Impact of Diabetes Mellitus on Adverse Outcomes After Meningioma Surgery.

OBJECTIVE: We sought to investigate the association between diabetes mellitus and incidence of adverse outcomes in patients who underwent meningioma surgery. METHODS: The 2012-2014 National Inpatient Sample database was used. Prolonged length of stay was indicated by values greater than the 90th percentile of the sample. The Fisher exact test and analysis of variance were used to compare demographics, hospital characteristics, comorbidity, and complications among race cohorts. Logistic regression was used to analyze the independent effect of diabetes on adverse outcomes. RESULTS: After selecting for patients with primary diagnosis of meningioma who underwent a resection procedure, 7745 individuals were identified and divided into diabetic (n = 1518) and nondiabetic (n = 6227) cohorts. Demographics, hospital characteristics, and comorbidities were significantly different among the 2 cohorts. Average length of stay was longer in diabetic patients (8.15 vs. 6.04 days, P < 0.001), and total charges were higher in diabetic patients ($139,462.66 vs. $123,250.71, P < 0.001). Multivariate regression indicated diabetic patients have higher odds of experiencing a complication (odds ratio [OR] 1.442, 95% confidence interval [CI] 1.255-1.656, P < 0.001) and in-hospital mortality (OR 1.672, 95% CI 1.034-2.705, P = 0.036) after meningioma surgery. Analysis of individual postoperative complications revealed that diabetic patients experienced increased odds of pulmonary (OR 1.501, 95% CI 1.209-1.864, P < 0.001), neurologic (OR 1.690, 95% CI 1.383-2.065, P < 0.001), and urinary/renal complications (OR 2.618, 95% CI 1.933-3.545, P < 0.001). In addition, diabetic patients were more likely to have a prolonged length of stay (OR 1.694, 95% CI 1.389-2.065, P < 0.001). CONCLUSIONS: Diabetes is an important factor associated with complications after meningioma surgery. Preventative measures must be taken to optimize postoperative outcomes in these patients.

Evaluation of simple and cost-effective immuno- haematological markers to predict outcome in hospitalized severe COVID-19 patients, with a focus on diabetes mellitus - A retrospective study in Andhra Pradesh, India.

BACKGROUND AND AIMS: COVID-19 pandemic has strained the health infrastructure globally, providing an opportunity to identify cost-effective biomarkers. We aimed to identify simple hematological prognostic markers in hospitalized severe COVID-19 patients with and without diabetes. METHODS: Retrospective study of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 154 patients, including diabetic subset n = 57) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for total leucocyte count (TLC), absolute neutrophil count (ANC), neutrophil lymphocyte ratio (NLR), and derived neutrophil lymphocyte ratio (dNLR) in order to prognosticate the outcome. RESULTS: Among 154 severe COVID-19 patients, significant association with mortality was seen with respect to TLC(p < 0.001), ANC (p < 0.001), NLR(p < 0.001) and dNLR(p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for TLC 8950 cells/mm3 (area under curve (AUC)-0.764, odds ratio (OR)-7.53), ANC 7679 cells/mm3 (AUC-0.789, OR-8.14), NLR 5.13 (AUC-0.741, OR-4.77), dNLR 3.44 (AUC -0.741, OR-4.43) respectively.In diabetic subset, the cut-offs for TLC was 8950 cells/mm3 (AUC -0.762, OR-14.9), ANC 6510 cells/mm3 (AUC -0.773, OR-16.8), NLR 5.13(AUC -0.678, OR-6) and dNLR 3.25(AUC -0.685, OR-4.7) respectively. CONCLUSIONS: In severe COVID-19 patients irrespective of diabetes, a simple, applicable total leucocyte count cut-off, 8950 cells/mm3 , together with easily derived cut-offs for ANC, NLR, dNLR may serve as cost-effective prognosticators of clinical outcome. A normal TLC may be misleading in the intensive care and the above applicable cut-off for TLC serves as an early warning tool for high-risk identification and better in-hospital management. Even with similar or lower cut-offs, diabetics had a higher mortality.

