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The Sencell sensor uses glucose-induced changes in an osmotic pressure chamber for continuous glucose measurement. A final device shall have the size of a grain of rice. The size limiting factor is the piezo-resistive pressure transducers inside the core sensor technology (resulting chamber volume: 70 µL. To achieve the necessary miniaturization, these pressure transducers were replaced by small (4000 × 400 × 150 nm³) nano-granular tunneling resistive (NTR) pressure sensors (chamber volume: 750 nL). For benchmark testing, we filled the miniaturized chamber with bovine serum albumin (BSA, 1 mM) and exposed it repeatedly to distilled water followed by 1 mM BSA solution. Thereafter, we manufactured sensors with glucose testing chemistry (ConcanavalinA/dextran) and investigated sensor performance with dynamic glucose changes between 0 and 300 mg/dL. Evaluation of the miniaturized sensors resulted in reliable pressure changes, both in the BSA benchmark experiment (30-35 mBar) and in the dynamic in vitro continuous glucose test (40-50 mBar). These pressure results were comparable to similar experiments with the previous larger in vitro sensors (30-50 mBar). In conclusion, the NTR pressure sensor technology was successfully employed to reduce the size of the core osmotic pressure chamber by more than 95% without loss in the osmotic pressure signal.
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Técnicas Biossensoriais , Glicemia , Pressão Osmótica , Automonitorização da Glicemia , Glucose , Miniaturização , Nanotecnologia , Técnicas Biossensoriais/métodosRESUMO
BACKGROUND: Increased intact proinsulin in plasma is a highly specific biomarker for a major disruption of insulin-processing in the pancreatic ß-cells with associated insulin resistance. Increased intact proinsulin in morning fasting plasma indicates not only incipient diabetes, but also increased risk of macrovascular events in the patient - of ten times before an actual diagnosis of diabetes - due to the convergence of ß-cell dysfunction, insulin resistance, and chronic systemic inflammation. This has raised the question as to whether a marked increase in intact proinsulin levels after oral glucose load in healthy subjects might be considered as indicative for ß-cell dysfunction and prediabetes. METHODS: A previous study from 2011 examined, inter alia, intact proinsulin levels in blood samples from twenty healthy study participants at baseline and two hours after an oral glucose tolerance test (OGTT) with 75 g glucose. Seventeen of the participants showed normal glucose levels at baseline and at two hours compared to 4 participants with normal intact proinsulin levels at baseline but increased intact proinsulin levels at two hours. RESULTS: All four patients went on to develop type 2 diabetes in the following 5 years. None of the other subjects from the previous investigation developed type 2 diabetes. CONCLUSIONS: As also confirmed by recent literature, intact proinsulin provides a powerful, easily measured biomarker for ß-cell dysfunction and insulin resistance in type 2 diabetes, as well as risk of future cardiovascular events regardless of the stage of diabetes.
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Diabetes Mellitus Tipo 2 , Teste de Tolerância a Glucose , Estado Pré-Diabético , Proinsulina/sangue , Adulto , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Insulina/metabolismo , Masculino , Estado Pré-Diabético/sangue , Estado Pré-Diabético/metabolismoRESUMO
BACKGROUND/AIMS: Parathyroid hormone (PTH) derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. METHODS: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 µg PTH-1-37, 20 µg PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. RESULTS: PTH was absorbed rapidly from the subcutaneous tissue with a median tmax of 30 minutes for 20 and 40 µg of PTH-1-37. tmax was 45 minutes for 20 µg PTH-1-34. Elimination half-lives were estimated as 76 ± 34 min and 70 ± 13 min for 20 µg and 40 µg PTH-1-37 (mean ± SD), and 78 ± 34 for 20 µg PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34) increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. CONCLUSIONS: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism.
