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1.
J Environ Pathol Toxicol Oncol ; 38(2): 133-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679276

RESUMO

The current study is a review of the literature on patients with diabetes who are diagnosed with colorectal cancer (CRC), encompassing recent research on CRC and the molecular level changes occurring in these patients on the basis of varying environmental as well as non-environmental factors. It has been noted that nearly 50% of all patients undergo the systemic treatment module; however, most of them exhibit drug resistance. In addition, targeted gene therapy has also been used in treatment but has been found to be effective only in patients with a specified molecular profile (or else this might lead to an increased risk of developing resistant mutations). This has led to increasing interest among researchers in finding innovative treatment options. Metformin, a biguanide, has been widely used in treating diabetes. The drug has been reportedly used in cases of hypothesis-generating retrospective population studies of diabetic patients showing reduced incidence of cancer. Metformin helps in reduction of excess insulin levels that possess various effects on cell signaling and metabolism. Nonetheless, there is need for an in-depth study on its molecular mechanism to fill any existing research gaps.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias Colorretais/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Insulina/efeitos adversos , Transdução de Sinais/efeitos dos fármacos
3.
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
4.
Clin Drug Investig ; 39(12): 1213-1221, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31552641

RESUMO

BACKGROUND AND OBJECTIVE: To avoid insulin-induced hypoglycemia and weight gain, the minimum dose of insulin should be used. In this study, therefore, we examined insulin dose reduction by ipragliflozin add-on therapy in Japanese patients with type 2 diabetes mellitus treated with long-acting basal insulin. METHODS: In this multicenter, open-label study, patients received one ipragliflozin 50-mg tablet once daily in combination with basal insulin for 24 weeks. The primary efficacy endpoint was the change and percent change in insulin dose from baseline to Week 24. Secondary efficacy endpoints included changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), glycoalbumin, cholesterol, leptin, adiponectin, C-peptide, glucagon, body weight, and blood pressure, and number of patients achieving withdrawal of insulin at the end of treatment (EOT). Treatment-emergent adverse events (TEAEs) were evaluated for safety. RESULTS: In total, 114 patients were screened, 103 were registered, and 97 completed the study. The mean age was 59 years and 72.8% of patients were male. The mean change in insulin dose from baseline at Week 24 was - 6.6 ± 4.4 units/day (p < 0.001); the mean percent change was - 29.87%. HbA1c, FPG, glycoalbumin, glucagon levels, body weight, and blood pressure significantly decreased from baseline to EOT (p < 0.05). Cholesterol, leptin, and adiponectin were unaffected. One patient was able to stop insulin treatment at Week 16. The incidence of TEAEs was 60.2%. Hypoglycemia (10.7%) and pollakiuria (13.6%) were the most common drug-related TEAEs. Conclusions Once-daily 50-mg ipragliflozin enabled a 30% dose reduction of insulin by Week 24 compared with baseline. No major safety concerns were raised. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02847091).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Tiofenos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Feminino , Glucosídeos/efeitos adversos , Humanos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tiofenos/efeitos adversos
5.
PLoS Med ; 16(8): e1002848, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31386659

