Interstitial Levels Research Articles

The effect of steroid injection into the shoulder on glycemia in patients with type 2 diabetes.

BackgroundInjections of corticosteroids into or around joints have been reported to increase blood glucose in patients with diabetes due to corticosteroid absorption into the bloodstream. However, the magnitude, duration, and clinical implications of local corticosteroid injections on glycemic control are not clear. The purpose of this study was to evaluate the effects of corticosteroid injection to the shoulder on glycemia in patients with type 2 diabetes mellitus using a continuous glucose monitoring device.MethodsTwenty-five patients with symptomatic shoulder problems and type 2 diabetes mellitus, not treated with insulin, prescribed a corticosteroid injection into the shoulder, were investigated. The patients were connected to a flash glucose monitoring system, which continuously monitored interstitial glucose levels. Data were collected 3 days before injection and for additional 11 days after corticosteroid injection. We analyzed glucose levels in the first 3 days (early postinjection) and on days 4-11 (late postinjection) after the injection and compared them to the preinjection period. The outcome measures included change in the average glucose levels, per patient, between the preinjection and postinjection periods and the differences in the time spent at glucose >180 mg/dL, >250 mg/dL, and >350 mg/dL, per patient, between the preinjection and postinjection periods.ResultsThe increase in the mean glucose level per patient was statistically significant from 136 mg/dL in the preinjection period to 159 mg/dL in the first 3 days after the injection and returned to normal thereafter. Time at blood glucose >250 mg/dL increased from 4.3% in the preinjection period to 9.5% on the first day after the injection. It then decreased to 7% on day 2, 3.8% on day 3, and 1.4% in the late postinjection period. New onset of glucose levels >350 mg/dL was found in 4 of 25 patients during the early postinjection period. In all 4 patients, the exposure to severe hyperglycemia (>350 mg/dL) was short. None of the patients required intensification of the antidiabetic treatment or insulin injections.ConclusionLocal corticosteroid injection to the shoulder can create a significant, short-term increase in systemic glucose levels in patients with D2DM not treated with insulin. Some of these patients may have periods with glucose above 350 mg %. However, these glycemic changes are short lived and are mostly limited to the 2-3 days after the injection. In addition, none of the patients in our study needed any change in antidiabetic treatment or any medical care after the injection.

Flash glucose monitoring system in special situations.

The management of diabetes mellitus (DM) requires maintaining glycemic control, and patients must keep their blood glucose levels close to the normal range to reduce the risk of microvascular complications and cardiovascular events. While glycated hemoglobin (A1C) is currently the primary measure for glucose management and a key marker for long-term complications, it does not provide information on acute glycemic excursions and overall glycemic variability. These limitations may even be higher in some special situations, thereby compromising A1C accuracy, especially when wider glycemic variability is expected and/or when the glycemic goal is more stringent. To attain adequate glycemic control, continuous glucose monitoring (CGM) is more useful than self-monitoring of blood glucose (SMBG), as it is more convenient and provides a greater amount of data. Flash Glucose Monitoring (isCGM /FGM) is a widely accepted option of CGM for measuring interstitial glucose levels in individuals with DM. However, its application under special conditions, such as pregnancy, patients on hemodialysis, patients with cirrhosis, during hospitalization in the intensive care unit and during physical exercise has not yet been fully validated. This review addresses some of these specific situations in which hypoglycemia should be avoided, or in pregnancy, where strict glycemic control is essential, and the application of isCGM/FGM could alleviate the shortcomings associated with poor glucose control or high glycemic variability, thereby contributing to high-quality care.

Changes in glycaemic control of oral anti-diabetic medications assessed by continuous glucose monitors among patients with type 2 diabetes: a protocol of network meta-analysis