Valuing health states of people with type 2 diabetes: Analyses of the nationwide representative linked databases.

AIMS/INTRODUCTION: To estimate preference-based measures of health-related quality of life associated with sociodemographic and clinical characteristics in type 2 diabetes patients. MATERIALS AND METHODS: Individuals with EuroQol-5 dimensions-3 levels data were identified from Taiwan's National Health Interview Survey in 2009 and 2013. Status of diabetes, comorbidities, complications and treatments were ascertained through data linkage to Taiwan's National Health Insurance Research Database. Multivariable ordinary least squares, Tobit and median regression analyses were used to estimate the coefficients that represented independent impacts of patients' characteristics on health-related quality of life. RESULTS: The mean health utility score for 2,104 participants was 0.838. Being female, aging, divorced/widowed, never worked or underweight, or having a lower monthly household income, injectable glucose-lowering therapy, comorbid connective tissue disease or depression were associated with lower health utilities. Having an amputation led to the largest reduction by 0.288 in health utilities, followed by debilitating stroke (0.266), heart failure (0.237), other coronary heart disease (0.185), kidney dialysis/transplant (0.148), coronary revascularizations (0.093), transient ischemic attack/stroke (0.078), diabetic neuropathy (0.062), polyneuropathy (0.055) and other neuropathy (0.043). CONCLUSIONS: Major vascular complications, connective tissue disease and depression are associated with considerably worse health-related quality of life. These health utility estimates can facilitate health economic evaluations to determine cost-effective strategies for diabetes management.

Assessment of the efficacy of α-lipoic acid in treatment of diabetes mellitus patients with erectile dysfunction: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus with erectile dysfunction (DMED) is one of the most common causes of disability in diabetic population, and its pathogenesis is related to a variety of factors. Because its pathogenesis is complex and the existing treatment methods have limitations, DMED is difficult to treat in clinical. Recently, some studies have shown that α-lipoic acid (ALA) is associated with DMED, but there is no systematic review and meta-analysis on the relationship between ALA and DMED. METHODS: We will search each database from the built-in until July 2020. The English literature mainly searches Cochrane Library, PubMed, EMBASE, and Web of Science, while the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Simultaneously we will retrieve clinical registration tests and grey literatures. This study only screen the clinical randomized controlled trials (RCTs) about ALA for DMED to assess its efficacy. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on whether or not heterogeneity exists. Erectile dysfunction (ED) will be diagnosed by the International Index of Erectile Function 5 (IIEF-5) score. Finally, meta-analysis was conducted by RevMan software version 5.3. RESULTS: This study will synthesize and provide high quality to evaluate the effectiveness of ALA supplementation for the treatment of DMED. CONCLUSION: This systematic review aims to provide new options for ALA supplementation treatment of DMED in terms of its efficacy and safety. PROSPERO REGISTRATION NUMBER: INPLASY202070130.

10 years Analysis of Diabetes-related Major Lower Extremity Amputations in Mexico.

BACKGROUND: Little is known about diabetes-related major lower extremity amputations (DMLEA) burden in México. AIM OF THE STUDY: To describe DMLEA hospitalization rates, in-hospital survival rates, characteristics associated with all-cause in-hospital mortality and direct costs of hospitalization during the 2005-2015 period, in the two principal Health Institutions in Mexico: the Mexican Institute of Social Security (IMSS) and the Ministry of Health (MoH). METHODS: A secondary data analysis was conducted using hospital discharge information obtained from administrative databases. Non-traumatic DMLEA hospitalizations in adults aged 20 years and over were analyzed. Hospitalization characteristics and in-hospital all-cause mortality risk were also assessed. Direct costs of hospitalization including length of hospital stay, surgical procedure, wound care and medical emergency consultation were accounted in U.S. dollars (USD, 2015). RESULTS: There were 34,051 DMLEA hospitalizations and 1,268 in-hospital deaths. DMLEA hospitalizations rates increase from 4.71-6.12 × 100,000 affiliates during 2005 and 2015 respectively for both institutions together. Females and age ≥60 years were associated with all-cause in-hospital death. The all-period direct costs of hospitalization amounted to $132.51 million USD ($86.30 in the IMSS and $46.21 in the MoH), and showed a sustained increment: from $4.14 million USD in 2005 to $24.84 million USD in 2015 (percentage increase 499.3%). CONCLUSIONS: In-hospital mortality was 3.7%. Female sex and age ≥60 years were characteristics associated with all-cause in-hospital death. The increase in the number of DMLEA hospitalizations and their direct costs, reflects a negative progression of diabetes in the two largest Health Institutions in Mexico.