RESUMO

BACKGROUND: Metformin is increasingly offered as an acceptable and economic alternative to insulin for treatment of gestational diabetes mellitus (GDM) in many countries. However, the impact of maternal metformin treatment on the trajectory of fetal, infant, and childhood growth is unknown. METHODS AND FINDINGS: PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and the Cochrane database were systematically searched (from database inception to 26 February 2019). Outcomes of GDM-affected pregnancies randomised to treatment with metformin versus insulin were included (randomised controlled trials and prospective randomised controlled studies) from cohorts including European, American, Asian, Australian, and African women. Studies including pregnant women with pre-existing diabetes or non-diabetic women were excluded, as were trials comparing metformin treatment with oral glucose-lowering agents other than insulin. Two reviewers independently assessed articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Outcome measures were parameters of fetal, infant, and childhood growth, including weight, height, BMI, and body composition. In total, 28 studies (n = 3,976 participants) met eligibility criteria and were included in the meta-analysis. No studies reported fetal growth parameters; 19 studies (n = 3,723 neonates) reported measures of neonatal growth. Neonates born to metformin-treated mothers had lower birth weights (mean difference -107.7 g, 95% CI -182.3 to -32.7, I2 = 83%, p = 0.005) and lower ponderal indices (mean difference -0.13 kg/m3, 95% CI -0.26 to 0.00, I2 = 0%, p = 0.04) than neonates of insulin-treated mothers. The odds of macrosomia (odds ratio [OR] 0.59, 95% CI 0.46 to 0.77, p < 0.001) and large for gestational age (OR 0.78, 95% CI 0.62 to 0.99, p = 0.04) were lower following maternal treatment with metformin compared to insulin. There was no difference in neonatal height or incidence of small for gestational age between groups. Two studies (n = 411 infants) reported measures of infant growth (18-24 months of age). In contrast to the neonatal phase, metformin-exposed infants were significantly heavier than those in the insulin-exposed group (mean difference 440 g, 95% CI 50 to 830, I2 = 4%, p = 0.03). Three studies (n = 520 children) reported mid-childhood growth parameters (5-9 years). In mid-childhood, BMI was significantly higher (mean difference 0.78 kg/m2, 95% CI 0.23 to 1.33, I2 = 7%, p = 0.005) following metformin exposure than following insulin exposure, although the difference in absolute weights between the groups was not significantly different (p = 0.09). Limited evidence (1 study with data treated as 2 cohorts) suggested that adiposity indices (abdominal [p = 0.02] and visceral [p = 0.03] fat volumes) may be higher in children born to metformin-treated compared to insulin-treated mothers. Study limitations include heterogeneity in metformin dosing, heterogeneity in diagnostic criteria for GDM, and the scarcity of reporting of childhood outcomes. CONCLUSIONS: Following intrauterine exposure to metformin for treatment of maternal GDM, neonates are significantly smaller than neonates whose mothers were treated with insulin during pregnancy. Despite lower average birth weight, metformin-exposed children appear to experience accelerated postnatal growth, resulting in heavier infants and higher BMI by mid-childhood compared to children whose mothers were treated with insulin. Such patterns of low birth weight and postnatal catch-up growth have been reported to be associated with adverse long-term cardio-metabolic outcomes. This suggests a need for further studies examining longitudinal perinatal and childhood outcomes following intrauterine metformin exposure. This review protocol was registered with PROSPERO under registration number CRD42018117503.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Pré-Escolar , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Lactente , Recém-Nascido , Insulina/efeitos adversos , Metformina/efeitos adversos , Gravidez
6.
J Pak Med Assoc ; 69(Suppl 2)(6): S75-S79, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31369537

RESUMO

Objective: In Vietnam, prevalence of diabetes in adults is estimated at 5.5% and the total cases of diabetes in adults was over 3,5 million in 2017. Hypoglycaemia is one of the most-observed adverse reaction associated with the consumption of insulin and oral hypoglycaemia agents. The objective is to report the hypoglycaemia cases in type 2 diabetes mellitus (T2DM) patients with medication therapies attending a secondary health facility. Methods: We conducted this retrospective research on 1,006 T2DM patients at Lam Dong General Hospital, Lam Dong province in three years between 2016 and 2018 using ICD-10 code of E11. A total of 523 eligible T2DM patients were enumerated to select hypoglycaemia cases while treated with insulin therapy or oral intake of hypoglycaemia agents. Information were extracted from hospital electronic databases, sensitive information was coded. Results: Among 523 eligible T2DM patients, 92.4% (n=483) patients experienced at least one symptom of hypoglycaemia. The mean age of the selected patients was 51.2}5.2. Females were dominated by males in terms of number. Frequency of hypoglycaemia symptoms was 0-1 time per week for most of patients. The main hypoglycaemia symptoms that most of patients with T2DM suffered were sweating and drowsiness (83% and 70% respectively). Seizures, headache and loss of consciousness accounted for lowest percentages. Conclusions: The frequency of hypoglycaemia in T2DM patients in Lam Dong General Hospital was very high. Physician consideration and patient education are necessary in hypoglycaemia management.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Administração Oral , Adulto , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/fisiopatologia , Hipoglicemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Estudos Retrospectivos , Centros de Cuidados de Saúde Secundários , Vietnã/epidemiologia
8.
Aerosp Med Hum Perform ; 90(8): 735-737, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31331425