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Hormônio Paratireóideo/farmacocinética , Fragmentos de Peptídeos/farmacocinética , Cálcio/sangue , Cálcio/metabolismo , Distúrbios do Metabolismo do Cálcio/tratamento farmacológico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Hormônio Paratireóideo/administração & dosagem , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/administração & dosagemRESUMO
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/sangue , Diabetes Mellitus Tipo 2/complicações , Hepatopatias/complicações , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The goal of this study was to investigate the effects of linagliptin compared with glimepiride on alpha and beta cell function and several vascular biomarkers after a standardized test meal. METHODS: Thirty-nine patients on metformin alone (age, 64 ± 7 years; duration of type 2 diabetes mellitus, 7.8 ± 4.5years, 27 male, 12 female; HbA1c , 57.2 ± 6.9 mmol/mol; mean ± SD) were randomized to receive linagliptin 5 mg (n = 19) or glimepiride (n = 20) for a study duration of 12 weeks. Glucagon-like peptide 1, blood glucose, insulin, intact proinsulin, glucagon, plasminogen activator inhibitor-1 (PAI-1), cyclic guanosinmonophosphat and asymetric dimethylarginin levels were measured in the fasting state and postprandial at 30-min intervals for a duration of 5 h. The areas under the curve (AUC0-300 min ) were calculated for group comparisons. RESULTS: HbA1c , fasting and postprandial glucose levels improved in both groups. An increase in postprandial insulin (22595 ± 5984 pmol/L*min), postprandial intact proinsulin (1359 ± 658 pmol/L*min), postprandial glucagon (317 ± 1136 pg/mL*min) and postprandial PAI-1 levels (863 ± 467 ng/mL*min) could be observed during treatment with glimepiride, whereas treatment with linagliptin was associated with a decrease in postprandial insulin (-8007 ± 4204 pmol/L*min), intact proinsulin (-1771 ± 426 pmol/L*min), postprandial glucagon (-1597 ± 1831 pg/mL*min) and PAI-1 levels (-410 ± 276 ng/mL*min). CONCLUSIONS: Despite an improvement in blood glucose control in both groups, linagliptin reduced postprandial insulin, proinsulin, glucagon and PAI-levels. These results indicate an improvement in postprandial alpha and beta cell function, as well as a reduced postprandial vascular risk profile during treatment with linagliptin.
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Glicemia/metabolismo , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ilhotas Pancreáticas/fisiologia , Metformina/uso terapêutico , Período Pós-Prandial/fisiologia , Purinas/uso terapêutico , Quinazolinas/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Quimioterapia Combinada , Feminino , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Ilhotas Pancreáticas/efeitos dos fármacos , Linagliptina , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Proinsulina/sangue , Purinas/farmacologia , Quinazolinas/farmacologia , Fatores de Risco , Compostos de Sulfonilureia/farmacologiaRESUMO
INTRODUCTION: Patients in intensive care units (ICUs) frequently lose control over their fecal continence leading to fecal incontinence (FI). We provide an overview of existing medical devices, which are supposed to alleviate FI-related problems. AREAS COVERED: Fecal management systems (FMS) prevent infections and complications. They reduce the risk of pressure ulcers and fecal incontinence. The systems enhance patient comfort and mitigate emotional distress during illness. Furthermore, FMS facilitate nursing care by reducing the incontinence-related workload. Finally, these systems can help minimize treatment costs by preventing complications, and reduction of extended hospital stays and additional treatments. Several well accepted systems made of silicone are on the market. A polyurethane-based soft balloon FMS (hygh-tec® basic-plus) has also been introduced, offering more comfort to the patient, safer handling for the healthcare professionals, and provides reliable leakproof access to the patient's colon. In addition to contamination-free fecal diversion, the trans-anal sealing mechanism of the device also allows for irrigation and delivery of medication into the colon. EXPERT OPINION: FMS in ICUs are integral to patient care and dignity. Recognizing and prioritizing the importance of these systems is essential for providing the highest standard of care to critically ill patients in the ICU.
