Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22.923
Filtrar
1.
Int J Nanomedicine ; 14: 7743-7758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571874

RESUMO

Purpose: Peptide drugs have been used in therapy various diseases. However, the poor bioavailability of peptide drugs for oral administration has limited their clinical applications, on account of the acidic environment and digestive enzymes inside the human gastrointestinal tract. To enhance stability in the human gastrointestinal tract, bioavailability, and targeted drug delivery of peptide drugs through oral administration, a vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized. Materials and methods: A vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized via the N,N'-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and 1H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB12 (CSAD-VB12/insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB12/insulin as spherical nanoparticles. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells by CCK-8 test. Caco-2 cell model was used to measure the apparent permeability (Papp) of insulin, CSAD/insulin and CSAD-VB12/insulin. Furthermore, confocal was used to confirm the endocytosis of intestinal enterocytes. Type 1 diabetes mice were used to evaluate the intestinal absorption and retention effect of test nanoparticles. Results: They were observed as spherical nanoparticles in the size of 30-50 nm. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB12/insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB12/insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy. Conclusion: CSAD-VB12 derivatives enhance the small intestinal absorption efficacy and retention of peptide by oral administration, which indicated that it could be a promising candidate for oral peptide delivery in the prospective clinical application.


Assuntos
Alginatos/química , Sistemas de Liberação de Medicamentos , Peptídeos/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Vitamina B 12/química , Administração Oral , Alginatos/síntese química , Animais , Células CACO-2 , Morte Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Insulina/administração & dosagem , Insulina/farmacologia , Insulina/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Vitamina B 12/síntese química
2.
Cochrane Database Syst Rev ; 9: CD012544, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31476798

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is a common medical condition that complicates pregnancy and causes adverse maternal and fetal outcomes. At present, most treatment strategies focus on normalisation of maternal blood glucose values with use of diet, lifestyle modification, exercise, oral anti-hyperglycaemics and insulin. This has been shown to reduce the incidence of adverse outcomes, such as birth trauma and macrosomia. However, this involves intensive monitoring and treatment of all women with GDM. We propose that using medical imaging to identify pregnancies displaying signs of being affected by GDM could help to target management, allowing low-risk women to be spared excessive intervention, and facilitating better resource allocation. OBJECTIVES: We wanted to address the following question: in women with gestational diabetes, does the use of fetal imaging plus maternal blood glucose concentration to indicate the need for medical management compared with glucose concentration alone reduce the risk of adverse perinatal outcomes? SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (29 January 2019), ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) (both on 29 January 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials, including those published in abstract form only. Studies using a cluster-randomised design and quasi-randomised controlled trials were both eligible for inclusion, but we didn't identify any. Cross-over trials were not eligible for inclusion in our review.We included women carrying singleton pregnancies who were diagnosed with GDM, as defined by the trials' authors. The intervention of interest was the use of fetal biometry on imaging methods in addition to maternal glycaemic values for indicating the use of medical therapy for GDM. The control group was the use of maternal glycaemic values alone for indicating the use of such therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors extracted data and checked them for accuracy. MAIN RESULTS: Three randomised controlled trials met the inclusion criteria for our systematic review - the studies randomised a total of 524 women.We assessed the three included studies as being at a low to moderate risk of bias; the nature of the intervention made it difficult to achieve blinding of participants and personnel and none of the trial reports contained information about methods of allocation concealment (and were therefore assessed as being at an unclear risk of selection bias).In all studies, the intervention was the use of fetal biometry on ultrasound to identify fetuses displaying signs of fetal macrosomia, and the use of this information to indicate the use of medical anti-hyperglycaemic treatments. Those pregnancies were subject to more stringent blood glucose targets than those without signs of fetal macrosomia.Maternal outcomesThe use of fetal biometry in addition to maternal blood glucose concentration (compared with maternal blood glucose concentration alone) may make little or no difference to the incidence of caesarean delivery (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.59 to 1.10; 2 trials, 428 women; low-certainty evidence). We are unclear about the results for hypertensive disorders of pregnancy (RR 0.80, 95% CI 0.34 to 1.89; 2 trials, 325 women) due to very low-certainty evidence. The included trials did not report on development of type 2 diabetes in the mother or maternal hypoglycaemia.Fetal and neonatal outcomesThe use of fetal biometry may make little or no difference to the incidence of neonatal hypoglycaemia (RR 0.90, 95% CI 0.57 to 1.42; 3 trials, 524 women; low-certainty evidence). Very low-certainty evidence means that we are unclear about the results for large-for-gestational age (RR 0.81, 95% CI 0.38 to 1.74; 3 trials, 524 women); shoulder dystocia (RR 0.33, 95% CI 0.01 to 7.98; 1 trial, 96 women); a composite measure of perinatal morbidity or mortality (RR 1.00, 95% CI 0.21 to 4.71; 1 study, 96 women); or perinatal mortality (RR 0.33, 95% CI 0.01 to 7.98; 1 trial, 96 women). AUTHORS' CONCLUSIONS: This review is based on evidence from three trials involving 524 women. The trials did not report some important outcomes of interest to this review, and the majority of our secondary outcomes were also unreported. The available evidence ranged from low- to very low-certainty, with downgrading decisions based on limitations in study design, imprecision and inconsistency.There is insufficient evidence to evaluate the use of fetal biometry (in addition to maternal blood glucose concentration values) to assist in guiding the medical management of GDM, on either maternal or perinatal health outcomes, or the associated costs.More research is required, ideally larger randomised studies which report the maternal and infant short- and long-term outcomes listed in this review, as well as those outcomes relating to financial and resource implications.