RESUMO

INTRODUCTION: Due to the risk of hypoglycemia-related incapacitation, diabetic pilots requiring insulin are assessed as unfit according to the International Civil Aviation Organization and most national authorities. Some authorities, such as those from Canada, the United Kingdom, and the United States, permit selected insulin-treated pilots (ITDM-pilots) to fly subject to a protocol requiring pre- and in-flight capillary glucose measurements to show safe levels (>100-<300 mg · dl-1). Critics of such permission question the practicability of these in-flight measurements and whether clinically desired glycemic targets can be achieved while keeping glucose levels in the safe range. Subcutaneous continuous glucose monitoring (CGM) has recently been approved by the FDA as a stand-alone method to provide accurate glucose levels and treatment decision guidance in patients. This commentary considers that use of CGM by ITDM pilots facilitates practicability and recording of in-flight glucose measurements and facilitates achievement of clinically desired glycemic targets without increasing hypoglycemia risks.Strollo F, Simons R, Mambro A, Strollo G, Gentile S. Continuous glucose monitoring for in-flight measurement of glucose levels of insulin-treated pilots. Aerosp Med Hum Perform. 2019; 90(8):735-737.


Assuntos
Medicina Aeroespacial/métodos , Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/prevenção & controle , Insulina/administração & dosagem , Medicina Aeroespacial/instrumentação , Diabetes Mellitus Tipo 2/sangue , Estudos de Viabilidade , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Insulina/efeitos adversos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Pilotos
9.
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
10.
Diabetes Metab Syndr ; 13(2): 901-903, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336543

RESUMO

Patients with acromegaly have soft tissue overgrowth that induced characteristic clinical presentation. A growth hormone-secreting adenoma of the anterior pituitary gland is the most common cause of acromegaly. Metabolic and somatic features of acromegaly caused by high serum concentrations of insulin-like growth factor-I (IGF-I) and excess growth hormone (GH) production. we present a case of 'pseudoacromegaly' with an acromegaloid features, suppressed IGF-I levels and marked elevation of serum insulin. Endocrinologists should consider this diagnosis when assessing patients with clinical features of acromegaly and insulin resistance, in the absence of elevated levels of GH and IGF-I.


Assuntos
Acromegalia/patologia , Hipoglicemiantes/efeitos adversos , Resistência à Insulina , Insulina/efeitos adversos , Acromegalia/induzido quimicamente , Acromegalia/complicações , Adulto , Feminino , Humanos , Prognóstico , Adulto Jovem
11.
J Pediatr Endocrinol Metab ; 32(8): 843-849, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31318694

RESUMO

Background To evaluate the safety of fasting during the holy month of Ramadan among children and adolescent with type 1 diabetes (T1D). Methods A retrospective cohort study of 50 children and adolescents with T1D whose mean age was 12.7 ± 2.1 years was conducted. Twenty-seven patients (54%) were on multiple daily injections (MDI) insulin regimen and 23 (46%) were on insulin pump therapy. Before fasting for Ramadan, children and their families were evaluated and educated about diabetes management during Ramadan. Hemoglobin A1c (HbA1c), weight, number of days fasted, hypoglycemia and hyperglycemia episodes, and emergency hospital visits were collected and analyzed after completing the month. Participants were compared according to the insulin treatment regimen and their glycemic control level before Ramadan. Results The children were able to fast 20 ± 9.9 days of Ramadan, and the most common cause for breaking the fast was mild hypoglycemia (7.8% among all cases). There was no significant difference between the two insulin regimen groups in breaking fast days, frequency of hypo- or hyperglycemia, weight and HbA1c changes post Ramadan. Patients with HbA1c ≤ 8.5% were able to fast more days during Ramadan with significantly less-frequent hypoglycemic attacks as compared to patients with HbA1c > 8.5 (1.2 ± 1.5 vs. 3.3 ± 2.9 days of hypoglycemia, p = 0.01, respectively). Conclusions Fasting for children with T1D above the age of 10 years is feasible and safe in both pump and non-pump users, and well-controlled patients are less likely to develop complications. Education of the families and their children before Ramadan, along with intensive monitoring of fasting children during the month are crucial.


