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1.
Expert Opin Pharmacother ; 21(15): 1799-1803, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33108240

RESUMO

INTRODUCTION: The majority of patients with type 1 diabetes mellitus (T1DM) do not achieve glycemic targets. In addition, treatment with insulin is associated with increased risk for hypoglycemia and weight gain. Accordingly, there is an unmet need for new safe and effective glucose-lowering agents in this population. Sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2, has been recently approved for use in patients with T1DM. AREAS COVERED: The authors review the major trials that have evaluated the safety and efficacy of sotagliflozin and provide their expert opinion. EXPERT OPINION: Even though sotagliflozin reduces HbA1 c levels and does not appear to increase the risk for hypoglycemia in most patients, the substantially increased risk for diabetic ketoacidosis limits the use of this agent to a carefully selected subgroup of patients with T1DM. Based on the existing evidence, sotagliflozin should be considered only in patients who have failed to achieve adequate glycemic control despite optimal insulin therapy, are at low risk for diabetic ketoacidosis, have been adequately trained to recognize this complication and are able to be in close contact with their physician.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/metabolismo , Cetoacidose Diabética/induzido quimicamente , Glicosídeos/administração & dosagem , Glicosídeos/efeitos adversos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Risco , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo
2.
J Diabetes Sci Technol ; 14(6): 1065-1073, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33063556

RESUMO

BACKGROUND: Amidst the coronavirus disease 2019 (COVID-19) pandemic, continuous glucose monitoring (CGM) has emerged as an alternative for inpatient point-of-care blood glucose (POC-BG) monitoring. We performed a feasibility pilot study using CGM in critically ill patients with COVID-19 in the intensive care unit (ICU). METHODS: Single-center, retrospective study of glucose monitoring in critically ill patients with COVID-19 on insulin therapy using Medtronic Guardian Connect and Dexcom G6 CGM systems. Primary outcomes were feasibility and accuracy for trending POC-BG. Secondary outcomes included reliability and nurse acceptance. Sensor glucose (SG) was used for trends between POC-BG with nursing guidance to reduce POC-BG frequency from one to two hours to four hours when the SG was in the target range. Mean absolute relative difference (MARD), Clarke error grids analysis (EGA), and Bland-Altman (B&A) plots were calculated for accuracy of paired SG and POC-BG measurements. RESULTS: CGM devices were placed on 11 patients: Medtronic (n = 6) and Dexcom G6 (n = 5). Both systems were feasible and reliable with good nurse acceptance. To determine accuracy, 437 paired SG and POC-BG readings were analyzed. For Medtronic, the MARD was 13.1% with 100% of readings in zones A and B on Clarke EGA. For Dexcom, MARD was 11.1% with 98% of readings in zones A and B. B&A plots had a mean bias of -17.76 mg/dL (Medtronic) and -1.94 mg/dL (Dexcom), with wide 95% limits of agreement. CONCLUSIONS: During the COVID-19 pandemic, CGM is feasible in critically ill patients and has acceptable accuracy to identify trends and guide intermittent blood glucose monitoring with insulin therapy.


Assuntos
Glicemia/análise , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Estado Terminal/terapia , Monitorização Fisiológica/instrumentação , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Adulto , Idoso , Betacoronavirus/fisiologia , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Estado Terminal/epidemiologia , Estado Terminal/mortalidade , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/terapia , Estudos de Viabilidade , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Hiperglicemia/mortalidade , Hiperglicemia/terapia , Insulina/administração & dosagem , Sistemas de Infusão de Insulina , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Pandemias , Projetos Piloto , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Sistemas Automatizados de Assistência Junto ao Leito , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos
3.
Arch Pathol Lab Med ; 144(10): 1204-1208, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002153

RESUMO

CONTEXT.­: Glycemic control requires accurate blood glucose testing. The extent of hematocrit interference is difficult to assess to assure quality patient care. OBJECTIVE.­: To predict the effect of patient hematocrit on the performance of a glucose meter and its corresponding impact on insulin-dosing error. DESIGN.­: Multilevel mixed regression was conducted to assess the extent that patient hematocrit influences Roche Accu-Chek Inform II glucose meters, using the Radiometer ABL 837 as a reference method collected during validation of 35 new meters. Regression coefficients of fixed effects for reference glucose, hematocrit, an interaction term, and random error were applied to 4 months of patient reference method results extracted from the laboratory information system. A hospital inpatient insulin dose algorithm was used to determine the frequency of insulin dose error between reference glucose and meter glucose results. RESULTS.­: Fixed effects regression for method and hematocrit predicted biases to glucose meter results that met the "95% within ±12%" for the US Food and Drug Administration goal, but combinations of fixed and random effects exceeded that target in emergency and hospital inpatient units. Insulin dose errors were predicted from the meter results. Twenty-eight percent of intensive care unit, 20.8% of hospital inpatient, and 17.7% of emergency department results were predicted to trigger a ±1 insulin dose error by fixed and random effects. CONCLUSIONS.­: The current extent of hematocrit interference on glucose meter performance is anticipated to cause insulin error by 1-dose category, which is likely associated with low patient risk.