Assuntos
Biometria/métodos , Diabetes Gestacional/terapia , Macrossomia Fetal/prevenção & controle , Complicações na Gravidez/prevenção & controle , Feminino , Humanos , Insulina/uso terapêutico , Gravidez , Resultado da Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Undersea Hyperb Med ; 46(4): 437-445, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509900

RESUMO

Introduction: To determine if hyperbaric oxygen (HBO2) therapy has an effect on diabetic blood glucose levels (BGL) and, if so, the extent of this effect. Also, to examine factors that exacerbate any observed effect. Methods: This was a retrospective review of prospectively collected quality data on diabetics undergoing HBO2. Pre- and post-treatment BGL were recorded. Pre-treatment BGL ⟨120 mg/dL received glucose supplementation. Hypoglycemia was defined as BGL ⟨70 mg/dL. BGL ⟨90 mg/dL was included as an elevated hypoglycemia threshold. Results: 77 patients representing 1,825 treatments were included for analysis. No patient had deleterious side effects or required emergency care. BGL decreased in 75.4% of treatments in this group, with a median decrease of 25 mg/dL (IQR=54 mg/dL; range of decreased 374 mg/dL to increased 240 mg/dL). A statistically significant greater percentage of treatments of patients with type 2 diabetes resulted in a decrease in BGL (1598 or 77.5%) compared to treatments of patients with type 1 diabetes (169 or 51.5%) (χ2(1, N=1767) =55.37, p⟨0.001). 1.1% of treatments had post-HBO2 serum glucose ⟨90 mg/dL, and 0.2% of treatments had post-HBO2 serum glucose ⟨70 mg/dL. The majority (70%) of patients with post-HBO2 BGL ⟨90 mg/dL were maintained on insulin alone (χ2(2, N=20) =12.4, p=0.002). Well-controlled diabetics (i.e., those with all BGLs within 50 mg/dL over all pre-HBO2 treatments) had no post-HBO2 BGL ⟨70 mg/dL or ⟨90 mg/dL. Conclusion: Our results suggest that HBO2 does not cause a clinically significant decrease in diabetic patient BGL. No patient in our study had deleterious side effects or required emergency care. We found that glucose level of ⟨90 mg/dL occurred more often in those who use insulin. Hyperbaric patients who exhibit consistent BGL values may represent a group who could be managed similarly to the non-diabetic population.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Oxigenação Hiperbárica , Idoso , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Oxigenação Hiperbárica/efeitos adversos , Oxigenação Hiperbárica/estatística & dados numéricos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Estudos Retrospectivos , Esteroides/efeitos adversos
4.
Lancet ; 394(10205): 1265-1273, 2019 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-31533908