Assuntos
Peso Corporal , Diabetes Mellitus Tipo 1/tratamento farmacológico , Jejum/efeitos adversos , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Sistemas de Infusão de Insulina/efeitos adversos , Insulina/administração & dosagem , Adolescente , Biomarcadores/análise , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/epidemiologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Incidência , Insulina/efeitos adversos , Islamismo , Kuweit/epidemiologia , Masculino , Prognóstico , Estudos Retrospectivos
12.
Diab Vasc Dis Res ; 16(4): 385-395, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31271312

RESUMO

AIM: Analyse the effects of professional flash glucose monitoring system (FreeStyle Libre Pro™) on glycaemic control in insulin-treated type 2 diabetes. METHODS: Primary (n = 17) and secondary care centres (n = 5) randomised 148 type 2 diabetes patients into three groups: (A) self-monitoring of blood glucose (n = 52), (B) self-monitoring of blood glucose and two Libre Pro sensor wears (n = 46) or (C) self-monitoring of blood glucose and four sensor wears (n = 50). Primary endpoint was time in range (glucose 3.9-10 mmol/L) within group C comparing baseline with days 172-187. Predefined secondary endpoints included HbA1c, hypoglycaemia and quality of life measures analysed within and between groups (clinicaltrials.gov, NCT02434315). RESULTS: In group C, time in range in the first 14 days (baseline) and days 172-187 was similar at 15.0 ± 5.0 and 14.1 ± 4.7 h/day (mean ± SD), respectively, (p = 0.1589). In contrast, HbA1c reduced from baseline to study end within group C by 4.9 ± 8.8 mmol/mol (0.44% ± 0.81%; p = 0.0003). HbA1c was also lower in group C compared with A at study end by 5.4 ± 1.79 mmol/mol (0.48% ± 0.16%; p = 0.0041, adjusted mean ± SE), without increased time in hypoglycaemia (p = 0.1795). Treatment satisfaction scores improved in group C compared with A (p = 0.0225) and no device-related serious adverse events were reported. CONCLUSIONS: Libre Pro can improve HbA1c and treatment satisfaction without increasing hypoglycaemic exposure in insulin-treated type 2 diabetes individuals managed in primary/secondary care centres.


Assuntos
Automonitorização da Glicemia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Atenção Primária à Saúde , Atenção Secundária à Saúde , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Regulação para Baixo , Inglaterra , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
13.
Adv Mater ; 31(30): e1901051, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31165524

RESUMO

Insulin-dependent patients with diabetes mellitus require multiple daily injections of exogenous insulin to combat hyperglycemia. However, administration of excess insulin can lead to hypoglycemia, a life-threatening condition characterized by abnormally low blood glucose levels (BGLs). To prevent hypoglycemia associated with intensive insulin therapy, a "smart" composite microneedle (cMN) patch is developed, which releases native glucagon at low glucose levels. The cMN patch is composed of a photo-crosslinked methacrylated hyaluronic acid (MeHA) microneedle array with embedded multifunctional microgels. The microgels incorporate zwitterionic moieties that stabilize loaded glucagon and phenylboronic acid moieties that provide glucose-dependent volume change to facilitate glucagon release. Hypoglycemia-triggered release of structurally unchanged glucagon from the cMN patch is demonstrated in vitro and in a rat model of type 1 diabetes (T1D). Transdermal application of the patch prevented insulin-induced hypoglycemia in the diabetic rats. This work is the first demonstration of a glucose-responsive glucagon-delivery MN patch for the prevention of hypoglycemia, which has a tremendous potential to reduce the dangers of intensive insulin therapy and improve the quality of life of patients with diabetes and their caregivers.


