RESUMO
Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.
Assuntos
Automonitorização da Glicemia , Diabetes Mellitus , Sistemas de Infusão de Insulina , Humanos , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Automonitorização da Glicemia/instrumentação , Glicemia/análise , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Inteligência Artificial , Registros Eletrônicos de SaúdeRESUMO
Diabetes Technology Society hosted its annual Diabetes Technology Meeting on November 4 to November 6, 2021. This meeting brought together speakers to discuss various developments within the field of diabetes technology. Meeting topics included blood glucose monitoring, continuous glucose monitoring, novel sensors, direct-to-consumer telehealth, metrics for glycemia, software for diabetes, regulation of diabetes technology, diabetes data science, artificial pancreas, novel insulins, insulin delivery, skin trauma, metabesity, precision diabetes, diversity in diabetes technology, use of diabetes technology in pregnancy, and green diabetes. A live demonstration on a mobile app to monitor diabetic foot wounds was presented.
Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Gravidez , TecnologiaRESUMO
Continuous subcutaneous insulin infusion (CSII) therapy is becoming increasingly popular. CSII provides convenient insulin delivery, precise dosing, easy adjustments for physical activity, stress, or illness, and integration with continuous glucose monitors in hybrid or other closed-loop systems. However, even as insulin pump hardware and software have advanced, technology for insulin infusion sets (IISs) has stayed relatively stagnant over time and is often referred to as the "Achilles heel" of CSII. To discuss barriers to insulin pump therapy and present information about advancements in, and results from clinical trials of extended wear IISs, Diabetes Technology Society virtually hosted the "Improving the Patient Experience with Longer Wear Infusion Sets Symposium" on December 1, 2021. The symposium featured experts in the field of IISs, including representatives from Steno Diabetes Center Copenhagen, University of California San Francisco, Stanford University, Medtronic Diabetes, and Science Consulting in Diabetes. The webinar's seven speakers covered (1) advancements in insulin pump therapy, (2) efficacy of longer wear infusion sets, and (3) innovations to reduce plastics and insulin waste.
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Insulina , Sistemas de Infusão de Insulina , Avaliação de Resultados da Assistência ao PacienteRESUMO
OBJECTIVE: We tested the feasibility of using sitagliptin-a dipeptidyl peptidase-IV inhibitor-for depressive symptoms in type 2 diabetes (T2D). METHODS: In a feasibility, double-blind, randomized controlled trial, we recruited people aged 18 to 75 years with T2D (glycated hemoglobin A1c levels ≥53 and ≤86 mmol/mol prescribed oral hypoglycemic therapy) and comorbid depressive symptoms (Patient Health Questionnaire-9 score ≥10) from family practices in South London. Eligible patients were randomized to sitagliptin 100 mg per day or matched placebo for 12 weeks. The primary feasibility outcomes were participation rates, attrition rates, and adverse events. The primary clinical outcomes were depressive symptoms (Patient Health Questionnaire-9 and 16-item Quick Inventory of Depressive Symptomatology scores) at 12 weeks as assessed using analyses of covariance. Ranges of treatment effects were estimated using Cohen d and associated 95% confidence intervals, where negative values favored sitagliptin over placebo. RESULTS: Of 153 people screened across 32 practices, 44 were randomized (22 to each arm). The mean (standard deviation) age was 58.8 (8.3) years, 46% were female, and 52% were of non-white ethnicity. Of those treated, 1 patient (4.5%) in each arm withdrew, and there were no group differences in adverse events. Despite improving 12-week glycated hemoglobin A1c (d = -1.19 [95% confidence interval = -1.90 to -0.48), improvement in 12-week Quick Inventory of Depressive Symptomatology score with sitagliptin was inferior to placebo across the range of estimated treatment effects (d = 0.71 [0.13 to 1.30]). Effects of sitagliptin on inflammation were inconsistent (d = -0.32 [-0.81 to 0.17] for high-sensitivity C-reactive protein). CONCLUSIONS: Repositioning of oral hypoglycemic therapy for depressive symptoms in T2D is feasible. However, in this unpowered feasibility study, we did not detect evidence of superiority of sitagliptin over placebo. The results are cautioned by the small sample size and limited treatment duration.Trial Registration: EudraCT: 2015-004527-32.
Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Depressão/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Pessoa de Meia-Idade , Fosfato de Sitagliptina/uso terapêutico , Resultado do TratamentoRESUMO
Diabetes Technology Society hosted its annual Diabetes Technology Meeting on November 12 to November 14, 2020. This meeting brought together speakers to cover various perspectives about the field of diabetes technology. The meeting topics included artificial intelligence, digital health, telemedicine, glucose monitoring, regulatory trends, metrics for expressing glycemia, pharmaceuticals, automated insulin delivery systems, novel insulins, metrics for diabetes monitoring, and discriminatory aspects of diabetes technology. A live demonstration was presented.
Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus , Inteligência Artificial , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus/tratamento farmacológico , Humanos , TecnologiaRESUMO
Technological advances have had a major effect on the management of type 1 diabetes. In addition to blood glucose meters, devices used by people with type 1 diabetes include insulin pumps, continuous glucose monitors, and, most recently, systems that combine both a pump and a monitor for algorithm-driven automation of insulin delivery. In the next 5 years, as many advances are expected in technology for the management of diabetes as there have been in the past 5 years, with improvements in continuous glucose monitoring and more available choices of systems that automate insulin delivery. Expansion of the use of technology will be needed beyond endocrinology practices to primary-care settings and broader populations of patients. Tools to support decision making will also need to be developed to help patients and health-care providers to use the output of these devices to optimise diabetes management.
Assuntos
Tecnologia Biomédica , Diabetes Mellitus Tipo 1/terapia , Glicemia/análise , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Insulina/administração & dosagem , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Monitorização Fisiológica/instrumentaçãoRESUMO
OBJECTIVE: We tested whether inflammation is associated with worsening depressive symptoms in type 2 diabetes and examined whether sex moderated this association. RESEARCH DESIGN AND METHODS: In a prospective cohort study of people with newly diagnosed type 2 diabetes, we measured depressive symptoms over a 2-year follow-up using the Patient Health Questionnaire-9 (PHQ-9). The independent variable was a composite inflammation burden score at diagnosis of diabetes, derived from hs-CRP, white cell count, interleukin (IL)-1ß, IL-1 receptor antagonist, monocyte chemotactic protein-1, and vascular endothelial growth factor concentrations. General linear models assessed 1) the association between overall inflammation burden and estimated marginal mean PHQ-9 score (ln transformed) at 2 years and 2) whether sex interacted with elevated inflammation burden (above-median score) in predicting change in PHQ-9 score. Models were adjusted for age, ethnicity, BMI, blood pressure, cholesterol, HbA1c, antidepressants, anti-inflammatory medications, and baseline ln PHQ-9 score. RESULTS: Of 1,174 people with complete inflammation data, mean (SD) age was 56.7 (11.0) years and 46.1% were of nonwhite ethnicity and 44.1% female. After full adjustment, inflammation burden was not associated with worsening ln PHQ-9 score (P = 0.65). However, female sex interacted with elevated inflammation in predicting higher 2-year ln PHQ-9 score (ß = 0.32, P = 0.005), showing that the difference by inflammation burden in females was 0.32 larger than in males. In post hoc comparisons, ln PHQ-9 score was higher in females than males with elevated inflammation (P = 0.003) but not with low inflammation (P = 0.34) burden. CONCLUSIONS: In type 2 diabetes, female sex confers specific vulnerability to the effects of inflammation on depressive symptoms.