Assuntos
Glicemia/análise , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Erros Médicos , Algoritmos , Hematócrito , Humanos , Medição de Risco , Estados Unidos
4.
Cochrane Database Syst Rev ; 10: CD004730, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33075159

RESUMO

BACKGROUND: The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/L (125 mg/dL); or oral glucose tolerance tests greater than 11.11 mmol/L (200 mg/dL) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/L (200 mg/dL); or glycated hemoglobin levels of at least 6.5%. This is an update of a previously published review. OBJECTIVES: To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of most recent register search: 10 September 2020. We searched online trials registries; date of most recent searches: 21 March 2020. SELECTION CRITERIA: Randomized controlled trials comparing all methods of pharmacological diabetes therapy in people with diagnosed CFRD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias in the included studies. Authors also used GRADE to assess the quality of the evidence. MAIN RESULTS: The searches identified 29 trials (45 references). Four included trials provide results: one short-term single-center cross-over trial (seven adults) comparing insulin with oral repaglinide and no medication in adults with CFRD and normal fasting glucose; one long-term multicenter trial (61 adults with CFRD) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (67 adults) comparing insulin with oral repaglinide; and one 12-week single-center cross-over trial (20 adults) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two ongoing trials of newly approved incretin mimics have been noted for possible future inclusion. Downgrading of the quality of the evidence was mainly due to risks of bias across all domains, but particularly due to concerns surrounding allocation concealment and selective reporting. There were also some concerns due to imprecision from small sample sizes and low event rates. Finally, there may be some bias due to the amounts of insulin and repaglinide given not being comparable. Data from one trial comparing insulin to placebo (39 participants) did not show any difference between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) or nutritional status (low-quality evidence). Similarly, no differences between groups were seen for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or quality of life (QoL). These results were mirrored in the narrative reports for the second trial in this comparison (seven participants). Data from the one-year trial comparing repaglinide to placebo (38 participants), showed no differences between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) and nutritional status (low-quality evidence). Also, no differences were seen between groups for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or QoL. These findings were mirrored in the narrative reports for the second trial (n = 7) in this comparison. Three trials compared insulin to repaglinide (119 participants). Data from one trial (n = 67) showed no difference in blood glucose levels at either 12 months (high-quality evidence) or 24 months; narrative reports from one trial (45 participants) reported no difference between groups, but the second trial (7 participants) reported a beneficial effect of insulin over repaglinide. Two trials (112 participants) found no difference between insulin and repaglinide in lung function or nutritional status (moderate-quality evidence). Two trials (56 participants) reported no difference in the number of hypoglycemic episodes (low-quality evidence). One trial (45 participants) reported no difference between groups in secondary infections and cystic fibrosis QoL. The single trial comparing glargine to neutral protamine Hagedorn insulin did not report directly on the review's primary outcomes, but did report no differences between groups in post-prandial glucose values and weight; neither group reported infectious complications. There was no difference in episodes of hypoglycemia (very low-quality evidence) and while there was no difference reported in QoL, all participants opted to continue treatment with glargine after the trial was completed. Mortality was not reported by any trial in any comparison, but death was not given as a reason for withdrawal in any trial. AUTHORS' CONCLUSIONS: This review has not found any conclusive evidence that any agent has a distinct advantage over another in controlling hyperglycemia or the clinical outcomes associated with CFRD. Given the treatment burden already experienced by people with cystic fibrosis, oral therapy may be a viable treatment option. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes and its impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. Specifically, investigators should evaluate adherence to different therapies and also whether there is benefit in using additional hypoglycemic agents as well as the newly approved incretin mimics. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should also be further investigated as adjuvant therapy to insulin.


Assuntos
Fibrose Cística/complicações , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Administração Oral , Viés , Glicemia/análise , Carbamatos/administração & dosagem , Fibrose Cística/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/etiologia , Jejum/sangue , Humanos , Hiperglicemia/tratamento farmacológico , Insulina Glargina/administração & dosagem , Insulina Isófana/administração & dosagem , Piperidinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Nat Med ; 26(9): 1380-1384, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908282