BackgroundContinuous glucose monitors (CGMs) can measure interstitial fluid glucose levels to provide comprehensive real-time glucose profile among people with type 2 diabetes. These can accurately detect glucose levels, hyperglycaemia and hypoglycaemia events compared with conventional self-monitoring. Increased application of CGMs provides a valuable opportunity to evaluate glucose control on oral anti-diabetic medications. This review will compare the efficacy and safety of oral anti-diabetic medications among patients with type 2 diabetes, evaluated by CGM.MethodsThe following databases will be searched: Cochrane Library, PubMed, EMBASE, CINAHL, PsycINFO, Scopus and grey literature (ClinicalTrials.gov, PsycEXTRA, ProQuest Dissertations, Google Scholar and Theses Global) for the identification of studies. The review will include and summarise evidence from randomised clinical trials that use CGMs for blood glucose management in adults (aged ≥ 18 years), published in English between January 2000 and May 2021 without any restrictions of countries. Reference list of all selected articles will independently be screened to identify additional studies left out in the initial search. Primary outcomes will be HbA1c (≤ 7.0%), time spent with hypoglycaemia (< 70 mg/dl) or hyperglycaemia (≥ 180 mg/dl). Secondary outcomes will be change in weight, blood pressure and related comorbidities (cardiovascular mortality, heart failure events, myocardial infarction and stroke). Study selection, data extraction and quality assessment will be conducted independently by at least two reviewers. A third reviewer will determine and resolve discrepancies. At least two independent reviewers will cross-check data synthesis. The quality of evidence of the review will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Tool.DiscussionThe review is anticipated to provide up to date evidence for further studies and clinic practices regarding glycaemic control, hypoglycaemia, and hyperglycaemia issues. The results will be published in a peer-reviewed journal.Trial registrationPROSPERO CRD42020188399.

Regulation of endothelial nitric oxide synthase in cardiac remodeling

ObjectivesOur previous study demonstrated that endothelial nitric oxide synthase (eNOS) gene serves as a candidate for modifiers of hypertrophic cardiomyopathy (HCM), which alters severity of HCM phenotypes. Herein, we sought to further elucidate the role of eNOS on cardiac myocyte hypertrophy and fibrosis, the major phenotypes of HCM. MethodsMale eNOS-deficient mice (eNOS−/−) and wild type control mice (eNOS+/+, C57B1/6 J) were used in this study. Myocyte size was analyzed in hematoxylin/eosin stained sections using an image analyzing system. Cardiac β-myosin heavy chain (β-MHC) and α-skeletal actin (α-SKA) levels, markers of myocyte hypertrophy were evaluated by Western blot. Cardiac collagen volume fraction (CVF) was examined in picrosirius red stained section using an image analyzing system. Cardiac expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and transforming growth factor beta 1 (TGF-β1), markers of fibrosis, were determined by Western blot. ResultsCompared to eNOS+/+ mice, we found that; 1) myocyte size was significantly increased in eNOS−/− mice; 2) cardiac expression of β-MHC was markedly elevated, while α-SKA levels remained unchanged in eNOS−/− mice; 3) cardiac total and interstitial CVF levels were significantly higher in eNOS−/− mice; and 4) cardiac TIMP-1 levels were significantly greater in eNOS−/− mice, however, cardiac TGF-β1 was not differently expressed between the two groups. ConclusionThe current study revealed that eNOS plays a beneficial role in cardiac remodeling, preventing the heart from development of myocyte hypertrophy and cardiac fibrosis. These findings support our previous report that eNOS may modify the severity of HCM phenotypes.

Circadian Disruption of Melatonin among Night Shift Workers and Its Effect on Glycemic Variability

Melatonin is a pineal gland secreted hormone controlling sleep wakefullness. Light is a stimulus and hence this hormone exhibits circadian rhythm. Melatonin has pleiotropic effects on carbohydrate and lipid metabolisms. Glycemic variability is defined as variations in interstitial glucose levels measured every 15 seconds using a sensor-based technique. It is the result of constant carbohydrate metabolism and insulin action. Melatonin also has rhythms that are more akin to a nocturnal hormone. It affects glycemic variability. Variability is associated with a very high cardiac risk factor. Melatonin rhythm may be disrupted in night shift workers as a result of light exposure during the night, with implications for insulin secretion and glycemic variability. Correlation provides greater insight into the rhythmic hormonal activity and altered glucose homeostasis that predispose to diabetes, and thus this study was done to establish the correlation. This study was done to evaluate the effect of melatonin levels on altering glycemic control among night shift workers. This case control study included 40night shift workers both male and female (cases) aged 25-35years and 40 healthy controls of same age group. Blood samples for melatonin estimation were collected at 9PM and 6AM (after night shift work) by venepuncture and serum separated. Serum melatonin levels were estimated by ELISA method. Fasting and post prandial blood glucose were estimated by GOD-POD method and glycemic variability analyzed by Abbott biosensors. Data was analyzed using SPSS package. Night shift workers were found to have decreased melatonin levels and altered blood glucose levels compared to the control group. Melatonin has a negative influence on glycemic variability. This fact was evidenced in our study. Hence this study will help us to understand and intervene.