Assuntos
Depressão/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/psicologia , Mediadores da Inflamação/sangue , Fatores Sexuais , Adulto , Idoso , Depressão/complicações , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Questionário de Saúde do Paciente , Estudos ProspectivosAssuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , HumanosAssuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Sistemas de Infusão de Insulina , Insulina/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Humanos , Hipoglicemiantes/administração & dosagem , Bombas de Infusão Implantáveis , Insulina/administração & dosagemRESUMO
AIMS/HYPOTHESIS: We examined the associations between depressive symptoms and diabetes distress with glycaemic control and diabetes complications over 2 years, after diagnosis of type 2 diabetes. METHODS: In a multi-ethnic, primary care cohort (n = 1735) of adults, all with recent (<6 months) diagnosis of type 2 diabetes, we measured the associations between depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score ≥10) and diabetes distress (Problem Areas in Diabetes [PAID] score ≥40), with change in 2 year HbA1c as the primary outcome and with incident rates of diabetes complications as secondary outcomes. Multivariate models were used to account for potential confounders. RESULTS: Of the 1651 participants (95.2%) of the total primary care cohort with available baseline PHQ-9 and PAID scores, mean ± SD age was 56.2 ± 11.1 years, 55.1% were men and 49.1% were of non-white ethnicity; 232 (14.1%) and 111 (6.7%) had depressive symptoms and diabetes distress, respectively. After adjustment for confounders, depressive symptoms were not associated with worsening HbA1c. After adjustment for age, sex, ethnicity, vascular risk factors and diabetes treatments, depressive symptoms were associated with increased risk of incident macrovascular complications (OR 2.78 [95% CI 1.19, 6.49], p = 0.018) but not microvascular complications. This was attenuated (p = 0.09) after adjustment for IL-1 receptor antagonist concentration. Diabetes distress was not associated with worsening HbA1c or incident complications. CONCLUSIONS/INTERPRETATION: In the first 2 years of type 2 diabetes, the effect of depressive symptoms and diabetes distress on glycaemic control is minimal. There was, however, an association between depressive symptoms and incidence of macrovascular complications. Elevated innate inflammation may be common to both depression and macrovascular diabetes complications, but these findings require replication.
Assuntos
Glicemia/análise , Depressão/complicações , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Adulto , Idoso , Depressão/psicologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/psicologia , Feminino , Hemoglobinas Glicadas , Orthohantavírus , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To compare glycemic control during continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) in people with type 2 diabetes to identify patient characteristics that determine those best treated by CSII. RESEARCH DESIGN AND METHODS: Randomized controlled trials were selected comparing HbA1c during CSII versus MDI in people with type 2 diabetes. Data sources included Cochrane database and Ovid Medline. We explored patient-level determinants of final HbA1c level and insulin dose using Bayesian meta-regression models of individual patient data and summary effects using two-step meta-analysis. Hypoglycemia data were unavailable. RESULTS: Five trials were identified, with 287 patients randomized to receive MDI and 303 to receive CSII. Baseline HbA1c was the best determinant of final HbA1c: HbA1c difference (%) = 1.575 - (0.216 [95% credible interval 0.371-0.043] × baseline HbA1c) for all trials, but with largest effect in the trial with prerandomization optimization of control. Baseline insulin dose was best predictor of final insulin dose: insulin dose difference (units/kg) = 0.1245 - (0.382 [0.510-0.254] × baseline insulin dose). Overall HbA1c difference was -0.40% (-0.86 to 0.05 [-4.4 mmol/mol (-9.4 to 0.6)]). Overall insulin dose was reduced by -0.25 units/kg (-0.31 to -0.19) (26% reduction on CSII), and by -24.0 units/day (-30.6 to -17.5). Mean weight did not differ between treatments (0.08 kg [-0.33 to 0.48]). CONCLUSIONS: CSII achieves better glycemic control than MDI in people with poorly controlled type 2 diabetes, with â¼26% reduction in insulin requirements and no weight change. The best effect is in those worst controlled and with the highest insulin dose at baseline.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Teorema de Bayes , Hemoglobinas Glicadas/metabolismo , Humanos , Injeções Subcutâneas , Ensaios Clínicos Controlados Aleatórios como AssuntoAssuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Difusão de Inovações , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Sistemas de Infusão de Insulina , Adolescente , Adulto , Pesquisa Biomédica/métodos , Criança , Terapia Combinada , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/uso terapêutico , Sistemas de Infusão de Insulina/efeitos adversos , Guias de Prática Clínica como AssuntoRESUMO
Cleaning products have long been a focus of efforts to improve sustainability and assure safety for the aquatic environment when disposed of after use. The latter is addressed at ingredient level through environmental risk assessment, including in formal frameworks such as REACH. Nevertheless, in the context of programs to improve overall sustainability, stakeholders demand both environmental safety assurance and progress at product level. Current product-level approaches for aquatic toxicity (e.g., USEtox™, Critical Dilution Volume) can be seen as predominantly hazard-based. The more logical approach would be risk-based, because ecotoxicity is generally threshold-dependent and hazard-based assessment produces conflicts with risk-based learnings. The development of a risk-based approach to assess formulated products is described: the International Association for Soaps, Detergents and Maintenance Products (A.I.S.E.) Charter Environmental Safety Check (ESC), which is consistent with the scientific principles underlying REACH. This is implemented through a simple spreadsheet tool and internal database of ingredient parameters including predicted no-effect concentration (PNEC) and removal rate. A novel feature is applying market volume information for both product types and ingredients to permit a risk-based calculation. To pass the ESC check, the projected environmental safety ratio (PESR) for each ingredient as formulated and dosed (unless cleared by a published risk assessment or exempted as inherently low risk) must be less than 1. The advantages of a risk-based approach are discussed. The strengths and limitations of various possible approaches to standard-setting, product-ranking and driving continuous improvement in respect of potential ecotoxic impacts on the aquatic environment are considered. It is proposed that as ecotoxicity is generally accepted to be threshold-dependent, with no effect below the threshold, the most constructive approach to continuous improvement of sustainability with regard to ecotoxicity is to focus efforts on instances where the safety margins for ingredients as used in specific products are narrow. This necessitates a risk-based approach. Integr Environ Assess Manag 2017;13:127-138. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of SETAC.