RESUMO

Despite the increasing adoption of insulin pumps and continuous glucose monitoring devices, most people with type 1 diabetes do not achieve their glycemic goals1. This could be related to a lack of expertise or inadequate time for clinicians to analyze complex sensor-augmented pump data. We tested whether frequent insulin dose adjustments guided by an automated artificial intelligence-based decision support system (AI-DSS) is as effective and safe as those guided by physicians in controlling glucose levels. ADVICE4U was a six-month, multicenter, multinational, parallel, randomized controlled, non-inferiority trial in 108 participants with type 1 diabetes, aged 10-21 years and using insulin pump therapy (ClinicalTrials.gov no. NCT03003806). Participants were randomized 1:1 to receive remote insulin dose adjustment every three weeks guided by either an AI-DSS, (AI-DSS arm, n = 54) or by physicians (physician arm, n = 54). The results for the primary efficacy measure-the percentage of time spent within the target glucose range (70-180 mg dl-1 (3.9-10.0 mmol l-1))-in the AI-DSS arm were statistically non-inferior to those in the physician arm (50.2 ± 11.1% versus 51.6 ± 11.3%, respectively, P < 1 × 10-7). The percentage of readings below 54 mg dl-1 (<3.0 mmol l-1) within the AI-DSS arm was statistically non-inferior to that in the physician arm (1.3 ± 1.4% versus 1.0 ± 0.9%, respectively, P < 0.0001). Three severe adverse events related to diabetes (two severe hypoglycemia, one diabetic ketoacidosis) were reported in the physician arm and none in the AI-DSS arm. In conclusion, use of an automated decision support tool for optimizing insulin pump settings was non-inferior to intensive insulin titration provided by physicians from specialized academic diabetes centers.


Assuntos
Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Glicemia/análise , Sistemas de Apoio a Decisões Clínicas/instrumentação , Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/uso terapêutico , Adolescente , Inteligência Artificial , Criança , Humanos , Insulina/administração & dosagem , Sistemas de Infusão de Insulina , Resultado do Tratamento , Adulto Jovem
6.
J Diabetes Sci Technol ; 14(6): 1035-1064, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32985262

RESUMO

This article is the work product of the Continuous Glucose Monitor and Automated Insulin Dosing Systems in the Hospital Consensus Guideline Panel, which was organized by Diabetes Technology Society and met virtually on April 23, 2020. The guideline panel consisted of 24 international experts in the use of continuous glucose monitors (CGMs) and automated insulin dosing (AID) systems representing adult endocrinology, pediatric endocrinology, obstetrics and gynecology, advanced practice nursing, diabetes care and education, clinical chemistry, bioengineering, and product liability law. The panelists reviewed the medical literature pertaining to five topics: (1) continuation of home CGMs after hospitalization, (2) initiation of CGMs in the hospital, (3) continuation of AID systems in the hospital, (4) logistics and hands-on care of hospitalized patients using CGMs and AID systems, and (5) data management of CGMs and AID systems in the hospital. The panelists then developed three types of recommendations for each topic, including clinical practice (to use the technology optimally), research (to improve the safety and effectiveness of the technology), and hospital policies (to build an environment for facilitating use of these devices) for each of the five topics. The panelists voted on 78 proposed recommendations. Based on the panel vote, 77 recommendations were classified as either strong or mild. One recommendation failed to reach consensus. Additional research is needed on CGMs and AID systems in the hospital setting regarding device accuracy, practices for deployment, data management, and achievable outcomes. This guideline is intended to support these technologies for the management of hospitalized patients with diabetes.


Assuntos
Glicemia/análise , Equipamentos e Provisões , Hospitalização , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Monitorização Fisiológica/instrumentação , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Automonitorização da Glicemia/normas , Criança , Consenso , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Complicações do Diabetes/sangue , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/terapia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Cálculos da Dosagem de Medicamento , Equipamentos e Provisões/normas , Feminino , Hospitais/normas , Humanos , Sistemas de Infusão de Insulina/normas , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Gravidez
7.
PLoS One ; 15(9): e0239091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915897

RESUMO

INTRODUCTION: To investigate the glycaemic response, macronutrient intake and insulin management in people with type 1 diabetes (T1D) compared to healthy individuals around a running competition. MATERIAL AND METHODS: This was a single-centre, prospective, controlled observational study performed in individuals with T1D and healthy people. 24 people (12 T1D) were included in this study (age: T1D 41±12 vs. healthy 38±6 years, females: 3 vs. 6, BMI: 25.53.0 vs. 22.9±2.8 kg/m2). Both groups received an intermittently scanned continuous glucose monitoring (isCGM; FreeStyle Libre 1, Abbott, USA) system to assess glycaemia 24 hours before, during and 24 hours after a running competition. During this period, participants recorded their food intake and insulin administration. Data were analysed via ANOVA and mixed model analyses with post-hoc testing (p≤0.05). RESULTS: For overall glycaemic ranges in comparison of groups, significant differences were found for time in range (T1D 63±21% vs. healthy 89±13%, p = 0.001), time above range (TAR) 1 (T1D 21±15% vs. healthy 0±0%, p<0.001) and TAR 2 (T1D 8 [0-16%] vs. healthy 0±0%, p<0.001). When glycaemic variability was assessed, people with T1D had a higher glycaemic variability compared to healthy individuals (p<0.0001). Basal insulin dose was significantly reduced when compared against the regular pre-study basal insulin dose (pre-study 22±6 vs. pre-competition day 11±9 (-50±41%), p = 0.02; competition day 15±5 (-32± 1%)). CONCLUSION: People with T1D have impaired glucose responses around a running competition compared to healthy individuals. However, basal insulin dose reductions were sufficient to prevent further dysglycaemia. CLINICAL TRIAL ID: drks.de; DRKS00019886.