An assessment of direct and indirect costs of dementia in Brazil.

BACKGROUND: To analyze costs associated with dementia based on a cross-sectional study in the Brazilian health system. METHODS: Direct and indirect costs were estimated by conducting comprehensive interviews on the use of resources in a sample of 156 patients with dementia treated at an outpatient memory clinic of a tertiary hospital. A regression model was used to determine the main determinants of costs associated with dementia. RESULTS: Global costs of dementia were US$1,012.35; US$1,683.18 and US$1,372.30 per patient/month for mild, moderate and severe stages, respectively. Indirect costs ranged from US$536.62 to US$545.17 according to severity. Dementia costs were influenced by medication, FAST score, and educational level of caregiver. DISCUSSION: The study represents an original contribution toward establishing direct and indirect costs of dementia in Brazil. Results indicate significant economic impacts, including projection of annual costs of US$16,548.24 per patient.

Association of the severity of diabetes-related complications with stage of breast cancer at diagnosis among elderly women with pre-existing diabetes.

PURPOSE: This study assessed the association between the severity of diabetes complications using diabetes complications severity index (DCSI) and stage of breast cancer (BC) at diagnosis among elderly women with pre-existing diabetes and incident BC. METHODS: Using Surveillance, Epidemiology and End Results-Medicare data, we identified women with incident BC during 2004-2011 and pre-existing diabetes (N = 7729). Chi-square tests were used to test for group differences in stage of BC at diagnosis. Multinomial logistic regression was used to examine the associations between the severity of diabetes complications and stage of BC at diagnosis. RESULTS: Overall, women with a DCSI = 2 and a DCSI ≥ 3 were more likely to be diagnosed at advanced stages as compared to those with no diabetes complications. In full adjusted association (after adding BC screening to the analysis model), the severity of diabetes complications was no longer an independent predictor of advanced stages at diagnosis. However, women with a DCSI = 2 were 26% more likely to be diagnosed at stage I (versus stage 0) of BC at diagnosis as compared to those without diabetes complications (OR 1.26, 95% CI 1.03-1.53). CONCLUSION: The increased likelihood of having advanced-stage BC at diagnosis associated with severity of diabetes-related complications appears to be mediated by lower rates of breast cancer screening among elderly women with pre-existing diabetes complications. Therefore, reducing disparity in receiving breast cancer screening among elderly women with diabetes may reduce the risk of advanced-stage breast cancer diagnosis.

Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis †.

