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Microencapsulating pancreatic islets in immunoprotective hydrogels is a promising cellular therapy for type 1 diabetes. However, a major factor limiting the encapsulated islet efficacy is inflammatory/hypoxia mediated oxidative stress, resulting in impaired insulin secretion and ultimately islet cell death. Fucoidan, a natural polysaccharide, possess strong anti-oxidant properties but its effects on beta cells and encapsulation is unknown. Here, we assessed the anti-oxidant effect of fucoidan on beta cells and its effect on encapsulated beta cell viability and function, using fucoidans extracted from two different seaweeds, namely Fucus vesiculosus (FF) and Ascophyllum nodosum (FA). FF exhibited significantly higher total antioxidant capacity and free radical scavenging activity, significantly alleviating intracellular oxidative stress in INS1E beta cells, when compared to FA. In presence of high glucose, FF fucoidans significantly increased insulin secretion both in a dose- and time-dependent manner. Viability, ATP levels and high-glucose responsiveness of rat islets encapsulated in fucoidan-containing hydrogel (Fucogel) microcapsules were significantly higher compared to those encapsulated in pure alginate microcapsules. Similar results were obtained with INS1E pseudo-islets and neonatal pig islets. Fucogels can provide a redox-modulatory niche and an immune barrier in the same time, presenting as an outstanding biomaterial for bioengineered immunoprotective beta cell replacement devices.

Neuropathy is the most frequent symptomatic complication of diabetes. Diabetic polyneuropathy (DPN) is the most common variety of neuropathy, which represents chronic symmetrical sensorimotor polyneuropathy. (DPN) typically begins as a generalized asymptomatic dysfunction of peripheral nerve fibers, which may be revealed by electromyography. However, nerve conduction study (NCS) is a sensitive method for early detecting of peripheral neuropathy. We have performed NCS in 69 children with poorly compensated diabetes type I aged 7-18 y. Study protocol included testing of peripheral motor and sensory nerve conduction velocities (NCVs) and compound motor and sensory nerve action potential amplitudes. We revealed subclinical abnormalities, which were symmetric, suggestive of DPN and reflecting disorders of predominantly motor, rather than sensory nerves. In addition, nerve conduction abnormalities were correlated with high HbA1c level, patient age and disease (diabetes) duration. Poor metabolic control was the most important contributor to abnormal electrophysiological parameters.

Introduction: Cardiomyopathy in type 1 diabetes (T1D) is accompanied by impaired mitochondrial function, oxidative stress and lipotoxicity. We showed that cardiomyocyte (CM) Krüppel-like factor 5 (KLF5) is increased in streptozotocin-induced T1D and induces Peroxisome Proliferator Activated Receptor (PPAR)α in mice. Hypothesis: KLF5 upregulation by FOXO1 induces diabetic cardiomyopathy (DbCM). Methods and Results: Analyses in CM from diabetic patients showed higher KLF5 mRNA levels compared to non-diabetic individuals. In vitro mechanistic and in vivo analyses in αMHC- Foxo1 -/- mice revealed that FOXO1 stimulates KLF5 expression via direct promoter binding. Genetic inhibition of CM FOXO1 alleviated DbCM. Additionally, AAV-mediated CM-specific KLF5 overexpression in C57Bl/6 (WT) mice induced cardiac dysfunction. Mice with CM-specific KLF5 constitutive expression (αMHC-rtTA- Klf5 ), which we generated, recapitulated cardiomyopathy without T1D. Moreover, Pparα -/- mice with T1D, had higher CM-KLF5 levels and developed DbCM, suggesting that KLF5-driven DbCM is PPARα-independent. Additionally, CM-KLF5 induced oxidative stress through increased NADPH oxidase (NOX)4 expression and lower mitochondria abundance. Conversely, KLF5 inhibition prevented NOX4 upregulation and superoxide formation. Furthermore, CM-KLF5 promoted NOX4 expression via direct promoter binding. Antioxidant treatment in diabetic WT and αMHC-rtTA- Klf5 mice alleviated cardiac dysfunction partially, suggesting other pathways that contribute in KLF5-induced DbCM. For that, we performed cardiac lipidome analysis where we found clustering of αMHC-rtTA- Klf5 with diabetic WT mice. Of note, KLF5 inhibition in diabetic mice resulted in similar lipidome with non-diabetic WT mice. Individual lipid species analysis showed increased ceramide accumulation in diabetic WT and αMHC-rtTA- Klf5 mice that was reversed upon KLF5 inhibition. Thus, CM-KLF5 activation correlates with cardiac ceramide accumulation, that has been associated with cardiac lipotoxicity. Conclusions: In conclusion, T1D stimulates FOXO1, which induces CM-KLF5 expression that leads to oxidative stress and DbCM in a non-PPARα-dependent manner, as well as to cardiac ceramide accumulation.

Diabetes is a risk factor of heart failure and leads to cardiac dysfunction, a condition named diabetic cardiomyopathy (DCM). NAD redox imbalance is observed in diabetic tissues. However, whether NAD redox imbalance promotes cardiac dysfunction in DCM remains unknown. The objective of this study is to determine the causal role of NAD redox imbalance in DCM.Type 1 diabetes was induced in C57BL6 mice by streptozotocin (STZ) injections, and DCM was allowed to develop for 16 weeks. Diabetes-induced chronic stress led to systolic and diastolic cardiac dysfunction along with a lowered NAD/NADH ratio. The diabetogenic protocol was applied to control and cardiac-specific Ndufs4-KO mice (cKO), a mouse model with lowered cardiac NAD/NADH without baseline cardiac dysfunction. Analyses of blood glucose and >200 metabolites in plasma showed no significant change in diabetic control and diabetic cKO mice, suggesting that their hearts experienced similar diabetic stress. Diabetic cKO hearts showed lowered NAD/NADH, aggravated contractile and relaxation dysfunction compared to the diabetic control hearts in both sexes. The data suggest that NAD redox imbalance exacerbated DCM. Collagen staining and transcript analyses of fibrosis-related genes showed no change in diabetic cKO hearts, signifying that the exacerbated dysfunction was due to cardiomyocyte dysfunction. A global protein acetylation was promoted in the diabetic cKO hearts with an increase in SOD2 acetylation levels at lysine-68 (SOD2-K68Ac) and enhanced protein oxidation. Diabetic cKO mice displayed enhanced levels of TnI S150 phosphorylation (TnI-S150Pi), but not phosphorylation of TnI-S23/24 or MyBPc-S282. These data suggest that enhanced oxidative stress and altered myofilament Ca 2+ sensitivity via TnI-S150Pi are responsible for the NAD redox imbalance-exacerbated DCM.To confirm the role of NAD redox imbalance in DCM, we elevated cardiac NAD levels in diabetic cKO mice by cardiac-specific expression of NAMPT. Expression of NAMPT in the heart improved cardiac systolic and diastolic function in diabetic cKO hearts. This was due to increased NAD/NADH ratio and reversed pathogenic mechanisms (lowered SOD2-K68Ac and TnI-S150Pi). This study supports the causal role of NAD redox imbalance in DCM.