Assuntos
Glicemia/fisiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Ingestão de Alimentos/fisiologia , Insulina/administração & dosagem , Corrida/fisiologia , Adolescente , Adulto , Idoso , Glicemia/análise , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia/estatística & dados numéricos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
8.
Med Care ; 58(10): 927-933, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32833937

RESUMO

BACKGROUND: Hypoglycemia related to antidiabetic drugs (ADDs) is important iatrogenic harm in hospitalized patients. Electronic identification of ADD-related hypoglycemia may be an efficient, reliable method to inform quality improvement. OBJECTIVE: Develop electronic queries of electronic health records for facility-wide and unit-specific inpatient hypoglycemia event rates and validate query findings with manual chart review. METHODS: Electronic queries were created to associate blood glucose (BG) values with ADD administration and inpatient location in 3 tertiary care hospitals with Patient-Centered Outcomes Research Network (PCORnet) databases. Queries were based on National Quality Forum criteria with hypoglycemia thresholds <40 and <54 mg/dL, and validated using a stratified random sample of 321 BG events. Sensitivity and specificity were calculated with manual chart review as the reference standard. RESULTS: The sensitivity and specificity of queries for hypoglycemia events were 97.3% [95% confidence interval (CI), 90.5%-99.7%] and 100.0% (95% CI, 92.6%-100.0%), respectively for BG <40 mg/dL, and 97.7% (95% CI, 93.3%-99.5%) and 100.0% (95% CI, 95.3%-100.0%), respectively for <54 mg/dL. The sensitivity and specificity of the query for identifying ADD days were 91.8% (95% CI, 89.2%-94.0%) and 99.0% (95% CI, 97.5%-99.7%). Of 48 events missed by the queries, 37 (77.1%) were due to incomplete identification of insulin administered by infusion. Facility-wide hypoglycemia rates were 0.4%-0.8% (BG <40 mg/dL) and 1.9%-3.0% (BG <54 mg/dL); rates varied by patient care unit. CONCLUSIONS: Electronic queries can accurately identify inpatient hypoglycemia. Implementation in non-PCORnet-participating facilities should be assessed, with particular attention to patient location and insulin infusions.


Assuntos
Registros Eletrônicos de Saúde , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Adulto , Idoso , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Pacientes Internados , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária/normas
9.
Diabetes Res Clin Pract ; 168: 108393, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32858098

RESUMO

BACKGROUND AND AIM: Jordan implemented abrupt and extreme lockdown measures to prevent the spread of COVID-19. This study aims to evaluate the effect of these measures on paediatric patients with type 1 diabetes in terms of acute metabolic complications and shortages in insulin and glucose measuring supplies. It also evaluates the caregivers' perceptions of the use of telemedicine during the lockdown. METHODS: This is a questionnaire-based cross-sectional study. It was completed using Google forms and patients/caregivers were asked to consent if they agreed to answer. RESULTS: 235 patients/families participated in the study. The mean age of the patients was 10.8 years ± 3.9 years (N = 229). Twenty-four children (10.2%) needed to visit the emergency department during the lockdown period which lasted for 10 weeks. Of these, eight (3.4%) were hospitalized due to acute metabolic complications. Families (58.3%) faced insulin shortages and 14% had to ration insulin, i.e., decrease the dose, during the lockdown. Glucose monitoring strips were rationed by 43.4% of families leading to more frequent low/high glucose readings in 75.5% of children of these families. Telemedicine using phones and social media applications was utilized for communication with healthcare professionals and continuing medical care. Most of the participants (85.5%) described it as a smooth and positive experience. CONCLUSIONS: The extreme lockdown due to COVID-19 pandemic caused insulin and glucose measuring equipment shortages in children with diabetes in Jordan. However, the use of telemedicine for providing guidance and support was perceived positively by the families.


Assuntos
Cuidado da Criança , Infecções por Coronavirus/epidemiologia , Países em Desenvolvimento , Diabetes Mellitus Tipo 1/terapia , Pneumonia Viral/epidemiologia , Quarentena , Telemedicina , Adolescente , Betacoronavirus , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Cuidadores/psicologia , Criança , Cuidado da Criança/métodos , Pré-Escolar , Estudos Transversais , Países em Desenvolvimento/estatística & dados numéricos , Diabetes Mellitus Tipo 1/sangue , Feminino , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Lactente , Insulina/administração & dosagem , Jordânia/epidemiologia , Masculino , Pandemias , Pais/psicologia , Percepção , Quarentena/psicologia , Inquéritos e Questionários , Telemedicina/instrumentação , Telemedicina/organização & administração , Telemedicina/normas , Adulto Jovem
10.
N Engl J Med ; 383(9): 836-845, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32846062