RESUMO

Technological advances have had a major effect on the management of type 1 diabetes. In addition to blood glucose meters, devices used by people with type 1 diabetes include insulin pumps, continuous glucose monitors, and, most recently, systems that combine both a pump and a monitor for algorithm-driven automation of insulin delivery. In the next 5 years, as many advances are expected in technology for the management of diabetes as there have been in the past 5 years, with improvements in continuous glucose monitoring and more available choices of systems that automate insulin delivery. Expansion of the use of technology will be needed beyond endocrinology practices to primary-care settings and broader populations of patients. Tools to support decision making will also need to be developed to help patients and health-care providers to use the output of these devices to optimise diabetes management.


Assuntos
Tecnologia Biomédica , Diabetes Mellitus Tipo 1/terapia , Glicemia/análise , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Insulina/administração & dosagem , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Monitorização Fisiológica/instrumentação
5.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(8): 949-952, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31537217

RESUMO

OBJECTIVE: To explore the effect of intensive insulin therapy (IIT) on high mobility group box-1/nuclear factor-ΚB (HMGB1/NF-ΚB) signaling pathway in severe traumatic brain injury (sTBI) patient with stress hyperglycemia. METHODS: Sixty-one sTBI patients with stress hyperglycemia [Glasgow coma scale (GCS) ≤ 8, three times of random blood glucose levels > 11.1 mmoL/L, glycosylated hemoglobin (HbA1c) < 0.065] admitted to the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from July 2015 to October 2017 were enrolled. Patients were divided into IIT group (29 cases, keeping blood glucose at 4.4-7.8 mmol/L) and conventional glycemic therapy (CGT) group (32 cases, keeping blood glucose at 7.8-12.2 mmo/L) according to the random number table method. Before treatment and 1, 7 and 14 days after treatment, the levels of plasma HMGB1 and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA); C-reactive protein (CRP) was determined by automatic biochemical analyzer, and NF-ΚB p65 gene expression in peripheral blood mononuclear cells was detected by real-time quantitative polymerase chain reaction (PCR). RESULTS: Nine patients were withdrawn from the observation because the 4 consecutive blood glucose monitoring did not reach the target value, combined with severe infection, or abandoned the treatment with serious brain damage. Finally, 52 patients were enrolled in the analysis, including 28 in CGT group and 24 in IIT group. The levels of plasma HMGB1, TNF-α, CRP and the expression of NF-ΚB gene in monocytes of the two groups at 1 day after treatment were significantly higher than those before treatment, and reached the peak value, then gradually decreased. After 7 days of treatment, they were significantly lower than 1 day. The levels of plasma CRP and TNF-α in the IIT group were significantly lower than those in the CGT group [CRP (mg/L): 36.7±4.4 vs. 45.1±6.1, TNF-α (ng/L): 42.4±9.7 vs. 53.2±9.1, both P < 0.05], the level of HMGB1 in plasma and the expression of NF-ΚB p65 in monocytes were significantly lower than those in the CGT group after 14 days of treatment [HMGB1 (µg/L): 60.1±8.7 vs. 80.5±9.1, NF-ΚB p65 (ΔCt): 35.8±8.5 vs. 53.5±7.3, both P < 0.05]. CONCLUSIONS: IIT inhibits the inflammatory response in sTBI patients with stress hyperglycemia through HMGB1/NF-ΚB pathway.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Proteína HMGB1/metabolismo , Hiperglicemia/metabolismo , Insulina/uso terapêutico , NF-kappa B/metabolismo , Glicemia , Automonitorização da Glicemia , Humanos , Leucócitos Mononucleares , Fator de Necrose Tumoral alfa
6.
Internist (Berl) ; 60(9): 887-894, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31396651

RESUMO

A multitude of short-acting and long-acting insulin analogues are currently available for the treatment of diabetes mellitus, which mimic physiological insulin secretion better than normal insulins. By the use of ultrarapid insulin analogues postprandial glucose increases can be significantly reduced. Newer long-acting insulin analogues have a very stable action profile and reduce the rate of hypoglycemia, especially nocturnal hypoglycemia, even more than first generation long-acting insulin analogues. Future developments focus on a further acceleration of prandial insulin effects with a simultaneous shorter effect time and an even more prolonged action of long-acting insulin analogues.