Diabetes is a serious, long-term condition that occurs when the body cannot produce any or enough insulin or cannot effectively use the insulin it produces. Diabetes type I (DT1) -a chronic, life-long, non-curable disease with high percentage of complications. Several studies have proved that special diet, appropriate exercises and long-term lifestyle changes can help in managing of diabetes, holding it in a compensated form and decreasing complications severity. However, it’s not easy to manage DT1. All over the world exist governmental and nongovernmental organizations, called “School of Diabetes” that educate patients in how to control their disease. The aim of this paper is to propose a patient-specific, multilevel and predictive model, using meal and exercise guidelines based on a comparative analysis of modern Schools of Diabetes (USA, Russia, China), having a problem-oriented dataset built upon the Diabetes Data Set (UCI) and personal data records from a targeted group of 5 patients with DT1. Obtained results from creating 5 patientspecific models and a 3 month investigation period show that the proposed modelling technique can decrease patients’ HbA1c and heart rate values.

Background: Medical devices are increasingly being reported to cause contact allergic dermatitis reactions. Objective: Review of patients with diabetes type I referred for suspected allergic contact dermatitis to insulin pump or glucose sensor systems. Method: We have reviewed 11 referred diabetes mellitus patients investigated for allergic contact dermatitis reactions to medical devices and specifically Dexcom G6®. Extracts from the medical devices were analysed. Results: The majority of patients was children, the majority had relevant allergies and particularly allergy to isobornyl acrylate which was also found in the glucose sensor system Dexcom G6®. Conclusions: The following case reports bring in focus the fact that patients sensitized through use of one medical device and being advised the use of another, or find another product for a while useful, are not by necessity free from future episodes of allergic contact dermatitis. The case reports emphasize the need for collaboration since it is impossible for even well-equipped laboratories to properly investigate the medical devices when information on the substances used in production is not uniform and complete and material to investigate are scarce. The importance of adequate patch test series and testing with own material and furthermore the importance to re-analyse medical devices and re-analyse test data are emphasized. (Less)

Introduction: Adults with type 1 diabetes (T1D) have at least a two-fold risk of developing coronary artery disease (CAD) compared to adults without diabetes (Non-DM); Periodontal disease is also increased in T1D, due at least in part to hyperglycemia. There is increasing recognition that periodontal disease is linked to CAD through systemic inflammation, which may be a mechanism through which diabetes increases CAD. In this study, we examined the association between self-reported gum disease and coronary artery calcium (CAC) in the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) cohort. Methods: There were 1416 adults (652 with T1D, 764 Non-DM, mean±SD age 37±8years, 48% men) enrolled in the CACTI cohort in 2000. The cohort completed four visits between 2000 and 2018: at baseline and after 3, 6 and 14 years of follow-up. At each visit, participants self-reported gum disease diagnosis. CAC volume was measured by computed tomography at each visit and was square root transformed for analysis. Linear mixed effects models were used to examine the association between self-reported gum disease and change in CAC volume. Results: At baseline, 12% of Non-DM and 16% of T1D participants (p=0.054) reported having gum disease. The prevalence of gum disease increased across visits to 18% in participants with T1D vs. 13% in Non-DM participants at visit 2 (p=0.01); 22% in participants with T1D at visit 3 vs. 14% in Non-DM participants (p=0.0009) and 25% in participants with T1D vs. 17% in Non-DM participants at visit 4 (p=0.023). Self-reported gum disease was associated with a significantly greater increase in CAC volume over time (Table, p Conclusion: Periodontal disease prevalence was increased in adults with T1D, and was independently associated with increase in CAC volume over 14 years of follow-up in this population.

Introduction: Brachial artery distensibility is reduced in type 1 diabetes and can predict future coronary artery disease (CAD). Although women generally have reduced cardiovascular risk as compared with men, type 1 diabetes increases cardiovascular risk to a greater degree in women such that their cardiovascular risk matches that in men. Sex differences in arterial distensibility may contribute to the increased cardiovascular risk in women with type 1 diabetes. Hypothesis: We tested the hypothesis that brachial distensibility differed by sex and by diabetes status in a cohort of adults with and without type 1 diabetes. Methods: We measured brachial distensibility via DynaPulse instrument (PulseMetric, San Diego, CA) in 268 adults with type 1 diabetes (mean age 44±9 years) and 373 adults without diabetes (mean age 47 ±8 years) who completed clinical study visits 8±0.89 years apart. A linear mixed model was used to calculate mean brachial distensibility by age at the study visits in men and women by diabetes status. This model was adjusted for age, sex, diabetes status, and visit number. An age group*sex*diabetes interaction was used to calculate least squares means (LSmeans) brachial distensibility and examine trends in each stratum of interest. Results: Brachial distensibility decreases with increasing age (Figure 1). This reduction is greatest for women with type 1 diabetes and smallest for men without diabetes, with decreases from the oldest to youngest age group of 2.6 %/mmHg and 0.98 %/mmHg, respectively. Prior to the age of 40 years, women have better brachial distensibility than men regardless of diabetes status, while men have better brachial distensibility than women beginning in the 40-45 years age group. Conclusions: Women experience a steeper decline in their brachial distensibility than men regardless of diabetes status. Rapid reduction in brachial distensibility may contribute to the increases in cardiovascular risk in women with type 1 diabetes.

Introduction: Pulmonary function is reduced and arterial stiffening is increased in type 1 diabetes. While increased arterial stiffness is associated with greater risk of cardiovascular disease in type 1 diabetes, the association between reduced pulmonary function and health outcomes in this population is less understood. The subendocardial viability ratio (SEVR), a ratio comparing myocardial perfusion to cardiac workload, may provide useful information pulmonary function and myocardial hypoxemia in the context of pulmonary function in type 1 diabetes. Hypothesis: We tested the hypothesis that impaired pulmonary function (i.e., percent predicted forced vital capacity [FVCpp], forced expiratory volume at 1 second [FEV 1 pp], and FEV 1 /FVC), is associated with reduced SEVR in adults with and without type 1 diabetes. Methods: We conducted pulse wave analysis on 208 adults with type 1 diabetes (mean age 52±9 years) and 285 adults without diabetes (mean age 55±8 years) to obtain the outcome measure of SEVR. All participants underwent non-bronchodilated spirometry testing to obtain FVCpp, FEV 1 pp, and FEV 1 /FVC. Independent t-tests were used to test the difference by diabetes status in each pulmonary function measure and the SEVR. Linear regression models were used to test the association between each pulmonary function measure and SEVR after adjustment for age, sex, diabetes status, smoking status, and heart rate. Results: FVCpp and FEV 1 pp were both significantly lower in type 1 diabetes (87.5% and 85.6%, respectively) compared to controls without diabetes (95.6% and 94.9%, respectively; p1 /FVC (97.5% vs. 99.0%, p=0.07). SEVR was also significantly lower in type 1 diabetes (137.5 vs. 159.6, p1 pp were associated with SEVR. FVCpp was associated with 0.086 greater SEVR per SD (p=0.002), and FEV 1 pp was associated with 0.058 greater SEVR per SD (p=0.04). FEV 1 /FVC was not significantly associated with SEVR (p=0.37). In the model testing FVCpp, type 1 diabetes was associated with 0.18 lower SEVR (p1 pp, type 1 diabetes was associated with 0.19 lower SEVR (p1 /FVC, type 1 diabetes was still associated with 0.20 lower SEVR (p Conclusions: In conclusion, reduced pulmonary function was associated with reduced SEVR in cross-sectional analysis, but type 1 diabetes remained independently associated with reduced SEVR after accounting for reduced pulmonary function. The mechanism between pulmonary function and SEVR is unclear, but future research may reveal pathways or shared etiologies in type 1 diabetes.