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Rapid and sensitive detection of pathogens is critical in interrupting the transmission chain of infectious diseases. Currently, real-time (RT-)PCR represents the gold standard for the detection of SARS-CoV-2. RNase HII-assisted amplification (RHAM) is a promising technology, enabling reliable point-of-care (PoC) testing; however, its diagnostic accuracy has not yet been investigated. The present study compared the Pluslife Mini Dock (RHAM technology), with Abbott ID Now and Cepheid GeneXpert IV. The positive percent agreement (PPA) and negative percent agreement (NPA) were determined in 100 SARS-CoV-2 positive and 210 SARS-CoV-2 negative samples. Further, the reliability of the Pluslife Mini Dock was investigated in different SARS-CoV-2 variants (Delta and Omicron subvariants). The PPA was 99.00% for Pluslife, 100.00% for Abbott ID Now, and 99.00% for Cepheid GeneXpert, with an NPA of 100.00%, 98.90%, and 93.72%, respectively. Abbott ID Now demonstrated the highest rate of invalid results. All SARS-CoV-2 analysed variants were detected by the Pluslife device. Altogether, the Pluslife Mini Dock demonstrated a PPA of 99.16% (235/237) for CT < 36 and an NPA of 100.00% (313/313), respectively. In conclusion, the Pluslife Mini Dock demonstrated better analytical performance than Abbott ID Now and Cepheid GeneXpert IV, representing a highly accurate and rapid PoC alternative to RT-PCR.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/virologia , Estudos Retrospectivos , Testes Imediatos , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos , Reprodutibilidade dos Testes , Teste de Ácido Nucleico para COVID-19/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
Numerous rheological and microvascular alterations characterize the vascular pathology in patients with type 2 diabetes mellitus (T2DM). This study investigated effects of vildagliptin in comparison to glimepiride on retinal microvascular blood flow and erythrocyte deformability in T2DM.Fourty-four patients with T2DM on metformin monotherapy were included in this randomized, exploratory study over 24 weeks. Patients were randomized to receive either vildagliptin (50 mg twice daily) or glimepiride individually titrated up to 4 mg in addition to ongoing metformin treatment. Retinal microvascular blood flow (RBF)and the arteriolar wall to lumen ratio (WLR) were assessed using a laser doppler scanner. In addition, the rythrocyte elongation index (EI) was measured at different shear stresses using laserdiffractoscopy.Both treatments improved glycaemic control (p < 0.05 vs. baseline; respectively). While only slight changes in RBF and the WLR could be observed during treatment with glimepiride, vildagliptin significantly increased retinal bloodflow and decreased the arterial WLR (p < 0.05 vs. baseline respectively). The EI increased during both treatments over a wide range of applied shear stresses (p < 0.05 vs. baseline). An inverse correlation could be observed between improved glycaemic control (HbA1c) and EI (r = -0.524; p < 0.0001) but not with the changes in retinal microvascular measurements.Our results suggest that vildagliptin might exert beneficial effects on retinal microvascular blood flow beyond glucose control. In contrast, the improvement in erythrocyte deformability observed in both treatment groups,seems to be a correlate of improved glycaemic control.
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Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Deformação Eritrocítica/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Microcirculação/efeitos dos fármacos , Nitrilas/uso terapêutico , Pirrolidinas/uso terapêutico , Vasos Retinianos/efeitos dos fármacos , Compostos de Sulfonilureia/uso terapêutico , Adamantano/uso terapêutico , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Quimioterapia Combinada , Feminino , Alemanha , Hemoglobinas Glicadas/metabolismo , Humanos , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Vasos Retinianos/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , VildagliptinaRESUMO
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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New European medical device regulations require the performance of postmarketing surveillance evaluations for blood glucose meters (BGMs). We conducted an ISO15197:2015-conform system performance evaluation with the approved glucose dehydrogenase (GDH)-based Wellion NEWTON BGM. One hundred subjects were enrolled into the study (44 female, 56 male, 43 healthy subjects, 23 type 1 diabetes, 34 type 2 diabetes, age: 53.7 ± 15.8 years). In addition, manipulated heparinized whole blood was used for a laboratory interference test with ten selected substances (interference definition: substance-induced bias > 10%). The mean absolute relative difference (MARD) was 4.7%, and 100% of the values were in zones A (99.7%) and B (0.3%), respectively, of the consensus error grid. Interference was observed with xylose only, which is a known interfering substance for GDH-based BGMs.
