cumulative microvascular and macrovascular complications (respective odds ratios [ORs] with 95% confidence interval [95% CI], comparing between GRS 2-3 and GRS 5-6, were 7.31 [2.03 to 26.35], 3.92 [1.75 to 8.76], and 2.33 [1.13 to 4.79]). CONCLUSION: This study demonstrated, for the first time, the effect conferred by specific combined genetic variants in TCF7L2 and KCNQ1 on diabetic vascular complications, predominantly with nephropathy and CAD. Such a specific pattern of gene variant combination may implicate in the progression of T2DM and life-threatening vascular complications.

Stem cell transplantation therapy for diabetic foot ulcer: a narrative review.

Diabetes mellitus is a chronic metabolic disease associated with high cardiovascular risk. A vascular complication of diabetes is foot ulcers. Diabetic foot ulcers are prevalent and substantially reduce the quality of life of patients who have them. Currently, diabetic foot ulcer is a major problem for wound care specialists, and its treatment requires considerable health care resources. So far, various therapeutic modalities have been proposed to treat diabetic foot ulcers and one of them is stem cell-based therapy. Stem cell-based therapy has shown great promise for the treatment of diabetic foot ulcers. This strategy has been shown to be safe and effective in both preclinical and clinical trials. In this review, we provide an overview of the stem cell types and possible beneficial effects of stem cell transplantation therapy for diabetic foot ulcers, and an overview of the current status of stem cell research in both preclinical and clinical trial stages of treatment strategies for diabetic foot ulcers.

Relationships between Islet-Specific Autoantibody Titers and the Clinical Characteristics of Patients with Diabetes Mellitus.

Background: Dysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients. Methods: A total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet ß-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics. Results: Compared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer. Conclusion: Diabetic patients with a high ISA titer, especially GADA titer, have worse islet ß-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.

Comparação da eficácia da retinografia colorida e da angiografia fluorescente no diagnóstico da retinopatia diabética / Comparing efficacy of fundus photography and fluorescein angiography in the diagnosis of diabetic retinopathy

RESUMO Objetivo: Avaliar a efetividade da retinografia colorida e a da angiografia fluorescente no diagnóstico e no rastreio da retinopatia diabética. Métodos: Estudo retrospectivo, com base na análise de resultados de ambos os exames de 398 pacientes diabéticos. Resultados: Os resultados da angiografia coincidiram com os da retinografia em 77,4% dos casos, e não houve diferença significativa no estadiamento e na identificação da retinopatia pelos dois métodos. Conclusão: Não houve diferença significativa em relação à capacidade diagnóstica da doença pelos métodos descritos, demonstrando não existir benefício em indicar a angiografia como avaliação inicial do paciente diabético.

ABSTRACT Objective: To assess effectiveness of fundus photography and fluorescein angiography in diagnosis and screening of diabetic retinopathy. Methods: A retrospective study of 398 diabetic patients, based on analysis of results of both tests. Results: Results of fluorescein angiography and fundus photography coincided in 77.4% of cases, and there was no significant difference in staging and identification of retinopathy by both methods. Conclusion: There was no significant difference between both methods regarding the capacity to diagnose the disease, showing no benefit in indicating fluorescein angiography as initial assessment of diabetic patients.

Disfunción endotelial en pacientes diabéticos con o sin úlceras del pie / Endothelial Dysfunction In Diabetic Patients With Or Without Foot Ulcers

Introducción. La disfunción endotelial juega un papel preponderante en la génesis de las complicaciones vasculares de la diabetes y precede a las evidencias anatómicas más tempranas de ateroesclerosis El Eco-Doppler vascular, mediante la determinación de laDilatación arterial flujo-dependiente en la arteria braquial ha demostrado una buena correlación con las pruebas invasivas parael diagnóstico de la Disfunción Endotelial. Objetivo: Determinar la presencia de Disfunción endotelial en pacientes diabéticos con o sin úlceras del pie. Método. Se diseñó un estudio observacional, prospectivo de corte transversal, tipo caso-control en pacientes diabéticos con y sin úlceras del pie, con un muestreo simple no probabilístico, con una población de estudio constituida por 100 pacientes diabéticos subdivididos en Grupo A (de estudio) 50 y Grupo B (control) 50. Resultados. La vasoactividad mediada por el flujo (VMF), en el grupo de estudio fue de 3,1% y en el grupo de control 4,3%, resultados ambos que traducen la presencia de disfunción endotelial, pero más intensa en los pacientes con úlceras del pie diabético. Conclusiones. La disminución de la vasoactividad mediada por el flujo constituye una manifestación temprana de la enfermedad arteriosclerótica, detectable inclusive antes de la aparición de eventos clínicos vasculares periféricos en pacientes diabéticos con o sin úlceras del pie. (AU)