RESUMO

BACKGROUND: A closed-loop system of insulin delivery (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes. METHODS: In a 16-week, multicenter, randomized, open-label, parallel-group trial, we assigned, in a 3:1 ratio, children 6 to 13 years of age who had type 1 diabetes to receive treatment with the use of either a closed-loop system of insulin delivery (closed-loop group) or a sensor-augmented insulin pump (control group). The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. RESULTS: A total of 101 children underwent randomization (78 to the closed-loop group and 23 to the control group); the glycated hemoglobin levels at baseline ranged from 5.7 to 10.1%. The mean (±SD) percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter increased from 53±17% at baseline to 67±10% (the mean over 16 weeks of treatment) in the closed-loop group and from 51±16% to 55±13% in the control group (mean adjusted difference, 11 percentage points [equivalent to 2.6 hours per day]; 95% confidence interval, 7 to 14; P<0.001). In both groups, the median percentage of time that the glucose level was below 70 mg per deciliter was low (1.6% in the closed-loop group and 1.8% in the control group). In the closed-loop group, the median percentage of time that the system was in the closed-loop mode was 93% (interquartile range, 91 to 95). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either group. CONCLUSIONS: In this 16-week trial involving children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with the use of a closed-loop system than with the use of a sensor-augmented insulin pump. (Funded by Tandem Diabetes Care and the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number, NCT03844789.).


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Bombas de Infusão Implantáveis , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adolescente , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Cetoacidose Diabética/etiologia , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos , Masculino , Pâncreas Artificial
11.
Orv Hetil ; 161(35): 1483-1487, 2020 08.
Artigo em Húngaro | MEDLINE | ID: mdl-32822327

RESUMO

Today, insulin hypersensitivity reactions are rare side effects of insulin therapy. In two-thirds of the suspected insulin allergy cases, the clinical symptoms are not related to insulin. The authors report the case of a 64-year-old female patient, by whom lymphocyte tarnsformation test (LTT) has been used to elucidate the background of allergic symptoms developed during insulin therapy. The performed LTT did not support hypersensitivity to insulin, however, the positive protamine test raised the suspicion of fish allergy. Complementary immunoserology also highlighted the coexistence of previously unrevealed thyroid disease. To our knowledge, this is the first documented case report in Hungary that attempts to address the real cause of a suspected hypersensitivity reaction to insulin by using LTT. Orv Hetil. 2020; 161(35): 1483-1487.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipersensibilidade a Drogas/complicações , Insulina/efeitos adversos , Ativação Linfocitária/efeitos dos fármacos , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Hungria , Insulina/administração & dosagem , Pessoa de Meia-Idade
12.
Int J Nanomedicine ; 15: 4877-4898, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753869

RESUMO

Background: Although dynamics and uses of modified nanoparticles (NPs) as orally administered macromolecular drugs have been researched for many years, measures of molecule stability and aspects related to important transport-related mechanisms which have been assessed in vivo remain as relatively under characterized. Thus, our aim was to develop a novel type of oral-based delivery system for insulin and to overcome barriers to studying the stability, transport mechanisms, and efficacy in vivo of the delivery system. Methods: NPs we developed and tested were composed of insulin (INS), dicyandiamide-modified chitosan (DCDA-CS), cell-penetrating octaarginine (r8), and hydrophilic hyaluronic acid (HA) and were physically constructed by electrostatic self-assembly techniques. Results: Compared to free-insulin, levels of HA-DCDA-CS-r8-INS NPs were retained at more desirable measures of biological activity in our study. Further, our assessments of the mechanisms for NPs suggested that there were high measures of cellular uptake that mainly achieved through active transport via lipid rafts and the macropinocytosis pathway. Furthermore, investigations of NPs indicated their involvement in caveolae-mediated transport and in the DCDA-CS-mediated paracellular pathway, which contributed to increasing the efficiency of sequential transportation from the apical to basolateral areas. Accordingly, high efficiency of absorption of NPs in situ for intestinal loop models was realized. Consequently, there was a strong induction of a hypoglycemic effect in diabetic rats of NPs via orally based administrations when compared with measures related to free insulin. Conclusion: Overall, the dynamics underlying and influenced by HA-DCDA-CS-r8-INS may hold great promise for stability of insulin and could help overcome interference by the epithelial barrier, and thus showing a great potential to improve the efficacy of orally related treatments.


