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2.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2217-2220, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018448

RESUMO

Type 1 diabetic patients characteristically exhibit a loss of insulin production, leading to chronic hyperglycemia and related complications. Herein we describe the design, synthesis and screening of novel oligopeptides for their potential to enhance the secretion of insulin from human pancreatic islets. The investigation of these compounds, based off the patented INGAP-PP sequence, aims to identify the peptide features key to maximizing insulin secretion.Clinical Relevance - This report describes the relative efficacy of selected novel compounds for potential Type 1 Diabetes Therapy. Tested on live human pancreatic islets, the compounds are evaluated for their enhancing/inhibitory effect on the secretion of insulin. These studies pave the way for future targeted drug therapies.


Assuntos
Diabetes Mellitus Tipo 1 , Ilhotas Pancreáticas , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Peptídeos/metabolismo
3.
Lancet Diabetes Endocrinol ; 8(10): 845-854, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32946821

RESUMO

BACKGROUND: The DEPICT-1 and DEPICT-2 studies showed that dapagliflozin as an adjunct to insulin in individuals with inadequately controlled type 1 diabetes improved glycaemic control and bodyweight, without increase in risk of hypoglycaemia. We aimed to determine the effect of dapagliflozin on urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) using pooled data from the DEPICT studies. METHODS: In this post-hoc analysis, we used data pooled from both DEPICT studies (DEPICT-1 ran from Nov 11, 2014, to Aug 25, 2017; DEPICT-2 ran from July 8, 2015, to April 18, 2018), in which participants were aged 18-75 years, with inadequately controlled type 1 diabetes and with a baseline UACR of at least 30 mg/g. In the DEPICT studies, participants were randomly assigned (1:1:1) to receive dapagliflozin (5 mg or 10 mg) or placebo all plus insulin, for 24 weeks, with a 28-week long-term extension (ie, 52 weeks in total). In this post-hoc analysis, we assessed the percentage change from baseline in UACR and in eGFR, up to 52 weeks. UACR, eGFR, and safety were assessed in all eligible participants who had received at least one dose of study drug. HbA1c, bodyweight, and systolic blood pressure were assessed in all participants who received at least one dose of study drug during the first 24-week period, and who had a baseline and any post-baseline assessment for that parameter. The DEPICT trials were registered with ClinicalTrials.gov, NCT02268214 (DEPICT-1), NCT02460978 (DEPICT-2), and are now complete. RESULTS: 251 participants with albuminuria at baseline were included in this post-hoc analysis; of whom 80 (32%) had been randomly assigned to dapagliflozin 5 mg, 84 (33%) to dapagliflozin 10 mg, and 87 (35%) to placebo. Compared with placebo, treatment with both dapagliflozin doses improved UACR over 52 weeks. At week 52, mean difference in change from baseline versus placebo in UACR was -13·3% (95% CI -37·2 to 19·8) for dapagliflozin 5 mg and -31·1% (-49·9 to -5·2) for dapagliflozin 10 mg. No notable change from baseline was seen in eGFR, with a mean difference in change from baseline versus placebo of 3·27 mL/min per 1·73 m2 (95% CI -0·92 to 7·45) for dapagliflozin 5 mg and 2·12 mL/min per 1·73 m2 (-2·03 to 6·27) for dapagliflozin 10 mg. Similar proportions of participants in each treatment group had adverse events and serious adverse events, including hypoglycaemia and diabetic ketoacidosis; no new safety signals were identified in this population. INTERPRETATION: Treatment with dapagliflozin resulted in UACR reduction, which might provide renoprotective benefits in individuals with type 1 diabetes and albuminuria. Dedicated prospective studies are needed to confirm these findings as prespecified endpoints. FUNDING: AstraZeneca.


