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1.
Rev Med Liege ; 75(1): 60-66, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31920046

RESUMO

The shift to injection therapy, after failure of oral antidiabetic agents, is often considered as a difficult step by both the patient with type 2 diabetes and the physician, a situation that may lead to clinical inertia. Schematically, two options may be considered, either starting insulin therapy with a preference for basal insulin analogues, or adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA). Each option has its advantages and disadvantages, which opens the road to personalized medicine. Nevertheless, the preference is increasingly given to GLP-1 AR, yet this solution is more limited by reimbursement conditions. A combination of the two approaches is also possible, with the recent commercialisation of fixed-ratio specialities combining a basal insulin analogue and a GLP-1 RA. This clinical case offers the opportunity to discuss all these different therapeutic options in a patient with poorly controlled type 2 diabetes despite a combination of oral antidiabetic agents, taking also into account the current conditions for reimbursement in Belgium.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Administração Oral , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem
2.
Internist (Berl) ; 61(1): 102-109, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31863132

RESUMO

The artificial pancreas (also referred to as closed-loop system) brings us one step closer to the decade-long dream of automated insulin delivery. The closed-loop system directs subcutaneous insulin delivery corresponding to the glucose concentration using a control algorithm. Evidence shows that closed-loop systems substantially improve glucose control and quality of life; however, fully automated closed-loop systems have not yet been accomplished. Active input from patients is required for mealtime insulin dosing and corrections. This article provides an overview on the current state of development of the artificial pancreas in the treatment of diabetes.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Insulina/uso terapêutico , Pâncreas Artificial , Algoritmos , Humanos , Hipoglicemia/prevenção & controle , Qualidade de Vida
3.
Braz J Med Biol Res ; 53(1): e8652, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31859911

RESUMO

Glycemic variability (GV) may be linked to the development of diabetic complications by inducing inflammation, oxidative stress, and endothelial dysfunction. Flash glucose monitoring (FGM) provides a novel method of continuously monitoring interstitial glucose levels for up to 14 days. This study randomly assigned poorly controlled type 2 diabetes mellitus patients treated with metformin and multiple daily injections of insulin (n=60) to either continuous subcutaneous insulin infusion (CSII) treatment or CSII in combination with liraglutide (CSII+Lira) treatment for 14 days during hospitalization. GV was assessed using a FGM system; weight and cardiometabolic biomarkers were also evaluated. The coefficient of variation was significantly reduced in the CSII+Lira group (P<0.001), while no significant change was observed in the CSII group. The changes differed significantly between the two groups in mean amplitude of glycemic excursions (P=0.004), standard deviation (P=0.006), and the percentage of time in the target range (4-10 mmol/L, P=0.005 and >10 mmol/L, P=0.028). The changes in mean of daily differences, interquartile range, and percentage of time in hypoglycemia (<3.3 mmol/L) and hyperglycemia (>13.9 mmol/L) identified by FGM showed no difference. Treatment with liraglutide increased serum adiponectin [33.5 (3.5, 47.7) pg/mL, P=0.003] and heme oxygenase-1 levels [0.4 (-0.0, 1.8) ng/mL, P=0.001] and reduced serum leptin levels [-2.8 (3.9) pg/mL, P<0.001]. Adding the glucagon-like peptide-1 analog liraglutide improved GV, weight, and some cardiometabolic risk markers. The FGM system is, therefore, shown to be a novel and useful method for glucose monitoring.


Assuntos
Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Liraglutida/administração & dosagem , Adulto , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto
6.
Georgian Med News ; (294): 72-76, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687953

