RESUMEN
Background: Endogenous insulin supplementation is essential for individuals with type 1 diabetes (T1D). However, current treatments, including pancreas transplantation, insulin injections, and oral medications, have significant limitations. The development of engineered cells that can secrete endogenous insulin offers a promising new therapeutic strategy for type 1 diabetes (T1D). This approach could potentially circumvent autoimmune responses associated with the transplantation of differentiated ß-cells or systemic delivery of viral vectors. Methods: We utilized CRISPR/Cas9 gene editing coupled with homology-directed repair (HDR) to precisely integrate a promoter-free EMCVIRES-insulin cassette into the 3' untranslated region (UTR) of the GAPDH gene in human HEK-293T cells. Subsequently quantified insulin expression levels in these engineered cells, the viability and functionality of the engineered cells when seeded on different cell vectors (GelMA and Cytopore I) were also assessed. Finally, we investigated the therapeutic potential of EMCVIRES-based insulin secretion circuits in reversing Hyperglycaemia in T1D mice. Result: Our results demonstrate that HDR-mediated gene editing successfully integrated the IRES-insulin loop into the genome of HEK-293T cells, a non-endocrine cell line, enabling the expression of human-derived insulin. Furthermore, Cytopore I microcarriers facilitated cell attachment and proliferation during in vitro culture and enhanced cell survival post-transplantation. Transplantation of these cell-laden microcarriers into mice led to the development of a stable, fat-encapsulated structure. This structure exhibited the expression of the platelet-endothelial cell adhesion molecule CD31, and no significant immune rejection was observed throughout the experiment. Diabetic mice that received the cell carriers reversed hyperglycemia, and blood glucose fluctuations under simulated feeding stimuli were very similar to those of healthy mice. Conclusion: In summary, our study demonstrates that Cytopore I microcarriers are biocompatible and promote long-term cell survival in vivo. The promoter-free EMCVIRES-insulin loop enables non-endocrine cells to secrete mature insulin, leading to a rapid reduction in glucose levels. We have presented a novel promoter-free genetic engineering strategy for insulin secretion and proposed an efficient cell transplantation method. Our findings suggest the potential to expand the range of cell sources available for the treatment of diabetes, offering new avenues for therapeutic interventions.
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Diabetes Mellitus Tipo 1 , Edición Génica , Hiperglucemia , Células Secretoras de Insulina , Insulina , Humanos , Animales , Hiperglucemia/terapia , Hiperglucemia/metabolismo , Ratones , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Insulina/genética , Células HEK293 , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/genética , Edición Génica/métodos , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Sitios Internos de Entrada al Ribosoma/genética , Regiones Promotoras Genéticas , Sistemas CRISPR-CasRESUMEN
Diabetes mellitus is currently approaching epidemic proportions and disproportionately affects patients in the hospital setting. In the United States, individuals living with diabetes represent over 17 million emergency department visits and 8 million admissions annually. The management of these patients in the hospital setting is complex and differs considerably from the outpatient setting. All patients with hyperglycemia should be screened for diabetes, as in-hospital hyperglycemia portends a greater risk for morbidity, mortality, admission to an intensive care unit, and increased hospital length of stay. However, the definition of hyperglycemia, glycemic targets, and strategies to manage hyperglycemia in the inpatient setting can vary greatly depending on the population considered. Moreover, the presenting illness, changing nutritional status, and concurrent hospital medications often necessitate thoughtful consideration to adjustments of home diabetes regimens and/or the initiation of new insulin doses. This review article will examine core concepts and emerging new literature surrounding inpatient diabetes management, including glycemic targets, insulin dosing strategies, noninsulin medications, new diabetes technologies, inpatient diabetes management teams, and discharge planning strategies, to optimize patient safety and satisfaction, clinical outcomes, and even hospital financial health.
