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BACKGROUND: Modern biomarkers for the assessment of liver cell damage are indicative for distinct hepato-cellular deteriorations. We investigated the prevalence of these markers in healthy subjects and patients with early stage type 2 diabetes mellitus (T2DM) on metformin monotherapy. METHODS: The study was performed with blood from 36 healthy subjects (17 females, age: 43 ± 12.4 years, BMI: 22.6 ± 1.5 kg/m2) and 32 T2DM patients (15 females, age: 57 ± 7.9 years, BMI: 35.0 ± 6.3 kg/m2, HbA1c: 7.3 ± 0.8%). Parameters for liver cell damage included ALT and AST and alpha-glutathione-S-transferase (α-GST, acute liver injury), keratin 18 (K18, cell necrosis), caspase-cleaved K18 (ccK18, cell apoptosis), and collagen IV (C-IV, fibrosis). In addition, insulin, intact proinsulin, and hsCRP were determined for staging insulin resistance, ß-cell dysfunction, and chronic systemic inflammation. RESULTS: Differences were seen for mean ALT (T2DM: 36 ± 19 U/L vs. control: 20 ± 8 U/L, p < 0.001) but not for mean AST (26 ± 15 U/L vs. 25 ± 5 U/L, n.s.). All other biomarkers but insulin were higher in the T2DM group (intact proinsulin: 10 ± 6 pmol/L vs. 2 ± 1 pmol/L; hsCRP: 4.8 ± 2.7 mg/L vs. 1.1 ± 0.8 mg/L, α-GST: 17.3 ± 12.2 µg/L vs. 9.5 ± 0.2 µg/L, K18: 235 ± 125 U/L vs. 100 ± 33 U/L, ccK18: 280 ± 158 U/L vs. 167 ± 35 U/L, C-IV: 114 ± 28 µg/L vs. 92 ± 20 µg/L, all p < 0.001). Elimination of seven T2DM patients with elevated ALT or AST values did not change the overall results, which were also independent from the stage of the underlying diabetes disorders. CONCLUSIONS: Potential indications of liver cell damage were detected in T2DM patients with more specific biomarkers, which would not have been detected by ALT and AST alone.
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Biomarcadores/sangre , Diabetes Mellitus Tipo 2/complicaciones , Hepatopatías/complicaciones , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Background: We conducted a prospective placebo-controlled double-blind randomized Study to assess the impact of a single dose of a nutritional Supplement (AB001) on alcohol absorption in healthy subjects. Other objectives were the impact on breath alcohol content, cognitive function 1 hour after alcohol uptake and tolerability. Method: A total of 24 healthy volunteers were enrolled into the study (12 male, 12 female, age: 28.3 ± 10.8 years, BMI: 23.5 ± 5.7 kg/m²). On the experimental day, they ingested a light breakfast together with a single dose (2 capsules) of AB001 (or placebo) and drank 2 moderate glasses of spirit (a total of 0.6 g/kg body weight). Breath alcohol tests and blood draws for determination of blood alcohol levels were performed for up to 6 hours. After crossover, the experiment was repeated in the following week. Areas under the curves were calculated to determine alcohol absorption rates. Results: There was a significant reduction of blood alcohol by 10.1% (P < .001) with AB001, when compared to placebo. There was a less pronounced but also significant reduction of alcohol in the breath test by 7.2% (P < .05). No difference in the cognitive function test between AB001 and placebo could be observed 60 minutes after alcohol ingestion (22.6 ± 8.0 seconds vs 23.0 ± 11.2 seconds, n.s.). The supplement uptake was well tolerated and there were no adverse events related to the study intervention. Conclusion: Uptake of a single dose of AB001 shortly before drinking alcohol significantly reduced plasma alcohol and breath alcohol concentrations, but the effect was less pronounced compared to chronic uptake as shown previously.
