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1.
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
2.
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
3.
Cochrane Database Syst Rev ; 8: CD009966, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32803882

RESUMO

BACKGROUND: Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017. OBJECTIVES: To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I2 = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I2 = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I2 = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause). AUTHORS' CONCLUSIONS: The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Adamantano/efeitos adversos , Adamantano/análogos & derivados , Adamantano/uso terapêutico , Viés , Causas de Morte , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Jejum/sangue , Hemoglobina A Glicada/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Insulina/uso terapêutico , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Nitrilos/efeitos adversos , Nitrilos/uso terapêutico , Pioglitazona , Complicações Pós-Operatórias/etiologia , Pirrolidinas/efeitos adversos , Pirrolidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fosfato de Sitagliptina/efeitos adversos , Fosfato de Sitagliptina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico , Transplantados , Vildagliptina
4.
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
5.
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
6.
Int J Nanomedicine ; 15: 4191-4203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606672

RESUMO

Purpose: To characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat. Material and Methods: The chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks. Results: The nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group. Conclusion: The nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.


Assuntos
Antrodia/química , Diabetes Mellitus Experimental/tratamento farmacológico , Nanopartículas/química , Reprodução , Ubiquinona/análogos & derivados , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Jejum/sangue , Glutationa Peroxidase/metabolismo , Humanos , Insulina/efeitos adversos , Insulina/sangue , Rim/efeitos dos fármacos , Rim/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Estreptozocina , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
7.
Cardiovasc Diabetol ; 19(1): 107, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631337

RESUMO

BACKGROUND: In randomised clinical trials, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors reduced cardiovascular events in patients with type 2 diabetes (T2D) at high cardiovascular risk, as compared to standard care. However, data comparing these agents in patients with T2D who are at moderate risk is sparse. METHODS: From Danish national registries, we included patients with T2D previously on metformin monotherapy, who started an additional glucose-lowering agent [GLP-1 RA, SGLT-2 inhibitor, dipeptidyl peptidase-4 (DPP-4) inhibitor, sulfonylurea (SU), or insulin] in the period 2010-2016. Patients with a history of cardiovascular events [heart failure (HF), myocardial infarction (MI) or stroke] were excluded. Patients were followed for up to 2 years. Cause-specific adjusted Cox regression models were used to compare the risk of hospitalisation for HF, a composite endpoint of major adverse cardiovascular events (MACE) (MI, stroke or cardiovascular death), and all-cause mortality for each add-on therapy. Patients who initiated DPP-4 inhibitors were used as reference. RESULTS: The study included 46,986 T2D patients with a median age of 61 years and of which 59% were male. The median duration of metformin monotherapy prior to study inclusion was 5.3 years. Add-on therapy was distributed as follows: 13,148 (28%) GLP-1 RAs, 2343 (5%) SGLT-2 inhibitors, 15,426 (33%) DPP-4 inhibitors, 8917 (19%) SUs, and 7152 (15%) insulin. During follow-up, 623 (1.3%, range 0.8-2.1%) patients were hospitalised for HF-hazard ratios (HR) were 1.11 (95% CI 0.89-1.39) for GLP-1 RA, 0.84 (0.52-1.36) for SGLT-2 inhibitors, 0.98 (0.77-1.26) for SU and 1.54 (1.25-1.91) for insulin. The composite MACE endpoint occurred in 1196 (2.5%, range 1.5-3.6%) patients, yielding HRs of 0.82 (0.69-0.97) for GLP-1 RAs, 0.79 (0.56-1.12) for SGLT-2 inhibitors, 1.22 (1.03-1.49) for SU and 1.23 (1.07-1.47) for insulin. 1865 (3.9%, range 1.9-9.0%) died from any cause during follow-up. HRs for all-cause mortality were 0.91 (0.78-1.05) for GLP-1 RAs, 0.79 (0.58-1.07) for SGLT-2 inhibitors, 1.13 (0.99-1.31) for SU and 2.33 (2.08-2.61) for insulin. CONCLUSION: In a nationwide cohort of metformin-treated T2D patients and no history of cardiovascular events, the addition of either GLP-1 RA or SGLT-2 inhibitor to metformin treatment was associated with a similar risk of hospitalisation for HF and death, and a lower risk of MACE for GLP-1 RA when compared with add-on DPP-4 inhibitors. By contrast, initiation of treatment with SU and insulin were associated with a higher risk of MACE. Additionally, insulin was associated with an increased risk of all-cause mortality and hospitalisation for HF.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Idoso , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Quimioterapia Combinada , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Humanos , Hipoglicemiantes/efeitos adversos , Incretinas/efeitos adversos , Insulina/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Admissão do Paciente , Sistema de Registros , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Compostos de Sulfonilureia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
8.
Rev Med Suisse ; 16(697): 1191-1196, 2020 Jun 10.
Artigo em Francês | MEDLINE | ID: mdl-32520457