Introduction: Increasing incidence of type 1 diabetes (T1D) coupled with increasing life expectancy have resulted in an unprecedented number of older adults living with T1D. However, little is known about the burden of aging and diabetes-related complications in this unique group. We hypothesized that older adults with T1D would have greater diabetes and aging-related burden compared to an age, sex, race/ethnicity, and education-matched group of older adults with type 2 diabetes (T2D). Methods: We compared the following characteristics by diabetes type among older adults (aged ≥60) with T1D (n=805) and T2D (n=249) from the Study of Longevity in Diabetes (SOLID) using chi-squared tests: diabetes history (age of onset, diabetes duration); diabetes-related complications (retinopathy, neuropathy, nephropathy, severe hypo- and hyperglycemia resulting in hospitalization/emergency department utilization), cardiovascular disease (stroke, MI, coronary bypass), and geriatric syndromes (depression, incontinence, memory problems and functional impairment). Results: Average age at diagnosis and duration of diabetes, respectively, were 28 years old and 40 years duration for T1D and 56 years old and 13 years duration for T2D (Table 1). Compared to T2D, participants with T1D were more likely to report history of retinopathy, neuropathy, nephropathy, lifetime hypo- and hyperglycemic events resulting in hospitalization/emergency department utilization, and history of a coronary bypass. By contrast, those with T2D were more likely to be incontinent and have functional impairment. Conclusions: Our results show that diabetes-related complications are more prevalent in those with T1D than in comparable adults with T2D, while certain geriatric syndromes were more prevalent in those with T2D. Older adults with T1D are a growing population with unique diabetes-specific and aging-related considerations. Additional research is needed to understand the interplay of aging and diabetes in this group to inform patient care .

Introduction: Studies have shown poorer cognitive function in children and adolescents with type 1 diabetes (T1D) as compared to non-diabetic peers. However, little is known about cognitive function in older adults with T1D. Hypothesis: We hypothesized that older adults with T1D and type 2 diabetes (T2D) would have greater cognitive impairment than age, sex, race/ethnicity, and education-matched controls without diabetes. Methods: We compared baseline cognitive impairment among older adults (aged ≥60) from the Study of Longevity in Diabetes (SOLID) with T1D (n=771), T2D (=234) and no diabetes (n=253). Cognitive tests assessed three cognitive domains identified via factor analysis (language, executive function, episodic memory). All cognitive test scores were standardized and cognitive impairment was defined as 1.5 SD below the mean. In logistic regression models adjusted for age, sex, education, and race/ethnicity, we examined the association between diabetes status (T1D, T2D or no diabetes) and cognition on each cognitive domain and on global cognition (average of scores on the 3 domains). Results: In adjusted regression models, compared to older adults without diabetes, those with T1D were more likely to have impaired cognitive function on the language (OR=2.13, 95% CI: 1.08, 4.17) and executive function domains (OR=2.66, 95% CI: 1.36, 5.22). No significant differences in global cognitive impairment or impairment on the episodic memory domain were observed for T1D and no significant differences on any domain were observed for T2D. Conclusions: Our findings suggest that older adults with T1D have greater cognitive impairment than their peers without diabetes; findings were specific to the language and executive function domains, with episodic memory being unaffected. No increase in cognitive impairment was observed for older adults with T2D. Additional research is needed to understand the causes and potentially modifiable factors associated with impaired cognition among older adults with T1D.

Background: Type 1 diabetes mellitus (T1DM) is a common chronic disorder of childhood and adolescence. T1DM induced cardiomyopathy has a different entity than T2DM as it relies on different pathophysiological mechanisms, and rarely coexists with hypertension and obesity. Evaluation of right ventricular (RV) function in diabetic patients has been neglected despite the important contribution of RV to the overall cardiac function that affects the course and prognosis of diabetic cardiomyopathy (DCM). Objective: To assess RV myocardial performance in asymptomatic T1DM using speckle tracking and standard echo parameters and correlate it with functional capacity using treadmill stress test. Patients and methods: Thirty-nine patients with TIDM (Group 1, mean age 18.2 ± 1.7y, BMI = 26.2 ± 3.9 kg/m2), without cardiac problems and 15 apparently healthy matched subjects as a control group (Group 2, mean age 18.8 ± 2.3 y, BMI = 22.8 ± 3.3 kg/m2) were enrolled. RV function was evaluated using conventional, tissue Doppler and 2D speckle tracking echocardiography (2D-STE). The peak RV global longitudinal strain (RV-GLS) was obtained. Functional capacity was assessed by treadmill exercise test and estimated in metabolic equivalent (METs). Results: In this study; the diabetic group showed statistically highly significant decrease in the average RV-GLS (−14.0 ± 6.9 in group 1 vs. −22.7 ± 2.5 in group 2, P

Good management of diabetes requires at the same time self-regulation behaviour and a balanced involvement of family components. This cross-sectional study’s aims were: understanding fear of injections and perceptions of family conflicts in preadolescents and adolescents with type 1 diabetes mellitus and their mothers, comparing their perceptions, and identifying the risk factors impacting patients’ quality of life. Eligibility criteria were: treatment for diabetes mellitus type I, currently aged 10–18 years, attending the hospital for annual hospital follow-ups. Exclusion criteria were: intellectual disabilities, inability to complete questionnaires alone and neuropsychiatric illness with active pharmacotherapy. The study design was cross-sectional. Participants were one hundred and two patients (Mean age = 14.6, SD = 2.4, age range = 10–19 years, Females = 52 and Males = 50) and their mothers (Mean age = 46.9, SD = 6.2, age range = 27–63 years), who filled in self and proxy-report questionnaires (N total= 204). The results showed that 20% of patients and 14.7% of their mothers reported clinical scores for fear of self-injection and blood testing. The mothers reported lower fear of injecting and higher family conflicts compared with the patients. Age, fear of injecting and family conflicts were significantly associated with patients’ quality of life perceptions. Clinical considerations and recommendations are given based on the empirical results.

Aim. To study the specific activity of the microemulsion form of the matrix insulin transdermal delivery system in vivo on the experimental streptozotocin model of type I diabetes.Materials and methods.Male rats (n = 25) were randomized to the experimental and control groups. TDS insulin with a microemulsion composition was applicated to the animals of the experimental group (n = 15) for 4 days with daily replacement of TDS and control of the glycemia level. The glycemia level of the control group rats (n = 10) was determined throughout the experiment. The blood glucose concentration was measured using glucometer One Touch Select (USA). Results.The average blood glucose level in experimental group was 28.4 ± 2.3 mmol/l before application of TDS insulin. The average glycemic index was 21.2 ± 3.1 mmol/l (p < 0.001) during of TDS application. The blood glucose decrease was 26 ± 8% relative to baseline values. The glycemia was 28.4 ± 1.4 mmol/l in the control group rats throughout the experiment.Conclusion.A significant decrease of blood glucose level with TDS insulin application in rats with experimental type 1 diabetes demonstrates the existence of the specific activity of the microemulsion matrix transdermal delivery system of insulin.