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Diabetes Mellitus , Hipoglucemiantes , Pacientes Internos , Humanos , Diabetes Mellitus/terapia , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Hospitalización , Hiperglucemia/terapia , Hiperglucemia/tratamiento farmacológico , Glucemia/metabolismo , Manejo de la EnfermedadRESUMEN
Hyperglycemia in pregnancy due to pre-existing Type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) is rising globally with increasing rates of risk factors for metabolic disease. This review summarizes current evidence and recommendations from national and international guidelines for diagnosis and management of T2DM and GDM to optimize maternal and neonatal outcomes.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Hiperglucemia , Humanos , Embarazo , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Femenino , Hiperglucemia/diagnóstico , Hiperglucemia/terapia , Hipoglucemiantes/uso terapéutico , Embarazo en Diabéticas/terapia , Embarazo en Diabéticas/diagnóstico , Embarazo en Diabéticas/sangreRESUMEN
AIM: To determine whether it was feasible, safe and acceptable for ambulance clinicians to use capillary blood ketone meters for 'high-risk' diabetic ketoacidosis (DKA) recognition and fluid initiation, to inform the need for a full-powered, multi-centre trial. METHODS: Adopting a stepped-wedge controlled design, participants with hyperglycaemia (capillary blood glucose >11.0 mmol/L) or diabetes and unwell were recruited. 'High-risk' DKA intervention participants (capillary blood ketones ≥3.0 mmol/L) received paramedic-led fluid therapy. Participant demographic and clinical data were collated from ambulance and hospital care records. Twenty ambulance and Emergency Department clinicians were interviewed to understand their hyperglycaemia and DKA care experiences. RESULTS: In this study, 388 participants were recruited (Control: n = 203; Intervention: n = 185). Most presented with hyperglycaemia, and incidence of type 1 and type 2 diabetes was 18.5% and 74.3%, respectively. Ketone meter use facilitated 'high-risk' DKA identification (control: 2.5%, n = 5; intervention: 6.5%, n = 12) and was associated with improved hospital pre-alerting. Ambulance clinicians appeared to have a high index of suspicion for hospital-diagnosed DKA participants. One third (33.3%; n = 3) of Control and almost half (45.5%; n = 5) of Intervention DKA participants received pre-hospital fluid therapy. Key interview themes included clinical assessment, ambulance DKA fluid therapy, clinical handovers; decision support tool; hospital DKA management; barriers to hospital DKA care. CONCLUSIONS: Ambulance capillary blood ketone meter use was deemed feasible, safe and acceptable. Opportunities for improved clinical decision making, support and safety-netting, as well as in-hospital DKA care, were recognised. As participant recruitment was below progression threshold, it is recommended that future-related research considers alternative trial designs. CLINICALTRIALS: gov: NCT04940897.
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Ambulancias , Cetoacidosis Diabética , Hiperglucemia , Cetonas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucemia/análisis , Glucemia/metabolismo , Capilares , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/terapia , Cetoacidosis Diabética/terapia , Cetoacidosis Diabética/sangre , Cetoacidosis Diabética/diagnóstico , Servicios Médicos de Urgencia/métodos , Servicio de Urgencia en Hospital , Estudios de Factibilidad , Fluidoterapia/métodos , Hiperglucemia/sangre , Hiperglucemia/diagnóstico , Hiperglucemia/terapia , Cetonas/sangre , Adolescente , Adulto Joven , Anciano de 80 o más AñosRESUMEN
OBJECTIVES: Hyperglycemia is associated with poor outcome in large vessel occlusion (LVO) stroke, with mechanism for this effect unknown. MATERIALS AND METHODS: We used our prospective, multicenter, observational study, Blood Pressure After Endovascular Stroke Therapy (BEST), of anterior circulation LVO stroke undergoing endovascular therapy (EVT) from 11/2017-7/2018 to determine association between increasing blood glucose (BG) and intracerebral hemorrhage (ICH). Our primary outcome was degree of ICH, classified as none, asymptomatic ICH, or symptomatic ICH (≥4-point increase in National Institutes of Health Stroke Scale [NIHSS] at 24 h with any hemorrhage on imaging). Secondary outcomes included 24 h NIHSS, early neurologic recovery (ENR, NIHSS 0-1 or NIHSS reduction by ≥8 within 24 h), and 90-day modified Rankin Scale (mRS) using univariate and multivariable regression. RESULTS: Of 485 enrolled patients, increasing BG was associated with increasing severity of ICH (adjusted OR, aOR 1.06, 95 % CI 1.02-1.1, p < 0.001), higher 24 h NIHSS (aOR 1.22, 95 % CI 1.11-1.34, p < 0.001), ENR (aOR 0.90, 95 % CI 0.82-1.00, p < 0.002), and 90-day mRS (aOR 1.06, 95 % CI 1.03-1.09, p < 0.001) when adjusted for age, presenting NIHSS, ASPECTS, 24-hour peak systolic blood pressure, time from last known well, and successful recanalization. CONCLUSIONS: In the BEST study, increasing BG was associated with greater odds of increasing ICH severity. Further study is warranted to determine whether treatment of will decrease ICH severity following EVT.