RESUMO

Dysbacteriosis of the oral cavity is known to complicate the course of chronic catarrhal gingivitis resulting from functional disorders of the macroorganism ecosystem, decreased amount of probiotic and increased amount of opportunistic and pathogenic microflora. And natural immune response is activated first in this case. It differentiates pathogens by TLR. The aim - to enhance the efficacy of treatment of chronic catarrhal gingivitis in children suffering from type 1 diabetes mellitus by means of improving the methods of pharmacological correction on the basis of investigation of the indices of local natural immune response and microbiological properties of the disease. We formed 2 group of the study. Children received basic insulin therapy. The treatment of chronic catarrhal gingivitis in children from the main group were suggested the antiseptic solution "Decasan"; pill of a probiotic action "BioGaia ProDentis" and the immune modulator "Imupret". Children from the comparative group were treated according to the common scheme. Oral microflora of children after treatment was decreased by 69,42% of general microbial number in children from the main group. Natural immunity state was also indicative of the improved protective mechanisms of the oral cavity in children from the main subgroup in the dynamics of treatment: twice as less level of mRNA TLR-2 expression was found in the main subgroup and mRNA TLR-4 - 45,44%. Therefore, the initiated course of treatment concerning chronic catarrhal gingivitis promoted a considerable improvement of the periodontal tissue state in children.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Gengivite/imunologia , Gengivite/microbiologia , Doenças Periodontais/patologia , Anti-Infecciosos Locais/uso terapêutico , Criança , Comorbidade , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Ecossistema , Gengivite/tratamento farmacológico , Gengivite/epidemiologia , Humanos , Insulina/administração & dosagem , Doenças Periodontais/complicações , Doenças Periodontais/epidemiologia , Probióticos/administração & dosagem
7.
Pan Afr Med J ; 33: 309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692777

RESUMO

Introduction: Adherence to insulin therapy is a critical factor for adequate control of diabetes mellitus. Despite the multiple well-known benefits of adherence to insulin therapy, poor adherence remains to be a common cause of diabetes mellitus-related complications. A better management of diabetes mellitus requires determining the level of patient adherence and identifying why non-adherence to insulin therapy occurs. Therefore, this study was designed to assess the level of adherence to insulin therapy and associated factors among diabetes mellitus patients. Methods: The study was conducted from May 1 to July 1, 2018, using a cross-sectional study design. Interviewer-administered questionnaire was employed for data collection and systematic random sampling technique was used to select study participants. The collected data were entered using Epi data version 3.1.1 and exported to SPSS version 22 for analysis. Logistic analysis was carried out to check the level of association between adherence to insulin therapy and the independent variables with significance level of 0.05 at 95% confidence interval. Results: 273 respondents were selected with a 100% response rate. Near to one-fourth (24.2%) of the respondents were adherent to their insulin therapy. The study revealed that good knowledge of diabetes mellitus [AOR=6.51; 95% CI [1.58, 26.71], age [>30 years] [AOR=2.63; 95% CI [1.27, 5.42], knowledge regarding insulin self-injection [AOR=4.21; 95%CI [1.06,16.65], favorable attitude towards insulin injection [AOR=2.14; 95% CI [1.04,4.41], free-of-cost insulin therapy [AOR= 4.62, 95% CI [1.06,16.65], having of glucometer at home [AOR= 2.82, 95% CI [1.12,7.09], and being a member of Ethiopian diabetic association [AOR= 5.41, 95% CI [2.31,12.64] were found to significantly affect adherence to insulin therapy. Conclusion: Nearly one-fourth of the study participants were adherent to their insulin therapy. Good knowledge and favorable attitude towards insulin injection, good knowledge regarding diabetes mellitus, being a member of the Ethiopian Diabetes Association, age greater than thirty years old, free-of-cost insulin therapy and having glucometer at home were found to be significant predictors of adherence to insulin therapy.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Etiópia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hospitais Públicos , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Autoadministração , Inquéritos e Questionários , Adulto Jovem
8.
Pan Afr Med J ; 33: 322, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31692874