According to the results of immunological, biochemical studies of blood serum and oral fluid in 92 children with autoimmune diabetes mellitus in the period of the mixed occlusion investigated the cellular, humoral links of immunity and established the balance of bone metabolism at various stages of compensation endocrinopathy. Data were compared with similar parameters 48 children of I–II health groups. The obtained results allow asserting that with increasing severity of disease in children with autoimmune diabetes mellitus there is a significant weakening of the recovery processes of bone tissue, the development of local immunodeficiency, depression of cellular immunity in the presence of pronounced immunometabolic disorders.

Vascular complications induced by diabetes constitute the principal cause of morbidity and mortality in diabetic patients. It’s reported that carvacrol (CAR) possess a wide range of biological activities. The effect of CAR on diabetes-induced vasculopathy remains unknown. In this study, diabetic mice were created by intraperitoneal injection of streptozotocin to investigate whether CAR provided a protective effect against diabetes-induced vasculopathy and the underlying mechanisms. We found that CAR decreased blood glucose level of diabetic mice. Moreover, CAR ameliorated diabetes-induced aorta morphological alteration, evidenced by increased thickness of intima-media width and increased number of vascular smooth muscle cell (VSMC) layer. Further studies revealed that CAR inhibited the hypercontractility in the aorta of diabetic mice and VSMC in response to hyperglycemia, evidenced by decreased expression of smooth muscle (SM)-α-actin, and increased expression of Ki67 and PCNA. Furthermore, PI3K/Akt signal pathway was inhibited in the aorta of diabetic mice and VSMC in response to hyperglycemia, while CAR treatment activated PI3K/Akt signaling pathway. In conclusion, our results strongly suggested that CAR played a protective role in diabetes-induced aorta hypercontractility, possibly by activating PI3K/Akt signaling pathway. CAR is a potential drug for the treatment of diabetic vasculopathy.

Congenital heart defects (CHDs) are the leading cause of infant morbidity and mortality. The etiology is multifactorial and maternal pre-existing diabetes is a non-genetic risk factor, which perturbs embryonic development and increases the risk of CHDs by 3-to 5-fold. We have previously demonstrated that maternal hyperglycemia (matHG) leads to an increase in reactive oxygen species and reduced nitric oxide bioavailability and found an epigenetic mechanism for altered expression of Notch1 , a gene critical for endocardial cushion formation, cardiomyocyte (CM) differentiation, outflow tract development, and ventricular trabeculation. We also noted spectrum of cardiac defects in developing embryos when exposed to increased severity of matHG, the underlying molecular basis of which remains unclear. To this end, we hypothesized that matHG alters gene-expression of cardiac progenitor cells in a spatiotemporal manner to predispose embryos to diabetes-induced CHDs. To test cell-specific responses to HG, murine embryonic cell-lines [AVM, atrioventricular cushion mesenchymal and ECC1, endothelial] were cultured in normal (NG, 5.5mM) and different doses of HG (10, 25 and 40mM). RNA-seq was performed after 48hrs of treatment and gene-set enrichment analysis of AVM NG and HG (25mM) identified genes associated with metabolic processes, response to oxidative-stress (OS), chromatin regulation and altered Wnt/Notch signaling pathways with HG. Similarly, RNA-seq analysis of protein-coding genes in ECC1-HG revealed increasing numbers (8, 311, 1072) of differentially expressed genes compared to NG, and associated with OS, ATP-synthesis, cardiac development, suggesting a dose-response relationship. Additionally, a streptozotocin-induced murine model of diabetes was used to characterize the influence of matHG dose on CHD susceptibility. Examination of E9.5, E11.5, E13.5 embryos displayed defects in CM proliferation, ventricular trabeculation, thin ventricular myocardium and septal defects with matHG. Together, our in vitro transcriptomic analysis and in vivo histologic characterization support a variable molecular and phenotypic response to hyperglycemic stress during cardiac development that contribute to matHG associated CHDs.

Introduction: Cardiovascular events, i.e. cardiac arrest and arrhythmia, are the leading cause of death among patients with end-stage renal disease (ESRD). Kidney transplantation (KT) reduces mortality and is the preferred treatment for ESRD. Generally, preemptive KT, especially with a living donor, reduces mortality over KT after dialysis initiation. Mortality reduction by preemptive KT may vary by cause of ESRD. Hypothesis: Decreased all-cause mortality after preemptive KT varies by cause of ESRD. Methods: We studied 56,927 adult living donor KT recipients from 2000 to 2017 using the Scientific Registry of Transplant Recipients. We compared all-cause mortality in preemptive living donor KT recipients to those who underwent living donor KT within a year of starting dialysis, stratifying by cause of ESRD. We estimated the adjusted hazard ratio (aHR) of mortality comparing KT with Results: Compared to recipients on Conclusions: Our findings suggest that for particular ESRD patients, like those with type I diabetes, early counseling regarding preemptive KT and finding a living donor are imperative. Future studies should assess whether expedited review of potential living donors for these patients reduces mortality in this population at high risk of cardiovascular events.

Introduction: Severe hypoglycemia is common among those with type 1 diabetes (T1D). Hypoglycemia unawareness (HU) in T1D increases the risk of severe hypoglycemia more than five-fold. Prior work has established an association between severe hypoglycemia and impaired cognition. However, it is unknown if HU is associated with impaired cognition. Hypothesis: We hypothesized that HU would be associated with impaired cognition in a large cohort of older adults with T1D. Methods: We examined the association between HU and cognitive function using baseline data collected on 544 older adults with T1D from the Study of Longevity in Diabetes (SOLID). Self-reported HU was assessed using the 8-item Clarke Hypoglycemia Awareness Questionnaire, which captures frequency of hypoglycemia and awareness of symptoms. Participants with responses indicating ‘reduced awareness’ on ≥4 of the 8 items were categorized as having reduced awareness. Cognitive tests assessed four cognitive domains identified via factor analysis (language, executive function, episodic memory, attention). All cognitive test scores were standardized. Using generalized linear regression, we examined the association between HU and cognition on each of the four cognitive domains and on global cognition (average of scores on the 4 domains) in models adjusted for age and age, sex, education, race/ethnicity, and diabetes duration. Results: Overall, 27% of participants (n=149) had reduced hypoglycemia awareness. In fully adjusted models, compared to those with normal awareness, those with reduced hypoglycemia awareness had significantly lower scores on measures of language and global cognition; however, executive function, episodic memory and simple attention did not differ by HU status. Conclusions: Our results suggest that, among older adults with type 1 diabetes, HU may be associated with poorer cognition, specifically through language-related processes.

Introduction: Coronary artery disease (CAD) is especially burdensome among individuals with type 1 diabetes (TID). The AHA created metrics to monitor cardiovascular health (CVH) to promote primordial prevention. CVH metrics define 3 health behaviors (diet, physical activity, and smoking), and 4 health factors (BMI, total cholesterol, blood pressure and fasting glucose) as ideal, intermediate or poor based on set criteria. These CVH metrics have been shown to be related to cardiovascular outcomes in the general population. The purpose of this research is to describe the prevalence of CVH metrics in young adults with T1D, a group at particularly high risk for CAD , and assess the hypothesis that more favorable metrics protect against future hard CAD outcomes. Methods: Data are from the longitudinal Pittsburgh Epidemiology of Diabetes Complications (EDC) study. CVH metrics are defined by an average of measures taken at first visit and first follow up visit (1986-1990, “baseline”) for participants age ≥20 at study entry without prevalent CAD. CVH metrics were scored according to AHA criteria, with HbA1c in place of fasting glucose. Total CVH score (possible range 0-14) is the sum of subscores for each metric where poor=0, intermediate=1 and ideal=2. Cox proportional hazards models were used to assess the association between baseline CVH and CAD incidence during 25 years of follow-up. Results: Characteristics of the 463 individuals analyzed after exclusions (179 age Conclusions: CVH metric scores appear to be predictive of CAD in adults with T1D, demonstrating the value of promoting ideal CVH for CAD prevention.