Assuntos
Glicemia/metabolismo , Glucagon/administração & dosagem , Hipoglicemia/tratamento farmacológico , Agulhas , Animais , Reagentes para Ligações Cruzadas/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Liberação Controlada de Fármacos , Géis , Humanos , Ácido Hialurônico/análogos & derivados , Ácido Hialurônico/química , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Metacrilatos/química , Processos Fotoquímicos , Polimerização , Ratos , Adesivo Transdérmico
14.
BMC Endocr Disord ; 19(1): 61, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196059

RESUMO

BACKGROUND: Insulin-derived amyloidosis is a skin-related complication of insulin therapy that interferes with insulin therapy. Although toxicities of in vitro-formed insulin amyloid fibrils have been well studied, the toxicity of insulin-derived amyloidosis remains to be clarified. CASE PRESENTATION: A 58-year-old man with type 2 diabetes mellitus underwent a lower limb amputation due to diabetic gangrene. Several antibiotics including minocycline were administered for infection and sepsis. A hard mass at the insulin injection sites in the lower abdomen was discovered by chance four months later. Although no abnormal findings in the surface skin of the mass were observed, necrotic tissue was seen around the mass when a biopsy was performed. Histological and toxicity studies were performed for this patient and four other patients with abdominal masses at insulin injection sites. Histological and immunohistochemical studies showed that the masses had typical characteristics of amyloid deposits in all cases, whereas necrotic findings were seen adjacent to the amyloid deposit only in the case presented. Toxicity studies indicated that the amyloid tissue from the present case had significant cell toxicity compared to the control skin tissue or the amyloid tissues from the other four cases. CONCLUSIONS: This report showed that toxic insulin-derived amyloidosis can occur. In addition, this report suggested that toxic insulin-derived amyloidosis may cause necrosis in the surrounding tissue. Although the toxic amyloid deposit of insulin-derived amyloidosis was found in only one patient, no structural differences between toxic and non-toxic deposits were seen on histological and immunohistochemical studies.


Assuntos
Amiloidose/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Amiloidose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
J Pediatr Endocrinol Metab ; 32(8): 837-841, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31228861

RESUMO

Background Arterial stiffness is a consequence of aging, but there are several diseases that contribute to this process. The evaluation of pulse wave velocity (PWV) allows a dynamic evaluation of vascular distensibility and the detection of atherosclerosis at an early stage. It was intended to evaluate the PWV in children and adolescents with type 1 diabetes mellitus (T1DM) and to compare their outcome according to the type of treatment used. Methods Forty-eight patients were randomly selected. Inclusion criteria: T1DM, under intensive insulin therapy (multiple daily insulin administrations [MDI] or continuous insulin infusion system [CIIS]). Exclusion criteria: existence of another chronic pathology or microvascular complications. Echocardiography was performed and three measurements of PWV were done, with their mean calculated. Results Most of the children and adolescents presented a PWV ≥ the 75th centile. There was a statistically significant difference for hemoglobin A1c (HbA1c) (7.8 in CIIS vs. 9 in MDI, p < 0.05). There were not statistically significant differences in the PWV between the two groups. This can be attributed to the fact that children with CIIS are those who previously presented greater glycemic instability. There was a significant correlation between PWV and disease duration (Pearson's correlation coefficient [r] = 0.314, p = 0.036). Conclusions This study showed that in children and adolescents with T1DM, there is an important prevalence of arterial stiffness, translated by an increase in PWV. This increase in PWV appears to exist even in very young children with little disease evolution time.