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BACKGROUND: It is widely accepted that many medications exhibit inter-individual variability in their efficacy and toxicity due to polymorphisms in genes encoding drug-metabolising enzymes. One of the most often cited examples in this context is thiopurine S-methyltransferase (TPMT) polymorphism. TPMT is a phase 2 detoxification enzyme that catalyzes the S-methylation of thiopurine drugs such as thioguanine and 6-mercaptopurine. Approximately 11% of the Caucasian population carry a heterozygous deficiency of this enzyme causing intermediate enzyme activity, whereas 0.3% show a homozygous deficiency. In both cases, severe myelosuppression can develop upon treatment with thiopurines. These are commonly used in the treatment of leukemia. Therefore, genotyping of patients before treatment is absolutely necessary. Development of a fast and reliable real-time PCR application for TPMT genotyping would greatly improve thiopurine treatment regimens and allow the avoidance of adverse drug reactions. METHODS: Blood was obtained from a Caucasian cohort of 143 individuals. After extraction of DNA, all samples were genotyped for TPMT polymorphisms *2, *3A, *3B, and *3C by real-time PCR as well as by PCR-RFLP as the reference method, in order to validate the new method. RESULTS: Four different genotypes were found in the population studied. Of the 143 individuals investigated, 1 was heterozygous for TPMT*2 (0.70%), 2 were heterozygous for TPMT*3B (1.40%), and 8 heterozygous for TPMT-*3C (5.60%). No homozygous genotype could be identified. In total, 7.7% of the individuals carried mutations. Results from the newly developed real-time PCR were 100% concordant with those obtained using standard PCR-RFLP analysis, leading to 100% sensitivity and specificity. The hands-on time is approximately one third of the time needed for standard PCR-RFLP methods. CONCLUSIONS: A new high-throughput genotyping method could be successfully established and optimised for the commonly found mutant alleles TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B (G460A), and TPMT*3C (A719G) via real-time PCR on the LightCycler (Roche) instrument and using the standard PCR-RFLP as reference method.
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Genótipo , Ensaios de Triagem em Larga Escala/métodos , Metiltransferases/genética , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Estudos de Coortes , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
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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BACKGROUND: Testing the potential influence of interfering substances on the measurement performance of needle sensors for continuous glucose monitoring (CGM) is a challenging task. For proper function, the sensors need an almost stable fluidic environment. Previously published in vitro interference experiments were measuring under static concentration conditons. Our experimental setup allows for interference testing with dynamic changes of the interferent concentrations. METHODS: We designed a macrofluidic test stand that is fueled by several high-pressure liquid chromatography (HPLC) pumps generating programmable glucose and/or interferent gradients in phosphate-buffered saline (PBS). After optimizing experimental parameters (channel dimensions, temperature, flow rates, gradient slopes, buffer, pH etc.), we validated the setup using Dexcom G6 (G6) and Freestyle Libre 2 (L2) sensors with/without interferents, and using YSI 2300 Stat plus as the reference glucose device at room temperature. RESULTS: Both sensors tracked the programmed glucose changes. After calibration, G6 results closely matched glucose reference readings, while L2 routinely showed ~50% to 60% lower readings, most likely because of the factory-based calibration and temperature compensation. Gradients of maltose, acetaminophen, and xylose were employed to further validate the setup. As expected, both sensors were not affected by maltose. We confirmed previous findings regarding susceptibility of G6 readings to acetaminophen and L2 readings to xylose. Signals from both sensors are influenced by temperature in a linear fashion. CONCLUSIONS: Our experimental in vitro setup and protocol may provide a useful method to dynamically test CGM sensors for interfering substances. This may help to improve the accuracy of future CGM sensor generations.