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Biomarcadores , Glucemia , Hemorragia Cerebral , Evaluación de la Discapacidad , Procedimientos Endovasculares , Índice de Severidad de la Enfermedad , Humanos , Procedimientos Endovasculares/efectos adversos , Masculino , Anciano , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Glucemia/metabolismo , Factores de Tiempo , Factores de Riesgo , Hemorragia Cerebral/terapia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/sangre , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Biomarcadores/sangre , Anciano de 80 o más Años , Recuperación de la Función , Medición de Riesgo , Hiperglucemia/sangre , Hiperglucemia/diagnóstico , Hiperglucemia/terapia , Hiperglucemia/complicaciones , Estados Unidos , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatologíaRESUMEN
OBJECTIVES: This study's aims were to describe the outcomes of patients with diabetes presenting with their first ED visit for hyperglycemia, and to identify predictors of recurrent ED visits for hyperglycemia. METHODS: Using linked databases, we conducted a population-based cohort study of adult and pediatric patients with types 1 and 2 diabetes presenting with a first ED visit for hyperglycemia from April 2010 to March 2020 in Ontario, Canada. We determined the proportion of patients with a recurrent ED visit for hyperglycemia within 30 days of the index visit. Using multivariable regression analysis, we examined clinical and socioeconomic predictors for recurrent visits. RESULTS: There were 779,632 patients with a first ED visit for hyperglycemia. Mean (SD) age was 64.3 (15.2) years; 47.7% were female. 11.0% had a recurrent visit for hyperglycemia within 30 days. Statistically significant predictors of a recurrent visit included: male sex, type 1 diabetes, regions with fewer visible minority groups and with less education or employment, higher hemoglobin A1C, more family physician or internist visits within the past year, being rostered to a family physician, previous ED visits in the past year, ED or hospitalization within the previous 14 days, access to homecare services, and previous hyperglycemia encounters in the past 5 years. Alcoholism and depression or anxiety were positive predictors for the 18-65 age group. CONCLUSIONS: This population-level study identifies predictors of recurrent ED visits for hyperglycemia, including male sex, type 1 diabetes, regions with fewer visible minority groups and with less education or employment, higher hemoglobin A1C, higher previous healthcare system utilization (ED visits and hospitalization) for hyperglycemia, being rostered to a family physician, and access to homecare services. Knowledge of these predictors may be used to develop targeted interventions to improve patient outcomes and reduce healthcare system costs.
ABSTRAIT: OBJECTIFS: Les objectifs de cette étude étaient de décrire les résultats des patients diabétiques présentant leur première visite aux urgences pour hyperglycémie, et d'identifier les prédicteurs des visites récurrentes aux urgences pour hyperglycémie. MéTHODES: À l'aide de bases de données couplées, nous avons mené une étude de cohorte basée sur la population de patients adultes et pédiatriques atteints de diabète de type 1 et 2 présentant une première visite aux urgences pour l'hyperglycémie d'avril 2010 à mars 2020 en Ontario, au Canada. Nous avons déterminé la proportion de patients présentant une visite récurrente à l'urgence pour hyperglycémie dans les 30 jours suivant la visite d'index. À l'aide d'une analyse de régression multivariée, nous avons examiné les prédicteurs cliniques et socioéconomiques des visites récurrentes. RéSULTATS: Il y avait 779 632 patients avec une première visite à l'urgence pour hyperglycémie. L'âge moyen (ET) était de 64,3 (15,2) ans; 47,7% étaient des femmes. 11,0 % avaient une visite récurrente pour hyperglycémie dans les 30 jours. Les prédicteurs statistiquement significatifs d'une visite récurrente comprenaient le sexe masculin, le diabète de type 1, les régions comptant moins de groupes de minorités visibles et ayant moins d'études ou d'emploi, une hémoglobine A1C plus élevée, plus de visites chez un médecin de famille ou un interniste au cours de la dernière année, être inscrit auprès d'un médecin de famille, consulter le service d'urgence au cours de la dernière année, être hospitalisé au cours des 14 derniers jours, avoir accès à des services de soins à domicile et avoir été confronté à une hyperglycémie au cours des 5 dernières années. L'alcoolisme et la dépression ou l'anxiété étaient des prédicteurs positifs pour le groupe des 18-65 ans. CONCLUSIONS: Cette étude au niveau de la population identifie des prédicteurs de visites récurrentes aux urgences pour l'hyperglycémie, y compris le sexe masculin, le diabète de type 1, les régions avec moins de groupes de minorités visibles et avec moins d'études ou d'emploi, plus d'hémoglobine A1C, l'utilisation antérieure plus élevée du système de soins de santé (visites aux urgences et hospitalisation) pour l'hyperglycémie, le fait d'être inscrit auprès d'un médecin de famille et l'accès aux services de soins à domicile. La connaissance de ces prédicteurs peut être utilisée pour élaborer des interventions ciblées afin d'améliorer les résultats pour les patients et de réduire les coûts du système de santé.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Servicio de Urgencia en Hospital , Hiperglucemia , Humanos , Masculino , Femenino , Servicio de Urgencia en Hospital/estadística & datos numéricos , Hiperglucemia/epidemiología , Hiperglucemia/terapia , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/epidemiología , Ontario/epidemiología , Adulto , Recurrencia , Estudios Retrospectivos , Estudios de Cohortes , Anciano , Factores de Tiempo , Adolescente , Visitas a la Sala de EmergenciasRESUMEN
