RESUMEN
The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), American Association of Clinical Endocrinology (AACE) and Diabetes Technology Society (DTS) convened a panel of internists and diabetologists to update the ADA consensus statement on hyperglycaemic crises in adults with diabetes, published in 2001 and last updated in 2009. The objective of this consensus report is to provide up-to-date knowledge about the epidemiology, pathophysiology, clinical presentation, and recommendations for the diagnosis, treatment and prevention of diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) in adults. A systematic examination of publications since 2009 informed new recommendations. The target audience is the full spectrum of diabetes healthcare professionals and individuals with diabetes.
Asunto(s)
Cetoacidosis Diabética , Hiperglucemia , Humanos , Cetoacidosis Diabética/terapia , Cetoacidosis Diabética/epidemiología , Adulto , Consenso , Diabetes Mellitus/epidemiología , Coma Hiperglucémico Hiperosmolar no Cetósico/terapiaRESUMEN
AIMS: Limited data exist about the use of insulin degludec in the hospital. This multicentre, non-inferiority, open-label, prospective randomized trial compared the safety and efficacy of insulin degludec-U100 and glargine-U100 for the management of hospitalized patients with type 2 diabetes. METHODS: In total, 180 general medical and surgical patients with an admission blood glucose (BG) between 7.8 and 22.2 mmol/L, treated with oral agents or insulin before hospitalization were randomly allocated (1:1) to a basal-bolus regimen using degludec (n = 92) or glargine (n = 88), as basal and aspart before meals. Insulin dose was adjusted daily to a target BG between 3.9 and 10.0 mmol/L. The primary endpoint was the difference in mean hospital daily BG between groups. RESULTS: Overall, the randomization BG was 12.2 ± 2.9 mmol/L and glycated haemoglobin 84 mmol/mol (9.8% ± 2.0%). There were no differences in mean daily BG (10.0 ± 2.1 vs. 10.0 ± 2.5 mmol/L, p = .9), proportion of BG in target range (54·5% ± 29% vs. 55·3% ± 28%, p = .85), basal insulin (29.6 ± 13 vs. 30.4 ± 18 units/day, p = .85), length of stay [median (IQR): 6.7 (4.7-10.5) vs. 7.5 (4.7-11.6) days, p = .61], hospital complications (23% vs. 23%, p = .95) between treatment groups. There were no differences in the proportion of patients with BG <3.9 mmol/L (17% vs. 19%, p = .75) or <3.0 mmol/L (3.7% vs. 1.3%, p = .62) between degludec and glargine. CONCLUSION: Hospital treatment with degludec-U100 or glargine-U100 is equally safe and effective for the management of hyperglycaemia in general medical and surgical patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/análisis , Hospitales , Humanos , Hipoglucemiantes/efectos adversos , Pacientes Internos , Insulina Glargina/efectos adversos , Insulina de Acción Prolongada , Estudios ProspectivosRESUMEN
AIM: To assess whether treatment with sitagliptin, starting before surgery and continued during the hospital stay, can prevent and reduce the severity of perioperative hyperglycaemia in patients with type 2 diabetes undergoing coronary artery bypass graft (CABG) surgery. MATERIALS AND METHODS: We conducted a double-blinded, placebo-controlled trial in adults with type 2 diabetes randomly assigned to receive sitagliptin or matching placebo starting 1 day prior to surgery and continued during the hospital stay. The primary outcome was difference in the proportion of patients with postoperative hyperglycaemia (blood glucose [BG] > 10 mmol/L [>180 mg/dL]) in the intensive care unit (ICU). Secondary endpoints included differences in mean daily BG in the ICU and after transition to regular wards, hypoglycaemia, hospital complications, length of stay and need of insulin therapy. RESULTS: We included 182 participants randomized to receive sitagliptin or placebo (91 per group, age 64 ± 9 years, HbA1c 7.6% ± 1.5% and diabetes duration 10 ± 9 years). There were no differences in the number of patients with postoperative BG greater than 10 mmol/L, mean daily BG in the ICU or after transition to regular wards, hypoglycaemia, hospital complications or length of stay. There were no differences in insulin requirements in the ICU; however, sitagliptin therapy was associated with lower mean daily insulin requirements (21.1 ± 18.4 vs. 32.5 ± 26.3 units, P = .007) after transition to a regular ward compared with placebo. CONCLUSION: The administration of sitagliptin prior to surgery and during the hospital stay did not prevent perioperative hyperglycaemia or complications after CABG. Sitagliptin therapy was associated with lower mean daily insulin requirements after transition to regular wards.