Assuntos
Medicamentos Biossimilares , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Insulina/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipoglicemia , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Período Pós-Prandial , Qualidade de Vida
7.
Postgrad Med ; 131(7): 423-437, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382796

RESUMO

Hyperglycemia on hospital admission is a common phenomenon in acute ischemic stroke patients and represents an independent predictor of poor clinical outcome with or without acute recanalization therapies (systemic thrombolysis or mechanical thrombectomy). Effective restoration of normoglycemia is considered to be beneficial, but conclusive evidence from randomized controlled clinical trials and specific recommendations are lacking. In addition, aggressive glucose control can be complicated by hypoglycemia leading to early neurological deterioration. We conducted a systematic literature review with the aim of addressing several questions: timing of glucose control, target range, type of insulin delivery, duration and practicability of glucose-lowering protocols. Special issues regarding mechanical thrombectomy and glycemic variability can then be investigated in future trials which are also being considered.


Assuntos
Isquemia Encefálica/terapia , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Acidente Vascular Cerebral/terapia , Glicemia/metabolismo , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Hospitalização , Humanos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hipoglicemia/induzido quimicamente , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Trombectomia , Terapia Trombolítica
10.
Rev Med Chil ; 147(4): 451-457, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344206

RESUMO

BACKGROUND: Few studies have evaluated the details of insulin therapy for type 1 diabetes mellitus (T1D) in Chile. AIM: To describe clinical features and treatment details of adults with T1D and its association with metabolic control. MATERIAL AND METHODS: Review of medical records of patients with T1D treated in a clinical network. Demographic and clinical features, types and doses of insulin and glycated hemoglobin levels were registered. The use flash glucose monitors (FGM) and insulin pumps (CSII) were also recorded. RESULTS: 205 records were reviewed, with T1d lasting 12 ± 10 years. Twenty six percent had hypothyroidism, 1% had celiac disease, 12% had hypertension, 20% had dyslipidemia; 13% had diabetic retinopathy, 2% had diabetic nephropathy, 8% had neuropathy and 2% cardiovascular diseases. Mean body mass index was 25 kg/ m2 and mean glycated hemoglobin was 8%. Eighty-two percent used multiple daily injections, 18% used CSII and 24% used FGM. As basal insulin, 35% used slow acting analogs and 65% used ultra-slow analogs. As rapid acting insulin, 69 patients used Lispro, 79 Aspart and 50 Glulisin. Bolus doses were calculated using only capillary glucose in 22%, while 78% also considered carbohydrate consumption. Variables significantly associated to better control were the use of carbohydrates for dosing rapid insulin (A1c 7,85% vs 8,59%, p = 0,008), use of CSII (A1c 7,36% vs 8,16%, p = 0,008), and basal dose < 0,4 U/kg (A1c 7,81% vs 8,58%, p = 0,003). There were no differences regarding insulin type or use of FGM. CONCLUSIONS: The use of formulas considering carbohydrates for dosing rapid insulin, use of infusion pumps and physiological doses of basal insulin are significantly associated with a better metabolic control in adults with T1d.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Adulto , Análise de Variância , Chile , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Hemoglobina A Glicada/análise , Humanos , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Rev Bras Enferm ; 72(3): 700-706, 2019 Jun 27.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31269135

RESUMO

OBJECTIVE: To evaluate the effect of educational intervention in the adherence to self-care activities and functional health literacy and numeracy in people with type 2 diabetes mellitus. METHODS: This was a quasi-experimental study conducted in two units of the Brazilian Family Health Strategy, involving people with diabetes. Educational interventions occurred in three meetings, weekly, lasting 60 minutes on average. Data were collected using the Questionário de Autocuidado com o Diabetes, before and after the interventions. RESULTS: 55 people participated in the study. After the interventions, the greatest difference for a better adherence to self-care was the item "inspecting the inside of the shoes before putting them on", with 3.29 days in the week delta at analytical level. The worst was "taking insulin shots as recommended", with 0.00 days a week delta at basic level. CONCLUSION: Educational interventions had a positive effect on adherence to self-care and functional literacy in health.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Alfabetização em Saúde/métodos , Autocuidado/métodos , Idoso , Brasil , Diabetes Mellitus Tipo 2/psicologia , Feminino , Promoção da Saúde/métodos , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade
12.
J Assoc Physicians India ; 67(4): 34-38, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31309793