The motility of the gastrointestinal tract is coordinated in part by rhythmic slow waves, and disrupted slow-wave patterns are linked to functional motility disorders. At present, there are no treatment strategies that primarily target slow-wave activity. This study assessed the use of pacing to suppress glucagon-induced slow-wave dysrhythmias in the small intestine. Slow waves in the jejunum were mapped in vivo using a high-resolution surface-contact electrode array in pigs (n = 7). Glucagon was intravenously administered to induce hyperglycemia. Slow-wave propagation patterns were categorized into antegrade, retrograde, collision, pacemaker, and uncoupled activity. Slow-wave characteristics such as period, amplitude, and speed were also quantified. Postglucagon infusion, pacing was applied at 4 mA and 8 mA and the resulting slow waves were quantified spatiotemporally. Antegrade propagation was dominant throughout all stages with a prevalence of 55 ± 38% at baseline. However, glucagon infusion resulted in a substantial and significant increase in uncoupled slow waves from 10 ± 8% to 30 ± 12% (P = 0.004) without significantly altering the prevalence of other slow-wave patterns. Slow-wave frequency, amplitude, and speed remained unchanged. Pacing, particularly at 8 mA, significantly suppressed dysrhythmic slow-wave patterns and achieved more effective spatial entrainment (85%) compared with 4 mA (46%, P = 0.039). This study defined the effect of glucagon on jejunal slow waves and identified uncoupling as a key dysrhythmia signature. Pacing effectively entrained rhythmic activity and suppressed dysrhythmias, highlighting the potential of pacing for gastrointestinal disorders associated with slow-wave abnormalities.NEW & NOTEWORTHY Glucagon was infused in pigs to induce hyperglycemia and the resulting slow-wave response in the intact jejunum was defined in high resolution for the first time. Subsequently, with pacing, the glucagon-induced dysrhythmias were suppressed and spatially entrained for the first time with a success rate of 85%. The ability to suppress slow-wave dysrhythmias through pacing is promising in treating motility disorders that are associated with intestinal dysrhythmias.
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Motilidad Gastrointestinal , Glucagón , Yeyuno , Animales , Porcinos , Motilidad Gastrointestinal/fisiología , Yeyuno/fisiopatología , Intestino Delgado/fisiopatología , Femenino , Hiperglucemia/terapia , MasculinoRESUMEN
BACKGROUND: Hypertension, hyperlipidemia, and hyperglycemia have emerged as global health concerns of paramount significance. With the burgeoning popularity of mind-body therapy, cardiovascular patients have increasingly exhibited a vested interest in the practice of Tai Chi. The objective of this study seeks to quantitatively assess the impact of Tai Chi interventions on blood pressure, lipid levels, and glucose concentrations among the elderly population, thereby explaining the optimal intervention protocol. METHODS: An extensive search was conducted across multiple databases, including Web of Science, PubMed, CNKI, WANFANG DATA, RISS, KISS, and DBPIA, comprising English, Korean, and Chinese literature. The search strategy employed a retrieval method of subject term 1 + subject term 2, which included both full names and abbreviations of the terms. Specifically, "taijiquan" or "Tai Chi" were set as the Term 1, while Term 2 was set as "blood pressure," "BP," "Fasting blood glucose," "FBG," "Triglyceride," and "TG." Thereafter, the retrieved articles were filtered in accordance with the PICOS method. Risk of bias assessment was performed using RoB 2.0, while data analysis was conducted using Comprehensive Meta-Analysis 3.7. RESULTS: A total of 57 studies, including 3,856 research subjects, were eligible for inclusion. The findings of the primary effect quantitative synthesis demonstrated that Tai Chi exerted an improvement on systolic blood pressure (SBP) (ES = -0.764, p < .001), diastolic blood pressure (DBP) (ES = -0.426, p = .001), triglyceride (TG) (ES = -0.452, p < .001), and fasting blood glucose concentrations (FBG) (ES = -0.552, p = .002) among middle-aged and elderly individuals. Subgroup analysis further revealed that the intervention effects were significantly influenced by the characteristics of the research subjects and the specific intervention protocol employed. CONCLUSION: Tai Chi, as a gentle form of aerobic exercise, exerts a profound impact on reducing blood pressure, fasting blood glucose levels, and triglyceride concentrations among middle-aged and elderly individuals. Notably, the intervention effect is particularly pronounced among male patients afflicted with hypertension, hyperglycemia, and hyperlipidemia. Based on the collective advantages underscored by this research, we strongly recommend engaging in Tai Chi exercises for a minimum duration of 16 weeks, with each session lasting 30-50 min and conducted 6-7 times per week, without any restrictions on the style employed.