Assuntos
Aterosclerose/etiologia , Biomarcadores/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Análise de Onda de Pulso , Rigidez Vascular , Adolescente , Adulto , Aterosclerose/sangue , Aterosclerose/diagnóstico , Glicemia/análise , Criança , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Sistemas de Infusão de Insulina , Masculino , Prognóstico , Fatores de Risco , Adulto Jovem
16.
Cardiovasc Diabetol ; 18(1): 63, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138207

RESUMO

BACKGROUND: Diabetes mellitus (DM) on insulin is a patient-related factor in the assessment of surgical risk based on the EuroSCORE II and, as such, it confers additional risk on outcomes after transcatheter aortic valve implantation (TAVI). The aim of this study was to investigate the effect of diabetes mellitus treated with insulin and oral antidiabetic drugs on clinical outcomes after TAVI. METHODS: This study is an analysis of 2000 patients who underwent TAVI between 2008 and 2015. Patients were stratified post hoc into the following categories: without diabetes (n = 1337), with diabetes treated with oral antidiabetic drugs (OAD; n = 387) and with diabetes treated using insulin (n = 276). RESULTS: There was no significant difference in device success (89.5% vs 89.4% vs 88.8%, adjusted odds ratio (adjOR) 1.10 [95% confidence interval (CI) 0.64-1.91]) and VARC-2-defined major complications among the three groups of patients (without DM, OAD, and insulin, respectively). Minor but not major or disabling strokes (adjOR 2.19; 95% CI 1.11-4.3) and overall renal complications (but not stage 2/3 alone) (adjOR 1.46; 95% CI 1.18-1.81) were more common in patients with diabetes than in those without diabetes. Insulin-treated patients had a significantly lower survival rate than that of patients with orally treated diabetes and of those without diabetes at 1 year (75.7% vs. 84.5% vs 84.7%, pairwise p < 0.01) and 3 years (56.9% vs. 65.9% vs. 67.9%, adj. p < 0.05) after TAVI. However, insulin-treated diabetes was not identified as an independent risk factor for higher mortality in the first (HR 1.29; 95% CI 0.97-1.72, p = 0.084) and 3rd years (HR 1.21; 95% CI 0.98-1.49; p = 0.079) after multivariable adjustment. CONCLUSIONS: Although insulin-dependent DM is an established component of surgical risk assessment, it was not identified as an independent factor associated with reduced survival in TAVI. DM treated with oral antidiabetic drugs or insulin may have less role in decision making of treatment in TAVI candidates.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Substituição da Valva Aórtica Transcateter/mortalidade , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidade , Feminino , Alemanha/epidemiologia , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Masculino , Complicações Pós-Operatórias/mortalidade , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
17.
Vnitr Lek ; 65(4): 295-299, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091950

RESUMO

Hypoglycemia is a side effect of the therapy primarily with insulin, sulphonylurea derivates and glinides. Its therapy is based on the immediate ingestion of sacharides, preferably glucose. Amount of 15-20 g is recommended as its optimal dose, although several recent studies are suggesting amount related to the patient´s weight. The therapy of severe hypoglycemia in the non-professional settings is based on glucagon injection, in the professional ones intravenous administration of glucose is preferable option.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Hipoglicemiantes , Insulina , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucagon , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/efeitos adversos , Insulina/uso terapêutico
18.
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
19.
Nutrients ; 11(5)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126048