Diabetic foot is a severe public health issue, yet rare studies investigated its global epidemiology. Here we performed a systematic review and meta-analysis through searching PubMed, EMBASE, ISI Web of science, and Cochrane database. We found that that global diabetic foot ulcer prevalence was 6.3% (95%CI: 5.4-7.3%), which was higher in males (4.5%, 95%CI: 3.7-5.2%) than in females (3.5%, 95%CI: 2.8-4.2%), and higher in type 2 diabetic patients (6.4%, 95%CI: 4.6-8.1%) than in type 1 diabetics (5.5%, 95%CI: 3.2-7.7%). North America had the highest prevalence (13.0%, 95%CI: 10.0-15.9%), Oceania had the lowest (3.0%, 95% CI: 0.9-5.0%), and the prevalence in Asia, Europe, and Africa were 5.5% (95%CI: 4.6-6.4%), 5.1% (95%CI: 4.1-6.0%), and 7.2% (95%CI: 5.1-9.3%), respectively. Australia has the lowest (1.5%, 95%CI: 0.7-2.4%) and Belgium has the highest prevalence (16.6%, 95%CI: 10.7-22.4%), followed by Canada (14.8%, 95%CI: 9.4-20.1%) and USA (13.0%, 95%CI: 8.3-17.7%). The patients with diabetic foot ulcer were older, had a lower body mass index, longer diabetic duration, and had more hypertension, diabetic retinopathy, and smoking history than patients without diabetic foot ulceration. Our results provide suggestions for policy makers in deciding preventing strategy of diabetic foot ulceration in the future. Key messages Global prevalence of diabetic foot is 6.3% (95%CI: 5.4-7.3%), and the prevalence in North America, Asia, Europe, Africa and Oceania was 13.0% (95%CI: 10.0-15.9%), 5.5% (95%CI: 4.6-6.4%), 5.1% (95%CI: 4.1-6.0%), 7.2% (95%CI: 5.1-9.3%), and 3.0% (95% CI: 0.9-5.0%). Diabetic foot was more prevalent in males than in females, and more prevalent in type 2 diabetic foot patients than in type 1 diabetic foot patients. The patients with diabetic foot were older, had a lower body mass index, longer diabetic duration, and had more hypertension, diabetic retinopathy, and smoking history than patients without diabetic foot.

[APPLICATION OF INTEGRAL INDICATOR FOR ASSESSMENT OF OXIDATIVE STRESS IN MEN WITH PATHOSPERMIA AND TYPE 1 DIABETES].

This study introduces a method for assessing the individual degree of oxidative stress (integral indicator) in men with pathospermia and type 1 diabetes, based on lipid peroxidation parameters. The study population consisted of three groups of patients. The study group included 15 men with type 1 diabetes (mean age 28 ± 3.8 years) and abnormal semen analyses: oligozoospermia, asthenozoospermia and oligoasthenozoospermia. The comparison group consisted of 20 people (average age 30 ± 2.5 years) without type 1 diabetes, but with changes in semen, similar to those in the study group. The control group was formed of 30 men (mean age 28 ± 4.3 years) with complete reproductive function and without type 1 diabetes. The mechanisms of lipid peroxidation development were found to differ between patients with and without type 1 diabetes. In pathospermic patients without carbohydrate metabolism disorders, activation of lipid peroxidation processes was most pronounced at the stage of primary product formation--diene conjugates, while in patients with type 1 diabetes and pathospermia--at the stage of formation of ketodienes and conjugated trienes, and TBA- active products. It is recommended to take into account the integral indicator of the lipid peroxidation intensity in the development of methods for correction and prevention of reproductive disorders in men with type 1 diabetes and impaired spermatogenesis.

Cost to government and society of chronic kidney disease stage 1-5: a national cohort study.

BACKGROUND: Costs associated with chronic kidney disease (CKD) are not well documented. Understanding such costs is important to inform economic evaluations of prevention strategies and treatment options. AIM: To estimate the costs associated with CKD in Australia. METHODS: We used data from the 2004/2005 AusDiab study, a national longitudinal population-based study of non-institutionalised Australian adults aged ≥25 years. We included 6138 participants with CKD, diabetes and healthcare cost data. The annual age and sex-adjusted costs per person were estimated using a generalised linear model. Costs were inflated from 2005 to 2012 Australian dollars using best practice methods. RESULTS: Among 6138 study participants, there was a significant difference in the per-person annual direct healthcare costs by CKD status, increasing from $1829 (95% confidence interval (CI): $1740-1943) for those without CKD to $14 545 (95% CI: $5680-44 842) for those with stage 4 or 5 CKD (P < 0.01). Similarly, there was a significant difference in the per-person annual direct non-healthcare costs by CKD status from $524 (95% CI: $413-641) for those without CKD to $2349 (95% CI: $386-5156) for those with stage 4 or 5 CKD (P < 0.01). Diabetes is a common cause of CKD and is associated with increased health costs. Costs per person were higher for those with diabetes than those without diabetes in all CKD groups; however, this was significant only for those without CKD and those with early stage (stage 1 or 2) CKD. CONCLUSION: Individuals with CKD incur 85% higher healthcare costs and 50% higher government subsidies than individuals without CKD, and costs increase by CKD stage. Primary and secondary prevention strategies may reduce costs and warrant further consideration.