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OBJECTIVES: The aim of this study was to validate an active matrix metalloproteinase (MMP-8) point-of-care diagnostic tool in COVID-19 patients with periodontal disease. SUBJECTS, MATERIALS, AND METHODS: Seventy-two COVID-19-positive and 30 COVID-19-negative subjects were enrolled in the study. Demographic data were recorded, periodontal examination carried out, and chairside tests run for evaluating the expression of active MMP-8 (aMMP-8) in the site with maximum periodontal breakdown via gingival crevicular fluid sampling as well as via a mouth rinse-based kit for general disease activity. In COVID-19-positive patients, the kits were run again once the patients turned COVID-19 negative. RESULTS: The overall (n = 102) sensitivity/specificity of the mouthrinse-based kits to detect periodontal disease was 79.41%/36.76% and that of site-specific kits was 64.71%/55.88% while adjusting for age, gender, and smoking status increased the sensitivity and specificity (82.35%/76.47% and 73.53%/88.24, respectively). Receiver operating characteristic (ROC) analysis for the adjusted model revealed very good area under the ROC curve 0.746-0.869 (p < .001) and 0.740-0.872 (p < .001) (the aMMP-8 mouth rinse and site-specific kits, respectively). No statistically significant difference was observed in the distribution of results of aMMP-8 mouth rinse test (p = .302) and aMMP-8 site-specific test (p = .189) once the subjects recovered from COVID-19. CONCLUSIONS: The findings of the present study support the aMMP-8 point-of-care testing (PoCT) kits as screening tools for periodontitis in COVID-19 patients. The overall screening accuracy can be further increased by utilizing adjunctively risk factors of periodontitis. The reported noninvasive, user-friendly, and objective PoCT diagnostic methodology may provide a way of stratifying risk groups, deciding upon referrals, and in the institution of diligent oral hygiene regimens.
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COVID-19 , Doenças Periodontais , Periodontite , COVID-19/diagnóstico , Teste para COVID-19 , Humanos , Metaloproteinase 8 da Matriz/metabolismo , Antissépticos Bucais , Doenças Periodontais/diagnóstico , Periodontite/diagnóstico , Testes ImediatosRESUMO
BACKGROUND: We analyzed specific effects of an add-on therapy with pioglitazone compared to metformin and their combination in patients with basal insulin treatment on biomarkers of CV risk. METHODS: In this double-blind, randomized, multicentre, active comparator controlled trial, 121 patients with type 2 diabetes were enrolled. Inclusions: treatment with basal insulin, HbA(1C) 6.5%-8.5%, age 30-75 years. After glargine therapy over 2 weeks for titration towards FBG ≤ 7.8 mmol/L, patients received either (A) bid 850 mg metformin (n = 42), (B) bid 15 mg pioglitazone (n = 40), or (C) 30 mg pioglitazone plus 1.7 g metformin (n = 39) over 6 months. Matrix Metal Proteinase 9 (MMP-9) was primary objective, together with biomarkers of CV risk. RESULTS: Pioglitazone (B) reduced MMP-9 versus baseline by 54.1 ± 187.1 ng/mL, with metformin (A) it was increased by 49.6 ± 336.2 ng/mL (p = 0.0345; B vs. A), and with the combination of both (C) it was decreased by 67.8 ± 231.4 ng/mL (A vs. C: p = 0.0416; B vs. C: p = 0.8695). After logarithmic transformation due to high variances the exploratory results showed significance for A vs. B (p = 0.0043) and for A vs. C (p = 0.0289).Insulin dosage was reduced by 7.3 units in group B (p < 0.0001), by 6.0 units in C (p = 0.0004), but was increased by 2.5 units (p = 0.1539) in A at follow up. Reduction in hs-CRP was significant within treatment groups for B (p = 0.0098) and C (p < 0.0001), and between the groups for A vs. C (p = 0.0124). All three single regimens reduced PAI-1. Adiponectin was significantly elevated in B and C (p < 0.0001) and between-groups. HbA(1C) was only significantly decreased in the combination group. No significant effects were observed for NFkB and PGFα. peripheral edema were seen in 11.9% vs. 40.0% vs. 20.5%, and weight change was -0.7 kg vs. +4.3 kg vs. +2.7 kg (A vs. B vs. C). CONCLUSIONS: Addition of pioglitazone but not of metformin reduces MMP-9, hs-CRP and increased insulin sensitivity and adiponectin in this study. The combination of both had no additional effect on inflammation. Pioglitazone is suggested to be a rational add-on therapy to basal insulin in patients with high CV risk.