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Hiperglucemia , Hiperlipidemias , Hipertensión , Taichi Chuan , Anciano , Humanos , Masculino , Persona de Mediana Edad , Glucemia , Presión Sanguínea , Ayuno , Hiperglucemia/terapia , Hipertensión/terapia , FemeninoRESUMEN
BACKGROUND: Synchronized intestinal electrical stimulation (SIES), in which intestinal electrical stimulation (IES) is delivered in synchronization with the intrinsic slow wave of small intestine, was previously reported to be more potent in accelerating small intestine transit than IES delivered at fixed frequency and phase. We hypothesized that SIES is more potent in suppressing postprandial blood glucose by enhancing the release of glucagon-like peptide-1 (GLP-1) and insulin. MATERIALS AND METHODS: Rats underwent long-term implant of two pairs of electrodes at the duodenum for IES and SIES, respectively. Acute hyperglycemia was induced with glucagon, and the oral glucose tolerance test was performed on separate days with IES, SIES, or sham (no stimulation). RESULTS: 1. Glucagon reduced the percentage of normal slow wave in sham (70.9% ± 4.1%) from (84.9% ± 2.6%, p = 0.006) of control, which was ameliorated by SIES (82.5% ± 3.3%, p = 0.031). 2. IES and SIES reduced glucagon-induced increase of blood glucose (192 mg/dl) at 30 minutes by 17% and 20%, respectively. SIES showed a further inhibitory effect at 60 minutes (147 vs 171 mg/dl, p = 0.003, vs sham). 3. Compared with sham (139 pg/ml), GLP-1 at 30 minutes was increased in both IES (158 pg/ml) and SIES (169 pg/ml). GLP-1 level was still high at 60 minutes in rats with SIES. 4. At 30 minutes, the plasma insulin level was increased by 18.8 µIU/ml with SIES, which was significantly higher than that with sham (7.1 µIU/ml, p < 0.001) and IES (13.2 µIU/ml, p = 0.041). CONCLUSION: SIES is more effective than IES in reducing glucagon-induced acute hyperglycemia by enhancing the release of GLP-1 and insulin.
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Glucagón , Hiperglucemia , Ratas , Animales , Glucemia , Hiperglucemia/inducido químicamente , Hiperglucemia/terapia , Péptido 1 Similar al Glucagón , Insulina , Estimulación EléctricaRESUMEN
Diabetes mellitus is a highly prevalent disease characterized by hyperglycaemia that damages the vascular system, leading to micro- (retinopathy, neuropathy, nephropathy) and macrovascular diseases (cardiovascular disease). There are also secondary complications of diabetes (cardiomyopathy, erectile dysfunction or diabetic foot ulcers). Stem cell-based therapies have become a promising tool targeting diabetes symptoms and its chronic complications. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are of great importance because of their abundance, non-invasive isolation and no ethical limitations. Characteristics that make ADMSCs good candidates for cell-based therapy are their wide immunomodulatory properties and paracrine activities through the secretion of an array of growth factors, chemokines, cytokines, angiogenic factors and anti-apoptotic molecules. Besides, after transplantation, ADMSCs show great ex vivo expansion capacity and differentiation to other cell types, including insulin-producing cells, cardiomyocytes, chondrocytes, hepatocyte-like cells, neurons, endothelial cells, photoreceptor-like cells, or astrocytes. Preclinical studies have shown that ADMSC-based therapy effectively improved visual acuity, ameliorated polyneuropathy and foot ulceration, arrested the development and progression of diabetic kidney disease, or alleviated the diabetes-induced cardiomyocyte hypertrophy. However, despite the positive results obtained in animal models, there are still several challenges that need to be overcome before the results of preclinical studies can be translated into clinical applications. To date, there are several clinical trials or ongoing trials using ADMSCs in the treatment of diabetic complications, most of them in the treatment of diabetic foot ulcers. This narrative review summarizes the most recent outcomes on the usage of ADMSCs in the treatment of long-term complications of diabetes in both animal models and clinical trials.