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Procedimientos Quirúrgicos Cardíacos , Diabetes Mellitus Tipo 2 , Hiperglucemia , Adulto , Anciano , Glucemia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hiperglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Persona de Mediana Edad , Fosfato de Sitagliptina/uso terapéutico , Resultado del TratamientoRESUMEN
AIM: To compare a glucagon-like peptide-1 receptor agonist with basal insulin at hospital discharge in patients with uncontrolled type 2 diabetes in a randomized clinical trial. METHODS: A total of 273 patients with glycated haemoglobin (HbA1c) 7%-10% (53-86 mol/mol) were randomized to liraglutide (n = 136) or insulin glargine (n = 137) at hospital discharge. The primary endpoint was difference in HbA1c at 12 and 26 weeks. Secondary endpoints included hypoglycaemia, changes in body weight, and achievement of HbA1c <7% (53 mmol/mol) without hypoglycaemia or weight gain. RESULTS: The between-group difference in HbA1c at 12 weeks and 26 weeks was -0.28% (95% CI -0.64, 0.09), and at 26 weeks it was -0.55%, (95% CI -1.01, -0.09) in favour of liraglutide. Liraglutide treatment resulted in a lower frequency of hypoglycaemia <3.9 mmol/L (13% vs 23%; P = 0.04), but there was no difference in the rate of clinically significant hypoglycaemia <3.0 mmol/L. Compared to insulin glargine, liraglutide treatment was associated with greater weight loss at 26 weeks (-4.7 ± 7.7 kg vs -0.6 ± 11.5 kg; P < 0.001), and the proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia was 48% versus 33% (P = 0.05) at 12 weeks and 45% versus 33% (P = 0.14) at 26 weeks in liraglutide versus insulin glargine. The proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia and no weight gain was higher with liraglutide at 12 (41% vs 24%, P = 0.005) and 26 weeks (39% vs 22%; P = 0.014). The incidence of gastrointestinal adverse events was higher with liraglutide than with insulin glargine (P < 0.001). CONCLUSION: Compared to insulin glargine, treatment with liraglutide at hospital discharge resulted in better glycaemic control and greater weight loss, but increased gastrointestinal adverse events.
Asunto(s)
Diabetes Mellitus Tipo 2 , Liraglutida , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Quimioterapia Combinada , Hemoglobina Glucada/análisis , Hospitales , Humanos , Hipoglucemiantes/efectos adversos , Insulina Glargina/efectos adversos , Liraglutida/efectos adversos , Alta del Paciente , Resultado del TratamientoRESUMEN
OBJECTIVE: DPP-4 inhibitors (DPP-4i) have been shown to be effective for the management of inpatient diabetes. We report pooled data from 3 prospective studies using DPP-4i in general medicine and surgery patients with type 2 diabetes (T2D). METHODS: We combined data from 3 randomized studies comparing DPP-4i alone or in combination with basal insulin or a basal-bolus insulin regimen. Medicine (n = 266) and surgery (n = 319) patients admitted with a blood glucose (BG) between 140 and 400 mg/dL, treated with diet, oral agents, or low-dose insulin therapy were included. Patients received DPP-4i alone (n = 144), DPP-4i plus basal insulin (n = 158) or basal-bolus regimen (n = 283). All groups received correctional doses with rapid-acting insulin for BG >140 mg/dL. The primary endpoint was differences in mean daily BG between groups. Secondary endpoints included differences in hypoglycemia and hospital complications. RESULTS: There were no differences in mean hospital daily BG among patients treated with DPP-4i alone (170 ± 37 mg/dL), DPP-4i plus basal (172 ± 42 mg/dL), or basalbolus (172 ± 43 mg/dL), P = .94; or in the percentage of BG readings within target of 70 to 180 mg/dL (63 ± 32%, 60 ± 31%, and 64 ± 28%, respectively; P = .42). There were no differences in length of stay or complications, but hypoglycemia was less