Direct medical cost of type 2 diabetes in singapore.

Due to the chronic nature of diabetes along with their complications, they have been recognised as a major health issue, which results in significant economic burden. This study aims to estimate the direct medical cost associated with type 2 diabetes mellitus (T2DM) in Singapore in 2010 and to examine both the relationship between demographic and clinical state variables with the total estimated expenditure. The National Healthcare Group (NHG) Chronic Disease Management System (CDMS) database was used to identify patients with T2DM in the year 2010. DM-attributable costs estimated included hospitalisations, accident and emergency (A&E) room visits, outpatient physician visits, medications, laboratory tests and allied health services. All charges and unit costs were provided by the NHG. A total of 500 patients with DM were identified for the analyses. The mean annual direct medical cost was found to be $2,034, of which 61% was accounted for by inpatient services, 35% by outpatient services, and 4% by A&E services. Independent determinants of total costs were DM treatments such as the use of insulin only (p<0.001) and the combination of both oral medications and insulin (p=0.047) as well as having complications such as cerebrovascular disease (p<0.001), cardiovascular disease (p=0.002), peripheral vascular disease (p=0.001), and nephropathy (p=0.041). In this study, the cost of DM treatments and DM-related complications were found to be strong determinants of costs. This finding suggests an imperative need to address the economic burden associated with diabetes with urgency and to reorganise resources required to improve healthcare costs.

Structural and functional assessment of the brain in European Americans with mild-to-moderate kidney disease: Diabetes Heart Study-MIND.

BACKGROUND: Advanced chronic kidney disease (CKD) is associated with altered cerebral structure and function. Relationships between mild-to-moderate CKD and brain morphology and cognitive performance were evaluated in European Americans (EAs). METHODS: A total of 478 EAs with estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2) and urine albumin:creatinine ratio (UACR) < 300 mg/g, most with type 2 diabetes (T2D), were included. Measures of total intracranial volume (TICV), cerebrospinal fluid volume, total white matter volume (TWMV), total gray matter volume (TGMV), total white matter lesion volume (TWMLV), hippocampal white matter volume (HWMV) and hippocampal gray matter volume (HGMV) were obtained with magnetic resonance imaging. Cognitive testing included memory (Rey Auditory Visual Learning Test), global cognition (Modified Mini-Mental State Examination) and executive function (Stroop Task, Semantic Fluency, Digit Symbol Substitution Test). Associations with CKD were assessed using log-transformed eGFR and UACR, adjusted for age, sex, body mass index, smoking, hemoglobin A1c, blood pressure, diabetes duration, cardiovascular disease and education. RESULTS: Participants were 55.2% female, 78.2% had T2D; mean ± SD age 67.6 ± 9.0 years, T2D duration 16.4 ± 6.5 years, eGFR 92.0 ± 22.3 mL/min/1.73 m(2) and UACR 23.8 ± 39.6 mg/g. In adjusted models, eGFR was negatively associated with TICV only in participants with T2D [parameter estimate (ß): -72.2, P = 0.002]. In non-diabetic participants, inverse relationships were observed between eGFR and HGMV (ß: -1.0, P = 0.03) and UACR and normalized TWMLV (ß: -0.2, P = 0.03). Kidney function and albuminuria did not correlate with cognitive testing. CONCLUSIONS: In EAs with mild CKD enriched for T2D, brain structure and cognitive performance were generally not impacted. Longitudinal studies are necessary to determine when cerebral structural changes and cognitive dysfunction develop with progressive CKD in EAs.