Proteins are already used for more than 100 years to treat or prevent diseases in humans. It started in the early 1890s with “serum therapy” for the treatment of diphtheria and tetanus by Emile von Behring and others. The antiserum was obtained from immunized rabbits and horses. Behring received the Nobel Prize for Medicine in 1901 for this pioneering work on passive immunization. A next big step in the development of therapeutic proteins was the use of purified insulin isolated from pig or cow pancreas for the treatment of diabetes type I in the early 1920s by Banting and Best (in 1923 Banting received the Nobel Prize for this work). Soon after the discovery of insulin, the pharmaceutical company Eli Lilly started large-scale production of the pancreatic extracts for the treatment of diabetes. Within 3 years after the start of the experiments by Banting, already enough animal-derived insulin was produced to supply the entire North American continent. Compare this to the present average time-to-market of a new drug (from discovery to approval) of 13.5 years (Paul et al. 2010).

The article describes the infrequent disseminated necrobiosis lipoidica similar to a sarcoidosis form which developed at the five-year-old child affected by type 1 diabetes mellitus. The short review concerns the questions of an etiology, pathogenesis, clinical forms, diagnostics and the modern methods of treatment of the described pathology. In the review 26 sources of literature are used. The case is of interest to dermatovenereologists, endocrinologists, pediatricians.

Background: Diabetes education, with improvement in knowledge, attitudes and skills, leads to better control of the disease. The objective of this study was to assess knowledge of diabetic patients about symptoms, risk factors, complications and prevention . Methods: This cross-sectional study was carried out to define level of knowledge regarding diabetes among diabetic patients attending IPD and OPD from Geetanjali medical college and hospital in Udaipur, Rajasthan, India, during the study period of 1 st December 2015 to 30 th May 2016. A pre-constructed and pre tested questionnaire was used to assess the knowledge. Results: Among 300 respondents, males and females constituted 45% and 55% respectively. 96.0% aged ≥30 years. Nearly one third of patients were illiterates. About 64.3% of the patients have been diabetic since more than 5 years and majority of them 91.7% were of type II. Positive family history of diabetes was reported in 70% of patients. It was found that every patient under study knew that both genders could be involved with diabetes. The assessment regarding the knowledge of diabetes was good and they were having good knowledge about symptoms, risk factors and complications of diabetes. They also knew about the lifestyle which can prevent from diabetes . Conclusions: The overall average knowledge regarding diabetes was found among participants. Thus, still there is a need to provide periodic health education to the diagnosed patients so that this knowledge-application gap is narrowed down.

Diabetes increases the vulnerability of the heart to ischemic injury. Recent advances have shown that necroptosis is crucially involved in myocardial ischemia/reperfusion (I/R) injury. Our objectives were thus to extend our knowledge to whether and how necroptosis renders diabetic hearts more vulnerable to I/R injury, which involves activation of Ca 2+ -calmodulin-dependent protein kinase (CaMKII) by receptor-interacting protein 3 (RIP3). In this study, diabetes was induced by streptozotocin (40mg/kg, i.v.) and after 6 weeks, anesthetized open-chest diabetic and age-matched control C57 mice were subjected to 30-min regional ischemia (occlusion of LAD coronary artery) followed by 4-h reperfusion. Diabetic animals manifested significantly greater cardiac injury than their littermate controls. Notably, diabetic hearts were sensitized to I/R-induced myocardial necrosis, as evidenced by rise in lactate dehydrogenase (LDH) release and Evans blue dye (EBD) penetration. Notably, compared with control mice, the activation pattern of CaMKII in diabetic hearts subjected to I/R is altered by earlier advanced (60 min after reperfusion) phosphorylation and enhanced oxidation (21.5% increase). Then we proved that inhibition of CaMKII in early stage of I/R could effectively reduce myocardial necroptosis. Further, RIP3 expression and RIP3-CaMKII interaction are markedly enhanced in diabetic hearts during I/R. Inhibition of RIP3 markedly suppresses CaMKII activation and reduces necroptosis. Collectively, these findings identify enhanced RIP3-CaMKII pathway as a key regulator that increases myocardial necroptosis in diabetic I/R hearts.

Elevated plasma triglycerides (TG) and VLDL are often present in poorly controlled type 1 diabetes mellitus (T1DM). Furthermore, T1DM patients exhibit an increased risk of cardiovascular disease (CVD) despite normal or high HDL-cholesterol. There is a need for new mouse models to study T1DM lipid abnormalities because mice do not express cholesteryl ester transfer protein (CETP), which transfers cholesteryl ester (CE) from HDL to VLDL and other lipoproteins in exchange for TG, and because mice do not exhibit human-like HDL populations. To develop a physiologically relevant model, we crossed a virally-induced mouse model of T1DM ( Ldlr -/- ;Gp Tg ) deficient in the LDL receptor with human apolipoprotein A-I ( APOA1 ) transgenic mice. These mice (n=8-10) were injected with a liver-specific adeno-associated virus driving expression of human CETP, mimicking the human CETP activity/apoA-I ratio, and the 3 major human HDL subpopulations. Using this model ( APOA1 Tg ;Ldlr -/- ;Gp Tg ), we examined the impact of diabetes on dyslipidemia, HDL particle concentration (HDL-P), and serum HDL function. Induction of diabetes increased plasma TG and cholesterol, primarily due to an increase in VLDL, as compared with non-diabetic (ND) littermates. The dyslipidemia was associated with increases in hepatic TG content and hepatic TG production rate (2-fold over ND). Moreover, resident peritoneal macrophages from diabetic mice exhibited a 5-fold increase in CE loading, increased lipid raft content (20%), and increased Tnfa (3-fold) and Il1b mRNA (4-fold), as compared with ND littermates. In addition, T1DM mice had increased small, medium and large HDL-P (2-fold) concentrations compared with ND controls. Serum HDL from T1DM mice showed a significant increase in its cholesterol efflux capacity through both ABCA1 and ABCG1. Thus, in this humanized mouse model, poorly controlled T1DM leads to elevated plasma TG and VLDL due in part to increased hepatic TG production. This dyslipidemia is associated with higher HDL-P and an increase in serum HDL’s cholesterol efflux capacity, likely due to the increased plasma HDL-P. We have found similar changes in HDL concentration and function in humans with T1DM, suggesting that our mouse model might provide insights into CVD risk in T1DM patients.