common with DPP-4i alone (2%) compared to DPP-4i plus basal (9%) and basal-bolus (10%); P = .004. CONCLUSION: Treatment with DPP-4i alone or in combination with basal insulin is effective and results in a lower incidence of hypoglycemia compared to a basal-bolus insulin regimen in general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood glucose; BMI = body mass index; CI = confidence interval; DPP-4i = dipeptidyl peptidase-4 inhibitors; HbA1c = hemoglobin A1c; OR = odds ratio; T2D = type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Medicina , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Humanos , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Insulina Glargina , Estudios ProspectivosRESUMEN
OBJECTIVE: Glargine and detemir insulin are the two most commonly prescribed basal insulin analogues for the ambulatory and inpatient management of diabetes. The efficacy and safety of basal insulin analogues in the hospital setting has not been established. METHODS: This observational study compared differences in glycemic control and outcomes in non-intensive care unit patients with blood glucose (BG) >140 mg/dL who were treated with glargine or detemir, between January 1, 2012, and September 30, 2015, in two academic centers. RESULTS: Among 6,245 medical and surgical patients with hyperglycemia, 5,749 received one or more doses of glargine, and 496 patients received detemir during the hospital stay. There were no differences in the mean daily BG (glargine, 182 ± 46 mg/dL vs. detemir, 180 ± 44 mg/dL; P = .70). There were no differences in mortality, hospital complications, or re-admissions between groups (all, P>.05). After adjusting for potential confounders, there was no statistically significant difference in hypoglycemia rates between treatment groups. Patients treated with detemir required higher total daily basal insulin doses (0.27 ± 0.16 units/kg/day vs. 0.22 ± 0.15 units/kg/day; P<.001). Glargine-treated patients had statistically longer length of stay; however, this difference may not be clinically relevant (6.8 ± 7.4 days vs. 6.0 ± 6.3 days; P<.001). CONCLUSION: Our study indicates that treatment with glargine and detemir results in similar inpatient glycemic control in general medicine and surgery patients. Detemir treatment was associated with higher daily basal insulin dose and number of injections. A prospective randomized study is needed to confirm these findings. ABBREVIATIONS: BG = blood glucose BMI = body mass index CI = confidence interval eGFR = estimated glomerular filtration rate HbA1c = glycated hemoglobin ICD-9 = International Classification of Diseases, ninth revision ICU = intensive care unit IQR = interquartile range LOS = length-of-stay OR = odd ratio.
Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina Detemir/uso terapéutico , Insulina Glargina/uso terapéutico , Anciano , Glucemia/análisis , Diabetes Mellitus/sangre , Femenino , Humanos , Hiperglucemia/sangre , Pacientes Internos , Tiempo de Internación , Masculino , Persona de Mediana EdadRESUMEN
The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), American Association of Clinical Endocrinology (AACE), and Diabetes Technology Society (DTS) convened a panel of internists and diabetologists to update the ADA consensus statement on hyperglycemic crises in adults with diabetes, published in 2001 and last updated in 2009. The objective of this consensus report is to provide up-to-date knowledge about the epidemiology, pathophysiology, clinical presentation, and recommendations for the diagnosis, treatment, and prevention of diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) in adults. A systematic examination of publications since 2009 informed new recommendations. The target audience is the full spectrum of diabetes health care professionals and individuals with diabetes.