Assuntos
Quitosana/química , Ácido Hialurônico/química , Insulina/administração & dosagem , Nanopartículas Multifuncionais/química , Nanopartículas/química , Administração Oral , Animais , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Morte Celular/efeitos dos fármacos , Quitosana/síntese química , Diabetes Mellitus Experimental/tratamento farmacológico , Impedância Elétrica , Endocitose/efeitos dos fármacos , Guanidinas/síntese química , Guanidinas/química , Humanos , Ácido Hialurônico/síntese química , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Insulina/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Masculino , Muco/metabolismo , Nanopartículas/ultraestrutura , Ratos , Solubilidade , Suínos
13.
Life Sci ; 259: 118159, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32763288

RESUMO

AIMS: Parkinson's disease dementia (PDD) is one of the most common non-motor symptoms of advanced Parkinson's disease (PD). This study aimed to determine whether intranasal insulin has protective effects on cognition in the rat PD model induced by 6-hydroxylase dopamine (6-OHDA) through the insulin signaling pathway. MATERIALS AND METHODS: The rats were given intranasal insulin administration for six weeks after unilateral medial forebrain bundle (MFB) injection of 6-OHDA. Then a series of cognitive-behavioral tests, immunofluorescence, and immunoblotting was performed on the rats. KEY FINDINGS: The results demonstrated that the injection of 6-OHDA in the unilateral MFB damaged working memory and long-term habituation of rats in the T-maze rewarded alternation test and hole-board test. Besides, rats with unilateral 6-OHDA injury performed poorly in terms of escape latency and average speed during the hidden platform training phase rather than in the probe trial of the Morris Water Maze (MWM) test. Immunofluorescence results showed that unilateral 6-OHDA injury in MFB led to the massive death of ipsilateral-substantia nigra (SN) tyrosine hydroxylase (TH)-positive neurons. Western blot results further indicated that 6-OHDA-induced necrosis of ipsilateral-SN dopaminergic neurons reduced the levels of p-Akt (Ser473) and p-GSK3ß (Ser9) in the ipsilateral-hippocampus. SIGNIFICANCE: These findings provide a solid evidence base for the relationship between PD cognitive impairment and insulin signaling pathways.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Glicogênio Sintase Quinase 3 beta/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Proteína Oncogênica v-akt/efeitos dos fármacos , Doença de Parkinson/complicações , Transdução de Sinais/efeitos dos fármacos , Administração Intranasal , Animais , Encéfalo/patologia , Disfunção Cognitiva/psicologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Doença de Parkinson/psicologia , Ratos , Ratos Wistar
14.
Yakugaku Zasshi ; 140(8): 1013-1024, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741859

RESUMO

Novel dosage form designs aiming at patient centric drug therapy are summarized here based on my carrier research in this field. The common key word for this research is particle design. The topics will be divided into two parts, based on the type of particle: coarse particles (powder) and colloidal particles. The former includes the preparation and characterization of functional particles prepared using a spray dryer. Solid dispersions, solvent deposition particles and dry emulsion systems are described. Polymer coated liposomes are described as a useful drug delivery carrier in several administration routes. As chitosan, a mucoadhesive polymer, was used as a coating polymer, the resultant chitosan-coated liposome was found to work as a good carrier for peptide drugs such as insulin and calcitonin in the gastrointestinal tract after oral administration. In another administration route (inhalation), polymer-coated liposomes enhanced the absorption of the drugs. Liposomal carriers applied to the surface of the eye as eye drops are able to deliver drugs to the posterior part of the eye, such as the retina. As a typical example of patient centric dosage form design, particle designs for the preparation of orally disintegrating tablets and films were introduced in one of our recent studies on oral dosage form design.


Assuntos
Formas de Dosagem , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Lipossomos , Tamanho da Partícula , Administração por Inalação , Administração Oral , Calcitonina/administração & dosagem , Quitosana , Coloides , Humanos , Insulina/administração & dosagem , Polímeros
15.
Nat Commun ; 11(1): 3746, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32719315

RESUMO

Recently, the clinical proof of concept for the first ultra-long oral insulin was reported, showing efficacy and safety similar to subcutaneously administered insulin glargine. Here, we report the molecular engineering as well as biological and pharmacological properties of these insulin analogues. Molecules were designed to have ultra-long pharmacokinetic profile to minimize variability in plasma exposure. Elimination plasma half-life of ~20 h in dogs and ~70 h in man is achieved by a strong albumin binding, and by lowering the insulin receptor affinity 500-fold to slow down receptor mediated clearance. These insulin analogues still stimulate efficient glucose disposal in rats, pigs and dogs during constant intravenous infusion and euglycemic clamp conditions. The albumin binding facilitates initial high plasma exposure with a concomitant delay in distribution to peripheral tissues. This slow appearance in the periphery mediates an early transient hepato-centric insulin action and blunts hypoglycaemia in dogs in response to overdosing.