Atherosclerotic vascular disease is the major cause of mortality in diabetic patients. Evidence from our laboratory and others showed that long non-coding RNAs (lncRNAs) play important roles in diabetic vascular complications. Here we investigated role of lncRNAs in hyperglycemia-induced macrophage dysfunction and accelerated atherosclerosis in diabetes. Hyperglycemia (~300-400 mg/dl) was induced in atherosclerosis-prone ApoE -/- mice by low dose Streptozotocin injections (50mg/kg/day i.p., 5 days) and were sacrificed at 20 weeks’ post diabetes. Aortic root F4/80 immunohistochemistry and morphometric analysis showed increased macrophage infiltration and enhanced atherosclerosis respectively in diabetic vs non-diabetic ApoE -/- mice. RNA-seq analysis identified ~45 up-regulated lncRNAs in bone marrow macrophages (BMM) from diabetic versus non-diabetic ApoE -/- mice. Among these, one of the robustly induced (~7.5 log 2 fold) lncRNA candidate was small nucleolar RNA host gene 18 ( Snhg18) located on mouse chromosome 15. Gene expression analysis by RT-qPCR validated Snhg18 upregulation in BMM from diabetic ApoE -/- mice and in peritoneal macrophages from type 2 diabetic db/db vs control db/+ mice. Moreover, diabetic-ApoE -/- aortic tissue also demonstrated increased expression of Snhg18 as compared to non-diabetic ApoE -/- s . Additionally, Snhg18 was significantly increased in high glucose (HG) (25mM) treated RAW mouse macrophages in vitro . A human ortholog, SNHG18 , located on chromosome 5 was also significantly increased in HG treated human THP1 monocytes. Cellular fractionation of RAW macrophages demonstrated that Snhg18 was localized in both cytoplasmic and nuclear compartments. Overexpression of Snhg18 in RAW macrophages significantly increased expression of proinflammatory ( Il1b , Il6 , and Tnf) and proatherogenic ( Thbs1 ) genes but downregulated a nearby gene, Semaphorin 5A ( Sema5a). These results suggest that diabetes induced lncRNA Snhg18 upregulates macrophage inflammatory phenotype to modulate diabetes induced accelerated macrophage dysfunction and atherosclerosis development.

Introduction: Patients suffering from Type 1 diabetes (T1D) have increased risk of developing atherosclerosis. T1D is a chronic autoimmune metabolic disease characterized by a deficiency in insulin secretion and hyperglycemia, promoting oxidative stress and low-grade inflammation in part via advanced glycation end products (AGE). Recently, we and others showed that necroptosis, a newly defined pro-inflammatory programmed cell death, drives advanced atherosclerosis. Given that diabetes accelerates inflammation and atherosclerosis, we hypothesized that hyperglycemia may exacerbate macrophage necroptosis to drive atherosclerotic lesion formation. Methods/Results: Male Ldlr-/- mice were lethally irradiated, transplanted with bone-marrow from WT or Rip3 -/- mice and then administered streptozotocin (STZ) or vehicle daily for 5 days to induce T1D, prior to being fed a western diet for 6 wks. As expected, STZ-treated WT BMT Ldlr -/- mice had a marked increased in atherosclerotic aortic lesion area compared to non-diabetic mice (1.08%±0.30 vs 2.13%±0.45). which was blunted in Rip3 -/- BMT Ldr -/- mice (arch: 49% reduction, sinus: 54% reduction, pRip3 -/- BMDMs cultured in HG. Mechanistically, treatment of BMDMs cultured in HG with oxLDL+s100A8/9 increased the expression of Rip3 and Mlkl (~5-fold and ~2-fold respectively), which may drive necroptotic cell death during hyperglycemia. Conclusion: Deletion of Rip3 markedly halts atherosclerotic progression in a STZ-induced T1D mouse model by inhibiting macrophage necroptosis induced by both atherogenic ligands (oxLDL) and soluble AGE products (s100A8/9).

Objective: to carry out comparative analysis of long-term compensation of carbohydrate metabolism in children with diabetes type 1 undergoing different types of insulin therapy and using different means of its introduction. Material and methods . We analyzed data of 77 medical histories of children with diabetes type 1. The patients were divided into 3 groups depending on the type of insulin and the way of its introduction. We analyzed both initial and current for the moment of the experiment parameters of glycosylated hemoglobin levels, frequency of blood glucose self-testing, presence of acute complications of diabetes mellitus. Results . The children undergoing continuous subcutaneous insulin introduction revealed significant decrease of glycosylated hemoglobin levels and absence of acute complications of diabetes. The group of children using insulin analogues for a long time had significantly lower glycemia variability and revealed no acute complications of diabetes. Conclusions . We revealed long-term compensation of carbohydrate metabolism in the children with diabetes type I who used insulin pump therapy.

Lactobacillus johnsonii N6.2 mitigates the onset of type 1 diabetes (T1D) in biobreeding diabetes-prone rats, in part, through changes in kynurenine:tryptophan (K:T) ratios. The goal of this pilot study was to determine the safety, tolerance, and general immunological response of L. johnsonii N6.2 in healthy subjects. A double-blind, randomized clinical trial in 42 healthy individuals with no known risk factors for T1D was undertaken to evaluate subject responses to the consumption of L. johnsonii N6.2. Participants received 1 capsule/day containing 108 colony-forming units of L. johnsonii N6.2 or placebo for 8 weeks. Comprehensive metabolic panel (CMP), leukocyte subpopulations by complete blood count (CBC) and flow cytometry, serum cytokines, and relevant metabolites in the indoleamine-2,3-dioxygenase pathway were assessed. L. johnsonii N6.2 survival and intestinal microbiota was analyzed. Daily and weekly questionnaires were assessed for potential effects of probiotic treatment on general wellness. The administration of L. johnsonii N6.2 did not modify the CMP or CBC of participants suggesting general safety. In fact, L. johnsonii N6.2 administration significantly decreased the occurrence of abdominal pain, indigestion, and cephalic syndromes. As predicted, increased serum tryptophan levels increased resulting in a decreased K:T ratio was observed in the L. johnsonii N6.2 group. Interestingly, immunophenotyping assays revealed that monocytes and natural killer cell numbers were increased significantly after washout (12 weeks). Moreover, an increase of circulating effector Th1 cells (CD45RO+CD183+CD196-) and cytotoxic CD8+ T cells subset was observed in the L. johnsonii N6.2 group. Consumption of L. johnsonii N6.2 is well tolerated in adult control subjects, demonstrates systemic impacts on innate and adaptive immune populations, and results in a decreased K:T ratio. These data provide support for the safety and feasibility of using L. johnsonii N6.2 in prevention trials in subjects at risk for T1D. Fil: Marcial, Guillermo Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina. University of Florida. Department of Microbiology and Cell Science; Estados Unidos Fil: Ford, Amanda. University of Florida; Estados Unidos Fil: Haller, Michael. University of Florida; Estados Unidos Fil: Gezan, Salvador A.. University of Florida; Estados Unidos Fil: Harrison, Natalie A.. University of Florida; Estados Unidos Fil: Cai, Dan. University of Florida; Estados Unidos Fil: Meyer, Julie L.. University of Florida; Estados Unidos Fil: Pery, Daniel J.. University of Florida; Estados Unidos Fil: Atkinson, Mark A.. University of Florida; Estados Unidos Fil: Wasserfall, Clive H.. University of Florida; Estados Unidos Fil: Garrett, Timothy. University of Florida; Estados Unidos Fil: Gonzalez, Claudio Fabricio. University of Florida; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Brusko, Todd M.. University of Florida; Estados Unidos Fil: Dahl, Wendy J.. University of Florida; Estados Unidos Fil: Lorca, Graciela L.. University of Florida; Estados Unidos