RESUMO

Pump therapy has existed for over 40 years and provides a more flexible delivery of insulin. To date, almost 25% of type 1 diabetic patients have chosen this therapeutic option. In recent years, it has also been offered to patients with type 2 insulin-requiring diabetes. The choice of insulin pump is based on its indication, the patient's preference, lifestyle and knowledge of the disease. A risk of developing ketoacidosis in case of interruption of insulin delivery exists. Its implementation therefore requires a specialized interdisciplinary care team available in case of emergency.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Insulina/uso terapêutico , Pacientes Ambulatoriais , Cetoacidose Diabética/etiologia , Cetoacidose Diabética/prevenção & controle , Cetoacidose Diabética/terapia , Humanos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos
9.
Cardiovasc Diabetol ; 19(1): 83, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534570

RESUMO

BACKGROUND: Current evidence about the cardiovascular safety of glucagon-like peptide-1 receptor agonist (GLP-1ra) possesses limited generalizability to real-world patients with type 2 diabetes (T2D) in usual practice. This study aimed to investigate the comparative cardiovascular safety of GLP-1ra in comparisons with dipeptidyl peptidase-4 inhibitor (DPP-4i), sulfonylurea (SU), and insulin in a real-world population with T2D. METHODS: Adults with newly-diagnosed T2D were identified from Taiwan's National Health Insurance Research Database in 2003-2014. A prevalent new-user cohort design was adopted to include a broad representation of real-world T2D patients being treated with GLP-1ra. The between-group comparability of baseline patient characteristics was achieved by matching on (1) initiation time of study drugs, (2) prior exposure to glucose-lowering agents, and (3) diabetes severity and complications, comorbidities, and concomitant cardiovascular medications using propensity scores. The primary outcome was a composite of cardiovascular disease (CVD) events and assessed up to the end of 2015. Cox modeling was employed to assess the association between study drugs and outcomes. RESULTS: A total of 3195 GLP-1ra stable users was identified in 2011-2014. 1893, 1829, and 1367 GLP-1ra stable users were 1:1 matched to DPP-4i, SU and insulin users, respectively. Compared to DPP-4i, SU and insulin, the use of GLP-1ra was associated with a lower risk of composite CVD events [hazard ratio (95% confidence interval) 0.73 (0.57-0.96), 0.76 (0.57-1.00), and 0.81 (0.62-1.07), respectively]. Subgroup analyses revealed that GLP-1ra versus DPP-4i yielded a greater cardiovascular benefit in those without established CVD versus those with established CVD. CONCLUSIONS: This comparison study extends the supporting evidence for the cardiovascular safety of GLP-1ra to a broad spectrum of real-world T2D patients using GLP-1ra.


Assuntos
Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Incretinas/uso terapêutico , Insulina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Feminino , Humanos , Incretinas/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Compostos de Sulfonilureia/efeitos adversos , Taiwan/epidemiologia , Fatores de Tempo , Resultado do Tratamento
10.
Cardiovasc Diabetol ; 19(1): 72, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493344