Introduction. Endothelial dysfunction plays a preponderant role in the genesis of vascular complications of diabetes and precedes the earliest anatomical evidence of atherosclerosis. Vascular Echo-Doppler, by determining the flow-dependent arterial dilation inthe brachial artery, has demonstrated a good correlation with invasive tests for the diagnosis of Endothelial Dysfunction. Objective: To determine the presence of endothelial dysfunction in diabetic patients with or without foot ulcers. Method. An observational,prospective, cross-sectional, case-control study was designed in diabetic patients with and without foot ulcers, with a simple non-probabilistic sampling, with a study population consisting of 100 diabetic patients subdivided into Group A (of study) 50 and Group B (control) 50. Results. The flow-mediated vasoactivity (VMF) in the study group was 3.1% and 4.3% in the control group, both results that reflect the presence of endothelial dysfunction, but more intense in patients with diabetic foot ulcers. Conclusions: The decrease in flow-mediated vasoactivity constitutes an early manifestation of arteriosclerotic disease, detectable even before the appearance of peripheral vascular clinical events in diabetic patients with or without foot ulcers. (AU)

Relationship between cerebrovascular disease and peripheral vascular disease in patients with type 2 diabetes mellitus / 中国基层医药

Objective:To compare the incidence of carotid artery and lower extremity arterial disease between patients with type 2 diabetes mellitus complicated by cerebrovascular disease and those with no cerebrovascular disease and investigate the risk relationship between diabetic peripheral vascular disease and cerebrovascular disease.Methods:A total of 133 patients with type 2 diabetes mellitus complicated by cerebrovascular disease who received treatment in the Department of Endocrinology, The First People's Hospital of Kunming, China between June 2015 and June 2016 were included in the observation group. Sixty-six type 2 diabetes mellitus patients with no cerebrovascular disease were included in the control group. The incidence and severity of carotid artery and lower extremity arterial disease were compared between the observation and control groups. Stepwise logistic regression was performed taking whether cerebrovascular disease exists as a dependent variable. The risk factors for developing cerebrovascular disease in patients with type 2 diabetes mellitus were investigated.Results:The number of patients who had carotid plague in the observation group was significantly higher than that in the control group [66.17% (88/133) vs. 42.42% (28/66)]. Cervical vascular disease in the observation group was severer than that in the control group. In the observation group, 24.81% (33/133) of patients had rough carotid intima, and 9.02% (12/133) of patients had no rough carotid intima. In the control group, 33.33% (22/66) of patients had rough carotid intima, and 24.24% (16/66) of patients had no rough carotid intima. There was significant difference in the incidence of rough carotid intima between observation and control groups ( χ2 = 14.140, P = 0.030). The proportion of patients who had lower extremity carotid plaque in the observation group was higher than that in the control group [72.93% (97/133) vs. 42.42% (28/66)]. Lower extremity arterial disease in the observation group was severer than that in the control group. In the observation group, 22.56% (30/133) of patients had rough intima of lower extremity arteries and 4.51% (6/133) of patients had no rough intima of lower extremity arteries. In the control group, 33.33% (22/66) of patients had rough intima of lower extremity arteries and 24.24% (16/66) of patients had no rough intima of lower extremity arteries. There was significant difference in the proportion of rough intima of lower extremity arteries between observation and control groups ( χ2 = 24.030, P < 0.001). Logistic regression analysis showed that age, glycosylated hemoglobin, and the presence of lower extremity vascular disease were the risk factors for cerebrovascular disease [95% CI = 1.098 (1.051 -1.146), 1.240 (1.015-1.515), 3.802 (1.094-13.212)]. Conclusion:Peripheral vascular disease in patients with type 2 diabetes mellitus complicated by cerebrovascular disease is severer than that in patients with type 2 diabetes mellitus but without cerebrovascular disease. Aging, poor blood glucose control and lower extremity vascular disease are the risk factors for developing cerebrovascular disease in patients with type 2 diabetes mellitus. Lower extremity vascular disease has a certain value for predicting the occurrence of cerebrovascular disease in patients with type 2 diabetes mellitus.