CD73 induces GM-CSF/MDSC-mediated suppression of T cells to accelerate pancreatic cancer pathogenesis.

Metabolic alterations regulate cancer aggressiveness and immune responses. Given the poor response of pancreatic ductal adenocarcinoma (PDAC) to conventional immunotherapies, we investigated the link between metabolic alterations and immunosuppression. Our metabolic enzyme screen indicated that elevated expression of CD73, an ecto-5’–nucleotidase that generates adenosine, correlates with increased aggressiveness. Correspondingly, we observed increased interstitial adenosine levels in tumors from spontaneous PDAC mouse models. Diminishing CD73 by genetic manipulations ablated in vivo tumor growth, and decreased myeloid-derived suppressor cells (MDSC) in orthotopic mouse models of PDAC. A high-throughput cytokine profiling demonstrated decreased GM-CSF in mice implanted with CD73 knockdowns. Furthermore, we noted increased IFN-γ expression by intratumoral CD4+ and CD8+ T cells in pancreatic tumors with CD73 knockdowns. Depletion of CD4+ T cells, but not CD8+ T cells abrogated the beneficial effects of decreased CD73. We also observed that splenic MDSCs from Nt5e knockdown tumor-bearing mice were incompetent in suppressing T cell activation in the ex vivo assays. Replenishing GM-CSF restored tumor growth in Nt5e knockout tumors, which was reverted by MDSC depletion. Finally, anti-CD73 antibody treatment significantly improved gemcitabine efficacy in orthotopic models. Thus, targeting the adenosine axis presents a novel therapeutic opportunity for improving the anti-tumoral immune response against PDAC.

New technology of diabetes management: learning together and in situation

The introduction of a new technology for the management of diabetes raises questions about their actual use. This is the case with the Freestyle Libre sensor, a tool that measures the interstitial glucose levels. Some studies have provided recommendations about its use, but little is known about how users learn to use it in the daily management of the disease. This ethnographic research explores this issue in the context of a summer camp for young people living with diabetes. The results describe three different levels (material, epistemic and moral) at which learning occurs. They show that its use requires an active appropriation process, the importance of a setting that promotes interactions between the participants and that the features of the tend to reconfigure the expert-lay person relationship.

Free interstitial levels of metformin in the liver of healthy and diabetic Wistar rats

In the present study, free interstitial levels reached by metformin in the liver were investigated in control and diabetic rats by microdialysis. Firstly, a bioanalytical method using an HPLC-UV system to determine the drug concentration in microdialysis samples was validated. The blood glucose levels and biochemical parameters were investigated in control and diabetic animals. Following that, both groups received a dose of 50 mg/kg of metformin iv bolus and the free interstitial levels reached in the liver were assessed by microdialysis. The method was validated according to FDA guidelines being suitable to quantify free concentrations of metformin in the liver of control and diabetics rats. Free exposure to metformin was similar in control and diabetic animals: AUC0-∞ 118.50 ± 40.18 vs 112.93 ± 50.25 µg.h/mL, respectively. The half-life in tissue was similar to that described in the literature for plasma. Hence diabetes induced by streptozotocin after administration of nicotinamide in our study did not damage the renal and hepatic function of the animals. The levels reached in the liver were 1.6 times higher than the free plasma concentrations, demonstrating higher liver penetration of metformin. This is the first investigation in liver interstitial concentration of metformin in control and diabetic rats.

Allergic Reaction Following Implantation of a Blood Glucose Sensor.

Increasing incidence and onset at a younger age has changed the treatment strategy of diabetes mellitus (DM) towards prevention, delaying the onset, and minimizing disease complications. Self-monitoring blood glucose systems and continuous glucose monitoring systems are routinely preferred in diabetic children.Flash glucose monitoring system has come as an entirely new concept in glucose monitoring by providing much greater data than blood glucose testing while being more affordable than the continuous glucose monitors. The FreeStyle Libre provides ‘flash glucose monitoring’ with glucose readings by scanning a sensor rather than pricking the patient’s finger. The sensor measures interstitial tissue glucose levels every minute via a disposable round sensor with a small catheter inserted under the skin that can be worn for up to 14 days. The entire system’s on-body sensor patch worn on the back of the upper arm is disposable. However, the mild erythema may occur on the skin and disappear spontaneously after 24 hours from the detachment of the sensor. Similar skin lesions were observed in diabetic patients, and there was moderate to severe itching in 0.5% of the cases and moderate erythema in 4% of cases

Surface and Subsurface Quality of Titanium Grade 23 Machined by Electro Discharge Machining.