RESUMO

Introduction: Diabetic ketoacidosis (DKA) is a severe metabolic complication of diabetes. Recent years have seen a marked increase in prevalence of diabetic ketoacidosis, but mortality is low. This study aimed to describe the epidemiological, clinical, therapeutic and prognostic features of patients with severe or moderate DKA admitted to the Emergency Department. Methods: He conducted a prospective, descriptive study including patients with moderate or severe DKA. Standardized care protocol. We studied the epidemiological, clinical, therapeutic and prognostic features of these patients. Results: The study involved 185 patients with moderate or severe DKA. The average age of patients was 38+/-18 years, with a sex ratio of 0.94. Known diabetes was reported in 159 patients (85%) of whom 116 had type 1 diabetes. The most common factors of decompensation were treatment discontinuation in 42% and infection in 32%. Average blood glucose was 32.7+/-12 mmol/L, pH =7.14+/-0.13, HCO3- =7.2+/-3.56 mmol/L. The mean duration of intravenous insulin was 17.3 +/- 16 hours. Hypoglycaemia was reported in 26 patients (14%), hypokalemia in 80 (43%) patients and hyperchloraemic mineral acidosis in 43 patients (23%). Intrahospital mortality was 2.1%. Conclusion: Diabetic ketoacidosis occurs in young subjects treated with insulin therapy. Treatment is based on intravenous insulin associated with correction of fluid deficit. Complications mainly include hypokalemia and hypoglycemia and mortality is low.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Cetoacidose Diabética/epidemiologia , Insulina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Cetoacidose Diabética/tratamento farmacológico , Serviço Hospitalar de Emergência , Feminino , Humanos , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Hipoglicemiantes/administração & dosagem , Hipopotassemia/epidemiologia , Hipopotassemia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
9.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(9): 534-539, nov. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-184375

RESUMO

Objetivo: Menos de un tercio de los pacientes con diabetes tipo 1 (DT1) consiguen el objetivo de punto de corte establecido como control metabólico óptimo (HbA1c < 7%). Sin embargo, reducciones porcentuales de HbA1c y la prevención de hipoglucemias graves (HG) han demostrado beneficios clínicamente relevantes. Por ello, el objetivo de este estudio ha sido evaluar la efectividad de la terapia con infusión subcutánea continua de insulina (ISCI) a los 5 años de seguimiento en una cohorte de pacientes de una unidad especializada mediante objetivos combinados de descenso de HbA1c y ausencia de HG. Material y métodos: Estudio observacional retrospectivo que incluye a 178 pacientes que iniciaron terapia ISCI de manera consecutiva entre los años 2003 y 2008. Se han analizado las características basales de los individuos, la HbA1c inicial y a los 5 años de tratamiento con ISCI y la presencia o no de HG. Se calcularon las variables combinadas: a) descenso de al menos 0,5 puntos de HbA1c y ausencia de HG en los últimos 2 años; b) HbA1c a los 5 años < 7,5% sin HG en los últimos 2 años; c) HbA1c < 8,5% sin HG en los últimos 2 años, y d) descenso ≥ 0,5 puntos y/o HbA1c < 7,5% a los 5 años sin presencia de HG en los 2 últimos años de seguimiento. Resultados: Veintisiete de los 178 pacientes fueron excluidos debido a pérdida del seguimiento o abandono de la terapia ISCI. Se analizó a 151 pacientes (edad 37,4 ± 10,5 años, 64% mujeres, 19,2 ± 10,7 años de evolución de la DT1). Las 2 indicaciones principales para el inicio de ISCI fueron: control metabólico subóptimo (60,9%) e HG o hipoglucemia desapercibida (28,5%). Las HbA1c de la cohorte total y de control metabólico subóptimo fueron de 8,0 ± 1,2 y 8,4 ± 1,1% al inicio de la terapia ISCI y de 7,8 ± 1,2 y 8,0 ± 1,3% a los 5 años (p = 0,104 y p = 0,016), respectivamente. En la cohorte global un 55,5% de los pacientes alcanzaron a los 5 años el objetivo combinado HbA1c < 7,5% y/o un descenso ≥ 0,5% sin HG. Conclusiones: Tras 5 años de terapia ISCI más de la mitad de nuestros pacientes consiguen el objetivo combinado de reducción significativa de HbA1c y ausencia de HG. La utilización de objetivos combinados nos ofrece la posibilidad de evaluar la efectividad de las terapias en la DT1 desde un punto de vista más cercano a su significado clínico