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Background: Regular alcohol consumption, e.g. by social drinking, is a potential source of consecutive health problems in many countries worldwide. A probiotic nutritional supplement (AB001) has been developed to reduce alcohol absorption from the intestine tract and to mitigate potential health care risks. Methods: This randomized placebo-controlled double-blind crossover study was conducted with 24 healthy subjects (13 male, 11 female, age: 25.4 ± 7.7 years, BMI: 23.6 ± 2.5 kg/m²). The subjects were randomized to take 2 capsules/day of AB001 or placebo for 1 week prior to an alcohol exposure experiment. On the experimental day, they ingested a light breakfast and drank a moderate glass of spirit (0.3 g/kg body weight). Breath alcohol tests and blood draws for determination of blood alcohol levels were performed for up to 6 hours. After crossover, the experiment was repeated in the following week. Areas under the curves were calculated to determine alcohol absorption rates. Results: A significant reduction of blood alcohol levels by 70.3% (P < 0.005 vs. placebo) was seen with AB001, (breath test: -30.7%; P < 0.005 vs. placebo). No difference was seen in a cognitive function test performed 60 minutes after alcohol ingestion (22.4 ± 7.7 seconds vs. 22.7 ± 5.6 seconds, n.s.). There were no adverse events or serious adverse events reported in this study. Conclusions: One week of supplementation with AB001 resulted in a substantially reduced absorption of alcohol into the body. Regular uptake of AB001 may help to prevent liver and other organ damage, and may reduce the negative medical and economical impact of social drinking on the individual and the society.
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IL-10 plays a central role in restraining the vigor of inflammatory responses, but the critical cellular sources of this counter-regulatory cytokine remain speculative in many disease models. Using a novel IL-10 transcriptional reporter mouse, we found an unexpected predominance of B cells (including plasma cells) among IL-10-expressing cells in peripheral lymphoid tissues at baseline and during diverse models of in vivo immunological challenge. Use of a novel B cell-specific IL-10 knockout mouse revealed that B cell-derived IL-10 nonredundantly decreases virus-specific CD8(+) T cell responses and plasma cell expansion during murine cytomegalovirus infection and modestly restrains immune activation after challenge with foreign Abs to IgD. In contrast, no role for B cell-derived IL-10 was evident during endotoxemia; however, although B cells dominated lymphoid tissue IL-10 production in this model, myeloid cells were dominant in blood and liver. These data suggest that B cells are an underappreciated source of counter-regulatory IL-10 production in lymphoid tissues, provide a clear rationale for testing the biological role of B cell-derived IL-10 in infectious and inflammatory disease, and underscore the utility of cell type-specific knockouts for mechanistic limning of immune counter-regulation.
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Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Interleucina-10/fisiología , Animales , Subgrupos de Linfocitos B/virología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Linfocitos T CD8-positivos/virología , Modelos Animales de Enfermedad , Femenino , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/metabolismo , Infecciones por Herpesviridae/patología , Mediadores de Inflamación/fisiología , Interleucina-10/biosíntesis , Interleucina-10/deficiencia , Interleucina-10/genética , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Tejido Linfoide/inmunología , Tejido Linfoide/patología , Tejido Linfoide/virología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Muromegalovirus/inmunología , Células 3T3 NIHRESUMEN
BACKGROUND: The pain associated with pricking the fingertip for blood glucose self-testing is considered to be a major burden in diabetes treatment. This study was performed to evaluate the system accuracy of the invasive TensorTip Combo Glucometer (CoG) device component in accordance with ISO15197:2015 requirements and to explore the accuracy of the noninvasive tissue glucose prediction component. METHODS: One hundred samples were obtained from people with type 1 and type 2 diabetes and healthy volunteers (43 females, 57 males; age: 53 ± 16 years), with glucose distribution as requested by the ISO standard. Three strip lots were tested twice by healthcare professionals in comparison to YSI 2300 Stat Plus reference method followed by a noninvasive tissue glucose reading (NI-CoG). Mean Absolute (Relative) Difference (MARD) was calculated and a consensus error grid (CEG) analysis was performed. RESULTS: The ISO system accuracy criteria were met with the invasive strip technology by 586/600 of the data points (97.1%) and for each strip lot separately. All invasive results (100%) were within CEG-zone A and total MARD was calculated to be 7.1%. With the noninvasive reading, 99% of raw data points were in A + B (91.1% and 7.8%), and the total MARD was calculated to be 18.1%. DISCUSSION: The invasive component of the CoG device was shown to be in full compliance with the current ISO15197 criteria. Good results were also obtained with the NI-CoG tissue glucose prediction. This noninvasive technology would potentially be suitable for frequent pain-free glucose monitoring in many people with diabetes.