Electrical Discharge Machining (EDM) is a non-traditional cutting technology that is extensively utilized in contemporary industry, particularly for machining difficult-to-cut materials. EDM may be used to create complicated forms and geometries with great dimensional precision. Titanium alloys are widely used in high-end applications owing to their unique intrinsic characteristics. Nonetheless, they have low machinability. The current paper includes an experimental examination of EDM’s Ti-6Al-4V ELI (Extra Low Interstitials through controlled interstitial element levels) process utilizing a graphite electrode. The pulse-on current (IP) and pulse-on time (Ton) were used as control parameters, and machining performance was measured in terms of Material Removal Rate (MRR), Tool Material Removal Rate (TMRR), and Tool Wear Ratio (TWR). The Surface Roughness (SR) was estimated based on the mean roughness (SRa) and maximum peak to valley height (SRz), while, the EDMed surfaces were also examined using optical and SEM microscopy and cross-sections to determine the Average White Layer Thickness (AWLT). Finally, for the indices above, Analysis of Variance (ANOVA) was conducted, whilst semi-empirical correlations for the MRR and TMRR were given using the Response Surface Method (RSM). The results show that the pulse-on time is the most significant parameter of the machining process that may increase the MRR up to 354%. Pulse-on current and pulse-on time are shown to have an impact on the surface integrity of the finished product. Furthermore, statistics, SEM, and EDX images on material removal efficiency and tool wear rate are offered to support the core causes of surface and sub-surface damage. The average microhardness of the White Layer (WL) is 1786 HV.

Correlation of Cerebral and Subcutaneous Glycerol in Severe Traumatic Brain Injury and Association with Tissue Damage

BackgroundThis study is a substudy of a prospective consecutive double-blinded randomized study on the effect of prostacyclin in severe traumatic brain injury (sTBI). The aims of the present study were to investigate whether there was a correlation between brain and subcutaneous glycerol levels and whether the ratio of interstitial glycerol in the brain and subcutaneous tissue (glycerolbrain/sc) was associated with tissue damage in the brain, measured by using the Rotterdam score, S-100B, neuron-specific enolase (NSE), the Injury Severity Score (ISS), the Acute Physiology and Chronic Health Evaluation Score (APACHE II), and trauma type. A potential association with clinical outcome was explored.MethodsPatients with sTBI aged 15–70 years presenting with a Glasgow Coma Scale Score ≤ 8 were included. Brain and subcutaneous adipose tissue glycerol levels were measured through microdialysis in 48 patients, of whom 42 had complete data for analysis. Brain tissue damage was also evaluated by using the Rotterdam classification of brain computed tomography scans and the biochemical biomarkers S-100B and NSE.ResultsIn 60% of the patients, a positive relationship in glycerolbrain/sc was observed. Patients with a positive correlation of glycerolbrain/sc had slightly higher brain glycerol levels compared with the group with a negative correlation. There was no significant association between the computed tomography Rotterdam score and glycerolbrain/sc. S-100B and NSE were associated with the profile of glycerolbrain/sc. Our results cannot be explained by the general severity of the trauma as measured by using the Injury Severity Score or Acute Physiology and Chronic Health Evaluation Score.ConclusionsWe have shown that peripheral glycerol may flux into the brain. This effect is associated with worse brain tissue damage. This flux complicates the interpretation of brain interstitial glycerol levels. We remind the clinicians that a damaged blood–brain barrier, as seen in sTBI, may alter the concentrations of various substances, including glycerol in the brain. Awareness of this is important in the interpretation of the data bedside as well in research.

Incidence and Characterization of Concealed Cardiac Amyloidosis Among Unselected Elderly Patients Undergoing Post-mortem Examination.