Asunto(s)
Cetoacidosis Diabética , Humanos , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/terapia , Adulto , Hiperglucemia/complicaciones , Hiperglucemia/epidemiología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Consenso , Coma Hiperglucémico Hiperosmolar no Cetósico/terapia , Coma Hiperglucémico Hiperosmolar no Cetósico/fisiopatologíaRESUMEN
OBJECTIVE: Automated insulin delivery (AID) has rarely been studied in adults with type 2 diabetes. We tested the feasibility of using AID for type 2 diabetes with the Omnipod 5 System in a multicenter outpatient trial. RESEARCH DESIGN AND METHODS: Participants previously were using either basal-only or basal-bolus insulin injections, with or without the use of a continuous glucose monitor (CGM), and had a baseline HbA1c ≥8% (≥64 mmol/mol). Participants completed 2 weeks of CGM sensor data collection (blinded for those not previously using CGM) with their standard therapy (ST), then transitioned to 8 weeks of AID. Participants who previously used basal-only injections used the AID system in manual mode for 2 weeks before starting AID. Antihyperglycemic agents were continued at clinician discretion. Primary safety outcomes were percentage of time with sensor glucose ≥250 mg/dL and <54 mg/dL during AID. Additional outcomes included HbA1c and time in target range (TIR) (70-180 mg/dL). RESULTS: Participants (N = 24) had a mean (± SD) age of 61 ± 8 years, baseline HbA1c of 9.4% ± 0.9% (79 ± 10 mmol/mol), and diabetes duration of 19 ± 9 years. Percentage of time with sensor glucose ≥250 mg/dL decreased with AID by 16.9% ± 16.2% (P < 0.0001), whereas percentage of time at <54 mg/dL remained low during both ST and AID (median [interquartile range] 0.0% [0.00%, 0.06%] vs. 0.00% [0.00%, 0.03%]; P = 0.4543). HbA1c (± SD) decreased by 1.3% ± 0.7% (14 ± 8 mmol/mol; P < 0.0001) and TIR increased by 21.9% ± 15.2% (P < 0.0001) without a significant change in total daily insulin or BMI with AID. CONCLUSIONS: Findings from this feasibility trial of AID in adults with type 2 diabetes with suboptimal glycemic outcomes justify further evaluation of this technology in this population.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Persona de Mediana Edad , Anciano , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , Automonitorización de la Glucosa Sanguínea , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Glucemia , Insulina Regular Humana/uso terapéutico , Sistemas de Infusión de InsulinaRESUMEN
Traditionally, the care of critically ill patients with diabetes or stress hyperglycemia in the intensive care unit (ICU) demands the use of continuous intravenous insulin (CII) therapy to achieve narrow glycemic targets. To reduce the risk of iatrogenic hypoglycemia and to achieve glycemic targets during CII, healthcare providers (HCP) rely on hourly point-of-care (POC) arterial or capillary glucose tests obtained with glucose monitors. The burden of this approach, however, was evident during the beginning of the pandemic when the immediate reduction in close contact interactions between HCP and patients with COVID-19 was necessary to avoid potentially life-threatening exposures. Taking advantage of the advancements in current diabetes technologies, including continuous glucose monitoring (CGM) devices integrated with digital health tools for remote monitoring, HCP implemented novel protocols in the ICU to care for patients with COVID-19 and hyperglycemia. We provide an overview of research conducted in the ICU setting with the use of initial CGM technology to current devices and summarize our recent experience in the ICU.
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COVID-19 , Diabetes Mellitus , Hiperglucemia , Humanos , Glucemia , Automonitorización de la Glucosa Sanguínea/métodos , Insulina , Unidades de Cuidados Intensivos , Insulina Regular HumanaRESUMEN
BACKGROUND: We studied a smart insulin pen cap that can be plugged to several brand of insulin pens, to track insulin administration via smart-phone Bluetooth technology, with alarm/reminder system aiming. METHODS: This pilot randomized, cross-over design study assessed the use of a smart insulin pen cap in improving adherence, glycemic control and patient satisfaction in insulin-treated patients with poorly controlled type 2 diabetes. Eighty patients on basal insulin ± oral agents with hemoglobin A1C (HbA1c) between 7.0% and 12.0% were randomized to a 12-week active phase receiving alarms/reminders and a 12-week control/masked phase without feedback. We assessed differences between groups on treatment adherence, insulin omission, and mistiming of insulin injections, HbA1c, treatment satisfaction (using Diabetes Treatment Satisfaction Questionnaire Status). RESULTS: Compared to the control/masked phase, the active phase resulted in lower mean daily blood glucose (147.0 ± 34 vs 157.6 ± 42 mg/dL, P < .01); and greater reduction in HbA1c from baseline (-0.98% vs -0.72%, P = .006); however, no significant differences in treatment adherence, insulin omission or insulin mistiming were observed. High patient satisfaction scores were reported in both active and control phases, with DTSQc of 15.5 ± 3.7 and 14.9 ± 3.6, respectively. Statistical models showed no residual effect after cross-over between active and control phases. CONCLUSIONS: The results of this pilot study indicates that this smart insulin pen cap was effective in improving glycemic control with overall good satisfaction in insulin treated patients with type 2 diabetes. Future studies are needed to confirm its potential for improving care in insulin treated patients with diabetes.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes , Estudios Cruzados , Hemoglobina Glucada , Proyectos Piloto , Insulina , Glucemia , Insulina Regular HumanaRESUMEN