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Automonitorización de la Glucosa Sanguínea/instrumentación , Glucemia/análisis , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Tiras Reactivas , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: In recent clinical trials, use of the MyGlucoHealth blood glucose meter (BGM) and electronic diary was associated with an unusual reporting pattern of glycemic data and hypoglycemic events. Therefore, the performance of representative BGMs used by the patients was investigated to assess repeatability, linearity, and hematocrit interference in accordance with regulatory guidelines. METHOD: Ten devices and 6 strip lots were selected using standard randomization and repeatability procedures. Venous heparinized blood was drawn from healthy subjects, immediately aliquoted and adjusted to 5 target blood glucose (BG) ranges for the repeatability and 11 BG concentrations for the linearity tests. For the hematocrit interference test, each sample within 5 target BG ranges was split into 5 aliquots and adjusted to hematocrit levels across the acceptance range. YSI 2300 STAT Plus was used as the laboratory reference method in all experiments. RESULTS: Measurement repeatability or precision was acceptable across the target BG ranges for all devices and strip lots with coefficient of variation (CV) between 3.4-9.7% (mean: 5.7%). Linearity was shown by a correlation coefficient of .991; however, a positive bias was seen for BG <100 mg/dL (86% measurements did not meet ISO15197:2015 acceptance criteria). Significant hematocrit interference (up to 20%) was observed for BG >100 mg/dL (ISO15197:2015 acceptance criteria: ±10%), while the results were acceptable for BG <100 mg/dL. CONCLUSIONS: The BGM met repeatability requirements but demonstrated a significant measurement bias in the low BG range. In addition, it failed the ISO15197:2015 criteria for hematocrit interference.
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Glucemia/análisis , Técnicas de Laboratorio Clínico , Diabetes Mellitus/sangre , Equipos y Suministros/normas , Acceso a Internet , Artefactos , Automonitorización de la Glucosa Sanguínea/instrumentación , Automonitorización de la Glucosa Sanguínea/normas , Técnicas de Laboratorio Clínico/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Hematócrito/instrumentación , Hematócrito/métodos , Hematócrito/normas , Humanos , Modelos Lineales , Tiras Reactivas/normas , Reproducibilidad de los ResultadosRESUMEN
Background: We evaluated the Wellion Galileo GLU/KET blood and ketone (ß-Hydroxybutyrate, ß-OHB) meter to demonstrate that it meets ISO15107:2015 regulatory approval criteria. Research Design and Methods: A total of 100 subjects (52 female, age: 30 to 84 years, diabetes: 10 type 1/90 type 2) with blood glucose levels distributed over the entire measurement range as required by the ISO15197 protocol were tested (double determinations with 3 strip lots and two devices). A similar test protocol was followed to test ß-OHB strip performance (reference devices: YSI 2300plus for glucose and STANBIO ß-HOB LiquiColor TestKit for ß-OHB). Precision was tested for glucose with 3 blood glucose concentrations (ß-OHB: 2 control solutions). Results: All glucose test-strip lots met the strict ISO acceptance criteria. Mean absolute relative difference (MARD) was 4.9% and all data pairs were in zone A of the consensus error grid. The ß-OHB test-strips also met the pre-defined acceptance criteria. Within-run and between-run precision was calculated to be 2.3% and 0.7% for the glucose strips (3.7%/0.8% for the ketone strips). Conclusions: When tested according to the ISO15197:2015 guideline, the device showed very accurate measurement performance for glucose and ß-OHB testing and fully met regulatory accuracy approval criteria.