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Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Tiazolidinedionas/uso terapêutico , Adiponectina/sangue , Adulto , Idoso , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Metformina/efeitos adversos , Pessoa de Meia-Idade , Pioglitazona , Fatores de Risco , Tiazolidinedionas/efeitos adversosRESUMO
The aim of the present study was to compare the effect of PIO (pioglitazone) or GLIM (glimepiride) on erythrocyte deformability in T2DM (Type 2 diabetes mellitus). The study covered 23 metformin-treated T2DM patients with an HbA1c (glycated haemoglobin) >6.5%. Patients were randomized to receive either PIO (15 mg, twice a day) or GLIM (1 mg, twice a day) in combination with metformin (850 mg, twice a day) for 6 months. Blood samples were taken for the measurement of fasting glucose, HbA1c, fasting insulin, intact proinsulin, adiponectin and Hct (haematocrit). In addition, the erythrocyte EI (elongation index) was measured using laser diffractoscopy. Both treatments significantly improved HbA1c levels (PIO, -0.9+/-1.1%; GLIM, -0.6+/-0.4%; both P<0.05) and resulted in comparable HbA1c levels after 6 months (PIO, 6.5+/-1.2%; GLIM, 6.2+/-0.4%) Treatment with PIO reduced fasting insulin levels (-8.7+/-15.8 milli-units/l; P=0.098), intact proinsulin levels (-11.8+/-9.5 pmol/l; P<0.05) and Hct (-1.3+/-2.3%; P=0.09), whereas adiponectin levels increased (8.2+/-4.9 microg/ml; P<0.05). No significant change in these parameters was observed during GLIM treatment. PIO improved the EI, resulting in a significant increase in EI at all physiological shear stress ranges (0.6-6.0 Pa; P<0.05). The improvement in EI correlated with the increase in adiponectin levels (r=0.74; P<0.001), and inversely with intact proinsulin levels (r=-0.47; P<0.05). This is the first study showing an improvement in EI during treatment with PIO, which was associated with an increase in adiponectin and a decrease in intact proinsulin levels, but independent of glycaemic control.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Deformação Eritrocítica/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Tiazolidinedionas/farmacologia , Adulto , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Pioglitazona , Estresse Mecânico , Compostos de Sulfonilureia/farmacologia , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêuticoRESUMO
BACKGROUND: The cytochrome P450 1A2 (CYP1A2) gene encodes one of the most important enzymes of the Phase I drug metabolism, which is involved in the metabolism of many lipophilic xenobiotics, such as haloperidol, theophylline, phenacetine, and others. The recently discovered single nucleotide polymorphisms CYP1A2*1C (-3860G-->A) in the 5' flanking region of the gene and CYP1A2*1F (-163C-->A) in intron 1 seem to interfere with the expression rate or catalytic function of the enzyme. Polymorphism carriers may either have a risk of reduced drug degradation and side effects, or may present with an increased induction of enzymatic activity resulting in clinical non-response to the prescribed therapy. We investigated two populations, a mental disease group and a healthy control group, to identify whether these two genetic variants are correlated with the general development of a mental disorder and if they could potentially be used as predictive markers for manifestation of the same. METHODS: Using specifically designed primers, we established a high-throughput multiplex screening realtime PCR method for the two polymorphisms on the CYP1A2 gene with the Roche LightCycler instrument. RESULTS: We analysed the two cohorts to identify whether one of the two described genetic variants may be associated with the manifestation of a mental disorder in general. For the CYP1A2*1C variant, we identified an allele frequency of 1.7% for both cohorts. For the CYP1A*1F polymorphism, we found an allele frequency of 74.5% for the mental disease group and 68.6% for the healthy control group. CONCLUSIONS: This new diagnostic method of multiplex detection may be helpful to routinely identify carriers of CYP1A2 variants and to improve the therapeutic effectiveness by selection of the most appropriate therapeutic regimen. As a result of this pilot study, there appeared to be no significant correlation between the existence of one of the investigated genetic variants and the development of a mental disorder.