Islet cells antibodies of a pancreas (ICA) are the sensitive and high–specific serological marker of diabetes type I (IDDM). Serum of 50 children (less than 16 yr.old) and 46 adult patients with IDDM was tested for ICA with indirect immunofluorescence. The control group consisted of 10 children and 40 adults without endocrinologic disorders. Serial cryosections of human pancreas 5 mkm thick were incubated with patients serum for 30 min. After the unbound serum proteins were washed away with phosphate buffered saline (0.01M, pH 7.2) the section was incubated with FITC labeled antiserum against human immunoglobulins. Specific cytoplasmic fluorescence of islet cells was scored as positive test result. No specific staining was found in serum of the control group and specificity of the method was 100%. In adults and children at onset of IDDM ICA were found statistically more frequently than in patients with longstanding disease: 75,6 % v.s. 21,8 % (p

Aim: a comparison of the clinical manifestations tuberculosis (TB) in patients with TB and TB combined with different type9s of diabetes mellitus (DM). Materials and methods: we studied 245 patients who were divided into 3 groups. The first group included 45 patients with pulmonary tuberculosis combined with diabetes mellitus (DM) I type, the second -69 patients with pulmonary tuberculosis combined with diabetes type II and the third-130 patients with pulmonary tuberculosis without DM. Results: it was found that tuberculomas in patients with diabetes type I diagnosed in 33.3% of patients, with type II diabetes – in 31.9%, and in patients without diabetes only in 8.4% (respectively,p 1-3 2-3 1-3 =0,01,p 2-3 1-3 M.tuberculosis (MTB) was detected in sputum of 68.9% of patients with diabetes type I, in 72.5%- of patients with diabetes type II and in 58,8% of patients without DM (p 2-3 1-3 2-3 Conclusion: Clinical manifestations of pulmonary tuberculosis in patients with combined diabetes have their own characteristics. In these patients, in contrast to patients with pulmonary tuberculosis was significantly more diagnosed tuberculom with destruction.

INTRODUCTION Cardiovascular autonomous neuropathy (CAN) in diabetes has not been still defined clinically and aetiopathogenetically. OBJECTIVE The aim of this study was to determine the influence of disease duration, glycoregulation degree and diabetes type on damage of the cardiovascular part of the autonomous nervous system in our group of patients. METHOD This study included diabetics, (100 patients) the same number of patients with diabetes type I and II as well as 20 healthy individuals in the control group. Classic Ewing's cardiovascular tests were used for CAN diagnosis: 1. the cardiovascular response to Valsalva manoeuvre, 2. the cardiovascular response to deep breathing (the so-called E/I ratio), 3. the cardiovascular response to rising (the so-called 30/15 ratio), 4. the test of orthostatic hypotension and 5. the TA response to handgrip. It has been arbitrarily taken that patients, whose score of 'parasympathetic' tests (Valsalva manoeuvre, E/I ratio, 30/15) is equal or bigger than 1.5 (out of possible 3), have damage of the parasympathetic part of the autonomous nervous system while patients, whose score of 'sympathetic tests' (the test of orthostatic hypotension and TA response to hand-grip is equal or bigger than 1 (out of possible 2), have damage of the sympathetic part of the autonomous nervous system. The patients whose total score is equal or bigger than 2 have cardiovascular autonomous neuropathy. The glycoregulation degree is determined by the level of HbA1c. RESULTS There is a statistically significant, positive correlation between the values of the parasympathetic score and disease duration as well as between the total score, that is, CAN and disease duration. The connection between the sympathetic score, that is, damage of the sympathetic part of the autonomous nervous system and disease duration has not been observed. There is a positive correlation between the values of the parasympathetic score and HbA1c. The same pattern exists regarding the ratio of damage of the sympathetic part of the autonomous nervous system and the value of HbA1c, as well as the ratio of CAN, that is, the total score and HbA1c. Almost two- fold, a bigger coefficient of correlation between the sympathetic score and HbA1c in relation to the coefficient of correlation of the parasympathetic score and HbA1c, points to bigger sensitivity of the sympathetic part of the autonomous nervous system to subacute deterioration of glycoregulation. The correlation between the values of autonomous scores and diabetes type has not been noted. CONCLUSION Our results show that besides disease duration, the subacute deterioration of glycoregulation also leads to the appearance of cardiovascular autonomous dysfunction in diabetes. The sympathetic nervous tissue is functionally more sensitive than the parasympathetic one to metabolic disorders in diabetes. The cardiovascular autonomous dysfunction will occur independently of the type of diabetes.

Diabetes mellitus is becoming one of the major health problems in the developing countries. As the International Diabetes Federation suggests that the number of adults living with diabetes worldwide was increasing from time to time. The aim of this study is to assess the educational level of Diabetic patients as well as service given to them and the frequency of the disease over last four years at Dilla Referral Hospital. Data was collected through self administer/interviewer administer questionnaire and document review. According to this finding more exposure to diabetes disease, it must be was found an illiterate individuals 15 (37.50%) followed by Primary school, College and University level individuals 9 (22.50%), 6 (15.00%), 5 (12.50%) respectively. Diabetes type II diseases were highly prevalent across the year than Diabetes type I. The prevalence of diabetes mellitus is increasing and type II is more predominate than type I at Dilla Referral Hospital. Therefore, appropriate actions need to be taken to provide access like education and treatment in order to reduce associated complications

Introdução: De acordo com a Sociedade Brasileira de Diabetes, estima-se que existam no Brasil cerca de 5 milhões de pessoas com a patologia. No estado do Rio Grande do Sul há, provavelmente, 400.000 pacientes diabéticos23,27. Dentre as alterações que os indivíduos portadores de diabetes Mellitus podem apresentar, estão incluídos os distúrbios vestibulares. Objetivo: O presente trabalho teve por objetivo colaborar nas pesquisas de melhoria na qualidade de vida do paciente diabético e realizar pesquisa do nistagmo/ vertigem de posição e eletronistagmografia, a fim de identificar possíveis alterações. Forma de estudo: Clínico prospectivo. Material e método: 12 indivíduos portadores de diabetes Mellitus tipo I, usuários regulares de insulina, com idades entre 12 e 27 anos e componentes da Associação Riograndense de Apoio aos Diabéticos (ARAD). Para verificar as respostas vestibulares nos indivíduos portadores de diabetes Mellitus tipo I, foram realizados anamnese específica, meatoscopia, timpanometria, pesquisa do nistagmo/ vertigem de posição e eletronistagmografia na amostra selecionada. Resultados: Verificou-se Síndrome Vestibular Periférica Irritativa em 75% dos resultados alterados. Destes, 62,5% se tratavam de sujeitos sem queixa otoneurológica. Conclusões: Observou-se que o efeito do diabetes tipo I, na função vestibular, deve ser avaliado como as demais complicações diabéticas usuais, mesmo em pacientes assintomáticos, pois, com o diagnóstico etiológico precoce, é possível o auxílio na prevenção das complicações desta patologia.