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Diabetes Mellitus , Pie Diabético , Hiperglucemia , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Masculino , Animales , Tejido Adiposo/metabolismo , Pie Diabético/terapia , Células Endoteliales , Células Madre Mesenquimatosas/metabolismo , Hiperglucemia/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Diabetes Mellitus/metabolismoAsunto(s)
Biomarcadores , Glucemia , Hiperglucemia , Valor Predictivo de las Pruebas , Humanos , Pronóstico , Biomarcadores/sangre , Hiperglucemia/diagnóstico , Hiperglucemia/sangre , Hiperglucemia/terapia , Glucemia/metabolismo , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/sangre , Infarto del Miocardio/terapia , Infarto del Miocardio/fisiopatologíaRESUMEN
(1) Background: Hyperglycaemia that occurs during enteral nutrition (EN) should be prevented and treated appropriately since it can have important consequences for morbidity and mortality. However, there are few quality studies in the literature regarding the management of EN in this situation. The objective of this project was to attempt to respond, through a panel of experts, to those clinical problems regarding EN in patients with diabetes or stress hyperglycaemia (hereinafter referred to only as hyperglycaemia) for which we do not have conclusive scientific evidence; (2) Methods: The RAND/UCLA Appropriateness Method, a modified Delphi panel method, was applied. A panel of experts made up of 10 clinical nutrition specialists was formed, and they scored on the appropriateness of EN in hyperglycaemia, doing so in two rounds. A total of 2992 clinical scenarios were examined, which were stratified into five chapters: type of formula used, method of administration, infusion site, treatment of diabetes, and gastrointestinal complications. (3) Results: consensus was detected in 36.4% of the clinical scenarios presented, of which 23.7% were deemed appropriate scenarios, while 12.7% were deemed inappropriate. The remaining 63.6% of the scenarios were classified as uncertain; (4) Conclusions: The recommendations extracted will be useful for improving the clinical management of these patients. However, there are still many uncertain scenarios reflecting that the criteria for the management of EN in hyperglycaemia are not completely standardised. More studies are required to provide quality recommendations in this area.
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Diabetes Mellitus , Hiperglucemia , Humanos , Hiperglucemia/terapia , Nutrición Enteral/métodos , Consenso , Diabetes Mellitus/terapia , Alimentos FormuladosRESUMEN
Stress induced hyperglycemia is the body's protect response against strong (patho-physiological and/or psychological) stress, sometimes the blood glucose level is too high due to out of the body's adjustment. Renal glucose threshold (about 9 mmol/L) is a window of glucose leak from capillary to interstitial tissue. It is important to keep blood glucose level < 9 mmol/L, for reducing vascular sclerosis as well as organs hypoperfusion, meanwhile pay attention to preventing more dangerous hypoglycemia. Glucose, as the main energy substrate, should be daily supply and its metabolism should be monitored. We used to talk "nutritional support". Support is conform the physiological ability of host, but therapy is to coordinate and change pathophysiology. So, nutritional support is not equal to nutritional therapy. For critical ill patients, we need to emphasize "nutritional therapy", i.e, do not give nutritional treatment without metabolic monitoring, make up for deficiencies and avoid metabolites overloading, rational adjustment to protect and coordinate organs function.
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Glucemia , Hiperglucemia , Humanos , Glucemia/metabolismo , Enfermedad Crítica/terapia , Hiperglucemia/terapia , Apoyo Nutricional , GlucosaRESUMEN
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by high blood glucose and is associated with high morbidity and mortality among the diabetic population. Uncontrolled chronic hyperglycaemia causes increased formation and accumulation of different oxidative and nitrosative stress markers, resulting in microvascular and macrovascular complications, which might seriously affect the quality of a patient's life. Conventional treatment strategies are confined to controlling blood glucose by regulating the insulin level and are not involved in attenuating the life-threatening complications of diabetes mellitus. Thus, there is an unmet need to develop a viable treatment strategy that could target the multi-etiological factors involved in the pathogenesis of diabetic complications. Stem cell therapy, a regenerative medicine approach, has been investigated in diabetic complications owing to their unique characteristic features of self-renewal, multilineage differentiation and regeneration potential. The present review is focused on potential therapeutic applications of stem cells in the treatment of microvascular diabetic complications such as nephropathy, retinopathy, and polyneuropathy.