Objective: Less than one third of patients with type 1 diabetes mellitus (T1DM) achieve the cut-off value proposed as good metabolic control by most guidelines, HbA1c < 7%. However, HbA1c reductions and prevention of severe hypoglycemia (SH) have shown clinically relevant benefits. The study objective therefore was to assess the effectiveness of continuous subcutaneous insulin infusion (CSII) therapy at 5 years of follow-up in a cohort of patients attending a specialized unit using HbA1c reduction and abscence of SH as combined goals. Methods: A retrospective, observational study on 178 patients with T1DM who started CSII treatment at Hospital Clinic of Barcelona between 2003 and 2008. HbA1c levels at baseline and after 5 years of treatment with CSII and presence or absence of SH were recorded. The combined variables calculated included: a) HbA1c reduction by ≥ 0.5 points and absence of SH in the last 2 years; b) HbA1c at 5 years < 7.5% and no SH in the last 2 years; c) HbA1c < 8.5% and no HG in the last 2 years, and d) HbA1c reduction by ≥ 0.5 points and/or HbA1c < 7.5% at 5 years with no SH in the last 2 years of follow-up. Results: Twenty-seven of the 178 patients were excluded due to loss to follow-up or CSII discontinuation. A total of 151 patients (aged 37.4 ± 10.5 years, 64% women, diabetes duration of 19.2 ± 10.7 years) were therefore analyzed. The 2 main reasons for starting CSII were suboptimal metabolic control (60.9%) and severe hypoglycemia/hypoglycemia unawareness (28.5%). HbA1c levels in the total cohort and in patients with suboptimal metabolic control were 8.0 ± 1.2 and 8.4 ± 1.1% at CSII start and 7.8 ± 1.2 and 8.0 ± 1.3% at 5 years of treatment (P = .104 and P = .016) respectively. In the overall cohort, 55.5% of patients achieved at 5 years the combined goal of HbA1c < 7.5% and/or HbA1c reductions ≥ 0.5% without SH. Conclusions: After 5 years of CSII therapy, more than half of the patients achieved the combined goal of significant HbA1c reduction and absence of SH. The use of combined goals offers the opportunity to assess the effectiveness of T1DM treatment from a clinically more meaningful point of view


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Insulina/administração & dosagem , Sistemas de Infusão de Insulina , Hipoglicemia/diagnóstico , Hipoglicemiantes/administração & dosagem , Hipoglicemia/tratamento farmacológico , Estudos Retrospectivos
10.
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
11.
N Engl J Med ; 381(18): 1707-1717, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31618560

RESUMO

BACKGROUND: Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes. METHODS: In this 6-month randomized, multicenter trial, patients with type 1 diabetes were assigned in a 2:1 ratio to receive treatment with a closed-loop system (closed-loop group) or a sensor-augmented pump (control group). The primary outcome was the percentage of time that the blood glucose level was within the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter), as measured by continuous glucose monitoring. RESULTS: A total of 168 patients underwent randomization; 112 were assigned to the closed-loop group, and 56 were assigned to the control group. The age range of the patients was 14 to 71 years, and the glycated hemoglobin level ranged from 5.4 to 10.6%. All 168 patients completed the trial. The mean (±SD) percentage of time that the glucose level was within the target range increased in the closed-loop group from 61±17% at baseline to 71±12% during the 6 months and remained unchanged at 59±14% in the control group (mean adjusted difference, 11 percentage points; 95% confidence interval [CI], 9 to 14; P<0.001). The results with regard to the main secondary outcomes (percentage of time that the glucose level was >180 mg per deciliter, mean glucose level, glycated hemoglobin level, and percentage of time that the glucose level was <70 mg per deciliter or <54 mg per deciliter [3.0 mmol per liter]) all met the prespecified hierarchical criterion for significance, favoring the closed-loop system. The mean difference (closed loop minus control) in the percentage of time that the blood glucose level was lower than 70 mg per deciliter was -0.88 percentage points (95% CI, -1.19 to -0.57; P<0.001). The mean adjusted difference in glycated hemoglobin level after 6 months was -0.33 percentage points (95% CI, -0.53 to -0.13; P = 0.001). In the closed-loop group, the median percentage of time that the system was in closed-loop mode was 90% over 6 months. No serious hypoglycemic events occurred in either group; one episode of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS: In this 6-month trial involving patients with type 1 diabetes, the use of a closed-loop system was associated with a greater percentage of time spent in a target glycemic range than the use of a sensor-augmented insulin pump. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; iDCL ClinicalTrials.gov number, NCT03563313.).