Background Research has shown that suicide risk is often present in patients suffering from type 1 diabetes mellitus (DM-1). Objectives The aim of the present paper was to investigate whether there was a relationship between DM-1 and suicidal behavior and to determine whether or not people affected by DM-1 are at an increased risk of completed suicide, attempted suicide, and suicidal ideation. Data sources We performed a careful MedLine, ExcerptaMedica, PsycLit, PsycInfo and Index Medicus search to identify all papers on the topic for the period 1970 to 2013 written in English. The following search terms were used: (suicide OR suicide attempt OR ideation) AND (diabetes mellitus). Where a title or abstract seems to describe a study eligible for inclusion, the full article was examined. Eligibility criteria We included only original articles published in English peer-reviewed journals. We excluded meta-analyses and systematic reviews, studies that were not clear about follow-up times, the method of statistical analysis, diagnostic criteria or the number of patients included, and studies only on patients affected by type 2 diabetes mellitus (DM-2). Results The research reviewed indicated that patients with DM-1 are at an increased risk for suicide, although no clear consensus exists regarding the level of the increased risk. Limitations The studies used different measurement techniques and different outcomes, and they assessed patients at different time points. Conclusions and implications Our findings support the recommendation that a suicide risk assessment of patients with DM-1 should be part of the routine clinical assessment. The assessment of patients at risk should consist of the evaluation of current and previous suicidal behaviors (both suicidal ideation and attempted suicide).

Background Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1. Materials and methods Rats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied. Results NCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin.

IntroductionDiabetes Mellitus (DM) affects 25.8 million people of all ages. Previous studies suggest a link between DM and several connective tissue pathologies including those of cartilage and bon...

Título: Autocuidados y educación terapéutica en diabetes. Una revisión bibliográfica. Objetivos: La Educación Terapéutica en Diabetes (ETD) influye en su la variabilidad pronóstica. El rigor del profesional de la salud debería ser el mismo tanto prescribiendo fármacos como dando normas de conducta. El objetivo del presente estudio fue revisar la literatura reciente relacionada con la diabetes, la educación terapéutica y los autocuidados. Metodología:Se realizó una búsqueda bibliográfica en las bases de datos PudMed, Cuiden, Ibecs, Lilacs, Scielo y Enfispo en febrero de 2012. El límite temporal fue de 5 años. Se buscaron las palabras clave en título, abstract y como descriptores. Resultados: Se identificaron un total de 194 artículos. El 29% se incluyeron en el estudio (n=54). El 64.4% de los trabajos fueron localizados en PudMed (n=124); no se encontró ningún resultado en la base de datos CUIDEN. El principal motivo de exclusión fue que los artículos no estaban relacionados directamente con el tema de la revisión en el 32.8% de los casos (n=65). Los trabajos con carácter cualitativo fueron los más abundantes (n=12). Conclusiones:La implantación de intervenciones educativas innovadoras centradas en los autocuidados parece tener beneficios sobre los pacientes diabéticos, mejorando el manejo de la enfermedad o las cifras de glucosa y hemoglobina glicosilada, facilitando el empowerment de los pacientes o diminuyendo el control paterno en diabéticos tipo I. Es necesaria más investigación experimental que aclare qué tipo de intervenciones educativas presentan mayores ventajas y beneficios para las personas diabéticas en diferentes contextos. Title: Self-care and therapeutic education in diabetes. A literature review. Aims: The therapeutic education in Diabetes (NTDS) influences in its variability prognostic, highlighting the fact that the rigour of the health professional should be the same both prescribing drugs as giving rules of conduct. The objective of the present study was to review the recent literature related to diabetes, therapeutic education and self-care. Methodology:A literature search was conducted PudMed, care, Ibecs, Lilacs, Scielo and Enfispo databases in February 2012. The time limit was 5 years and searched keywords in title and abstract as well as how descriptors. Findings: A total of 194 articles were identified. The 29 were included in the study (n=54). The 64.4 works were located in PudMed (n=124); not found any result in the database take care. The main reason for exclusion was that the articles were not directly related with the subject of the review in the cases (n=65) 32.8. Work with qualitative character were the most abundant (n=12). Conclusions:The implementation of innovative educational interventions focused on self-care seems to have benefits on diabetic patients, improving the management of the disease or the levels of glucose and glycosylated hemoglobin, facilitating the empowerment of patients or weaker parental control in diabetics type I. Further experimental research to clarify what kind of educational interventions have greater advantages and benefits for people with diabetes in different contexts is needed.

Granuloma annulare has been widely described in adults in association with systemic diseases such as type 1 diabetes mellitus. However in childhood this relationship remains unclear. We report the case of an 8-year-old girl, with multiple granuloma annulare as first clinical manifestation of type one diabetes mellitus.

Purpose Exposure of the retina to flickering light induces retinal vessel dilation in healthy subjects. Diabetes and related vascular disorders are able to change vascular endothelial function. Whether the dynamic reaction to luminance flicker stimulation in retinal branch arteries and veins differs between healthy volunteers and patients suffering from diabetes type I is investigated. Methods 35 patients with insulin dependent diabetes mellitus type I (age (mean±SD) 50,9 ± 8,6 years old) and in 35 age and gender matched medically healthy volunteers were examined. Vessel diameters of retinal vessel segments were assessed by Dynamic Vessel Analyzer (DVA). After baseline measurement (50 s) monochromatic rectangular flicker stimulation (530-600 nm, 12,5 Hz, 20 s) was applied 3 consecutive times. Results In most subjects fast vessel dilation compared to baseline and an ensuing reactive arterial constriction were observed. In detail we found: .....diabetes.....control mean maximal arterial dilation,[%]:...2,3±1,8**...4,1±2,5 time of max. arterial dilation during the stimulation,[s]:....19,3±10,9*...14,2±3,4 mean maximal venous dilation,[%]:....3,4±1,8*...4,7±1,8 There were statistically significant differences between the two examined groups as marked with *(p

Treatment of chronic wounds is a difficult problem of contemporary surgery. An opportunity of curing these wounds by means of cytokines, such as interleukin-1 (IL-1), is an issue of great interest. A clinical trial of IL-1β was performed in the patients with chronic wounds of different origin. Recombinant human IL-1β was applied in six ointment compositions containing active drug (0.05 to 5000 ng/ml) using a hydrophobic vehicle. The preparations were used to treat non-healing wounds and trophic ulcers in patients with diseases of lower extremities complicated by venous insufficiency or diabetes type I and II. Clinical examinations, wound area measurements and cytological analysis of wound smears were performed before starting the treatment and in the course of therapy. Clinical results for the wound lesions (2nd and 3rd phases) have demonstrated high efficacy of ointments containing IL-1β at 0.5 to 5000 ng/ml. The most efficient concentration was determined as 50 ng IL-1β in 1 ml of ointment. IL-1β treatment caused clinical improvement of wound healing in 90% of the patients, including those with diabetes. IL-1β application during 2nd and 3rd phases of wound process showed good correlations with cytological changes in wound cell smears. When using IL-1β-containing ointments, the terms of granulation and epithelisation terms were reduced, along with 1.5-fold increase in average healing rates, as compared to conventional treatment with Solcoseril and Vulnusan. Mechanisms of IL-1β action were similar for the patients with wounds of different origin. Application of IL-1β-containing requires daily changes of wound dressings with the ointment. What to complications, local allergic reactions were detected only in 1.9% of cases. To summarize, the results of our study provide an evidence that IL-1β-containing ointment is a useful drug for effective treatment of non-healing wounds and trophic ulcers in patients. (Med. Immunol., vol. 10, N 4-5, pp 439-448) .