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Ácido 3-Hidroxibutírico/sangre , Automonitorización de la Glucosa Sanguínea/instrumentación , Glucemia/análisis , Guías de Práctica Clínica como Asunto , Adulto , Anciano , Anciano de 80 o más Años , Automonitorización de la Glucosa Sanguínea/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: In recent randomized clinical trials, an unusual reporting pattern of glycemic data and hypoglycemic events potentially related to an internet enabled blood glucose meter (MyGlucoHealth, BGM) was observed. Therefore, this clinical study was conducted to evaluate the system accuracy of the BGM in accordance with the ISO15197:2015 guidelines with additional data collection. METHODS: To investigate system accuracy, 10 of 3088 devices and 6 of 23 strip lots, used in the trials, were selected by a randomization procedure and a standard repeatability assessment. YSI 2300 STAT Plus was used as the standard reference method. The samples were distributed as per the ISO15197:2015 recommendations with 20 additional samples in the hypoglycemic range. Each sample was tested with 6 devices and 6 strip lots with double determinations. RESULTS: Overall, 121 subjects with blood glucose values 26-423 mg/dL were analyzed, resulting in 1452 data points. In all, 186/1452 readings (12.8%) did not meet the ISO acceptance criteria. Data evaluated according to the FDA guidelines showed that 336/1452 (23.1%) readings did not meet the acceptance criteria. A clear bias toward elevated values was observed for BG <100 mg/dL (MARD: 11.0%). CONCLUSIONS: The results show that the BGM, although approved according to standard regulatory guidelines, did not meet the level of analytical accuracy required for clinical treatment decisions according to ISO 15197:2015 and FDA requirements. In general, caution should be exercised before selection of BGMs for patients and in clinical trials.
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Glucemia/análisis , Diabetes Mellitus/sangre , Hipoglucemia/diagnóstico , Acceso a Internet , Ensayos Clínicos Controlados Aleatorios como Asunto , Tecnología Inalámbrica/instrumentación , Automonitorización de la Glucosa Sanguínea/instrumentación , Automonitorización de la Glucosa Sanguínea/normas , Ensayos Clínicos como Asunto , Recolección de Datos/instrumentación , Recolección de Datos/normas , Endocrinología/instrumentación , Endocrinología/métodos , Endocrinología/normas , Diseño de Equipo/normas , Análisis de Falla de Equipo , Femenino , Humanos , Hipoglucemia/sangre , Hipoglucemia/epidemiología , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tecnología Inalámbrica/normasRESUMEN
BACKGROUND: Frequent blood glucose readings are the most cumbersome aspect of diabetes treatment for many patients. The noninvasive TensorTip Combo Glucometer (CoG) component employs dedicated mathematical algorithms to analyze the collected signal and to predict tissue glucose at the fingertip. This study presents the performance of the CoG (the invasive and the noninvasive components) during a standardized meal experiment. METHODS: Each of the 36 participants (18 females and males each, age: 49 ± 18 years, 14 healthy subjects, 6 type 1 and 16 type 2 patients) received a device for conducting calibration at home. Thereafter, they ingested a standardized meal. Blood glucose was assessed from capillary blood samples by means of the (non)invasive device, YSI Stat 2300 plus, Contour Next at time points -30, 0, 15, 30, 45, 60, 75, 90, 120, 150, and 180 minutes. Statistical analysis was performed by consensus error grid (CEG) and calculation of mean absolute relative difference (MARD) in comparison to YSI. RESULTS: For the noninvasive (NI) CoG technology, 100% of the data pairs were found in CEG zones A (96.6%) and B (3.4%); 100% were seen in zone A for the invasive component and Contour Next. MARD was calculated to be 4.2% for Contour Next, 9.2% for the invasive component, and 14.4% for the NI component. CONCLUSIONS: After appropriate individual calibration of the NI technology, both the NI and the invasive CoG components reliably tracked tissue and blood glucose values, respectively. This may enable patients with diabetes to monitor their glucose levels frequently, reliably, and most of all pain-free.
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Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Ingestión de Alimentos/fisiología , Comidas , Adulto , Anciano , Automonitorización de la Glucosa Sanguínea/instrumentación , Automonitorización de la Glucosa Sanguínea/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Periodo Posprandial , Estándares de Referencia , Adulto JovenRESUMEN
The pentose xylose is enriched in edible algae, and is increasingly used as a slowly metabolized carbohydrate in functional food. It is known to interfere with glucose-dehydrogenase-based (GDH) blood glucose measurement systems for patients self-testing. The aim of our study was to investigate the extent of xylose interference in commercially available blood glucose meters. A heparinized whole blood sample was manipulated to contain 3 different glucose concentrations (50-80 mg/dL, 130-160 mg/dL, and 250-300 mg/dL) and 4 different xylose concentrations (0 mg/dL, 25 mg/dL, 50 mg/dL, and 100 mg/dL). Each sample was measured 3 times with 2 different strip lots per test meter (AccuChek Aviva, AccuChek Connect, Contour Next, FreeStyle Freedom Lite, FreeStyle Insulinx, MyStar Extra, OneTouch Verio IQ, and Wellion Calla, reference: YSI GlucoStat analyzer). For analysis, we calculated the xylose capture rate, that is, the xylose amount wrongly displayed as glucose. No xylose interference was seen with 4 meters: AccuChek Aviva (mean capture rate 0%), AccuChek Connect (-2%), MyStar Extra (10%), and Wellion Calla (8%). In contrast, substantial interference was observed with Contour Next (100%), FreeStyle Freedom Lite (104%), FreeStyle Insulinx (120%), and OneTouch Verio IQ (162%). We observed xylose interference in several GDH-based meters. This may become important with increased use of xylose in dietary and functional food products, in particular in products designed for weight loss. Our findings may affect the meter selection for patients who are consuming such food products as part of their lifestyle treatment regimen.