Assuntos
Citocromo P-450 CYP1A2/genética , Transtornos Mentais/genética , Polimorfismo de Nucleotídeo Único , Citocromo P-450 CYP1A2/metabolismo , DNA/sangue , DNA/genética , DNA/isolamento & purificação , Marcadores Genéticos , Humanos , Íntrons/genética , Desnaturação de Ácido Nucleico , Reação em Cadeia da Polimerase/métodos , Polimorfismo Genético , Polimorfismo de Fragmento de RestriçãoRESUMO
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.
Assuntos
Automonitorização da Glicemia/instrumentação , Glicemia/análise , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Fitas Reagentes , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
This is a summary report of the most important aspects discussed during the YSI 2300 Analyzer Replacement Meeting. The aim is to provide the interested reader with an overview of the complex topic and propose solutions for the current issue. This solution should not only be adequate for the United States or Europe markets but also for all other countries. The meeting addendum presents three outcomes of the meeting.
Assuntos
Análise Química do Sangue/instrumentação , Automonitorização da Glicemia/instrumentação , Glicemia/análise , Ácido Láctico/sangue , Biomarcadores/sangue , Análise Química do Sangue/normas , Automonitorização da Glicemia/normas , Desenho de Equipamento , Humanos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
BACKGROUND: In patients with type 2 diabetes, glycemic control to target goals can only be achieved for a while by single-drug treatment. Antidiabetes therapy has to be adapted according to the individual course of the disease. This trial investigates the impact of Competact (Takeda Pharma, Aachen, Germany) (marketed as ActoplusMet in the United States)-a fixed combination of 850 mg of metformin with 15 mg of pioglitazone-for diabetes treatment in patients with insufficient glycemic control by metformin alone. STUDY DESIGN: This observational drug monitoring trial was performed at 1,480 study sites in Germany, and 4,866 complete patient data sets were included into the final analyses. Mean +/- SD age was 60.8 +/- 9.6 years (2,171 women, 2,691 men; disease duration, 6.7 +/- 4.7 years; body mass index [BMI], 31.0 +/- 5.2 kg/m(2)). In total, 43.8% of the patients received lipid-lowering drugs (antihypertensive medication, 74.3%). Main inclusion criteria were type 2 diabetes, metformin monotherapy, and an initial hemoglobin A1c (HbA1c) value between 6.6% and 9.9%. Parameters of glycemic control (HbA1c, fasting blood glucose [FBG]), blood pressure (BP), inflammation (high-sensitivity C-reactive protein [hsCRP]), and lipid metabolism (total cholesterol, high-density lipoprotein [HDL]-cholesterol, non-HDL-cholesterol, and triglycerides) were collected at baseline and after 4 months. RESULTS: All investigated parameters improved significantly (all P < 0.001) after 4 months of therapy with Competact (baseline vs. end point: systolic BP, 139.7 +/- 15.1 vs. 134.4 +/- 12.0 mm Hg; diastolic BP, 83.1 +/- 8.9 vs. 80.5 +/- 7.5 mm Hg; HbA1c, 7.8 +/- 1.0% vs. 7.0 +/- 0.8%; FBG, 9.0 +/- 2.6 vs. 7.0 +/- 1.7 mM; cholesterol, 5.7 +/- 1.1 mM vs. 5.3 +/- 0.9 mM; HDL-cholesterol, 1.2 +/- 0.4 mM vs. 1.3 +/- 0.4 mM; non-HDL-cholesterol, 4.5 +/- 1.2 mM vs. 4.0 +/- 0.9 mM; triglycerides, 2.5 +/- 1.0 mM vs. 2.1 +/- 0.8 mM; hsCRP, 3.2 +/- 2.6 mg/L vs. 2.7 +/- 2.3 mg/L). It is noteworthy that the BMI was not affected by Competact (31.0 +/- 5.2 kg/m(2) vs. 31.1 +/- 6.1 kg/m(2), P = 0.221). CONCLUSIONS: These observational results, obtained from a non-selected patient population under daily routine conditions, show the beneficial effects of a pioglitazone/metformin combination for diabetes patients with insufficient glycemic control under daily routine conditions.