Assuntos
Insulina/administração & dosagem , Engenharia de Proteínas , Administração Oral , Sequência de Aminoácidos , Animais , Glicemia/metabolismo , Simulação por Computador , Cães , Relação Dose-Resposta a Droga , Overdose de Drogas/sangue , Técnica Clamp de Glucose , Meia-Vida , Humanos , Hiperinsulinismo/tratamento farmacológico , Hipoglicemia/diagnóstico , Insulina/análogos & derivados , Insulina/química , Insulina/farmacocinética , Masculino , Estabilidade Proteica , Proteólise , Ratos Sprague-Dawley , Suínos , Resultado do Tratamento
16.
Obstet Gynecol ; 136(2): 411-416, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32649492

RESUMO

OBJECTIVE: To examine whether an insulin protocol for intrapartum glucose control among parturients with diabetes was associated with improved outcomes. METHODS: This is a retrospective cohort study of women with pregestational or gestational diabetes delivering a liveborn neonate at Northwestern Memorial Hospital. Before 2011, women with diabetes were given intravenous (IV) insulin or glucose during labor at the discretion of the on-call endocrinologist. In 2011, a standardized protocol was designed to titrate insulin and glucose infusions. Outcomes were compared between two time periods: January 2005-December 2010 (before implementation) and January 2012-December 2017 (after implementation) with 2011 excluded to account for a phase-in period. Maternal outcomes included intrapartum hyperglycemia (blood glucose greater than 125 mg/dL) and hypoglycemia (blood glucose less than 60 mg/dL). Neonatal outcomes included hypoglycemia (blood glucose less than 50 mg/dL), intensive care admission, and IV dextrose therapy. t tests, Wilcoxon rank sum tests, and χ tests were used for bivariable analyses. Linear and logistic multivariable regression were used to account for confounding factors. RESULTS: Of 3,689 women, 928 (25.2%) delivered before 2011. After protocol implementation, frequencies of both maternal intrapartum hyperglycemia (51.3% vs 37.9%) and hypoglycemia decreased (6.1% vs 2.5%), both P<.001; respective adjusted odds ratio [aOR] 0.64, 95% CI 0.54-0.77 and 0.50, 95% CI 0.33-0.78. The frequency of neonatal hypoglycemia, however, increased (36.6% vs 49.2%, P<.001; aOR 1.73, 95% CI 1.45-2.07). Admission to the neonatal intensive care unit and need for IV dextrose therapy were similar across time periods. CONCLUSION: A formal protocol to manage insulin and glucose infusions for parturients with diabetes was associated with improved intrapartum maternal glucose control, but an increased frequency of neonatal hypoglycemia.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Trabalho de Parto , Gravidez em Diabéticas/tratamento farmacológico , Adulto , Glicemia/análise , Protocolos Clínicos/normas , Diabetes Mellitus/tratamento farmacológico , Feminino , Glucose/administração & dosagem , Humanos , Hiperglicemia/epidemiologia , Hipoglicemia/epidemiologia , Infusões Intravenosas , Unidades de Terapia Intensiva Neonatal , Gravidez , Estudos Retrospectivos
17.
Diabetes Res Clin Pract ; 166: 108281, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32628980

RESUMO

AIMS: To evaluate the effect of continuous subcutaneous insulin infusion (CSII) on glycaemic control, hypoglycaemia and emotional distress in adults with type 1 diabetes (T1D) during the first 12 months. METHODS: 47 patients were started on CSII as per NICE guidelines. Anthropometric, clinical and biochemical parameters, hypoglycaemia rates and emotional distress measured by Problem Areas in Diabetes questionnaires (PAID) were recorded at baseline and during follow up at 3-6 months and 6-12 months. RESULTS: Mean HbA1c dropped by 1.1% (11.8 mmol/mol; p < 0.0001) at 3-6 months and by 0.8% (8.6 mmol/mol; p = 0.008) at 6-12 months. Most patients had improved HbA1c between 6.5 and 8.5% (48-69 mmol/mol) during these follow ups (68.3% and 71.5% respectively). Frequency of hypoglycaemia reduced from 338.2 to 187.2 and 155.3 per 100 patient years during follow ups. Severe hypoglycaemia also decreased from 48.9 to 8.5 and 6.3 per 100 patient years respectively. PAID scores improved from 29.8 ± 18.5 to 17.2 ± 14.0 (p = 0.0002) at 3-6 months and to 12.8 ± 11.7 (p < 0.00001) at 6-12 months. Reduction in HbA1c, insulin dose and PAID scores was more significant in group with HbA1c > 8.5% (69 mmol/mol) at baseline whereas improvement in episodes of hypoglycaemia and severe hypoglycaemic was more in patients who had HbA1c ≤ 8.5% before commencement of CSII therapy. CONCLUSIONS: CSII therapy led to early improvement in glycaemic control, rates of hypoglycaemia and diabetes specific emotional distress. As beneficial effects are recorded within the first few months, CSII therapy should be started more proactively in T1D.