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Automonitorización de la Glucosa Sanguínea , Glucemia/análisis , Xilosa , Glucosa 1-Deshidrogenasa , HumanosRESUMEN
BACKGROUND: Devices employing electrochemistry-based correction algorithms (EBCAs) are optimized for patient use and require special handling procedures when tested in the laboratory. This study investigated the impact of sample handling on the results of an accuracy and hematocrit interference test performed with BG*Star, iBG*Star; OneTouch Verio Pro and Accu-Chek Aviva versus YSI Stat 2300. METHODS: Venous heparinized whole blood was manipulated to contain three different blood glucose concentrations (64-74, 147-163, and 313-335 mg/dL) and three different hematocrit levels (30%, 45%, and 60%). Sample preparation was done by either a very EBCA-experienced laboratory testing team (A), a group experienced with other meters but not EBCAs (B), or a team inexperienced with meter testing (C). Team A ensured physiological pO2 and specific sample handling requirements, whereas teams B and C did not consider pO2. Each sample was tested four times with each device. In a separate experiment, a different group similar to group B performed the experiment before (D1) and after (D2) appropriate sample handling training. RESULTS: Mean absolute deviation from YSI was calculated as a metrix for all groups and devices. Mean absolute relative difference was 4.3% with team A (B: 9.2%, C: 5.2%). Team B had much higher readings and team C produced 100% of "sample composition" errors with high hematocrit levels. In a separate experiment, group D showed a result similar to group B before the training and improved significantly when considering the sample handling requirements (D1: 9.4%, D2: 4.5%, P < 0.05). CONCLUSIONS: Laboratory performance testing of EBCA devices should only be performed by trained staff considering specific sample handling requirements. The results suggest that healthcare centers should evaluate EBCA-based devices with capillary blood from patients in accordance with the instructions for use to achieve reliable results.
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Glucemia/análisis , Electroquímica/métodos , Manejo de Especímenes/métodos , Algoritmos , HumanosRESUMEN
In previous studies, meters employing dynamic electrochemistry (DE), have been shown to correct for hematocrit (HCT) interference. This laboratory investigation assessed the HCT stability of MyStar Extra (Sanofi) in comparison to 7 competitive devices (Accu-Chek Aviva Nano & Accu-Chek Performa, Roche Diagnostics; Contour XT and Contour Link, Bayer; FreeStyle Freedom Lite, Abbott; MyLife Pura, Ypsomed; OneTouch Verio Pro, LifeScan). Venous heparinized blood was freshly drawn, immediately aliquoted, and manipulated to contain 3 different blood glucose concentrations (50-80 mg/dL, 150-180 mg/dL, and 350-400 mg/dL) and 5 different HCT levels (20-25%, 30-35%, 40-45%, 50-55%, and 60-65%). After careful oxygenation to normal blood oxygen pressure, each of the 15 different samples was measured 8 times with 2 devices and 2 strip lots of each meter (32 measurements/meter/sample). YSI Stat 2300 served as laboratory reference method. Next to determination of the mean absolute relative deviation (MARD), stability to HCT influence was assumed, when less than 10% difference occurred between the highest and lowest mean glucose deviations in relation to HCT over all tested glucose ranges (HIF: hematocrit interference factor). Four of the devices showed stable performance: Contour XT (MARD: 1.3%/HIF: 6.1%), MyStar Extra (4.7%/7.1%), OneTouch Verio Pro (4.5%/7.3%), and Contour Link (6.3%/9.3%). The 4 other meters were influenced by HCT (Accu-Chek Performa: 4.7%/20.9%, Accu-Chek Aviva Nano: 4.5%/22.4%, FreeStyle Freedom Lite: 4.8%/24.5%; MyLife Pura: 6.4%/28.7%). In this study, all meters showed a good accuracy, but only 50% of them, including MyStar Extra, were shown to reliably correct for potential hematocrit influence on the meter results.