RESUMO

Objective: Widely used in the management of diabetes, insulin therapy is influenced by several patient preferences and physician choices. This article reports the findings of the IMPACT survey, designed to assess insights on various factors which influence the choice of insulin therapy in India. Methods: We administered a questionnaire which focused on the practice and patient profiles and the preferred regimens in specific clinical situations using a case scenario. Respondents were asked about preferred insulin regimens for various phases of life, comorbid conditions, dietary choices and psychological factors. Results: Overall, 314 doctors participated in the survey. Majority were general physicians (51%) and diabetologists (37%). In clinical practice, the most preferred regimens included premix insulin BD in adults (59%) and elderly (53%), and basal bolus therapy in pregnant women (>47%) and in acute illness (62%). Both regimens were equally preferred for symptomatic patients (41% basal bolus and 38% premix insulin) and those with renal or hepatic failure (36% each). Premix insulin was preferred for patients with high carbohydrate intake (73%) while basal bolus was preferred for patients with variable meal timings (39%) and in pronounced postprandial glucose excursions (45%). Insulin co-formulation and high-mix insulins were not a part of the survey questionnaire. Summary: Indian physicians exercise logic in the choice of insulin regimens. Preference is based on patient characteristics including glucophenotype, dietary patterns, psychosocial needs, clinical situations, and comorbid conditions.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Adulto , Idoso , Glicemia , Feminino , Humanos , Índia , Gravidez
13.
Clin Drug Investig ; 39(8): 805-819, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31317516

RESUMO

Glucagon-like peptide-1 receptor analogues/agonists (GLP-1RAs) are well established as effective adjuncts to lifestyle modification in the treatment of type 2 diabetes (T2D) as monotherapy or in combination with oral glucose-lowering drugs ± insulin. The six subcutaneous GLP-1RA formulations (i.e. twice-daily exenatide, once-daily liraglutide and lixisenatide, and once-weekly dulaglutide, exenatide and semaglutide) currently available in the EU and USA have many similarities, but also some unique features and properties. By stimulating GLP-1 receptors, GLP-1RAs increase insulin secretion and suppress glucagon release in a glucose-dependent manner, thereby improving clinical and patient-reported outcomes related to glycaemic control and weight. They also have been shown to reduce, or at least not increase, the risk of major cardiovascular outcomes. GLP-1RAs are generally well tolerated, with gastrointestinal and injection-site reactions being the most troublesome drug-related adverse events, and are associated with a very low intrinsic risk of hypoglycaemia. Treatment with GLP-1RAs should be customized to meet the clinical needs and personal preferences of the individual.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Administração Oral , Glicemia/efeitos dos fármacos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas
14.
Int J Evid Based Healthc ; 17 Suppl 1: S48-S52, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31283582

RESUMO

The prevalence of diabetes is on the rise worldwide especially in developed countries. The aim of glucose management in all types of diabetes is to minimize chronic and acute complications associated with diabetes. All patients with type 1 diabetes mellitus (T1DM) require insulin. Main areas of technology advances in diabetes are continuous subcutaneous insulin infusion (CSII) and also continuous glucose monitoring systems for the management of patients with both types of diabetes. It is very important to analyse the epidemiological situation within each country before and during the clinical practice guidelines (CPGs) development and implementation. The analyses will allow us to monitor the effect of the CPG after its implementation.The aim of this short communication is to analyse the epidemiology of prevalence and incidence of diabetes mellitus and use of CSII to inform development of CPGs in the Czech Republic.The analysis is developed based on the data managed by Institute of Health Information and Statistics of the Czech Republic. We used the National Register of Reimbursed Health Services 2015-2017 as primary source, and the annual report type A (Ministry of Health) 1-01: for Diabetology (A MH 004) 2007-2017 was used as validation source. The presented data are related to the year 2016 because we were able to validate them based on the data from 2015 to 2017 for this cohort of patients.The number of patients with T1DM is increasing in the Czech Republic with no significant sex difference. Life expectancy is about 11 years lower in the T1DM population. The majority of the patients are in older age; however, these are not treated with CSII compared with the younger population. From 61 533 patients with T1DM, 81% were reported with acute and chronic complications in 2016. Only 5011 of these patients were reported as using CSII.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , República Tcheca/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Incidência , Insulina/uso terapêutico , Sistemas de Infusão de Insulina/estatística & dados numéricos , Expectativa de Vida , Masculino , Prevalência
15.
Nat Med ; 25(8): 1266-1273, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285633