OBJECTIVE: In participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin. RESEARCH DESIGN AND METHODS: This randomized trial compared the efficacy and safety of insulin degludec and liraglutide (IDegLira) and basal-bolus among participants with high HbA1c ≥9.0-15.0%, previously treated with 2 or 3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n = 73) or IDegLira (n = 72). The primary end point was noninferiority (0.4%) in HbA1c reduction between groups. RESULTS: Among 145 participants (HbA1c 10.8% ± 1.3), there was no statistically significant difference in HbA1c reduction (3.18% ± 2.29 vs. 3.00% ± 1.79, P = 0.65; estimated treatment difference (ETD) 0.18%, 95% CI -0.59, 0.94) between the IDegLira and basal-bolus groups. IDegLira resulted in significantly lower rates of hypoglycemia <70 mg/dL (26% vs. 48%, P = 0.008; odds ratio 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24 ± 8.33 vs. 5.84 ± 6.18 kg, P = 0.001; ETD -4.60, 95% CI -7.33, -1.87). CONCLUSIONS: In participants with T2D and HbA1c ≥9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, and less weight gain compared with the basal-bolus regimen.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia , Humanos , Liraglutida/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada , Glucemia , Insulina de Acción Prolongada , Combinación de Medicamentos , Aumento de PesoRESUMEN
BACKGROUND: The magnitude of the response of the diabetes professional community to the COVID-19 pandemic is not known. We aimed to examine diabetes technology research trends and resources offered by professional organizations during this period. METHODS: We explored patterns of the response from the professional diabetes community to the pandemic by (1) systematically searching for articles related to diabetes, COVID-19, and diabetes technologies; (2) examining publication trends of research protocols (clinicaltrials.gov) and preprints (medRxiv); and (3) reviewing online resources from professional organizations including our website (COVIDinDiabetes.org; an Emory University-Diabetes Technology Society collaboration). RESULTS: We identified 492 articles published between December 2019 and December 2022 meeting our inclusion criteria. Telemedicine and continuous glucose monitoring were the most common reported technologies from most parts of the world. The largest number of preprint articles was published in 2020, with a decline in 2021 and 2022. The number of research protocols related to COVID-19 was the highest in 2020 and declined in 2021 and 2022. Resources from organizations included protocols adapted to treat patients with diabetes and COVID-19, training programs, emergency preparedness, and literature on diabetes and COVID-19. On our website (COVIDinDiabetes.org), there were 12 236 visits and 18 149 pageviews, with 1.6 actions per visits, with most visits coming from North America (N = 7233, 54.2%), South America (N = 2663, 21.8%), and Europe (N = 1219). CONCLUSIONS: We conclude that the COVID-19 pandemic promoted unprecedented global research productivity related to diabetes and COVID-19 and that the transition to the use of technology resources has been evident during this period.
Asunto(s)
COVID-19 , Diabetes Mellitus , Telemedicina , Humanos , COVID-19/epidemiología , Pandemias , Automonitorización de la Glucosa Sanguínea/métodos , Glucemia , Telemedicina/métodos , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapiaRESUMEN
Introduction: Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote glucose monitoring offers a solution to these shortcomings. Research Design and Methods: In a single-arm multicenter pilot trial, we tested the feasibility, safety, and effectiveness of the Omnipod 5 AID System with real-time continuous glucose monitoring (CGM) for up to 10 days in hospitalized patients with insulin-requiring diabetes on nonintensive care unit medical-surgical units. Primary endpoints included the proportion of time in automated mode and percent time-in-range (TIR 70-180 mg/dL) among participants with >48 h of CGM data. Safety endpoints included incidence of severe hypoglycemia and diabetes-related ketoacidosis (DKA). Additional glycemic endpoints, CGM accuracy, and patient satisfaction were also explored. Results: Twenty-two participants were enrolled; 18 used the system for a total of 96 days (mean 5.3 ± 3.1 days per patient), and 16 had sufficient CGM data required for analysis. Median percent time in automated mode was 95% (interquartile range 92%-98%) for the 18 system users, and the 16 participants with >48 h of CGM data achieved an overall TIR of 68% ± 16%, with 0.17% ± 0.3% time <70 mg/dL and 0.06% ± 0.2% time <54 mg/dL. Sensor mean glucose was 167 ± 21 mg/dL. There were no DKA or severe hypoglycemic events. All participants reported satisfaction with the system at study end. Conclusions: The use of AID with a disposable tubeless patch-pump along with remote real-time CGM is feasible in the hospital setting. These results warrant further investigation in randomized trials.