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Pâncreas Artificial , Adolescente , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Desenho de Equipamento , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pâncreas Artificial/efeitos adversos , Adulto Jovem
12.
Int J Nanomedicine ; 14: 8059-8072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632018

RESUMO

Background: Compared with random copolymers, block copolymerization is easier to prepare for nanoparticles with core-shell structure, and they will have better glucose sensitivity and higher insulin loading. Purpose: In our study, insulin-loaded poly (3-acrylamidophenylboronic acid-block-N-vinyl caprolactam) p(AAPBA-b-NVCL) nanoparticles were successfully prepared and were glucose-sensitive, which could effectively lower the blood sugar levels within 72 hrs. Methods: The polymer of p(AAPBA-b-NVCL) was produced by reversible addition-fragmentation chain transfer polymerization based on different ratios of 3-acrylamidophenylboronic acid (AAPBA) and N-vinylcaprolactam (NVCL), and its structure was discussed by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance . Next, the polymer was manufactured into the nanoparticles, and the characteristics of nanoparticles were detected by dynamic light scattering, lower critical solution temperature, and transmission electron microscopy. After that, the cell and animal toxicity of nanoparticles were also investigated. Results: The results demonstrated that p(AAPBA-b-NVCL) was successfully synthesized, and can be easily self-assembled to form nanoparticles. The new nanoparticles included monodisperse submicron particles, with the size of the nanoparticle ranged between 150 and 300nm and are glucose- and temperature-sensitive. Meanwhile, insulin can be easily loaded by p(AAPBA-b-NVCL) nanoparticles and an effective sustained release of insulin was observed when the nanoparticles were placed in physiological saline. Besides, MTT assay revealed that cell viability was more than 80%, and mice demonstrated no negative impact on blood biochemistry and heart, liver, spleen, lung, and kidney after intraperitoneal injection of 10 mg/kg/d of nanoparticles. This suggested that the nanoparticles were low-toxic to both cells and animals. Moreover, they could lower the blood sugar level within 72h. Conclusion: Our research suggested that these p(AAPBA-b-NVCL) nanoparticles might have the potential to be applied in a delivery system for insulin or other hypoglycemic proteins.


Assuntos
Acrilamidas/química , Ácidos Borônicos/química , Caprolactama/química , Sistemas de Liberação de Medicamentos , Glucose/análise , Insulina/administração & dosagem , Nanopartículas/química , Acrilamidas/síntese química , Animais , Glicemia/metabolismo , Ácidos Borônicos/síntese química , Caprolactama/análogos & derivados , Caprolactama/síntese química , Sobrevivência Celular/efeitos dos fármacos , Feminino , Hidrodinâmica , Concentração de Íons de Hidrogênio , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Células NIH 3T3 , Nanopartículas/ultraestrutura , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Temperatura Ambiente
13.
Ned Tijdschr Geneeskd ; 1632019 09 24.
Artigo em Holandês | MEDLINE | ID: mdl-31556504

RESUMO

New technological developments have an important impact on the treatment of type 1 diabetes patients. These advancements concern the administration of insulin through an insulin pump, glucose level measurement with a sensor positioned on the skin, and the growing dynamic interactive options to link the glucose sensor and insulin pump. In this article a brief overview is provided of the existing methods, plus a summary of a study into the effect of a hybrid closed loop. Points of discussion include applicability, tolerability, long-term results and outcome measures that are most relevant to patients.


Assuntos
Automonitorização da Glicemia/instrumentação , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Masculino
14.
Artigo em Inglês | MEDLINE | ID: mdl-31514391

RESUMO

Background: Structured education is needed to cultivate safe sharp disposal behavior among diabetic patients. Thus, this study aimed to assess the effectiveness of the Diabetes Community Sharp Disposal Education Module in improving knowledge and sharp disposal practice among Malaysian Type 2 diabetic patients. Methods: This quasi-experimental study was conducted at primary health clinics in two districts in Kelantan, a state in the North-East Region of Peninsular Malaysia. A total of 132 Type 2 diabetic patients on insulin therapy were involved, with 68 participants in each control and intervention group. The health education intervention was based on the validated Diabetes Community Sharp Disposal Education Module. The knowledge and practices were measured using a validated questionnaire at baseline, one month, and three months after the intervention. Results: There was a significant increment in the mean knowledge score for intervention group; from baseline to one month follow up and from baseline to three months follow up [Greenhouse-Geisser; F(1.5, 199.7) = 62.38, p < 0.001; effect size (η2) = 0.318]. Intervention group had significantly higher mean knowledge score as compared to control group; at one month and three months follow up [F(1, 134) = 17.38, p < 0.001; effect size (η2) = 0.115]. There was a statistically significant increment in the proportion of participants in the intervention group who practiced the proper community sharp disposal method over time, X2(2) = 52.061, p < 0.001. Conclusions: The Diabetes Community Sharp Disposal Education Module was an effective health education tool to improve knowledge and encourage Malaysian diabetic patients to engage with proper sharp disposal practices.