RESUMO

The ability to safely control transgene expression with simple synthetic gene switches is critical for effective gene- and cell-based therapies. In the present study, the signaling pathway controlled by human transient receptor potential (TRP) melastatin 8 (hTRPM8), a TRP channel family member1, is harnessed to control transgene expression. Human TRPM8 signaling is stimulated by menthol, an innocuous, natural, cooling compound, or by exposure to a cool environment (15-18 °C). By functionally linking hTRPM8-induced signaling to a synthetic promoter containing elements that bind nuclear factor of activated T cells, a synthetic gene circuit was designed that can be adjusted by exposure to either a cool environment or menthol. It was shown that this gene switch is functional in various cell types and human primary cells, as well as in mice implanted with engineered cells. In response to transdermal delivery of menthol, microencapsulated cell implants harboring this gene circuit, coupled to expression of either of two therapeutic proteins, insulin or a modified, activin type IIB, receptor ligand trap protein (mActRIIBECD-hFc), could alleviate hyperglycemia in alloxan-treated mice (a model of type 1 diabetes) or reverse muscle atrophy in dexamethasone-treated mice (a model of muscle wasting), respectively. This fully human-derived orthogonal transgene switch should be amenable to a wide range of clinical applications.


Assuntos
Receptores de Activinas Tipo II/sangue , Insulina/biossíntese , Canais de Cátion TRPM/fisiologia , Transgenes , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/uso terapêutico , Fosfatase Alcalina/genética , Animais , Temperatura Baixa , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Feminino , Regulação da Expressão Gênica , Células HEK293 , Humanos , Insulina/genética , Insulina/uso terapêutico , Mentol/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Distrofias Musculares/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos
16.
Diabetes Res Clin Pract ; 155: 107796, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31326458

RESUMO

AIM: The aim of this study was to analyze the efficacy, insulin sensitivity and safety in the event of administering sulfonylurea-based drugs and metformin in combination with basal insulin. METHODS: A randomized, open-label, parallel, 16-week trial was conducted across four study centers. The 97 type 2 diabetic patients were selected and randomized into two groups, the insulin glargine plus fixed-dose combination glimepiride 1 mg and metformin 500 mg twice daily group (the G/M group) and the insulin glargine plus glimepiride 4 mg once daily group (the G group). The primary endpoint evaluated was change in HbA1c. The secondary endpoints evaluated were changes in fasting blood glucose (FPG), 2-h post prandial glucose (PPG 2 h), insulin, and C-peptide levels. RESULTS: The G/M group was found to have experienced a significantly greater decrease in HbA1c, as well as PPG 2 h compared to the G group. While no significant intergroup difference was found regarding FPG in the ITT, the G/M group in the PP set experienced a significantly greater decrease in FPG. CONCLUSION: Comparison of combined therapy consisting of either the G/M group or the G group indicated that both forms of therapy are relatively safe but that the former more effectively decreases blood glucose levels.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Insulina/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Segurança
17.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(6): 376-384, jun.-jul. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-182854