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Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Hipoglucemia , Humanos , Glucemia , Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Estudios de Factibilidad , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Sistemas de Infusión de Insulina , Insulina Regular Humana/uso terapéutico , Proyectos PilotoRESUMEN
Genes, such as IFNG, which are expressed in multiple cell lineages of the immune system, may employ a common set of regulatory elements to direct transcription in multiple cell types or individual regulatory elements to direct expression in individual cell lineages. By employing a bacterial artificial chromosome transgenic system, we demonstrate that IFNG employs unique regulatory elements to achieve lineage-specific transcriptional control. Specifically, a one 1-kb element 30 kb upstream of IFNG activates transcription in T cells and NKT cells but not in NK cells. This distal regulatory element is a Runx3 binding site in Th1 cells and is needed for RNA polymerase II recruitment to IFNG, but it is not absolutely required for histone acetylation of the IFNG locus. These results support a model whereby IFNG uses cis-regulatory elements with cell type-restricted function.
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Linaje de la Célula/genética , Linaje de la Célula/inmunología , Regulación de la Expresión Génica/inmunología , Sitios Genéticos/inmunología , Interferón gamma/biosíntesis , Interferón gamma/genética , Animales , Células Cultivadas , Secuencia Conservada/genética , Secuencia Conservada/inmunología , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Humanos , Células Asesinas Naturales/enzimología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Células T Asesinas Naturales/enzimología , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/metabolismo , Transporte de Proteínas/genética , Transporte de Proteínas/inmunología , ARN Polimerasa II/metabolismo , Elementos Reguladores de la Transcripción/inmunología , Células TH1/enzimología , Células TH1/inmunología , Células TH1/metabolismo , Sitio de Iniciación de la TranscripciónRESUMEN
Background: Brown adipose tissue (BAT) plays a role in modulating energy expenditure. People with obesity have been shown to have reduced activation of BAT. Agents such as ß-agonists, capsinoids, thyroid hormone, sildenafil, caffeine, or cold exposure may lead to activation of BAT in humans, potentially modulating metabolism to promote weight loss. Methods: We systematically searched electronic databases for clinical trials testing the effect of these agents and cold exposure on energy expenditure/thermogenesis and the extent to which they may impact weight loss in adults. Results: A total of 695 studies from PubMed, Web of Science, and Medline electronic databases were identified. After the removal of duplicates and further evaluation, 47 clinical trials were analyzed. We observed significant heterogeneity in the duration of interventions and the metrics utilized to estimate thermogenesis/energy expenditure. Changes observed in energy expenditure do not correlate with major weight changes with different interventions commonly known to stimulate thermogenesis. Even though cold exposure appears to consistently activate BAT and induce thermogenesis, studies are small, and it appears to be an unlikely sustainable therapy to combat obesity. Most studies were small and potential risks associated with known side effects of some agents such as ß-agonists (tachycardia), sibutramine (hypertension, tachycardia), thyroid hormone (arrhythmias) cannot be fully evaluated from these small trials. Conclusion: Though the impact of BAT activation and associated increases in energy expenditure on clinically meaningful weight loss is a topic of great interest, further data is needed to determine long-term feasibility and efficacy.
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Tejido Adiposo Pardo , Obesidad , Adulto , Humanos , Tejido Adiposo Pardo/metabolismo , Obesidad/metabolismo , Metabolismo Energético , Pérdida de Peso , Termogénesis/fisiologíaRESUMEN
OBJECTIVE: Administration of supplemental sliding scale insulin for correction of hyperglycemia in non-intensive care unit (ICU) patients with type 2 diabetes is frequently used with basal-bolus insulin regimens. In this noninferiority randomized controlled trial we tested whether glycemic control is similar with and without aggressive sliding scale insulin treatment before meals and bedtime in patients treated with basal-bolus insulin regimens. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes with admission blood glucose (BG) 140-400 mg/dL treated with basal-bolus insulin were randomized to intensive (correction for BG >140 mg/dL, n = 108) or to nonintensive (correction for BG >260 mg/dL, n = 107) administration of rapid-acting sliding scale insulin before meals and bedtime. The groups received the same amount of sliding scale insulin for BG >260 mg/dL. Primary outcome was difference in mean daily BG levels between the groups during hospitalization. RESULTS: Mean daily BG in the nonintensive group was noninferior to BG in the intensive group with equivalence margin of 18 mg/dL (intensive 172 ± 38 mg/dL vs. nonintensive 173 ± 43 mg/dL, P = 0.001 for noninferiority). There were no differences in the proportion of target BG readings of 70-180 mg/dL, <70 or <54 mg/dL (hypoglycemia), or >350 mg/dL (severe hyperglycemia) or total, basal, or prandial insulin doses. Significantly fewer subjects received sliding scale insulin in the nonintensive (n = 36 [34%]) compared with the intensive (n = 98 [91%] [P < 0.0001]) group with no differences in sliding scale insulin doses between the groups among those who received sliding scale insulin (intensive 7 ± 4 units/day vs. nonintensive 8 ± 4 units/day, P = 0.34). CONCLUSIONS: Among non-ICU patients with type 2 diabetes on optimal basal-bolus insulin regimen with moderate hyperglycemia (BG <260 mg/dL), a less intensive sliding scale insulin treatment did not significantly affect glycemic control.