Background: The prevalence of cardiac amyloidosis (CA) is unknown.Aims and Methods: We sought to (a) determine the prevalence of CA in unselected patients ≥75 years undergoing autopsy, (b) characterize cardiological profiles of CA and non-CA patients by providing clinical-histological correlations, and (c) compare their cardiological profiles. After dedicated staining, the localization (interstitial or vascular) and the distribution (non-diffuse or diffuse) of amyloid deposition were analyzed. Cardiological data at last evaluation were retrospectively assessed for the presence of CA red-flags.Results: CA (50% light chains, 50% transthyretin) was found in 43% (n = 24/56) of the autopsied hearts. Atria were involved in 96% of cases. Amyloid localized both at the perivascular and interstitial levels (95.5 and 85%, respectively) with a slightly predominant non-diffuse distribution (58% of cases). Compared to the other patients, CA patients had a more frequent history of heart failure (HF) (79 vs. 47%, p = 0.014), advanced NYHA functional class (III-IV 25 vs. 6%, p = 0.047), atrial fibrillation (68 vs. 36%, p = 0.019), discrepancy between QRS voltage and left ventricular (LV) thickness (70 vs. 12%, p < 0.001), thicker LV walls (15 vs. 11 mm, p < 0.001), enlarged left atrium (49 vs. 42 mm, p = 0.019) and restrictive filling pattern (56 vs. 19%, p = 0.020). The presence of right ventricular amyloidosis seemed to identify hearts with a higher amyloid burden. Among the CA patients, >30% had ≥3 echocardiographic red-flags of disease.Conclusion: CA can be found in 43% of autopsied hearts from patients ≥75 years old, especially in patients with HF, LV hypertrophy and atrial fibrillation.

Hormonal, Histological, and Comparative Study of the Effect of Pure Ginseng on Testicular Function in the Breeding/Non-Breeding Season of Rams in Basrah.

This study aimed to investigate the effect of the administration of powdered Panax ginseng as a dietary supplement on testosterone concentration, spermatogenesis stimulating hormone, interstitial cell-stimulating hormone levels, sperms morphological characteristics, testis histological traits, and testicular size in the breeding and non-breeding season in adult rams. In total, 20 adult rams were included and randomly divided into three groups. The first group of adult rams (n=8) was subdivided into two subgroups of four rams (Sub-G1-B and Sub-G2-B). TheSub-G1-B and Sub-G2-B were fed 2 and 5 g of P. ginseng once a day, respectively, for 90 days during the breeding season. The second group of adult rams (n=8) was subdivided into two subgroups of four rams (Sub-G1-NB and Sub-G2-NB). The Sub-G1-NB and Sub-G2-NB were fed 2 and 5 g of P. ginseng once a day, respectively, for 90 days during the non-breeding season. The third group of adult rams (n=4) was considered the control group two times (in and out of the season). The results showed that the testosterone concentration and gonad protective and interstitial cell-stimulating hormone levels increased significantly (P<0.05) in both the experimental groups that received ginseng supplementation, compared to the control group in and out of the breeding season. The evaluation of sperm morphometric parameters, such as total sperm count, total motility, and progressive motility, showed superiority in improving the above-mentioned parameters. However, the total immotile sperms and non-progressive sperms underwent a significant decrease (P<0.05) in both experimental groups of ginseng supplemented, compared to the control group in and out of season. The angiogenesis of the seminiferous tubules increased significantly (P<0.05) in both experimental groups. Through a microscopic examination, the recorded data showed a significant increase in the population of spermatogonial stem cells as well as primary and secondary spermatocytes in both experimental groups. Values of testicular diameter showed a significant increase (P<0.05) after a period of 75 and 90 days following the initiation of treatments in both experimental groups, compared to the control group in and out of the season. It can be concluded that P. ginseng has some beneficial effects on the antioxidant status of the semen, the morphometric parameters, and other critical traits of sperm and testicles which are the important factors in male fertility.

Pros and cons of continuous glucose monitoring in the intensive care unit.