RESUMO

BACKGROUND: Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP4 inhibitors such as linagliptin (LG) on CVD risk, in patients with T2DM with established CKD has not been established. Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD) population. METHODS: 31 subjects taking metformin and/or Insulin were enrolled in this 12 weeks, double blind, randomized placebo matched trial, with 5 mg LG compared to placebo. Type 2 diabetes subjects (30-70 years old), HbA1c of 6.5-10%, CKD Stage 1-3 were included. CD34+ cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, biochemistry, resting energy expenditure and body composition were measured. Data were collected at week 0, 6 and 12. A mixed model regression analysis was done with p value < 0.05 considered significant. RESULTS: A double positive CD34/CD184 cell count had a statistically significant increase (p < 0.02) as determined by flow cytometry in LG group where CD184 is SDF1a cell surface receptor. Though mRNA differences in CD34+ve was more pronounced CD34- cell mRNA analysis showed increase in antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and prominent endothelial markers (PECAM1, VEGF-A, vWF and NOS3). Arterial stiffness measures such as augmentation Index (AI) (p < 0.04) and pulse wave analysis (PWV) were improved (reduced in stiffness) in LG group. A reduction in LDL: HDL ratio was noted in treatment group (p < 0.04). Urinary exosome protein examining podocyte health (podocalyxin, Wilms tumor and nephrin) showed reduction or improvement. CONCLUSIONS: In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34 + progenitor cells with a concomitant improvement in vascular and renal parameters at 12 weeks. Trial Registration Number NCT02467478 Date of Registration: 06/08/2015.


Assuntos
Antígenos CD34/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Células Progenitoras Endoteliais/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Linagliptina/uso terapêutico , Metformina/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Idoso , Biomarcadores/sangue , Células Cultivadas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , District of Columbia , Método Duplo-Cego , Quimioterapia Combinada , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Linagliptina/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Projetos Piloto , Receptores CXCR4/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Fatores de Tempo , Resultado do Tratamento
11.
Diabetes ; 69(5): 837-847, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32312900

RESUMO

Insulin resistance is an underappreciated facet of type 1 diabetes that occurs with remarkable consistency and considerable magnitude. Although therapeutic innovations are continuing to normalize dysglycemia, a sizable body of data suggests a second metabolic abnormality-iatrogenic hyperinsulinemia-principally drives insulin resistance and its consequences in this population and has not been addressed. We review this evidence to show that injecting insulin into the peripheral circulation bypasses first-pass hepatic insulin clearance, which leads to the unintended metabolic consequence of whole-body insulin resistance. We propose restructuring insulin therapy to restore the physiological insulin balance between the hepatic portal and peripheral circulations and thereby avoid the complications of life-long insulin resistance. As technology rapidly advances and our ability to ensure euglycemia improves, iatrogenic insulin resistance will become the final barrier to overcome to restore normal physiology, health, and life in type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Resistência à Insulina , Insulina/administração & dosagem , Insulina/efeitos adversos , Animais , Regulação da Expressão Gênica , Humanos
14.
Lakartidningen ; 1172020 02 13.
Artigo em Sueco | MEDLINE | ID: mdl-32068880

RESUMO

Biopsies from six diabetic patients with subcutaneous amyloid deposits formed by injected insulin have been sent to our laboratory during the last year. In all but one of the six patients a subcutaneous adipose tissue biopsy was taken due to suspicion of systemic amyloidosis. Four of these patients had renal insufficiency, with monoclonal gammopathy of undetermined significance (MGUS) in three while the fifth had heredity for transthyretin amyloidosis. In the sixth patient a biopsy was taken due to subcutaneous nodules at insulin injection sites. In all biopsies, large amounts of amyloid were present and their biochemical nature was elucidated by immunohistochemistry or western blot. The risk of incorrect interpretation with misdiagnosis of systemic amyloidosis is underlined. The consequences this may have on insulin treatment are insufficiently studied.