Changes of serum 25 hydroxyvitamin D 3 expression in diabetic patients and its correlation with macrovascular complications / 中国医师进修杂志

Objective:To analyze the changes of serum 25-hydroxyvitamin D 3[25-(OH)D 3] expression in diabetic patients and its correlation with macrovascular complications. Methods:Two hundreddiabetic patients admitted to Cangzhou Central Hospital from February 2018 to November 2019 were divided into macrovascular complications group (87 cases) and without macrovascular complicationsgroup (113 cases). According to the degree of 25-(OH)D 3 deficiency, 32 cases were divided into 25-(OH)D 3 normal group, 94 cases were mild deficiency group and 74 cases were moderate and severe deficiency group. At the same time, 168 outpatients were selected as control group. The levels of serum 25-(OH)D 3 were compared between diabetic group and control group, macrovascular complications group and without macrovascular complications group, and the correlation between the level of serum 25-(OH)D 3 and carotid intima-media thickness (IMT) was analyzed. Results:The level of serum 25-(OH)D 3 in diabetic group was lower than that in control group: (24.79 ± 3.02) μg/L vs. (39.18 ± 4.38) μg/L, the difference was statistically significant ( P<0.05). The level ofserum 25-(OH)D 3 in diabetic patients with macrovascular complications group was lower than that in without macrovascular complications group: (21.08 ± 2.64) μg/L vs. (27.65 ± 3.31) μg/L; while the IMT was higher than that without macrovascular complications group: (1.29 ± 0.13) mm vs. (0.93 ± 0.10) mm, the differences were statistically significant ( P<0.05). The incidence of macrovascular complications in 25-(OH)D 3 moderate and severe deficiency group was higher than that in 25-(OH)D 3 mild deficiency group and 25-(OH)D 3 normal group: 60.81%(45/74) vs. 40.43%(38/94), 12.50%(4/32), the difference was statistically significant ( χ2 = 21.896, P<0.05). The level of serum 25-(OH)D 3 in patients with diabetic macrovascular complications was negatively correlated with IMT ( r = -0.513, P<0.05). Conclusions:The level of serum 25-(OH)D 3 in diabetic patients is decreased, and the change of its concentration is related to the occurrence of macrovascular complications.

Associations between retinal microvasculature/microstructure and renal function in type 2 diabetes patients with early chronic kidney disease.

AIMS: To explore the associations between the microvascular/microstructural changes in the retina measured by optical coherence tomography angiography (OCTA) and renal function in type 2 diabetes patients with early chronic kidney disease (CKD). METHODS: This cross-sectional study, including 150 type 2 diabetes patients, was conducted from July 2017 to January 2019. We obtained retinal vessel density (VD) and retinal thickness using OCTA. The correlations between OCTA-derived parameters and CKD-related systemic data were assessed by multiple regression analyses. RESULTS: We found a significant decrease of VD in patients with CKD. Multiple regression analyses showed that: a) decreased eGFR (estimated glomerular filtration rate) was significantly correlated with decreased VD of superficial vascular complex (SVC) in macular area; b) increased UACR (urine albumin to creatinine ratio) was significantly associated with increased macular thickness; c) decreased HGB/HCT (Hemoglobin or Hematocrit) was significantly correlated with both decreased VD of SVC and increased retinal thickness in macular area. CONCLUSIONS: Decrease in the microcirculation of the retina and thickening of the macula associated with impaired renal function in type 2 diabetes. Our finding encourages the application of OCTA-derived metrics in diabetic eyes to monitor the progression of CKD.

From Endothelial Dysfunction to Arterial Stiffness in Diabetes Mellitus.

Prevalence of diabetes mellitus has increased drastically over time, especially in more populous countries such as the United States, India, and China. Patients with diabetes have an increased risk of major cardiovascular events such as acute myocardial infarction, cerebrovascular disease, and peripheral vascular disease. Arterial stiffness is a process related to aging and vascular, metabolic, cellular and physiological deterioration. In recent years, it has been described as an independent predictor of cardiovascular mortality and coronary artery disease. Additionally, it plays an important role in the measurement of chronic disease progression. Recent studies have suggested a strong relationship between diabetes mellitus and arterial stiffness since they share a similar pathophysiology involving endothelial dysfunction. The literature has shown that microvascular and macrovascular complications in diabetic patients could be screened and measured with arterial stiffness. Additionally, new evidence proposes that there is a relationship between blood glucose levels, microalbuminuria, and arterial stiffness. Moreover, arterial stiffness predicts cardiovascular risk and is independently associated with mortality in diabetic patients. Abnormal arterial stiffness values in diabetic patients should alert the clinician to the presence of vascular disease, which merits early study and treatment. We await more studies to determine if arterial stiffness could be considered a routine useful non-invasive tool in the evaluation of diabetic patients. There is enough evidence to conclude that arterial stiffness is related to the progression of diabetes mellitus.