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Automonitorización de la Glucosa Sanguínea/instrumentación , Glucemia/análisis , Electroquímica/instrumentación , Hematócrito , HumanosRESUMEN
BACKGROUND: Elevated fasting intact proinsulin is a biomarker of late-stage ß-cell-dysfunction associated with clinically relevant insulin resistance. In this pilot investigation, we explored the potential value of measuring intact proinsulin as a functional predictor of ß-cell exhaustion during an oral glucose tolerance test (OGTT). METHODS: The study was performed with 31 participants, 11 of whom were healthy subjects (7 female, age: 59 ± 20 years), 10 had impaired glucose tolerance (IGT, 6 female, 62 ± 10 years), and 10 had known type 2 diabetes (T2DM, 5 female, 53 ± 11 years, HbA1c: 7.0 ± 0.6%, disease duration: 8 ± 5 years). During OGTT, blood was drawn after 0 hours, 1 hour, and 2 hours for determination of glucose and intact proinsulin. Five years later, patients were again contacted to assess their diabetes status and the association to the previous OGTT results was analyzed. RESULTS: The OGTT (0 hours/1 hour/2 hours) results were as follows: healthy subjects: glucose: 94 ± 8 mg/dL/140 ± 29 mg/dL/90 ± 24 mg/dL, intact proinsulin: 3 ± 2 pmol/L/10 ± 7 pmol/L/10 ± 5 pmol/L); IGT: glucose: 102 ± 9 mg/dL/158 ± 57 mg/dL/149 ± 34 mg/dL, intact proinsulin: 7 ± 4 pmol/L/23 ± 8 pmol/L/28 ± 6 pmol/L; T2DM: glucose: 121 ± 20 mg/dL/230 ± 51 mg/dL/213 ± 34 mg/dL; intact proinsulin: 7 ± 7 pmol/L/26 ± 9 pmol/L/27 ± 10 pmol/L). Five years later, all of the IGT and 2 of the healthy subjects had developed T2DM and one had devloped IGT. All of them had elevated 2-hour proinsulin values in the initial OGTT, while patients with normal intact proinsulin results did not develop diabetes. CONCLUSIONS: Elevated 2-hour intact proinsulin levels during OGTT were predictive for later type 2 diabetes development. Further studies need to confirm our findings in larger populations.
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Diabetes Mellitus Tipo 2/diagnóstico , Trastornos del Metabolismo de la Glucosa/diagnóstico , Prueba de Tolerancia a la Glucosa , Células Secretoras de Insulina/metabolismo , Proinsulina/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Trastornos del Metabolismo de la Glucosa/sangre , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Factores de Riesgo , Factores de Tiempo , Regulación hacia ArribaRESUMEN
B cells were first discovered as antibody producing cells, as B-1 B cells and finally as effector cells. In recent years their capacity to serve as antigen presenting cells is increasingly appreciated, and better tools are needed to study their function. We have previously described a new mouse model, the iDTR mice, that allow for the Cre-mediated expression of the diphtheria toxin receptor, thus rendering cells that express the Cre-recombinase sensitivity to diphtheria toxin. Herein we describe a new mouse line, the B-DTR mice, where the CD19-Cre was crossed to the iDTR mice. B-DTR allows for the efficient and cost-effective depletion of different B cell subpopulations, but only partially plasma cells. These mice can therefore be used to study the importance of B cells versus plasma cells in different immune responses and autoimmune diseases.