Assuntos
Neuropatias Amiloides Familiares , Amiloidose , Insulina , Amiloide , Amiloidose/diagnóstico , Erros de Diagnóstico , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina , Insulina/administração & dosagem , Insulina/efeitos adversos , Patologistas
15.
Acta Diabetol ; 57(6): 743-749, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32025860

RESUMO

AIMS: Glucagon is used to resolve severe hypoglycemia in unconscious patients with diabetes, requiring third-party assistance. A few studies have shown that intranasal (IN) glucagon causes resolution of hypoglycemia in insulin-treated patients with type 1 (T1DM) diabetes. This systematic review and meta-analysis updates the comparison of the effectiveness of IN glucagon with injected intramuscular/subcutaneous (IM/SC) glucagon in treatment of hypoglycemia in T1DM. METHODS: Controlled randomized studies were considered; eight studies, published in English, were included in a meta-analysis (random-effects model). Intervention effect (resolution of hypoglycemia) was expressed as odds ratio (OR), with 95% confidence intervals. Meta-regression was employed to correlate the effect with size of studies, age of patients, basal blood glucose levels. RESULTS: In a total of 467 treatments in 269 patients with IN and IM/SC glucagon, the OR IN versus IM/SC was 0.61 (CI 0.13-2.82); since four of eight studies showed 100% effectiveness, a simulation was made with 1 failure for each treatment; in this simulation analysis, the OR was 0.80 (95% CI 0.28-2.32). Heterogeneity was low and not statistically significant. Publication bias was absent, and quality of papers was high. At meta-regression, no correlation was found between the effect and number of patients in each study, age of patients, basal blood glucose levels. No study formally compared IN versus IM/SC in unconscious patients. CONCLUSIONS: This meta-analysis indicates that in conscious T1DM patients IN glucagon and IM/SC glucagon are equally effective in resolution of hypoglycemia.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucagon/administração & dosagem , Hipoglicemia/tratamento farmacológico , Insulina/efeitos adversos , Administração Intranasal , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/epidemiologia , Glucagon/efeitos adversos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Injeções Intramusculares , Injeções Subcutâneas , Insulina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do Tratamento
16.
BMJ Case Rep ; 13(2)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32047088

RESUMO

A 71-year-old woman with metastatic squamous cell carcinoma of the lung and insulin-dependent type 2 diabetes mellitus presented with a necrotic lesion on her lower abdomen. Further history revealed that this was the site of repeat insulin injections with reuse of the same needles. On investigation, biopsy of the site was positive for broad, aseptate, right-angle branching fungal hyphae consistent with mucormycosis. Studies have shown that insulin needle reuse is a common practice among diabetics for several reasons, including cost and convenience. While the current American Diabetes Association guidelines suggest that this is an acceptable practice among the general population of diabetics, they advise against it in patients who are actively ill or immunocompromised. Discussion about insulin needle reuse should be of utmost importance among providers and their diabetic patients, especially for patients who are immunocompromised.


Assuntos
Abdome/patologia , Dermatomicoses/terapia , Reação no Local da Injeção/microbiologia , Injeções Subcutâneas/efeitos adversos , Mucormicose/etiologia , Mucormicose/terapia , Idoso , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Dermatomicoses/microbiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hospedeiro Imunocomprometido , Insulina/efeitos adversos , Neoplasias Pulmonares/complicações , Necrose , Nitrilos/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Vancomicina/uso terapêutico
17.
Int J Clin Pract ; 74(6): e13485, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32003099

RESUMO

BACKGROUND: Associations of fear of hypoglycemia with prescription of second-line insulin secretagogues (IS) or insulin and subsequent glycemic control in patients with type 2 diabetes were analysed using data from the DISCOVER study-a large, prospective, observational study. METHODS: Patients with type 2 diabetes initiating a second-line treatment after a first-line oral therapy were enrolled. Fear of hypoglycemia was assessed using baseline Hypoglycemia Fear Survey (HFS) worry score. Glycemic control was assessed using glycated haemoglobin (HbA1c) levels at 6-month and 1-year follow-up, and HbA1c change from baseline was analysed. To examine the association of baseline HFS worry scores with second-line use of IS or insulin, a hierarchical logistic model with country as random effect was used. RESULTS: A total of 6217 patients were analysed. The mean HFS worry score was 6.9 ± 11.4, while patients in the upper quartile had an HFS worry score ≥9. We divided patients into three groups according to their baseline HFS worry score (0, 1-8, ≥9). HFS worry score was associated with the use of first-line IS, but not the second-line treatment. Compared to treatments with no IS and insulin, a better HbA1c response to second-line IS or insulin was noted in patients with a baseline HFS worry score of 0 or 1-8, but not in patients with a baseline HFS worry score ≥9. CONCLUSION: HFS worry score was associated with the use of first-line IS and glycemic response to second-line IS or insulin in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02322762. Registered 23 December 2014.