Relationship between apolipoprotein E gene polymorphism and cerebral infraction in Chinese type 2 diabetes mellitus patients / 中华检验医学杂志

Objective@#To investigate the relationship between apolipoprotein E (APOE) gene polymorphism and cerebral infraction (CI) in Chinese type 2 diabetes mellitus (T2DM) patients.@*Methods@#This study included 245 samples of T2DM patients without cerebral infraction (CON group) (Male/Female, 128/117) and 270 samples of T2DM patients with cerebral infraction (CI group)(Male/Female, 145/125) from the department of endocrinology and neurology utilizing real-time fluorescence quantitative PCR technique. The t test and χ2 test were used to compare the differences between the two groups.@*Results@#Patients with a history of hypertension in the CI group (84.12%) were significantly higher than those in the CON group (70.42%) (χ2=15.91, P<0.05).The systolic blood pressure (142.78±20.52)mmHg of the CI group was significantly higher than that of the CON group (133.89±18.58)mmHg (t=-5.16, P<0.05).Compared with CON group, the frequency of genotypes of ε2/ε3 and ε3/ε4 in CI group was significantly higher, while the frequency of ε3/ε3 genotype was significantly lower (χ2=11.48, P<0.05); the allele frequency of APOE ε4 was higher while ε3 was lower in CI group than that in CON group (χ2=7.00, P<0.05). Logistic regression analysis showed that hypertension history (OR=1.95, P<0.05), high systolic blood pressure (OR=1.02, P<0.05), APOE genotypes of ε2/ε3 (OR=2.08, P<0.05) and ε3/ε4 (OR=1.85, P<0.05) were independent risk factors for cerebral infarction in T2DM patients.@*Conclusion@#The polymorphism of APOE gene may be related to cerebral infraction in Chinese T2DM patients.

Hongjingtian Injection Inhibits Proliferation and Migration and Promotes Apoptosis in High Glucose-Induced Vascular Smooth Muscle Cells.

BACKGROUND: Hongjingtian injection (HJT) is administered in the treatment of vascular diseases, including diabetic angiopathies (DA). However, its underlying mechanisms have not been examined systematically. METHODS: In this research, we explored potential mechanisms of HJT through network pharmacology. HG-stimulated A7r5 cells served as the cell model. Cell proliferation, migration and apoptosis were investigated. The effects on key targets and the AKT pathway were verified by Western blotting in experiments with the AKT inhibitor LY294002 or activator SC79. RESULTS: Network analysis predicted that HJT targeted 10 candidate targets and 15 pathways including cell proliferation, migration and apoptosis in response to DA. Functional experiments showed that HJT markedly suppressed the proliferation and migration and promoted the apoptosis of HG-induced VSMCs, which validated the prediction. Mechanistically, HJT significantly downregulated the expression of pAKT, MMP9, and PCNA, upregulated the expression of p53 and cleaved caspase-3 and increased the Bax/Bcl-2 ratio compared with the HG group. SC79, an AKT activator, partially reversed the inhibitory effects of HJT on HG-induced VSMCs, confirming the involvement of the AKT pathway. Furthermore, the presence of the AKT inhibitor LY294002 had a similar inhibitory effect as HJT. CONCLUSION: These findings systematically evaluate the potential mechanisms of HJT for the treatment of DA. HJT suppressed the proliferation and migration and promoted the apoptosis of HG-induced VSMCs partly by inhibiting the AKT pathway. Additionally, this study may provide a quick and effective way to investigate the molecular mechanisms of traditional Chinese medicine.

Rubeosis faciei diabeticorum is not associated with oxidative stress and skin autofluorescence.

BACKGROUND: Rubeosis faciei diabeticorum is a persistent facial erythema in patients with diabetes mellitus. The actual pathogenesis has not been studied. However, it is speculated to be a cutaneous diabetic microangiopathy. OBJECTIVE: Examine the correlation between the severity of facial erythema and the possible causes of microvascular diabetic complications, namely oxidative stress, hyperglycemia, and cutaneous accumulation of advanced glycation end-products . METHODS: Patients diagnosed with Type 2 diabetes mellitus (n=32) were enrolled in the study. The facial erythema index was measured using the Mexameter MX18; cutaneous accumulation of advanced glycation end-products was estimated by measuring skin auto fluorescence with the AGE Reader (DiagnOptics Technologies B.V. - Groningen, Netherlands). Glycated haemoglobin, total antioxidant status, and malondialdehyde were measured in blood by TBARS assay. The correlation between the selected variables was assessed by Spearman's rank test; p≤0.05 was considered statistically significant. RESULTS: There was a statistically significant correlation between total antioxidant status and the facial erythema index (ρ=0.398, p=0.024). Malondialdehyde, skin autofluorescence, glycated haemoglobin, body mass index, duration of diabetes, and age did not demonstrate statistically significant correlation with the facial erythema index. STUDY LIMITATIONS: This is an observational study. Elevation of total antioxidant status could have been caused by several factors that might have also influenced the development of rubeosis faciei, including hyperbilirubinemia and hyperuricemia. CONCLUSIONS: The results contradicted expectations. Total antioxidant status correlated positively with facial erythema index; however, there was no correlation with oxidative stress and skin autofluorescence. Further investigations should be conducted to reveal the cause of total antioxidant status elevation in patients with rubeosis faciei.