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Diabetes Mellitus Tipo 2 , Hiperglucemia , Glucemia , Humanos , Hiperglucemia/inducido químicamente , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Insulina Glargina/uso terapéutico , Insulina Regular Humana/uso terapéuticoRESUMEN
Remarkable advances in diabetes management have occurred since the discovery of insulin 100 years ago. Advances across a therapeutic spectrum, including pharmacotherapy, metabolic surgery, and diabetes technology, offer superior treatment options for diabetes management. New medication classes (glucagon-like peptide-1 receptor analogs and SGLT-2 inhibitors) have demonstrated cardiorenal benefits beyond glycemic control in type 2 diabetes mellitus, while evolving metabolic surgical interventions also help patients achieve diabetes remission. The use of artificial pancreas systems has shown consistent improvement in glycemic control in type 1 diabetes mellitus. It is time for policy changes to expand access to such advantageous therapies.
Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/cirugía , Receptor del Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , TecnologíaRESUMEN
OBJECTIVE: Real-time continuous glucose monitoring (rtCGM) in critically ill hospitalized patients holds promise; however, real-world data are needed. RESEARCH DESIGN AND METHODS: We placed Dexcom G6 CGM on intensive care unit (ICU) patients at Montefiore Medical Center with confirmed coronavirus disease 2019 (COVID-19) infection and glycemic variability. We analyzed inpatient CGM accuracy using point-of-care (POC) glucose-CGM matched pairs and included patients for analysis regardless of clinical status. RESULTS: We included 11 patients with CGM: 8 on continuous insulin infusion (CII), 8 on vasopressors, 8 intubated, 4 on high-dose glucocorticoids, 6 on renal replacement therapy, and 2 with anasarca. Accuracy was 12.58% for mean and 6.3% for median absolute relative difference. CGM reduced POC testing by â¼60% for patients on CII. CONCLUSIONS: In this real-world preliminary analysis of rtCGM during critical illness, we demonstrate early feasibility, considerable accuracy, and meaningful reduction in the frequency of POC glucose testing.
Asunto(s)
Glucemia/análisis , COVID-19 , Unidades de Cuidados Intensivos , Adulto , Anciano , Cuidados Críticos , Enfermedad Crítica/terapia , Femenino , Humanos , Insulina/uso terapéutico , Sistemas de Infusión de Insulina , Masculino , Persona de Mediana Edad , Pandemias , Sistemas de Atención de Punto , SARS-CoV-2RESUMEN
OBJECTIVE: The use of remote real-time continuous glucose monitoring (CGM) in the hospital has rapidly emerged to preserve personal protective equipment and reduce potential exposures during coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: We linked a hybrid CGM and point-of-care (POC) glucose testing protocol to a computerized decision support system for continuous insulin infusion and integrated a validation system for sensor glucose values into the electronic health record. We report our proof-of-concept experience in a COVID-19 intensive care unit. RESULTS: All nine patients required mechanical ventilation and corticosteroids. During the protocol, 75.7% of sensor values were within 20% of the reference POC glucose with an associated average reduction in POC of 63%. Mean time in range (70-180 mg/dL) was 71.4 ± 13.9%. Sensor accuracy was impacted by mechanical interferences in four patients. CONCLUSIONS: A hybrid protocol integrating real-time CGM and POC is helpful for managing critically ill patients with COVID-19 requiring insulin infusion.