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Complicaciones de la Diabetes , Diabetes Mellitus , Hiperglucemia , Humanos , Glucemia/metabolismo , Medicina Regenerativa , Complicaciones de la Diabetes/terapia , Hiperglucemia/complicaciones , Hiperglucemia/terapia , Células Madre/metabolismo , Diabetes Mellitus/terapiaRESUMEN
Phototherapeutics has shown promise in treating various diseases without surgical or drug interventions. However, it is challenging to use it in inner-body applications due to the limited light penetration depth through the skin. Therefore, we propose an organic light-emitting diode (OLED) catheter as an effective photobiomodulation (PBM) platform useful for tubular organs such as duodenums. A fully encapsulated highly flexible OLED is mounted over a round columnar structure, producing axially uniform illumination without local hotspots. The biocompatible and airtight OLED catheter can operate in aqueous environments for extended periods, meeting the essential requirements for inner-body medical applications. In a diabetic Goto-Kakizaki (GK) rat model, the red OLED catheter delivering 798 mJ of energy is shown to reduce hyperglycemia and insulin resistance compared to the sham group. Results are further supported by the subdued liver fibrosis, illustrating the immense potential of the OLED-catheter-based internal PBM for the treatment of type 2 diabetes and other diseases yet to be identified.
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Diabetes Mellitus Tipo 2 , Hiperglucemia , Animales , Ratas , Catéteres , Diabetes Mellitus Tipo 2/terapia , Duodeno , Hiperglucemia/terapia , FototerapiaRESUMEN
Diabetic cardiomyopathy, an increasingly global epidemic and a major cause of heart failure with preserved ejection fraction (HFpEF), is associated with hyperglycemia, insulin resistance, and intracardiomyocyte calcium mishandling. Here we identify that, in db/db mice with type 2 diabetes-induced HFpEF, abnormal remodeling of cardiomyocyte transverse-tubule microdomains occurs with downregulation of the membrane scaffolding protein cardiac bridging integrator 1 (cBIN1). Transduction of cBIN1 by AAV9 gene therapy can restore transverse-tubule microdomains to normalize intracellular distribution of calcium-handling proteins and, surprisingly, glucose transporter 4 (GLUT4). Cardiac proteomics revealed that AAV9-cBIN1 normalized components of calcium handling and GLUT4 translocation machineries. Functional studies further identified that AAV9-cBIN1 normalized insulin-dependent glucose uptake in diabetic cardiomyocytes. Phenotypically, AAV9-cBIN1 rescued cardiac lusitropy, improved exercise intolerance, and ameliorated hyperglycemia in diabetic mice. Restoration of transverse-tubule microdomains can improve cardiac function in the setting of diabetic cardiomyopathy and can also improve systemic glycemic control.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Insuficiencia Cardíaca , Hiperglucemia , Animales , Ratones , Glucemia , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/terapia , Insuficiencia Cardíaca/terapia , Calcio , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Volumen Sistólico , Antiarrítmicos , Cardiotónicos , Miocitos Cardíacos , Hiperglucemia/terapia , Proteínas Adaptadoras Transductoras de Señales , Aminoácidos , Inhibidores Enzimáticos , Terapia GenéticaRESUMEN
PURPOSE OF REVIEW: Critically ill patients usually develop insulin resistance and hyperglycemia, which is aggravated by early parenteral nutrition. In observational studies, the lowest mortality risk associates with glucose concentrations close to the antecedent average glucose level. This review summarizes the most recent evidence regarding glucose control in critical illness. RECENT FINDINGS: Although pioneer randomized controlled trials showed morbidity and mortality benefit by normalizing blood glucose in intensive care, the largest multicenter randomized controlled trial found increased mortality. Differences in glucose targets, the accuracy of the glucose control protocol, and differences in feeding strategy may explain these differences.Recent randomized controlled trials investigating the impact of individualized glucose control did not show benefits of targeting individualized or looser glucose values in critically ill patients with poorly controlled diabetes. SUMMARY: It remains unclear whether tight glucose control in critical illness is beneficial or not in the absence of early parenteral nutrition, which is currently being studied in the multicenter TGC-fast randomized controlled trial. Without new evidence, it seems prudent to avoid severe hyperglycemia and hypoglycemia in all patients.