Assuntos
Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 1/terapia , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Angústia Psicológica , Estresse Psicológico/etiologia , Adulto , Glicemia/análise , Glicemia/metabolismo , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Seguimentos , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estresse Psicológico/epidemiologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Diabetes Res Clin Pract ; 166: 108333, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32702468

RESUMO

AIMS: Predicting likely durability of glucose-lowering therapies for people with type 2 diabetes (T2D) could help inform individualised therapeutic choices. METHODS: We used data from UKPDS patients with newly-diagnosed T2D randomised to first-line glucose-lowering monotherapy with chlorpropamide-glibenclamide-basal insulin or metformin. In 2339 participants who achieved one-year HbA1c values <7.5% (<59 mmol/mol)-we assessed relationships between one-year characteristics and time to monotherapy-failure (HbA1c ≥ 7.5% or requiring second-line therapy). Model validation was performed using bootstrap sampling. RESULTS: Follow-up was median (IQR) 11.0 (8.0-14.0) years. Monotherapy-failure occurred in 72%-82%-75% and 79% for those randomised to chlorpropamide-glibenclamide-basal insulin or metformin respectively-after median 4.5 (3.0-6.6)-3.7 (2.6-5.6)-4.2 (2.7-6.5) and 3.8 (2.6- 5.2) years. Time-to-monotherapy-failure was predicted primarily by HbA1c and BMI values-with other risk factors varying by type of monotherapy-with predictions to within ±2.5 years for 55%-60%-56% and 57% of the chlorpropamide-glibenclamide-basal insulin and metformin monotherapy cohorts respectively. CONCLUSIONS: Post one-year glycaemic durability can be predicted robustly in individuals with newly-diagnosed T2D who achieve HbA1c values < 7.5% one year after commencing traditional monotherapies. Such information could be used to help guide glycaemic management for individual patients.


Assuntos
Clorpropamida/administração & dosagem , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glibureto/administração & dosagem , Insulina/administração & dosagem , Metformina/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/métodos , Prognóstico , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Reino Unido
19.
S Afr Med J ; 110(2): 154-158, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32657688

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM), a disorder of glucose intolerance first encountered during pregnancy, has far-reaching implications for both mother and child. Insulin therapy remains the 'gold standard' of care, with oral hypoglycaemic agents (OHAs) increasingly being viewed as potential alternatives. OBJECTIVES: To compare maternal and neonatal outcomes in two cohorts of women with GDM exposed to either insulin monotherapy or OHAs. METHODS: A retrospective medical record review at Chris Hani Baragwanath Academic Hospital in South Africa was conducted for women with GDM diagnosed using the 100 g oral glucose tolerance test and/or random capillary blood glucose >11.1 mmol/L in 2010 - 2014. The findings were compared with a previous audit at the same clinic for the period 1992 - 2002. Variables of interest included maternal demographics, maternal comorbidities, glycaemic indices, treatments used during pregnancy, and obstetric and neonatal outcomes. RESULTS: A total of 192 women with GDM were identified for 2010 - 2014, and there were 348 women in the previous audit (1992 - 2002). Baseline characteristics and outcomes of women in the two cohorts were similar apart from earlier presentation (mean (standard deviation) gestational age (GA) 27 (7.5) weeks v. 28.3 (6.4) weeks; p=0.04), lower GA at delivery (36.3 (3.6) weeks v. 37 (1.6) weeks); p=0.008) and lower macrosomia rates (12.5% v. 4.9%; p=0.011) in the later cohort. When comparing the individual OHAs against insulin in the later cohort, both agents were comparable to insulin in terms of maternal and neonatal outcomes. CONCLUSIONS: This study contributes to the paucity of data on the safety of OHAs in GDM pregnancy in terms of maternal and neonatal outcomes. OHAs were shown to be an effective alternative to insulin for women with GDM in whom lifestyle measures fail, particularly in a resource-poor setting.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Resultado da Gravidez , Administração Oral , Adulto , Estudos de Coortes , Feminino , Macrossomia Fetal/epidemiologia , Teste de Tolerância a Glucose , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , África do Sul
20.
Cardiovasc Diabetol ; 19(1): 115, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698837

RESUMO

The coronavirus disease 2019 (COVID-19) has been declared as pandemic by the World Health Organization and is causing substantial morbidity and mortality all over the world. Type 2 diabetes, hypertension, and cardiovascular disease significantly increase the risk for hospitalization and death in COVID-19 patients. Hypoglycemia and hyperglycemia are both predictors for adverse outcomes in hospitalized patients. An optimized glycemic control should be pursued in patients with diabetes and SARS-CoV-2 infection in order to reduce the risk of severe COVID-19 course. Both insulin and GLP-1RAs have shown optimal glucose-lowering and anti-inflammatory effects in type 2 diabetic patients and may represent a valid therapeutic option to treat asymptomatic and non-critically ill COVID-19 diabetic patients.


Assuntos
Betacoronavirus/patogenicidade , Glicemia/efeitos dos fármacos , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Incretinas/administração & dosagem , Insulina/administração & dosagem , Pneumonia Viral/terapia , Biomarcadores/sangue , Glicemia/metabolismo , Tomada de Decisão Clínica , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Interações entre Hospedeiro e Microrganismos , Humanos , Hipoglicemiantes/efeitos adversos , Incretinas/efeitos adversos , Insulina/efeitos adversos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Medição de Risco , Fatores de Risco , Resultado do Tratamento
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