Assuntos
Diabetes Mellitus Tipo 2/psicologia , Medo/psicologia , Hipoglicemia/psicologia , Secretagogos/efeitos adversos , Adulto , Ansiedade/psicologia , Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemia/induzido quimicamente , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
18.
Acta Diabetol ; 57(6): 681-687, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31953687

RESUMO

AIM: The aim of this study was to evaluate the 10-day initiation protocol for MiniMed 670G hybrid closed-loop (HCL) system in individuals with type 1 diabetes on multiple daily injection (MDI) in achieving desirable glycemic control. METHODS: An open-label single-arm, single-center, clinical investigation in children aged 7-18 years on MDI following a structured protocol: 2 days, HCL system assessment; 5 days, HCL system training (2-h sessions on 5 consecutive days with groups of 3-5 participants and families); 3 days, Manual Mode use of HCL system; 84 days, Auto Mode use of the HCL system, cumulating in 10 days from MDI to Auto Mode activation. RESULTS: A total of 30 children (age 10.24 ± 2.6 years) were enrolled in the study, and all completed the planned 84 days on Auto Mode. The participants used the sensor for a median of 92% of the time and spent a median of 89% in Auto Mode. The mean HbA1c decreased from 8.2 ± 1.4% (66 ± 15.3 mmol/mol) at baseline to 6.7 ± 0.5% (50 ± 5.5 mmol/mol) at the end of the study (p = 0.017). Time in range (70-180 mg/dL) increased from 46.9 ± 18.5% at baseline to 75.6 ± 6.9% in Auto Mode (p < 0.001). This was achieved while spending 2.8% of the time below 70 mg/dL and without any severe hypoglycemia or DKA. CONCLUSION: Children and adolescents with type 1 diabetes on MDI therapy can successfully initiate the HCL system, using a concise structured 10-day protocol.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adolescente , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Criança , Esquema de Medicação , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Injeções , Insulina/efeitos adversos , Masculino , Fatores de Tempo
19.
J Clin Nurs ; 29(9-10): 1704-1711, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31944477

RESUMO

AIMS AND OBJECTIVES: To identify determinants of quality of life among patients who had experienced hypoglycaemia and who were undergoing insulin treatment. BACKGROUND: Patients with diabetes receiving insulin treatment are at high risk for hypoglycaemia, which tends to affect their quality of life. DESIGN: With a cross-sectional and observational study design (see the STROBE checklist and Appendix S1). METHODS: One hundred and fifty patients with type 2 diabetes who had received insulin treatment and had experienced hypoglycaemia (<70 mg/dl) in the last 6 months were recruited. Data were collected from May 2016-February 2018 using the Knowledge of Hypoglycaemia Scale, Fear of Hypoglycaemia Scale, Social Support Scale and the simplified Taiwanese version of the Quality of Life Scale developed by the World Health Organization. RESULTS: Factors found to be associated with quality of life in patients with hypoglycaemia included having an educational level of senior high school or above, being on an insulin regimen only, engaging in regular exercise, diabetes complications, fear of hypoglycaemia and greater social support, which accounted for 28.5% of the total variance. CONCLUSIONS: During the process of glycaemic control, patients inevitably experience hypoglycaemic episodes. Therefore, healthcare providers should assist patients with disease management to improve their quality of life. Future studies should also recruit patients who claim to have experienced hypoglycaemic symptoms, rather than considering only those with blood glucose levels below 70 mg/dl, to expand the generalisability of the findings. Future studies may also focus on the management of hypoglycaemia in patients on an insulin regimen, and on examining the effect of health education programmes on prevention of hypoglycaemia. RELEVANCE TO CLINICAL PRACTICE: The present findings could provide a reference for healthcare providers to consolidate nursing care guidelines and to improve such patients' quality of life.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Hipoglicemia/psicologia , Qualidade de Vida , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipoglicemia/etiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade
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