Asunto(s)
Hiperglucemia , Resistencia a la Insulina , Humanos , Glucemia , Glucosa , Enfermedad Crítica/terapia , Hiperglucemia/terapia , Cuidados Críticos/métodos , Nutrición Parenteral , Insulina/uso terapéutico , Hipoglucemiantes , Estudios Multicéntricos como AsuntoRESUMEN
Hyperglycemia is commonly encountered in extremely preterm newborns and physiologically can be attributed to immaturity in several biochemical pathways related to glucose metabolism. Although hyperglycemia is associated with a variety of adverse outcomes frequently described in this population, evidence for causality is lacking. Variations in definitions and treatment approaches have further complicated the understanding and implications of hyperglycemia on the immediate and long-term effects in preterm newborns. In this review, we describe the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research. IMPACT: Hyperglycemia is common and less well described than hypoglycemia in extremely preterm newborns. Hyperglycemia can be attributed to immaturity in several cellular pathways involved in glucose metabolism in this age group. Hyperglycemia has been shown to be associated with a variety of adverse outcomes frequently described in this population; however, evidence for causality is lacking. Variations in definitions and treatment approaches have complicated the understanding and the implications of hyperglycemia on the immediate and long-term effects outcomes. This review describes the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research.
Asunto(s)
Hiperglucemia , Hipoglucemia , Recién Nacido , Humanos , Recien Nacido Prematuro , Hiperglucemia/complicaciones , Hiperglucemia/terapia , Causalidad , Hipoglucemia/complicaciones , Glucosa , Glucemia/metabolismoRESUMEN
Soy yogurt has been gaining popularity as a vegan food produced simply by soymilk fermentation with proper microbial manipulation. It is well known that soy containing rich isoflavones is beneficial for ameliorating hyperglycaemic disorders. Soy fermentation can improve the bioavailability of these precious nutrients. Lactiplantibacillus plantarum is one of the most abundant and frequently isolated species in soymilk manufacturing. Soy yogurts produced with efficient GABA (γ-aminobutyric acid)-producing L. plantarum and the deglycosylating activity of L. plantarum were functionally assessed in a STZ-induced hyperglycaemic mouse model. Hyperglycaemic mice were assigned into groups and treated with daily gavage of either dH2O, soymilk, soy yoghurts produced with high GABA-producing L. plantarum GA30 (LPGA30), low GABA-producing L. plantarum PV30 (LPPV30) or the soy yoghurts fortified with additional 30 mg g-1 GABA counterparts (GA + GABA and PV + GABA groups). Except the dH2O group, all soy yoghurt groups retained body weight with improved glucose homeostasis, glucose tolerance test results and renal tissue integrity, while the soymilk group shows partial benefits. Plasma GABA concentrations in the daily soy yoghurt-supplemented groups (LPGA30 and LPPV30) plateaued at 5 times higher than the average 0.5 µM in dH2O and soymilk groups, and their GABA-fortified soy yoghurt counterparts (GA + GABA and PV + GABA) groups were accountable for the restored plasma insulin levels. Gut microbiome analysis revealed dysbiosis in STZ-induced hyperglycemic mice of the dH2O group with breached out facultative anaerobic Proteobacteria over the normal phyla Firmicutes and Bacteroidetes. Restored gut microbiota with transitionally populated Actinobacteria was demonstrated in the LPGA30 group but not in the LPPV30 group. Soy yoghurts produced with efficient GABA-producing L. plantarum GA30 showed exceptional benefits in modulating gut microbiota with dominant genera of Enterococcus, Lactobacillus and Bifidobacterium, and the presence of some minor beneficial microbial communities including Akkermansia muciniphila, Butyricicoccus pullicaecorum, Corynebacterium spp. and Adlercreutzia spp. Efficient GABA-producing L. plantarum GA30 fermented soymilk to produce soy yoghurts that exhibit profound synergistic protections over rich soy isoflavones to restore pancreatic ß-cell functions for insulin production in STZ-induced hyperglycaemic mice. Additionally, the probiotic role of GABA-producing L. plantarum in re-establishing healthy gut microbiota in hyperglycaemic mice implies a possible symbiotic relationship, awaiting further exploration.