Vascular access choice in incident hemodialysis patients: a decision analysis.

Hemodialysis vascular access recommendations promote arteriovenous (AV) fistulas first; however, it may not be the best approach for all hemodialysis patients, because likelihood of successful fistula placement, procedure-related and subsequent costs, and patient survival modify the optimal access choice. We performed a decision analysis evaluating AV fistula, AV graft, and central venous catheter (CVC) strategies for patients initiating hemodialysis with a CVC, a scenario occurring in over 70% of United States dialysis patients. A decision tree model was constructed to reflect progression from hemodialysis initiation. Patients were classified into one of three vascular access choices: maintain CVC, attempt fistula, or attempt graft. We explicitly modeled probabilities of primary and secondary patency for each access type, with success modified by age, sex, and diabetes. Access-specific mortality was incorporated using preexisting cohort data, including terms for age, sex, and diabetes. Costs were ascertained from the 2010 USRDS report and Medicare for procedure costs. An AV fistula attempt strategy was found to be superior to AV grafts and CVCs in regard to mortality and cost for the majority of patient characteristic combinations, especially younger men without diabetes. Women with diabetes and elderly men with diabetes had similar outcomes, regardless of access type. Overall, the advantages of an AV fistula attempt strategy lessened considerably among older patients, particularly women with diabetes, reflecting the effect of lower AV fistula success rates and lower life expectancy. These results suggest that vascular access-related outcomes may be optimized by considering individual patient characteristics.

Chelation therapy for the management of diabetic complications: a hypothesis and a proposal for clinical laboratory assessment of metal ion homeostasis in plasma.

In a recent article, we presented the hypothesis that decompartmentalized metal ions are a major contributor to the development of diabetic complications and supported the use of chelation therapy for the treatment of diabetic complications [Nagai R, Murray DB, Metz TO, Baynes JW. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes 2012;61:549-59]. Evidence in support of this hypothesis included the observation that many drugs used in the treatment of diabetes are chelators, that advanced glycation end product (AGE) inhibitors and AGE breakers lack carbonyl-trapping or AGE-breaker activity but are potent chelators, and that simple copper chelators inhibit vascular pathology in diabetes and aging. In the present article, we extend this hypothesis, proposing the interplay between copper and iron in the development of pathology in diabetes and other chronic age-related diseases, including atherosclerosis and neurodegenerative diseases. We also discuss the need and provide a framework for the development of a clinical laboratory test to assess plasma autoxidative catalytic activity and transition metal homeostasis in vivo.

Assessment of high cardiovascular risk profiles for the clinician.

Diabetes mellitus (DM) is a major cardiovascular (CV) risk factor. General Framingham Risk Profile (GFRP) and World Health Organization/International Society of Hypertension (WHO/ISH) charts were used to assess CV risk in DM in Oman. The GFRP identified more patients with medium-risk DM; GFRP and WHO/ISH identified essentially equal numbers at very high risk. These were then used to evaluate statin usage in Oman, including economics. Google lists innumerable tools from organizations, hospitals, practitioners, magazines, societies, clinics, and medical associations. The GFRP and WHO/ISH calculations provided useful DM assessment of populations in Oman. Other major risk models are Adult Treatment Panel III, based on Framingham, and Reynolds Risk Score; the latter incorporates other factors such as family history, high-sensitivity C-reactive protein, and hemoglobin A(1c) (in DM). These models are useful in assessing specific populations. Individual practitioners with limited time may just evaluate patients as low, medium, and high CV risk based on general knowledge and then treat.

Epidemiology, mechanisms, and management of diabetic gastroparesis.