Diabetes mellitus affects people worldwide, and management of its acute complications or treatment-related adverse events is particularly important in critically ill patients. Previous reports have confirmed that hyperglycemia can increase the risk of mortality in patients cared in the intensive care unit (ICU). In addition, severe and multiple hypoglycemia increases the risk of mortality when using insulin or intensive antidiabetic therapy. The innovation of continuous glucose monitoring (CGM) may help to alert medical caregivers with regard to the development of hyperglycemia and hypoglycemia, which may decrease the potential complications in patients in the ICU. The major limitation of CGM is the measurement of interstitial glucose levels rather than real-time blood glucose levels; thus, there will be a delay in the treatment of hyperglycemia and hypoglycemia in patients. Recently, the European Union approved a state-of-art artificial intelligence directed loop system coordinated by CGM and a continuous insulin pump for diabetes control, which may provide a practical way to prevent acute adverse glycemic events related to antidiabetic therapy in critically ill patients. In this mini-review paper, we describe the application of CGM to patients in the ICU and summarize the pros and cons of CGM.

To Assess Liraglutide's Therapeutic Effect in Patients with Type 2 Diabetes Mellitus Using Flash Glucose Monitoring System.

PurposeLiraglutide, a type of glucagon-like peptide-1 receptor agonist, has significant anti-hyperglycaemic activity without increasing the incidence of hypoglycaemia. In addition, it can improve β-cell function and insulin resistance. The flash glucose monitoring system (FGMS) is a novel method to document consecutive and detailed interstitial glucose levels, further reflecting blood glucose levels. This study aimed to investigate the therapeutic effect of liraglutide on blood glucose management (glucose variability, hyperglycaemia, and the incidence of hypoglycaemia), β-cell function, and insulin resistance in patients with diabetes.Patients and MethodsThirty-three patients with type 2 diabetes mellitus were recruited in this study. On the basis of metformin monotherapy, these patients received liraglutide add-on treatment for 3 months. The FGMS was used to document glucose levels before and after add-on treatment. Parameters of glucose variability, blood glucose levels at specific time periods, and the incidence of hypoglycaemia were assessed according to FGMS data and compared before and after liraglutide add-on treatment. Further, β-cell function and insulin resistance were assessed and compared before and after liraglutide add-on treatment.ResultsAccording to FGMS monitoring data, liraglutide add-on treatment significantly improved general, within-day, and day-to-day glucose variability and the glucose-target-rate. Further, the specifically analysed blood glucose levels at different time periods showed that blood glucose levels significantly decreased at nocturnal, fasting, and postprandial periods after add-on treatment. The incidence of hypoglycaemia was comparable during the whole day, daytime, and night-time according to the prespecified cutoffs (3.9 mmol/L and 3.0 mmol/L) before and after add-on treatment. Analysis of other assessed parameters revealed significant differences in glycosylated hemoglobin A1c and fasting blood glucose levels as well as parameters of β-cell function and insulin resistance before and after add-on treatment.ConclusionIn type 2 diabetes mellitus, liraglutide treatment can effectively decrease glucose variability and ameliorate hyperglycaemia without increasing the incidence of hypoglycaemia. In addition, liraglutide can significantly improve the β-cell function and insulin resistance.

Effect of Transcutaneous Radial Artery Photobiomodulation on Continuous Measures of Interstitial Glucose in a Single Subject: A Brief Report.

Background: Intravenous blood irradiation with light is purported to reduce blood sugar levels in people with diabetes mellitus (DM). Transcutaneous light emitting devices are marketed for use in modulating glucose levels, yet evidence of effectiveness is scarce. Materials and methods: In a single subject (nondiabetic woman with significant family history of DM), transcutaneous photobiomodulation (PBM) at various wavelengths was applied to the radial artery immediately after a standardized meal, or at the peak glucose after the standardized meal. Data were compared with a "no intervention" control period. Interstitial glucose was measured every 5 min until return to baseline. Results: A single transcutaneous application of PBM at wavelength and dose combinations tested and when applied immediately after a test meal or at peak glucose postprandially did not affect interstitial glucose levels in a woman without DM. Conclusions: Future studies could include testing additional subjects, using repeated PBM applications and monitoring using blood glucose.

Glucose Profiles in Healthy Term Infants in the First 5 Days: The Glucose in Well Babies (GLOW) Study.

In this study, the plasma and interstitial (GCMS) glucose levels were measured in term healthy newborns for a period of 5 days to understand the changes in the glucose levels after birth. The findings suggest that in normal term healthy newborns if hypoglycaemia persists after the 4th day of life, then further investigations are needed to rule out other causes of persistent hypoglycaemia.