Assuntos
Detergentes/toxicidade , Poluentes Químicos da Água/toxicidade , Conservação dos Recursos Naturais/métodos , Detergentes/normas , Ecotoxicologia , Monitoramento Ambiental/métodos , Risco , Medição de Risco/métodos , Poluentes Químicos da Água/normas , Poluição Química da Água/estatística & dados numéricosAssuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina/efeitos adversos , Insulina/administração & dosagem , Causas de Morte , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/mortalidade , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemia/etiologia , Injeções Subcutâneas , Sistemas de Infusão de Insulina/economiaRESUMO
AIMS/HYPOTHESIS: Continuous subcutaneous insulin infusion (CSII) is an important treatment option for type 1 diabetes patients unable to achieve adequate glycemic control with multiple daily injections (MDI). Combining CSII with continuous glucose monitoring (CGM) in sensor-augmented pump therapy (SAP) with a low glucose-suspend (LGS) feature may further improve glycemic control and reduce the frequency of hypoglycemia. A cost-effectiveness analysis of SAP + LGS vs. CSII plus self-monitoring of blood glucose (SMBG) was performed to determine the health economic benefits of SAP + LGS in type 1 diabetes patients using CSII in the U.K. METHODS: Cost-effectiveness analysis was performed using the CORE diabetes model. Treatment effects were sourced from the literature, where SAP + LGS was associated with a projected HbA1c reduction of -1.49% vs. -0.62% for CSII, and a reduced frequency of severe hypoglycemia. The time horizon was that of patient lifetimes; future costs and clinical outcomes were discounted at 3.5% and 1.5% per annum, respectively. RESULTS: Projected outcomes showed that SAP + LGS was associated with higher mean quality-adjusted life expectancy (17.9 vs. 14.9 quality-adjusted life years [QALYs], SAP + LGS vs. CSII), and higher life expectancy (23.8 vs. 21.9 years), but higher mean lifetime direct costs (GBP 125,559 vs. GBP 88,991), leading to an incremental cost-effectiveness ratio (ICER) of GBP 12,233 per QALY gained for SAP + LGS vs. CSII. Findings of the base-case analysis remained robust in sensitivity analyses. CONCLUSIONS/INTERPRETATION: For UK-based type 1 diabetes patients with poor glycemic control, the use of SAP + LGS is likely to be cost-effective compared with CSII plus SMBG.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/economia , Infusões Subcutâneas/economia , Sistemas de Infusão de Insulina/economia , Insulina/administração & dosagem , Insulina/economia , Adulto , Automonitorização da Glicemia , Análise Custo-Benefício , Feminino , Humanos , Masculino , Método de Monte Carlo , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Depression is twice as common in people with type 1 or type 2 diabetes as in the general population, and is associated with poor outcomes. Evidence is growing that depression and type 2 diabetes share biological origins, particularly overactivation of innate immunity leading to a cytokine-mediated inflammatory response, and potentially through dysregulation of the hypothalamic-pituitary-adrenal axis. Throughout the life course, these pathways can lead to insulin resistance, cardiovascular disease, depression, increased risk of type 2 diabetes, and increased mortality. Proinflammatory cytokines might directly affect the brain, causing depressive symptoms. In type 1 diabetes, mediators of depression are not well studied, with research hindered by inconsistent definitions of depression and scarcity of observational, mechanistic, and interventional research along the life course. Despite few studies, evidence suggests that familial relationships and burden of a lifelong disorder with an onset early in personality development might contribute to increased vulnerability to depression. Overall, longitudinal research is needed to identify risk factors and mechanisms for depression in patients with diabetes, particularly early in the life course. Ultimately, improved understanding of shared origins of depression and diabetes could provide the potential to treat and improve outcomes of both disorders simultaneously. These shared origins are targets for primary prevention of type 2 diabetes.