Recent evidence of the significant impact of gastroparesis on morbidity and mortality mandates optimized management of this condition. Gastroparesis affects nutritional state, and in diabetics it has deleterious effects on glycemic control and secondary effects on organs that increase mortality. First-line treatments include restoration of nutrition and medications (prokinetic and antiemetic). We review the epidemiology, pathophysiology, impact, natural history, time trends, and treatment of gastroparesis, focusing on diabetic gastroparesis. We discuss pros and cons of current treatment options, including metoclopramide. Second-line therapeutic approaches include surgery, venting gastrostomy or jejunostomy, and gastric electrical stimulation; most of these were developed based on results from open-label trials. New therapeutic strategies for gastroparesis include drugs that target the underlying defects, prokinetic agents such as 5-hydroxytryptamine agonists that do not appear to have cardiac or vascular effects, ghrelin agonists, approaches to pace the stomach, and stem cell therapies.

Epidermal nerve fiber quantification in the assessment of diabetic neuropathy.

Assessment of cutaneous innervation in skin biopsies is emerging as a valuable means of both diagnosing and staging diabetic neuropathy. Immunolabeling, using antibodies to neuronal proteins such as protein gene product 9.5, allows for the visualization and quantification of intraepidermal nerve fibers. Multiple studies have shown reductions in intraepidermal nerve fiber density in skin biopsies from patients with both type 1 and type 2 diabetes. More recent studies have focused on correlating these changes with other measures of diabetic neuropathy. A loss of epidermal innervation similar to that observed in diabetic patients has been observed in rodent models of both type 1 and type 2 diabetes and several therapeutics have been reported to prevent reductions in intraepidermal nerve fiber density in these models. This review discusses the current literature describing diabetes-induced changes in cutaneous innervation in both human and animal models of diabetic neuropathy.

Bioimaging assessment and effect of skin wound healing using bone-marrow-derived mesenchymal stromal cells with the artificial dermis in diabetic rats.

We investigate the relationship between the fate and healing effect of transplanted mesenchymal stromal cells (MSCs) in a rat diabetic skin wound model. Rats are treated with streptozotocin to induce diabetic conditions. A full-thickness skin defect is surgically made on the head of diabetic rats, and covered with an artificial dermis impregnated with either bone marrow cells (BMCs) or bone-marrow-derived MSCs from firefly luciferase (luc) transgenic (Tg) rats. Wound healing is evaluated using planimetry and immunohistochemistry, and the fate of transplanted MSCs is determined using in-vivo luminescent imaging. The diabetic wound treated with MSCs-impregnated artificial dermis is significantly smaller than that treated with artificial dermis alone at 1 week postoperation. Photons of luc+ MSCs are detected at the transplanted site during healing (3 weeks), whereas those of luc+ MSCs are depleted only after 1 week postimplantation. Immunohistochemistry at the healing site treated with MSCs demonstrates that CD31+ vessels increase with expression of vascular endothelial growth factor, suggesting that MSCs accelerate angiogenesis. These findings suggest that transplanted MSCs could be retained at wound sites during the healing process in a diabetic rat model, and subsequently promote wound healing through angiogenesis.

Type 2 diabetes: assessment of endothelial lesion and fibrinolytic system markers.

This study aimed to investigate whether endothelial cells are damaged and to evaluate fibrinolytic system function in patients with type 2 diabetes. For this proposal, plasma levels of von Willebrand factor (an endothelial marker of injury), homocysteine (an inductor of endothelial injury), D-dimer (a marker of coagulation cascade activation) and plasminogen activator inhibitor-1 (a fibrinolysis marker) were measured in individuals with both type 2 diabetes and high blood pressure, with type 2 diabetes, with high blood pressure and in healthy control individuals. No significant differences among groups were observed for von Willebrand factor and homocysteine plasma levels. The type 2 diabetes and high blood pressure group presented a significant difference to the other groups for D-dimer and also presented high values for plasminogen activator inhibitor-1. The high blood pressure group and type 2 diabetes group presented separately higher values of plasminogen activator inhibitor-1 compared with the control group. High levels of D-dimer and plasminogen activator inhibitor-1 in patients with type 2 diabetes and high blood pressure with normoalbuminuria therefore indicate a state of hypercoagulability and hypofibrinolysis, despite no evident microvascular injury supported by normal levels of von Willebrand factor and homocysteine.