Abstract MP52: Hypertensive Stimuli Indirectly Stimulate Mouse Mesometrial Lymphangiogenesis Through Immune Cells

We previously reported increased renal lymphatic density in multiple mouse models of hypertension, and further augmenting renal lymphatics lowers blood pressure. However, whether interstitial levels of hypertensive stimuli have a direct effect on lymphatics or an indirect effect through secreted immune cell factors has not been examined. We hypothesized that hypertensive stimuli directly increases lymphatic endothelial cell (LEC) proliferation and increases sprouting of mouse mesometrial lymphatic vessels. Murine LECs were cultured and treated with angiotensin II (angII), salt, and asymmetric dimethylarginine (ADMA) for 24 hours. To mimic the in vivo environment, a lymphatic-specific reporter mouse (Prox1-tdTomato) mesometrium tissue explant was treated with either the same hypertensive stimuli or with hypertensive conditioned media for 8 days. Mesometrial vascular beds were cultured in DMEM supplemented with 20% fetal bovine serum to induce lymphatic sprouting and this was replenished every day. The conditioned media was made by treating murine splenocytes for 24 hours with the same hypertensive stimuli. These stimuli had no effect on murine LEC proliferation. Hypertensive stimuli significantly decreased mesometrial lymphatic vessel sprout length (SL) and sprout number (SN) compared to controls (control SL in pixels by ImageJ analysis: 34.0 ± 2.6, angII: 3.7 ± 2.6, salt: 2.67 ± 2.18, ADMA: 9.06 ± 5.12, all p&lt;0.05; control SN: 7 ± 3, angII: 0 ± 0, salt: 0 ± 0, ADMA: 1 ± 1, all p&lt;0.05). Conditioned media treatment normalized SL and SN by day 8 for all hypertensive stimuli except salt. In conclusion, hypertensive stimuli directly inhibit mesometrial lymphangiogenesis, but this was mitigated by hypertensive stimuli induced immune cell secreted factors.

Why Not Dipyridamole: a Review of Current Guidelines and Re-evaluation of Utility in the Modern Era.

Dipyridamole is an old anti-platelet and coronary vasodilator agent that inhibits platelet phosphodiesterase and increases interstitial adenosine levels. Its use in coronary artery disease (CAD) has fallen out of practice in the modern era with the advent of new anti-platelet agents, and most modern guidelines on the management of CAD either neglect to comment on its utility or outright recommend against it. The majority of the studies used in these guidelines are outdated and took place in an era when high doses of aspirin were used and statins were not widely utilized. There is growing evidence in rat models of dipyridamole’s synergy with statins through adenosine modulation resulting in significant myocardial protection against ischemia–reperfusion injury and limitation of infract size. The data in human studies are limited but show a similar potential synergy between dipyridamole and statins. It would thus be prudent to reconsider the recommendations against the use of dipyridamole in CAD and to re-evaluate its possible role and potential benefits through well-designed randomized trials combining it with statins, low-dose aspirin, and/or other anti-platelet agents.

28-LB: RTCGM Performance at Different Sensor Wear Sites during Prolonged Aerobic Exercise

Strenuous exercise may disrupt the local equilibria between vascular and interstitial glucose concentrations. We measured interstitial glucose levels during aerobic exercise in different anatomical regions with continuous glucose monitoring (CGM) sensors and compared them to capillary blood glucose (BG) levels. We enrolled 10 individuals, 7 with type 1 diabetes (T1D) and 3 without (healthy volunteers), for a 50-mile bicycle ride. Three CGM sensors (Dexcom G6) were placed on each participant, with one each in the upper arm, abdomen and thigh. BG values were obtained at the start of the ride and every 30 minutes thereafter. Accuracy of CGM levels was assessed for each insertion site as the mean absolute relative difference (MARD) and bias versus contemporaneous BG levels. Table shows that arm-worn sensors were more accurate in terms of MARD, and also had smaller numerical bias, than sensors placed in either the abdomen or thigh. Sensor accuracy was not significantly affected by the presence or absence of a diabetes diagnosis and accuracy metrics were consistent with those reported in the device’s instructions for use. CGM users may benefit from wearing sensors on the arm during sustained bicycle rides.View largeDownload slideView largeDownload slide DisclosureM. Mueller-korbsch: Research Support; Self; Dexcom, Inc., Menarini Group, Novo Nordisk Inc. L. Fruehwald: None. M. Heer: None. G. Rega-kaun: None. M. Fangmeyer-binder: None. P. Fasching: None.