Assuntos
Depressão/fisiopatologia , Depressão/psicologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/psicologia , Glicemia/fisiologia , Ritmo Circadiano/fisiologia , Comorbidade , Citocinas/fisiologia , Depressão/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Imunidade Inata/fisiologia , Insulina/fisiologia , Resistência à Insulina/fisiologia , Sistema Hipófise-Suprarrenal/fisiopatologiaRESUMO
OBJECTIVE: This study analyzed narratives about experiences of real-time continuous glucose monitoring (CGM) in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: People with type 1 diabetes using CGM and caregivers completed an online survey. Questions included duration of CGM, frequency of sensor wear, funding, and a free narrative about experiences or views about CGM. We used qualitative framework analysis to analyze 100 responses; 50% of participants were aged ≥ 18 years. RESULTS: Most participants (87%) used CGM with insulin pump therapy, 71% used sensors ≥ 75% of the time, and 66% received funding for CGM from the National Health Service. Four themes were identified: 1) metabolic control, 2) living with CGM (work and school, sleep, exercise, nutrition, frequency of self-monitoring of blood glucose [SMBG]), 3) psychological issues and patient/caregiver attitudes, and 4) barriers to CGM use (technical issues, financial issues, attitudes of healthcare professionals toward CGM). Despite some hassles, experiences were overwhelmingly positive, with improved glycemic control, diet and exercise management, quality of life, and physical and psychological well-being, as well as reduced frequency of SMBG. Technical problems included sensor inaccuracy and unreliability, and "alarm fatigue." The advantages of CGM used with an insulin pump with automatic suspension of insulin delivery during hypoglycemia were recorded by several participants, noting reduced hypoglycemia frequency and fear of nocturnal hypoglycemia. CONCLUSIONS: Patient and caregiver narratives indicate that CGM is a valuable addition to diabetes care for many with type 1 diabetes.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/psicologia , Narração , Adolescente , Adulto , Idoso , Atitude Frente a Saúde , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Automonitorização da Glicemia/psicologia , Cuidadores/psicologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Medo/psicologia , Feminino , Humanos , Hipoglicemia/epidemiologia , Hipoglicemia/psicologia , Insulina/administração & dosagem , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Autocuidado/psicologia , Adulto JovemRESUMO
Both lung disease and elevation of blood glucose are associated with increased glucose concentration (from 0.4 to ~4.0 mM) in the airway surface liquid (ASL). This perturbation of ASL glucose makes the airway more susceptible to infection by respiratory pathogens. ASL is minute (~1 µl/cm(2)) and the measurement of glucose concentration in the small volume ASL is extremely difficult. Therefore, we sought to develop a fluorescent biosensor with sufficient sensitivity to determine glucose concentrations in ASL in situ. We coupled a range of environmentally sensitive fluorophores to mutated forms of a glucose/galactose-binding protein (GBP) including H152C and H152C/A213R and determined their equilibrium binding properties. Of these, GBP H152C/A213R-BADAN (Kd 0.86 ± 0.01 mM, Fmax/F0 3.6) was optimal for glucose sensing and in ASL increased fluorescence when basolateral glucose concentration was raised from 1 to 20 mM. Moreover, interpolation of the data showed that the glucose concentration in ASL was increased, with results similar to that using glucose oxidase analysis. The fluorescence of GBP H152C/A213R-BADAN in native ASL from human airway epithelial cultures in situ was significantly increased over time when basolateral glucose was increased from 5 to 20 mM. Overall our data indicate that this GBP is a useful tool to monitor glucose homoeostasis in the lung.