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Antígenos CD19/metabolismo , Linfocitos B/metabolismo , Toxina Diftérica/farmacología , Integrasas/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Depleción Linfocítica , Animales , Linfocitos B/citología , Linfocitos B/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Factor de Crecimiento Similar a EGF de Unión a Heparina , Inmunoglobulinas/sangre , Proteínas Luminiscentes/metabolismo , Recuento de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Células Plasmáticas/efectos de los fármacos , Células Plasmáticas/metabolismo , Sindecano-1/metabolismoRESUMEN
BACKGROUND: Hematocrit (HCT) is known to be a confounding factor that interferes with many blood glucose (BG) measurement technologies, resulting in wrong readings. Dynamic electrochemistry has been identified as one possible way to correct for these potential deviations. The purpose of this laboratory investigation was to assess the HCT stability of four BG meters known to employ dynamic electrochemistry (BGStar and iBGStar, Sanofi; Wavesense Jazz, AgaMatrix; Wellion Linus, MedTrust) in comparison with three other devices (GlucoDock, Medisana; OneTouch Verio Pro, LifeScan; FreeStyle Freedom InsuLinx, Abbott-Medisense). METHODS: Venous heparinized blood was immediately aliquoted after draw and manipulated to contain three different BG concentrations (60-90, 130-160, and 280-320 mg/dl) and five different HCT levels (25%, 35%, 45%, 55%, and 60%). After careful oxygenation to normal blood oxygen pressure, each of the resulting 15 different samples was measured six times with three devices and three strip lots of each meter. The YSI Stat 2300 served as laboratory reference method. Stability to HCT influence was assumed when less than 10% difference occurred between the highest and lowest mean glucose deviations in relation to HCT concentrations [hematocrit interference factor (HIF)]. RESULTS: Five of the investigated self-test meters showed a stable performance with the different HCT levels tested in this investigation: BGStar (HIF 4.6%), iBGStar (6.6%), Wavesense Jazz (4.1%), Wellion Linus (8.5%), and OneTouch Verio Pro (6.2%). The two other meters were influenced by HCT (FreeStyle InsuLinx 17.8%; GlucoDock 46.5%). CONCLUSIONS: In this study, meters employing dynamic electrochemistry, as used in the BGStar and iBGStar devices, were shown to correct for potential HCT influence on the meter results. Dynamic electrochemistry appears to be an effective way to handle this interfering condition.
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Automonitorización de la Glucosa Sanguínea/instrumentación , Técnicas Electroquímicas/instrumentación , Hematócrito/instrumentación , Laboratorios , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus/sangre , Técnicas Electroquímicas/métodos , Hematócrito/métodos , Humanos , Reproducibilidad de los ResultadosRESUMEN
B cells were previously shown to mediate partial protection against CMV infection, as in the absence of B cells, latently infected mice were more susceptible to virus reactivation. It remains unclear if this effect stems from the loss of B cells as antibody producers or as antigen presenting cells. To address this fundamental question, we propose to make use of new mouse models that allow conditional ablation of B cells or that allow for the generation of mice with B cells that are not able to produce antibodies.
Asunto(s)
Linfocitos B/inmunología , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Animales , Anticuerpos Antivirales/inmunología , Depleción Linfocítica/métodos , Ratones , Modelos AnimalesRESUMEN
The AM fungal family Archaeosporaceae and the genus Archaeospora are rendered paraphyletic by the relationship with the Geosiphonaceae. This problem led to a more detailed study of the Archaeosporales. Members of the Archaeosporaceae were described as forming both glomoid and acaulosporoid spores, or solely acaulosporoid spores. However, we found that Glomus callosum fell into the same phylogenetic clade as A. leptoticha and A. gerdemannii, but exclusively formed glomoid spores. To resolve these inconsistencies, a genus, Ambispora gen. nov., typified by Ambispora fennica sp. nov., is erected based on morphological evidence and SSU and ITS region rDNA data. Ambispora contains three species known to produce both acaulosporoid and glomoid spores: A. fennica, A. leptoticha comb. nov. (basionym G. leptotichum), and A. gerdemannii comb. nov. (basionym G. gerdemannii). Another species, A. callosa comb. nov. (basionym G. callosum), is known only from glomoid spores. Ambispora is placed in a new family, the Ambisporaceae fam. nov. The Archaeosporaceae is maintained with the type species, Archaeospora trappei (basionym Acaulospora trappei), along with Intraspora schenckii (basionym Entrophospora schenckii). Acaulospora nicolsonii, known only from acaulosporoid spores, is discussed and is considered likely to belong in the Ambisporaceae, but is retained within its present genus because of inadequate morphological information and a lack of molecular data.