RESUMO

Introduction and objectives: The worldwide prevalence of type 2 diabetes mellitus increases in parallel to that of obesity. Liraglutide (LRG), a glucagon-like peptide-1 receptor agonist, can reduce body weight. This study assessed the metabolic efficacy of LRG in real-world clinical practice. Methods: An observational, retrospective cohort study including patients treated with LRG for at least one year (187 patients). Anthropometric and metabolic variables, a composite endpoint, factors predicting response to LRG, and cardiovascular risk over time were assessed. A linear mixed-effects model with a bivariate structure was constructed to investigate the time-dependent relationship between weight and HbA1c values. Results: HbA1c levels and weight significantly decreased in the first 12 weeks, and the decrease persisted at 12 and 24 months in all subgroups studied. Mean weight and HbA1c decreases after 24 months were 8.5kg and 1.7% respectively. HbA1c values <7% were achieved by 42% of patients at 12 months and by 40% at 24 months. Treatment with LRG allowed for reduction in insulin dose. No serious adverse events were noted. Cardiovascular risk decreased from high to moderate-low. Conclusions: Under standard clinical practice conditions, LRG achieved a better metabolic response than seen in clinical trials. Efficacy at 12 weeks of treatment is a good predictor of response. LRG allows for delaying or reducing insulin dose by improving both weight and glucose control. Cardiovascular risk improved


Introducción y objetivos: La prevalencia mundial de diabetes mellitus tipo 2 aumenta junto a la de la obesidad. Liraglutida (LRG), un agonista del receptor del péptido similar al GLP1, es un fármaco antidiabético capaz de reducir peso. Evaluamos en práctica clínica de vida real su eficacia metabólica. Método: Estudio de cohorte observacional retrospectivo. Se incluyeron los pacientes tratados al menos durante un año con LRG (187 pacientes). Evaluamos variables antropométricas, metabólicas, objetivos combinados, factores predictivos de respuesta y evolución del riesgo cardiovascular. Se construyó un modelo de efectos mixtos lineales de estructura bivariante para investigar la relación tiempo-dependiente entre el peso y los valores de HbA1c. Resultados: Descenso significativo de los valores de HbA1c y peso en las primeras 12 semanas de tratamiento, mantenido a los 12 y 24 meses, en todos los subgrupos estudiados. Reducción media de peso y HbA1c tras 24 meses de tratamiento de 8,5 kg y 1,7%. El valor de HbA1c fue <7% en 42% de pacientes a los 12 meses, 40% a los 24 meses. El tratamiento con LRG permitió reducir la dosis de insulina. No registramos eventos adversos graves. El riesgo cardiovascular mejoró. Conclusiones: Bajo condiciones de práctica clínica habitual la respuesta metabólica a LRG resultó mejor que la observada en ensayos clínicos. La eficacia a las 12 semanas de tratamiento es un buen predictor de respuesta. LRG permite retrasar o reducir la insulinoterapia. Los pacientes mejoraron su riesgo cardiovascular


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Liraglutida/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos , Liraglutida/metabolismo , Estudos Retrospectivos , Estudos de Coortes , Antropometria , Insulina/uso terapêutico
18.
Diabetes Res Clin Pract ; 154: 101-115, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31238059

RESUMO

We provided an updated systematic review with meta-analysis of randomized controlled trials (RCTs) assessing the metabolic effects of combination therapy of insulin and GLP-1RA (combo) in comparison with other injectable therapy. We searched PubMed, Cochrane Register of Controlled Trials, Scholar, and ClinicalTrials.gov for RCTs evaluating changes in HbA1c (primary outcome), proportion of patients at HbA1c target <7%, hypoglycaemia, and weight change (secondary end-points). We included 36 RCTs involving 14,636 patients. Compared with comparator therapies (overall analysis), the combo led to a significant HbA1c reduction (=-0.49%, 95% CI -0.61 to -0.38%, P < 0.001), more patients at HbA1c target [relative risk, (RR) = 1.77, 95% CI, 1.56, 2.01, P < 0.001], similar hypoglycaemic events (RR = 1.03, 95% CI, 0.88, 1.19, P = 0.728), and reduction in body weight (-2.5 Kg, 95% CI -3.1 to -1.8 kg, P < 0.001), with high heterogeneity in each analysis. The quality of the evidence was low for three of the considered outcomes. Compared with intensified insulin regimens (basal-plus/basal-bolus) the combo produced similar glycemic control with reduction of both hypoglycaemia, and body weight. Combination therapy of GLP-1RA and insulin could represent a valuable treatment strategy to improve glycemic control in the management of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Quimioterapia Combinada , Humanos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Endocr Pract ; 25(9): 899-907, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31170361