RESUMO

Post-prandial hyperglycemia is still a challenging issue in intensified insulin therapy. Data of 35 T1D patients during a four-week period were analyzed: RT-CGM (real time continuous glucose monitoring) record, insulin doses, diet (including meal photos), energy expenditure, and other relevant conditions. Patients made significant errors in carbohydrate counting (in 56% of cooked and 44% of noncooked meals), which resulted in inadequate insulin doses. Subsequently, a mobile application was programmed to provide individualized advice on prandial insulin dose. When using the application, a patient chooses only the type of categorized situation (e.g., meals with other relevant data) without carbohydrates counting. The application significantly improved postprandial glycemia as normoglycemia was reached in 95/105 testing sessions. Other important findings of the study include: A high intake of saturated fat (median: 162% of recommended intake); a low intake of fiber and vitamin C (median: 42% and 37%, respectively, of recommended intake); an increase in overweight/obesity status (according to body fat measurement), especially in women (median of body fat: 30%); and low physical activity (in 16/35 patients). The proposed individualized approach without carbohydrate counting may help reach postprandial normoglycemia but it is necessary to pay attention to the lifestyle habits of T1D patients too.


Assuntos
Glicemia/efeitos dos fármacos , Telefone Celular , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cálculos da Dosagem de Medicamento , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Estilo de Vida , Aplicativos Móveis , Período Pós-Prandial , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Carboidratos da Dieta/administração & dosagem , Metabolismo Energético , Exercício , Comportamento Alimentar , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudo de Prova de Conceito , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
J Surg Res ; 242: 157-165, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31078900

RESUMO

BACKGROUND: Limited data exist that compare the predominant cardiac preservation solutions (CPSs). MATERIALS AND METHODS: The United Network for Organ Sharing database was retrospectively reviewed from January 1, 2004 to March 31, 2018, for donor hearts. Of 34,614 potential donors, 21,908 remained after applying the exclusion criteria. The CPS analyzed included saline, the University of Wisconsin (UW), cardioplegia, Celsior, and Custodiol. The primary endpoints were recipient survival and posttransplant rejection. Logistic and Cox models were used to quantify survival endpoints. RESULTS: Saline was used as the CPS in 2549 patients (12%), UW in 10,549 (48%), cardioplegia in 1307 (6%), Celsior in 5081 (23%), and Custodiol in 2422 (11%). Donor age ranged from 15 to 68 y (mean = 32.0 y, median = 30.0 y), and 71% were male. Adjusted survival probabilities of recipients whose donor hearts were procured with saline was 96% 30 d, 90% 1 y, UW: 97% 30 d, 92% 1 y, cardioplegia: 95% 30 d, 87% 1 y, Celsior: 96% 30 d, 90% 1 y, and Custodiol: 97% 30 d, 92% 1 y. When these comparisons were adjusted for donor age, sex, ethnicity, ischemic time, recipient age, sex, ethnicity, creatinine, ventricular assist device (VAD), length of stay, region and days on waiting list, cardioplegia solution was demonstrated to have a higher risk of death (30 d, 1 y, overall) and posttransplant rejection versus UW (odds ratio 1.70, P = 0.001; odds ratio 1.63, P < 0.001; hazard ratio 1.22, P < 0.001; hazard ratio 1.21, P < 0.001, respectively). CONCLUSIONS: Cardioplegia solutions for cardiac preservation are associated with a higher mortality in heart transplant recipients.


Assuntos
Soluções Cardioplégicas/efeitos adversos , Rejeição de Enxerto/epidemiologia , Insuficiência Cardíaca/cirurgia , Soluções para Preservação de Órgãos/efeitos adversos , Preservação de Órgãos/efeitos adversos , Adenosina/efeitos adversos , Adolescente , Adulto , Idoso , Aloenxertos/efeitos dos fármacos , Alopurinol/efeitos adversos , Dissacarídeos/efeitos adversos , Eletrólitos/efeitos adversos , Feminino , Seguimentos , Glucose/efeitos adversos , Glutamatos/efeitos adversos , Glutationa/efeitos adversos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Coração/efeitos dos fármacos , Insuficiência Cardíaca/mortalidade , Transplante de Coração/efeitos adversos , Histidina/efeitos adversos , Humanos , Insulina/efeitos adversos , Masculino , Manitol/efeitos adversos , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Cloreto de Potássio/efeitos adversos , Procaína/efeitos adversos , Rafinose/efeitos adversos , Estudos Retrospectivos , Solução Salina/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
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