Assuntos
Diabetes Mellitus Tipo 2 , Resíduos Perigosos , Educação em Saúde/estatística & dados numéricos , Insulina/administração & dosagem , Eliminação de Resíduos de Serviços de Saúde , Idoso , Serviços de Saúde Comunitária , Diabetes Mellitus , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Inquéritos e Questionários
15.
Artigo em Inglês | MEDLINE | ID: mdl-31546871

RESUMO

Given the fact that physical exertion leads to blood glucose fluctuations, type one diabetes mellitus (T1D) may potentially constitute a barrier for obtaining a sufficient amount of exercise. The main purpose of the study was to compare the level of physical activity between children with T1D (n = 215) and healthy controls (n = 115) and to assess the physical activity of the study group in relation to the applied method of insulin therapy, i.e., the use of insulin pen vs. insulin pump. The level of physical activity was assessed with a hip-worn tri-axial accelerometer (ActiGraph GT3X+) used by the subjects for an uninterrupted period of seven days. Children with T1D had significantly lower median values of total time of moderate (213.3 vs. 272.1 min), vigorous (135.3 vs. 19.6 min) and moderate-to-vigorous (347.4 vs. 467.4 min) physical activity compared to healthy peers respectively, (p < 0.001) in all cases. In addition, the total median number of steps was significantly lower (53,631 vs. 67,542 steps), (p < 0.001). The method of insulin therapy was not associated with significant differences in physical activity level (p > 0.001). The level of physical activity in children and adolescents with T1D is lower than in their healthy peers and does not depend on the insulin therapy method.


Assuntos
Diabetes Mellitus Tipo 1/psicologia , Exercício , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Acelerometria , Adolescente , Estudos de Casos e Controles , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Sistemas de Infusão de Insulina , Masculino , Esforço Físico , Estudos Prospectivos
16.
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
17.
Diabetes Metab Syndr ; 13(4): 2625-2631, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405686

RESUMO

AIMS: To describe real-life experience with sensor-augmented pump therapy with predictive low-glucose management (SAPT-PLGM), in terms of hypoglycemia and glycemic control after one year of follow-up in T1D patients with hypoglycemia as the main indication of therapy. METHODS: Retrospective cohort study under real life conditions. Baseline and one-year follow-up variables of glycemic control, hypoglycemia and glycemic variability were compared. RESULTS: Fifty patients were included, 31 on prior treatment with SAPT with low-glucose suspend (LGS) feature and 19 on multiple dose insulin injections (MDI). Mean HbA1c decreased in the MDI group (8.24%-7.08%; p = 0.0001). HbA1c change was not significant in the SAPT-LGS group. Area under the curve (AUC) below 70 mg/dl improved in both SAPT-LGS and MDI groups while AUC, %time and events below 54 mg/dl decreased in SAPT-LGS group. Glycemic variability improved in the MDI group. Less patients presented severe hypoglycemia with SAPT-PLGM in both groups, however the change was non-significant. CONCLUSIONS: Under real life conditions, SAPT-PLGM reduced metrics of hypoglycemia in patients previously treaded with MDI and SAPT-LGS without deteriorating glycemic control in SAPT-LGS patients, while improving it in patients treated with MDI.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina/estatística & dados numéricos , Insulina/administração & dosagem , Adolescente , Adulto , Glicemia/análise , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
18.
Acta Diabetol ; 56(12): 1283-1292, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31407113

RESUMO

AIMS: Subcutaneous administration of insulin in patients suffering from diabetes is associated with the distress of daily injections. Among alternative administration routes, the oral route seems to be the most advantageous for long-term administration, also because the peptide undergoes a hepatic first-pass effect, contributing to the inhibition of the hepatic glucose output. Unfortunately, insulin oral administration has so far been hampered by degradation by gastrointestinal enzymes and poor intestinal absorption. Loading in lipid nanoparticles should allow to overcome these limitations. METHODS: Entrapment of peptides into such nanoparticles is not easy, because of their high molecular weight, hydrophilicity and thermo-sensitivity. In this study, this objective was achieved by employing fatty acid coacervation method: solid lipid nanoparticles and newly engineered nanostructured lipid carriers were formulated. Insulin and insulin analog-glargine insulin-were entrapped in the lipid matrix through hydrophobic ion pairing. RESULTS: Bioactivity of lipid entrapped peptides was demonstrated through a suitable in vivo experiment. Ex vivo and in vivo studies were carried out by employing fluorescently labelled peptides. Gut tied up experiments showed the superiority of glargine insulin-loaded nanostructured lipid carriers, which demonstrated significantly higher permeation (till 30% dose/mL) compared to free peptide. Approximately 6% absolute bioavailability in the bloodstream was estimated for the same formulation through in vivo pharmacokinetic studies in rats. Consequently, a discrete blood glucose responsivity was noted in healthy animals. CONCLUSIONS: Given the optimized ex vivo and in vivo intestinal uptake of glargine insulin from nanostructured lipid carriers, further studies will be carried out on healthy and diabetic rat models in order to establish a glargine insulin dose-glucose response relation.


Assuntos
Portadores de Fármacos , Insulina/administração & dosagem , Lipídeos , Nanopartículas , Administração Oral , Animais , Células Cultivadas , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Humanos , Insulina/análogos & derivados , Insulina/farmacocinética , Insulina Glargina/administração & dosagem , Insulina Glargina/análogos & derivados , Insulina Glargina/farmacocinética , Lipídeos/administração & dosagem , Lipídeos/química , Lipídeos/farmacocinética , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/metabolismo , Técnicas de Cultura de Órgãos , Tamanho da Partícula , Ratos , Ratos Wistar
19.
AAPS PharmSciTech ; 20(7): 298, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31456109

RESUMO

We aimed to investigate the absorption-enhancing effect (AEE) of caproyl-modified G2 PAMAM dendrimer (G2-AC) on peptide and protein drugs via the pulmonary route. In this study, G2 PAMAM dendrimer conjugates modified with caproic acid was synthesized, the pulmonary absorption of insulin as models with or without G2-AC were evaluated. The results indicated that G2-AC6 exhibited a greatest AEE for insulin in various caproylation levels of G2-AC. G2-AC6 could significantly enhance the absorption of insulin, and the AEE of G2-AC6 was concentration-dependent. In toxicity tests, G2-AC6 displayed no measurable cytotoxicity to the pulmonary membranes over a concentration range from 0.1% (w/v) to 1.0% (w/v). Measurements of the TEER and permeability showed that G2-AC6 significantly reduced the TEER value of CF and increased its Papp value. The results suggested that G2-AC6 could cross epithelial cells by means of a combination of paracellular and transcellular pathways. These findings suggested G2-AC6 at lower concentrations (below 1.0%, w/v) might be promising absorption enhancers for increasing the pulmonary absorption of peptide and protein drugs.


Assuntos
Materiais Biocompatíveis/metabolismo , Dendrímeros/metabolismo , Insulina/metabolismo , Nanopartículas/metabolismo , Absorção pelo Trato Respiratório/fisiologia , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Dendrímeros/administração & dosagem , Dendrímeros/química , Insulina/administração & dosagem , Insulina/química , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/química , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Wistar , Absorção pelo Trato Respiratório/efeitos dos fármacos
20.
Int J Nanomedicine ; 14: 4895-4909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456636

RESUMO

Introduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally. Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE). Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, -16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, -16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups. Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.


Assuntos
Liofilização , Insulina/administração & dosagem , Polieletrólitos/química , Polietilenoglicóis/administração & dosagem , Polietilenoimina/administração & dosagem , Administração Oral , Animais , Crioprotetores/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Ponto Isoelétrico , Masculino , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Fatores de Tempo
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