RESUMO

Objective: In early type 2 diabetes (T2DM), the administration of short-term intensive insulin therapy (IIT) can induce glycemic remission for a year thereafter, but this effect ultimately wanes. In this context, intermittently repeating short-term IIT could provide a strategy for maintaining the otherwise transient benefits of this intervention. However, the viability of this strategy would be contingent upon not inducing undesirable effects of insulin therapy such as excessive hypoglycemia and fat deposition. We thus sought to evaluate the effect of administering short-term IIT every 3 months on hypoglycemia, weight gain, and quality of life in early T2DM. Methods: In this 2-year pilot trial, 24 adults with T2DM of 2.0 ± 1.7 years duration and hemoglobin A1c of 6.4 (46 mmol/mol) ± 0.1% were randomized to 3 weeks of IIT (glargine, lispro) followed by either (1), repeat IIT for up to 2 weeks every 3 months or (2), daily metformin. IIT was titrated to target near-normoglycemia (premeal glucose 4 to 6 mmol/L; 2-hour postmeal <8 mmol/L). Participants were assessed every 3 months, with quality of life (QOL) evaluated annually. Results: The rate of hypoglycemia (<3.5 mmol/L) was low in the metformin and intermittent IIT arms (0.37 versus 0.95 events per patient-year; P = .28). There were no differences between the groups in changes over time in overall, central, or hepatic fat deposition (as reflected by weight [P = .10], waist-to-hip ratio [P = .58], and alanine aminotransferase [P = .64], respectively). Moreover, there were no differences between the groups in QOL at 1- and 2-years. Conclusion: Intermittent short-term IIT may be safely administered in early T2DM without excessive adverse impact on hypoglycemic risk, anthropometry, or QOL. Abbreviations: ALT = alanine aminotransferase; HbA1c = hemoglobin A1c; IIT = intensive insulin therapy; ISSI-2 = insulin secretion-sensitivity index-2; OGTT = oral glucose tolerance test; QOL = quality of life; SF-36 = medical outcomes study 36-item short-form health survey; T2DM = type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Insulina/uso terapêutico , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada , Humanos , Hipoglicemiantes , Qualidade de Vida , Ganho de Peso
20.
Endocr Pract ; 25(9): 935-942, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31170363

RESUMO

Objective: The clinical benefit of adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to basal-bolus or very high dose insulin regimens is unclear. This study investigated the impact of adding a GLP-1RA to a spectrum of insulin regimens (basal, basal-bolus, and U-500) to determine the impact on hemoglobin A1c (HbA1c), weight loss, and total daily insulin dose (TDD) over the course of 12 months. Methods: A retrospective chart review was conducted on 113 participants with type 2 diabetes mellitus using insulin therapy. Each participant's HbA1c, body weight, and TDD were recorded prior to initiation of GLP-1RA therapy and at the 3, 6, and 12-month time points while on combination therapy. Results: Across all participants, the HbA1c values decreased significantly from a baseline of 8.9 (74 mmol/mol) ± 0.14% to 8.2 (66 mmol/mol) ± 0.14% (P<.01) in the first 3 months, 8.0 (64 mmol/mol) ± 0.12% (P<.01) at 6 months, to 8.3 (67 mmol/mol) ± 0.14% (P<.01) at 12 months. There was no significant decrease in weight or TDD with the addition of a GLP-1RA overall or in different insulin groups. However, there was a clinically significant decrease in weight over the study duration. Conclusion: The results of this study suggest that adding a GLP-1RA to various insulin regimens may help to achieve glycemic goals while avoiding the less desirable side effects of weight gain and increasing insulin regimens. However, the expected weight loss and decrease in TDD may not be as sizable in the clinical setting. Abbreviations: DCOE = Diabetes Center of Excellence; DM = diabetes mellitus; GLP-1RA = glucagon-like peptide-1 receptor agonist; HbA1c = hemoglobin A1c; RCT = randomized controlled trial; TDD = total daily dose.


Assuntos
Diabetes Mellitus Tipo 2 , Insulina/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hemoglobina A Glicada , Humanos , Hipoglicemiantes , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA