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1.
Medicina (B Aires) ; 79(4): 241-250, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487242

RESUMO

Type 2 diabetes is a chronic, progressive disease with increasing prevalence and still late diagnostic. This leads to an increase in the incidence of chronic complications, with signifi cantly increasing health costs. There is also a delay in the onset of insulin therapy in patients with type 2 diabetes for causes related to both patients and physicians. Despite advances in treatment, a low proportion of patients achieve adequate glycemic control. The high hypoglycemia prevalence, consequence of insulin, has led to the development of a new generation long-acting basal insulins to achieve a more stable and prolonged action profile, reducing the variability and risk of hypoglycemia. The EDITION program evaluated the efficacy and safety of glargine U300 compared to glargine U100 in patients with type 1 and 2 diabetes at different stages of the disease. Gla-300 is a new formulation of insulin glargine which has a more stable and prolonged pharmacokinetic and pharmacodynamic profile. Gla-300 demonstrated efficacy and tolerability comparable to glargine U100, with a significant decrease in the risk of hypoglycemia, at night and in 24 hours, providing greater flexibility in the injection schedule, with a window of 6 hours. No increase in weight was observed compared to glargine U100. Bright study (2018) compared glargine U300 vs. degludec U100, demonstrating greater benefit in relation to the risk of hypoglycemia with Gla-300 during titration period. Gla-300 is a last-generation basal insulin, available to improve metabolic control, with a lower risk of hypoglycemia.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Insulina Glargina/farmacocinética , Medicina Baseada em Evidências , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Insulina Glargina/efeitos adversos
2.
Chem Pharm Bull (Tokyo) ; 67(8): 824-838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366832

RESUMO

We synthesized and evaluated novel 5-[2-(thiophen-2-yl)propan-2-yl]-4H-1,2,4-triazole derivatives as 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors. Optimization of the thiophene ring and the substituents on the 1,2,4-triazole ring produced 3,4-dicyclopropyl-5-{2-[3-fluoro-5-(trifluoromethyl)thiophen-2-yl]propan-2-yl}-4H-1,2,4-triazole monohydrochloride (9a), which showed potent and selective inhibitory activity against human 11ß-HSD1. Compound 9a was also metabolically stable against human and mouse liver microsomes. Oral administration of 9a to diabetic ob/ob mice lowered corticosterone levels in adipose tissue, and thereby reduced plasma glucose and insulin levels in a dose-dependent manner.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/farmacologia , Triazóis/farmacologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Administração Oral , Animais , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Células HEK293 , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Masculino , Camundongos , Camundongos Obesos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/administração & dosagem , Triazóis/química
3.
JAMA ; 322(4): 326-335, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31334795

RESUMO

Importance: Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown. Objectives: To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke. Design, Setting, and Participants: The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria. Interventions: Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity. Results: Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 529 [46%] women, 920 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08], P = .55; unadjusted risk difference, -0.83% [95% CI, -5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]). Conclusions and Relevance: Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT01369069.


Assuntos
Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Acidente Vascular Cerebral/complicações , Idoso , Isquemia Encefálica/complicações , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hiperglicemia/complicações , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Infusões Intravenosas , Injeções Subcutâneas , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
4.
Medicine (Baltimore) ; 98(30): e16575, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348290

RESUMO

BACKGROUND: Dapagliflozin, a novel inhibitor of sodium-glucose cotransporter-2 (SGLT-2), lowers blood glucose level by specifically inhibiting the activity of SGLT-2. Previous studies showed efficacy and safety of dapagliflozin combined with other antihyperglycemic agents in type 2 diabetes (T2DM), however, there are few studies for dapagliflozin as monotherapy. The aim of this study was to assess the efficacy and safety of dapagliflozin as a monotherapy in T2DM and provide theoretical basis for clinical rational use of drugs. METHODS: We did a systematic review and meta-analysis of randomized, placbo-controlled clinical studies in patients with type 2 diabetes. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database through October 2018, we also manually screened list of references to the previous meta-analysis of dapagliflozin in the treatment of type 2 diabetes. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. A meta-analysis was conducted by using RevMan 5.3 software. RESULTS: Six randomized controlled trials (RCTs) including 2033 patients were analyzed. Compared with placebo, dapagliflozin monotherapy was associated with a reduction in glycosylated hemoglobin A1c (HbA1c) (weighted mean difference [WMD]: -0.60%; 95% confidence interval [CI]: -0.67%, -0.52%; P < .00001), fasting plasam glucose (FPG) (WMD: -1.30 mmol/L; 95% CI: -1.52, -1.08; P < .00001), and body weight (WMD: -1.50 kg; 95% CI: -1.67, -1.32; P < .00001). Dapagliflozin was associated with an increased risk of urinary tract infections (relative risk [RR]: 1.74; 95% CI: 1.21, 2.49; P = .003) and genital tract infections (RR: 3.52; 95% CI: 2.06, 6.03; P < .00001). CONCLUSIONS: Dapagliflozin monotherapy was well tolerated and effective in reducing the level of HbA1c, FPG, and body weight in patients with T2DM without increasing hypoglycaemia, although it may increase the risk of urinary tract infections and genital tract infections. This meta-analysis provides an evidence for the treatment in patients with T2DM. However, more randomized clinical evidences are still needed to verify the results.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Hemoglobina A Glicada , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
5.
Chem Commun (Camb) ; 55(61): 8975-8978, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31290492
6.
Expert Opin Drug Saf ; 18(8): 691-701, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31150300

RESUMO

INTRODUCTION: Oral antidiabetic medications are important in many type 2 diabetes care plans. AREAS COVERED: The article summarizes the cardiovascular and renal safety data for DPP-4 inhibitors and SGLT-2 inhibitors and specific safety data particular to each class. EXPERT OPINION: DPP-4 and SGLT-2 inhibitors provide unique anti-hyperglycemic mechanisms. The cardiovascular safety profiles of DPP-4 inhibitors are promising, but do not show the strong CV risk reduction of empagliflozin and canagliflozin. The heart failure signal associated with DPP-4 inhibitor use is unclear with differing agents, demonstrating increased risk or maybe even protective effects. The risk reduction in cardiovascular disease associated with SGLT-2 inhibitors has translated to recommendations to consider these therapies early in the treatment pathway. Both classes have potential safety concerns that necessitate appropriate patient selection and thorough education on potential side-effects. DPP-4 inhibitors are considered to have neutral or in some studies beneficial renoprotective effects. SGLT-2 inhibitor safety effects on the kidney are more complex. There are reports of acute kidney injury occurring soon after initiating SGLT-2 inhibitor therapy. However, there are large recent studies that have demonstrated the beneficial effect of SGLT-2 inhibitors in slowing the progression of established chronic kidney disease.


Assuntos
Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Hipoglicemiantes/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Administração Oral , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Canagliflozina/administração & dosagem , Canagliflozina/efeitos adversos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Seleção de Pacientes , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
7.
J Nanobiotechnology ; 17(1): 74, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159842

RESUMO

BACKGROUND: Diabetes is one of the biggest medical challenges worldwide. The key to efficiently treat type 1 diabetes is to accurately inject insulin according to the blood glucose levels. In this study, we aimed to develop an intelligent insulin-releasing gold nanocluster system that responds to environmental glucose concentrations. RESULTS: We employed gold nanoclusters (AuNCs) as a novel carrier nanomaterial by taking advantage of their high drug-loading capacity. We prepared AuNCs in the protection of bovine serum albumin, and we decorated AuNCs with 3-aminophenylboronic acid (PBA) as a glucose-responsive factor. Then we grafted insulin onto the surface to obtain the glucose-responsive insulin-releasing system, AuNC-PBA-Ins complex. The AuNC-PBA-Ins complex exhibited high sensitivity to glucose concentration, and rapidly released insulin in high glucose concentration in vitro. In the type 1 diabetic mouse model in vivo, the AuNC-PBA-Ins complex effectively released insulin and regulated blood glucose level in the normoglycemic state for up to 3 days. CONCLUSIONS: We successfully developed a phenylboronic acid-functionalized gold nanocluster system (AuNC-PBA-Ins) for responsive insulin release and glucose regulation in type 1 diabetes. This nanocluster system mimics the function of blood glucose regulation of pancreas in the body and may have potential applications in the theranostics of diabetes.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Ouro/química , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Nanopartículas Metálicas/química , Animais , Glicemia/análise , Ácidos Borônicos/química , Bovinos , Hipoglicemiantes/química , Insulina/química , Masculino , Camundongos Endogâmicos C57BL , Soroalbumina Bovina/química
8.
N Engl J Med ; 381(9): 841-851, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31185157

RESUMO

BACKGROUND: Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide. METHODS: We assessed cardiovascular outcomes of once-daily oral semaglutide in an event-driven, randomized, double-blind, placebo-controlled trial involving patients at high cardiovascular risk (age of ≥50 years with established cardiovascular or chronic kidney disease, or age of ≥60 years with cardiovascular risk factors only). The primary outcome in a time-to-event analysis was the first occurrence of a major adverse cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The trial was designed to rule out 80% excess cardiovascular risk as compared with placebo (noninferiority margin of 1.8 for the upper boundary of the 95% confidence interval for the hazard ratio for the primary outcome). RESULTS: A total of 3183 patients were randomly assigned to receive oral semaglutide or placebo. The mean age of the patients was 66 years; 2695 patients (84.7%) were 50 years of age or older and had cardiovascular or chronic kidney disease. The median time in the trial was 15.9 months. Major adverse cardiovascular events occurred in 61 of 1591 patients (3.8%) in the oral semaglutide group and 76 of 1592 (4.8%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.57 to 1.11; P<0.001 for noninferiority). Results for components of the primary outcome were as follows: death from cardiovascular causes, 15 of 1591 patients (0.9%) in the oral semaglutide group and 30 of 1592 (1.9%) in the placebo group (hazard ratio, 0.49; 95% CI, 0.27 to 0.92); nonfatal myocardial infarction, 37 of 1591 patients (2.3%) and 31 of 1592 (1.9%), respectively (hazard ratio, 1.18; 95% CI, 0.73 to 1.90); and nonfatal stroke, 12 of 1591 patients (0.8%) and 16 of 1592 (1.0%), respectively (hazard ratio, 0.74; 95% CI, 0.35 to 1.57). Death from any cause occurred in 23 of 1591 patients (1.4%) in the oral semaglutide group and 45 of 1592 (2.8%) in the placebo group (hazard ratio, 0.51; 95% CI, 0.31 to 0.84). Gastrointestinal adverse events leading to discontinuation of oral semaglutide or placebo were more common with oral semaglutide. CONCLUSIONS: In this trial involving patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo. (Funded by Novo Nordisk; PIONEER 6 ClinicalTrials.gov number, NCT02692716.).


Assuntos
Doenças Cardiovasculares/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Hipoglicemiantes/administração & dosagem , Administração Oral , Idoso , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Feminino , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Risco
11.
BMC Complement Altern Med ; 19(1): 136, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215434

RESUMO

BACKGROUND: Tomato fruit (Lycopersicon esculentum Mill.) has been suggested to be useful for the prevention of diabetes. Esculeoside A is the main saponin compounds in tomatoes. This study investigated the hypoglycemic effects and the underlying mechanism of esculeoside A in C57BLKS/Leprdb (db/db) mice. METHODS: Wild-type C57BLKS (db/dm) mice were used in the db/dm mouse group and db/db mice were randomly divided into 2 groups: untreated and treated db/db mouse groups. Esculeoside A (100 mg/kg) was administered by gavage for 56 days to the treated db/db mouse group. Distilled water was administered to the db/dm mouse group and the untreated db/db mouse group. The blood and liver biochemical parameters and the expression of liver insulin signaling-related proteins were examined. RESULTS: The results showed that esculeoside A reduced the fasting blood glucose (FBG) levels and improved the glucose tolerance. Further investigation revealed that hepatic protein expressions of total AMP-activated protein kinase (T-AMPK), phosphorylated AMP-activated protein kinase (p-AMPK), insulin receptor substrate-1 (IRS-1), and glucokinase (GCK) were significantly upregulated after esculeoside A treatment. In contrast, the hepatic protein expression of phosphoenolpyruvate carboxykinase (PEPCK) was significantly downregulated by esculeoside A treatment. CONCLUSION: These findings suggested that esculeoside A has a potential of alleviating the metabolic abnormalities in db/db mice via regulation of AMPK/IRS-1 pathway. Our findings supported a possible application of esculeoside A as a functional supplement for diabetes treatment.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Proteínas Substratos do Receptor de Insulina/genética , Sapogeninas/administração & dosagem , Proteínas Quinases Ativadas por AMP/genética , Animais , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Glucoquinase/genética , Glucoquinase/metabolismo , Humanos , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Regulação para Cima
12.
N Engl J Med ; 380(23): 2215-2224, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167051

RESUMO

BACKGROUND: We previously reported that a median of 5.6 years of intensive as compared with standard glucose lowering in 1791 military veterans with type 2 diabetes resulted in a risk of major cardiovascular events that was significantly lower (by 17%) after a total of 10 years of combined intervention and observational follow-up. We now report the full 15-year follow-up. METHODS: We observationally followed enrolled participants (complete cohort) after the conclusion of the original clinical trial by using central databases to identify cardiovascular events, hospitalizations, and deaths. Participants were asked whether they would be willing to provide additional data by means of surveys and chart reviews (survey cohort). The prespecified primary outcome was a composite of major cardiovascular events, including nonfatal myocardial infarction, nonfatal stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, and death from cardiovascular causes. Death from any cause was a prespecified secondary outcome. RESULTS: There were 1655 participants in the complete cohort and 1391 in the survey cohort. During the trial (which originally enrolled 1791 participants), the separation of the glycated hemoglobin curves between the intensive-therapy group (892 participants) and the standard-therapy group (899 participants) averaged 1.5 percentage points, and this difference declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a period of 15 years of follow-up (active treatment plus post-trial observation), the risks of major cardiovascular events or death were not lower in the intensive-therapy group than in the standard-therapy group (hazard ratio for primary outcome, 0.91; 95% confidence interval [CI], 0.78 to 1.06; P = 0.23; hazard ratio for death, 1.02; 95% CI, 0.88 to 1.18). The risk of major cardiovascular disease outcomes was reduced, however, during an extended interval of separation of the glycated hemoglobin curves (hazard ratio, 0.83; 95% CI, 0.70 to 0.99), but this benefit did not continue after equalization of the glycated hemoglobin levels (hazard ratio, 1.26; 95% CI, 0.90 to 1.75). CONCLUSIONS: Participants with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had a lower risk of cardiovascular events than those who received standard therapy only during the prolonged period in which the glycated hemoglobin curves were separated. There was no evidence of a legacy effect or a mortality benefit with intensive glucose control. (Funded by the VA Cooperative Studies Program; VADT ClinicalTrials.gov number, NCT00032487.).


Assuntos
Glicemia/análise , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/sangue , Feminino , Seguimentos , Humanos , Hiperglicemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Veteranos
13.
Ter Arkh ; 91(4): 62-66, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31094478

RESUMO

AIM: To estimate clinical significance of lipohypertrophy (LH) without visual and palpable changes, detected by ultrasonography of subcutaneous fat. MATERIALS AND METHODS: This study included 140 diabetic patients who received insulin in basal-bolus regimen. Ultrasonography of subcutaneous fat was performed for LH diagnostics in these diabetic patients. Than clinical significance of LH without visual and palpable changes was estimated. HbA1c level, fasting and postprandial glucose, episodes of hypoglycemia, body mass index (BMI) and scheme of insulinotherapy were evaluated at the moment of LH, after 3 and 6 months in all patients. RESULTS: After changing injection sites, good results were demonstrated by measuring glucose and HbA1c level. Thus fasting glucose decreased from 9.03±1.98 mmol/l to 7.11±0.95 mmol/l (p=0.023). Postprandial glucose reduced from 10.27±2.72 mmol/l to 9.34±1.21 mmol/l (p=0.011). HbA1c level reduced from 9.27±1.75% to 7.43±1.02% (p=0.002). Also BMI decreased from 33.75±3.49 kg/m2 to 30.5±2.96 kg/m2 (p=0.018). CONCLUSION: LH without visual and palpable changes could worsen compensation of glycemic control and leads to hypoglycemia and chronic Somogyi rebound. So, LH without visual and palpable is as important and clinically significant as classic LH.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Lipodistrofia/induzido quimicamente , Gordura Subcutânea/diagnóstico por imagem , Ultrassonografia/métodos , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Lipodistrofia/sangue
14.
Int J Nanomedicine ; 14: 3055-3067, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118622

RESUMO

Purpose: The aim of this research was to develop a phospholipid complex based nanoemulsion system for oral insulin delivery. Methods: Insulin-phospholipid complex (IPC) was firstly prepared by an anhydrous co-solvent lyophilization method, and then encapsulated into the oil phase of nanoemulsion to obtain the IPC-based nanoemulsion (IPC-NE). Both water-in-oil (W/O) IPC-NE and oil-in-water (O/W) IPC-NE were formulated and evaluated for comparison. Results: The obtained W/O IPC-NE and O/W IPC-NE were both spherical in shape with a mean particle size of 18.6±0.79 nm and 27.3±1.25 nm, respectively. While both IPC-NEs exhibited enhanced Caco-2 cell monolayers permeability than IPC and insulin solution, W/O IPC-NE showed relatively greater protective effects against enzymatic degradation than O/W IPC-NE. Moreover, oral administration of W/O IPC-NE exhibited significant hypoglycemic effects, with 12.4-fold and 1.5-fold higher oral bioavailability compared with insulin solution and O/W IPC-NE, respectively. Conclusion: IPC-NEs, especially the W/O IPC-NE showed promising efficiency in vitro and in vivo, thus could be a potential strategy for oral insulin delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Insulina/administração & dosagem , Nanopartículas/química , Fosfolipídeos/química , Administração Oral , Animais , Transporte Biológico/efeitos dos fármacos , Glicemia/metabolismo , Células CACO-2 , Morte Celular/efeitos dos fármacos , Portadores de Fármacos , Liberação Controlada de Fármacos , Emulsões/administração & dosagem , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/farmacocinética , Insulina/farmacologia , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Permeabilidade , Ratos Sprague-Dawley , Suínos , Difração de Raios X
15.
Vnitr Lek ; 65(4): 248-255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091943

RESUMO

Insulin pump therapy represents nowadays the way of insulin administration most similar to the physiological insulin secretion. This form of intensified insulin regime is used mostly (but not exclusively) in type 1 diabetes patients. Insulin pump therapy can be efficiently combined with continuous glucose monitoring. Even there are available insulin pumps which can serve as continuous glucose monitoring signal receiver themselves and are capable to stop automatically basal insulin infusion to prevent hypoglycemia. By this technological combination it is possible to reach near normoglycemia without increasing the risk of severe hypoglycemia. In the Czech Republic this therapy is covered by insurance when defined indication criteria are fulfilled. To reach this therapy full potential the patient as well as the professionals must be trained properly to know all technical aspects of this therapy as well as it is necessary to gain further knowledge. Particularly important is knowledge on food nutrition content and on the glycemic effect of different meals. All these factors are discussed in details in the paper.


Assuntos
Automonitorização da Glicemia , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Glicemia , República Tcheca , Diabetes Mellitus Tipo 1/tratamento farmacológico , Educação Médica , Metas , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Médicos
16.
Diabetes Res Clin Pract ; 152: 111-118, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31121275

RESUMO

AIMS: In 2016 intermittently scanned continuous glucose monitoring (isCGM) became the first reimbursed CGM system in Belgium. Many children with type 1 diabetes (T1D) treated with multiple daily injections as well as with continuous subcutaneous insulin infusion (CSII) switched from self-monitoring of blood glucose to isCGM to monitor their treatment. In 2017 the Enlite® real-time CGM (rtCGM) system was reimbursed enabling its use with the Minimed® 640G insulin pump with integrated SmartGuard technology. In this study we compared the metabolic control during CSII with isCGM with that during rtCGM. Patient's satisfaction and side effects of the rtCGM system were also evaluated. METHODS: 20 children with T1D, aged 5-16 years, were included. Metabolic control during the last month of isCGM use was compared to that during the 3rd and 6th month of rtCGM. RESULTS: Three patients stopped early rtCGM mainly due to calibration burden. The HbA1c level and the mean glucose value in the other patients did not change after switching to the rtCGM system. Glucose variability was smaller (46.2% vs 38.4% and 36.4%, p = 0.000). Time in hypoglycemia (<70 mg/dl) was lower (7.4% vs 1.6% and 1.5%, p = 0.000). The main patient inconvenience was the sensor calibration. CONCLUSIONS: Our data show that during Enlite® rtCGM with the Minimed® 640G pump system glucose variability was smaller and the patients spent less time in hypoglycemia than during isCGM. The need for timely calibrations is considered as the main drawback of the system.


Assuntos
Análise Química do Sangue/métodos , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adolescente , Bélgica , Glicemia/metabolismo , Automonitorização da Glicemia/métodos , Criança , Pré-Escolar , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas , Masculino
17.
Int J Clin Pharmacol Ther ; 57(8): 393-401, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31131826

RESUMO

OBJECTIVE: Managing hypertension to prevent complications in patients with diabetes requires appropriate pharmacotherapy. This study aimed to analyze healthcare provider factors influencing prescriptions of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) as the first-line therapy in managing hypertension among patients with diabetes in primary care. MATERIALS: This study used National Health Insurance Claims Data in Korea. METHODS: We calculated the prescription rate of angiotensin-converting enzyme inhibitors (ACE inhibitors) or ARBs by dividing the number of patients prescribed an ACE inhibitor or an ARB by the number of patients with diabetes prescribed hypoglycemic agents and antihypertensive agents. We performed a logistic regression to investigate the factors influencing the prescription rate of ACE inhibitors or ARBs. RESULTS: The mean prescription rate of ACE inhibitors or ARBs was 69.8%. The prescription rate of ACE inhibitors or ARBs decreased with increasing physician and patient age. The rate was higher for male patients than for females. The rate was higher in institutions with a greater number of physicians and among internists than among general practitioners, surgery-related and internal medicine-related specialists. The rate was significantly influenced by the mean monthly number of patients with hypertension per medical institution, the number of physicians per medical institution, and the physician's age and specialty. CONCLUSION: The age and specialty of the prescribing physician influenced the use of ACE inhibitors or ARBs in patients with diabetes and hypertension in primary care. Efforts are needed to promote information exchange among physicians and the appropriate prescriptions of antihypertensive agents in patients with diabetes and hypertension in primary care.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Diabetes Mellitus , Hipertensão/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Fatores Etários , Feminino , Humanos , Hipertensão/complicações , Hipoglicemiantes/administração & dosagem , Masculino , República da Coreia , Especialização
18.
J Agric Food Chem ; 67(21): 5957-5967, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31066268

RESUMO

d- chiro-Inositol (DCI) is a biologically active component found in tartary buckwheat, which can reduce hyperglycemia and ameliorate insulin resistance. However, the mechanism underlying the antidiabetic effects of DCI remains largely unclear. This study investigated the effects and underlying molecular mechanisms of DCI on hepatic gluconeogenesis in mice fed a high fat diet and saturated palmitic acid-treated hepatocytes. DCI attenuated free fatty acid uptake by the liver via lipid trafficking inhibition, reduced diacylglycerol deposition, and hepatic PKCε translocation. Thus, DCI could improve insulin sensitivity by suppressing hepatic gluconeogenesis. Subsequent analyses revealed that DCI decreased hepatic glucose output and the expression levels of PEPCK and G6 Pase in insulin resistant mice through PKCε-IRS/PI3K/AKT signaling pathway. Likewise, such effects of DCI were confirmed in HepG2 cells with palmitate-induced insulin resistance. These findings indicate a novel pathway by which DCI prevents hepatic gluconeogenesis, reduces lipid deposition, and ameliorates insulin resistance via regulation of PKCε-PI3K/AKT axis.


Assuntos
Fígado Gorduroso/tratamento farmacológico , Inositol/administração & dosagem , Resistência à Insulina , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Quinase C-épsilon/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Proteína Quinase C-épsilon/genética , Proteínas Proto-Oncogênicas c-akt/genética
19.
BMC Health Serv Res ; 19(1): 284, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053136

RESUMO

BACKGROUND: In the UK, type 2 diabetes mellitus (T2D) is largely managed in primary care. Delay in the intensification to injectable therapy, a form of clinical inertia, is associated with worse glycaemic control. UK general practice is highly computerised, with care being recorded on computerised medical record systems; this allows for quantitative analysis of clinical care but not of the underpinning decision-making process. The aim of this study is to investigate perceptions of patients and clinicians in primary care on the initiation of injectable therapies in T2D, and the context within which those decisions are made. METHODS: This is a mixed methods study, taking a "realist evaluation" approach. The qualitative components comprise focus groups, interviews, and video recordings of simulated surgeries; the quantitative analysis: an overview of participating practices, elements of the video recording, and an online survey. We will recruit primary care clinicians (general practitioners and nurses) and patients from a representative sample of practices within the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network. Participants will be patients with T2D, and primary care clinicians. Focus groups and semi-structured interviews will be recorded, transcribed verbatim and analysed using Framework Analysis. The simulated surgeries will include cases that might be escalated to injectable therapy. The consultation will be reviewed using the Calgary-Cambridge model to assess communication and determination of adherence to national prescribing guidelines. We will conduct multi-channel video recording including screen capture, clinician and patient facial expressions, wide angle view of the consultation, and the computerised medical record screen. This allows annotation and qualitative analysis of the video recordings, and statistical analyses for the quantitative data. We will also conduct an online survey of primary care clinicians' attitudes to, and perceptions of, initiation of injectable therapies, which will be analysed using summary statistics. DISCUSSION: Results aim to provide a detailed insight into the dynamic two-way decision-making process underpinning use of injectable therapy for T2D. The study will provide insights into clinical practice and enable the development of training, interventions and guidelines that may facilitate, where appropriate, the intensification to injectable therapy.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Tomada de Decisão Clínica , Grupos Focais , Humanos , Injeções , Atenção Primária à Saúde/normas , Pesquisa Qualitativa
20.
Pharm Res ; 36(7): 99, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31087188

RESUMO

PURPOSE: To design and stabilize Liraglutide loaded poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) proper for oral administration. METHODS: PLGA NPs were prepared by means of double emulsion solvent evaporation method and optimized by applying 7-factor 2-level Plackett-Burman screening design. RESULTS: Spherical shaped NPs with homogeneous distribution, 188.95 nm particle size and 51.81% encapsulation efficiency were obtained. Liraglutide was successfully entrapped in the NPs while maintaining its native amorphous nature, and its structural integrity as well. CONCLUSION: Lira-PLGA NPs with the required Critical Quality Attributes (CQAs) were successfully designed by implementing a 7-factor 8-run Plackett Burman design into the extended Quality by Design (QbD) model, to elucidate the effect of formulation and process variables on the particle size, size-distribution, encapsulation efficiency and surface charge. As the developed nanoparticles maintained the native structure of the active pharmaceutical ingredient (API), they are promising compositions for the further development for the oral delivery of Lira. Graphical Abstract.


Assuntos
Portadores de Fármacos/química , Hipoglicemiantes/química , Liraglutida/química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Administração Oral , Liberação Controlada de Fármacos , Emulsões , Hipoglicemiantes/administração & dosagem , Liraglutida/administração & dosagem , Tamanho da Partícula
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