Assuntos
Albuminúria/prevenção & controle , Compostos Benzidrílicos/uso terapêutico , Biomarcadores/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/prevenção & controle , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Adolescente , Adulto , Idoso , Glicemia/análise , Creatinina/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Taxa de Filtração Glomerular , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adulto Jovem
4.
Cochrane Database Syst Rev ; 9: CD008294, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990945

RESUMO

BACKGROUND: Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review. OBJECTIVES: To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders. SEARCH METHODS: We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress. MAIN RESULTS: This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV1) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV1 % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events. AUTHORS' CONCLUSIONS: Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.


Assuntos
Antioxidantes/uso terapêutico , Doença Crônica/tratamento farmacológico , Flavonoides/uso terapêutico , Casca de Planta/química , Extratos Vegetais/uso terapêutico , Adolescente , Adulto , Asma/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Viés , Doenças Ósseas Metabólicas/tratamento farmacológico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Disfunção Erétil/tratamento farmacológico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Osteoartrite/tratamento farmacológico , Pinus , Ensaios Clínicos Controlados Aleatórios como Assunto , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Insuficiência Venosa/tratamento farmacológico
5.
Ther Umsch ; 77(7): 328-332, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32996423

RESUMO

Diabetes, hypoglycemia and driving instructions in Switzerland Abstract. Many individuals with diabetes participate in road traffic in a regular and safe manner. Studies suggest that type 1 diabetes leads to more traffic accidents. Hypoglycemia is a risk factor for driving mishaps. Therefore, patients with diabetes medication, which can cause hypoglycemia, have to be informed and adhere to the guidelines regarding suitability for driving. These guidelines are summarized in this review.


Assuntos
Condução de Veículo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Acidentes de Trânsito/prevenção & controle , Humanos , Suíça
6.
Ther Umsch ; 77(7): 312-318, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32996429

RESUMO

Closed-loop systems - Update 2020 Abstract. The artificial pancreas (also referred to as a Closed-loop system) represents the latest development in diabetes therapy. Closed-loop systems autonomously direct subcutaneous insulin infusion via a control algorithm based on real-time continuous glucose monitoring. Closed-loop systems have been tested in clinical studies since 2011, and were shown to improve glucose control by reducing hyper- and hypoglycaemia as well as glucose variability when compared with conventional insulin pump therapy. In 2016, the US regulatory authority approved the first hybrid-closed-loop system for the treatment of type 1 diabetes. Hybrid-closed loop systems are not yet fully automated and still require the user to be actively involved for insulin dosing at mealtimes. In spite of the remarkable progress, the delayed action profile of subcutaneously administered insulin and the need to wear multiple devices on the body remain challenging. The present review article summarizes the current state of the art of closed-loop systems in diabetes care and will address technical aspects, evidence from clinical studies as well as future developments in the field.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Pâncreas Artificial , Glicemia , Automonitorização da Glicemia , Humanos , Sistemas de Infusão de Insulina
7.
Acta Biomed ; 91(3): ahead of print, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32921748

RESUMO

Type 1 diabetes mellitus (T1DM) is rare in infants and toddlers and is usually associated with a relatively high mortality when complicated with diabetic ketoacidosis (DKA). In infants, the classical symptoms of DKA are atypical and therefore many infants with DKA are mistreated for infections. We report a case of DKA precipitated by COVID-19 in an 8-month-old infant with newly diagnosed diabetes mellitus. This case is reported in view of its rarity and originality. The relation between T1DM and COVID19 infection is discussed.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/etiologia , Pneumonia Viral/complicações , Biomarcadores/sangue , Glicemia/metabolismo , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/sangue , Cetoacidose Diabética/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Lactente , Insulina Detemir/uso terapêutico , Masculino , Pandemias , Pneumonia Viral/epidemiologia
8.
Medicine (Baltimore) ; 99(33): e20875, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871972

RESUMO

BACKGROUND: To systematically evaluate the efficacy and safety of sotagliflozin (SOTA) adjuvant therapy for type 1 diabetes mellitus (T1DM). METHODS: Through April 2019, the Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure databases were electronically searched to identify randomized controlled trials exploring SOTA adjuvant therapy for T1DM. Strict screening and quality evaluations of the obtained literature were performed independently by 2 researchers. Outcome indexes were extracted, and a meta-analysis of the data was performed using Revman 5.3 software. RESULTS: A total of 7 randomized controlled trials were included. The meta-analysis results showed that compared with the patients in the placebo group, the patients in the SOTA group had a lower hemoglobin A1c (mean difference [MD] = -0.28, 95% confidence interval [CI] [-0.34, -0.22], P < .01), lower total daily insulin use (MD = -8.89, 95% CI [-11.64, -6.13], P < .01), faster weight loss (MD = -3.03, 95% CI [-3.79, -2.26], P < .01), better fasting blood glucose and 2-hour postprandial blood glucose control (MD = -0.75, 95% CI [-1.04, -0.45], P < .01; MD = -2.42, 95% CI [-3.17, -1.67], P < .01), and a higher rate of well-controlled glucose levels (relative risk = 1.75, 95% CI [1.55, 1.99], P < .01), while no significant difference in the incidence of severe hypoglycemic events was found between the SOTA and placebo groups (risk difference [RD] = -0.01, 95% CI [-0.02, 0.00], P = .13). The incidence of diabetic ketoacidosis was higher in the SOTA group than in the placebo group (RD = 0.03, 95% CI [0.02, 0.04], P < .01). The incidence of genital mycotic infection was higher in the SOTA group than in the placebo group (RD = 0.06, 95% CI [0.05, 0.08], P < .01). No significant difference in the incidence of urinary tract infections was detected between the SOTA group and the placebo group (RD = 0.00, 95% CI [-0.01, 0.01], P = 0.97). CONCLUSIONS: SOTA is a potential drug for the treatment of T1DM and is effective for controlling blood sugar. The main adverse reactions to SOTA are genital mycotic infections and diabetic ketoacidosis. We must further assess the severity of diabetic ketoacidosis caused by SOTA.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicosídeos/efeitos adversos , Glicosídeos/uso terapêutico , Transportador 1 de Glucose-Sódio/efeitos adversos , Transportador 1 de Glucose-Sódio/uso terapêutico , Quimioterapia Adjuvante , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Medicine (Baltimore) ; 99(34): e20772, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846751

RESUMO

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic, immune-mediated disease characterized by the destruction of insulin producing cells and persistent hyperglycemia. At present, the drugs for type 1 diabetes mellitus can reduce blood glucose rapidly and effectively, but there are risks of hypoglycemia, large fluctuation of blood glucose, and chronic complications. Related research found that compared with continuous hyperglycemia, blood glucose fluctuations are more harmful to the chronic complications of diabetes. Blood glucose variation is closely related to the occurrence and development of chronic complications of diabetes. Sancai powder (SC) is made on the basis of 3 ancient Chinese medicine formulas, which has the effect of lowering blood glucose. There have been reports on the clinical study of SC in the treatment of diabetic patients, but there is no systematic evaluation of SC in the treatment of type 1 diabetes, so it is necessary to summarize and evaluate the existing evidence. METHODS AND ANALYSIS: This study will be conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols. We will search 3 English databases and 4 Chinese databases. Two methodologically trained researchers will read titles, abstracts, and full texts, and independently select eligible literature based on inclusion and exclusion criteria. After assessing the risk of bias and extracting data, we will conduct a meta-analysis of the results, including: standard deviation of blood glucose level, coefficient of variation, mean blood glucose, postprandial blood glucose fluctuation, hypoglycemia index, glycated hemoglobin, overall impact rate, and adverse effects. The heterogeneity of the data will be tested by Cochrane x2 and I2. Based on reliable subgroup effect guidance, we established 3 hypotheses for subgroup analysis: disease status at baseline, duration of intervention, and type of concomitant medication. Sensitivity analysis will be carried out to assess the stability of the results. The publication bias assessment will then be performed by funnel plot analysis and Egger test. Finally, we will use the "grading, evaluation, development and evaluation of recommendations" system to assess the quality of evidence. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: In our study, the evidence of SC in the treatment of reducing blood sugar fluctuation in type 1 diabetes will be comprehensively summarized and carefully evaluated. It will provide more options for clinical treatment of the disease. INPLASY REGISTRATION NUMBER: INPLASY202050052.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
10.
N Engl J Med ; 383(9): 836-845, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32846062

RESUMO

BACKGROUND: A closed-loop system of insulin delivery (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes. METHODS: In a 16-week, multicenter, randomized, open-label, parallel-group trial, we assigned, in a 3:1 ratio, children 6 to 13 years of age who had type 1 diabetes to receive treatment with the use of either a closed-loop system of insulin delivery (closed-loop group) or a sensor-augmented insulin pump (control group). The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. RESULTS: A total of 101 children underwent randomization (78 to the closed-loop group and 23 to the control group); the glycated hemoglobin levels at baseline ranged from 5.7 to 10.1%. The mean (±SD) percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter increased from 53±17% at baseline to 67±10% (the mean over 16 weeks of treatment) in the closed-loop group and from 51±16% to 55±13% in the control group (mean adjusted difference, 11 percentage points [equivalent to 2.6 hours per day]; 95% confidence interval, 7 to 14; P<0.001). In both groups, the median percentage of time that the glucose level was below 70 mg per deciliter was low (1.6% in the closed-loop group and 1.8% in the control group). In the closed-loop group, the median percentage of time that the system was in the closed-loop mode was 93% (interquartile range, 91 to 95). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either group. CONCLUSIONS: In this 16-week trial involving children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with the use of a closed-loop system than with the use of a sensor-augmented insulin pump. (Funded by Tandem Diabetes Care and the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number, NCT03844789.).


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Bombas de Infusão Implantáveis , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adolescente , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Cetoacidose Diabética/etiologia , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos , Masculino , Pâncreas Artificial
11.
Diabetes Res Clin Pract ; 167: 108354, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32739380

RESUMO

AIMS: Spain has been one of the worst affected countries by the COVID-19 pandemic. A very strict lockdown at home was imposed with a tough restriction of mobility. We aimed to evaluate the impact of this exceptional scenario on glucose profile of patients with T1D prone to hypoglycemia using standalone continuous glucose monitoring. METHODS: Patients with T1D prone to hypoglycemia using multiple daily injections and either a Dexcom G5® or a Free Style Libre® CGM systems for at least 6 months under the funding of National Health Service were included in an observational, retrospective study. Data were collected in two periods: pre-lockdown (PL), February 23rd-March 7th and within lockdown (WL), April 1st-14th 2020. The primary outcome was the difference in the proportion of time in target glucose range of 70-180 mg/dL (TIR). Additional glucometric data were also analysed. RESULTS: 92 patients were included: 40 women, age 42.8 ± 3.9 years, disease duration of 23.1 ± 12.6 years. Seventeen patients used Dexcom G5® and 75 Free Style Libre®. TIR 70-180 mg/dL (59.3 ± 16.2 vs 62.6 ± 15.2%), time > 180 (34.4 ± 18.0 vs 30.7 ± 16.9%), >250 (11.1 ± 10.6 vs 9.2 ± 9.7%) and Glucose Management Indicator (7.2 ± 0.8 vs 7.0 ± 0.8%) significantly improved (PL vs WL, respectively, p < 0.05). Time in hypoglycemia remained unchanged. CONCLUSIONS: Lockdown conditions imposed by the COVID-19 pandemic may be managed successfully in terms of glycemic control by population with T1D prone to hypoglycemia using CGM. The strict daily routine at home could probably explain the improvement in the time in glycemic target without increasing the time in hypoglycemia.


Assuntos
Automonitorização da Glicemia , Controle de Doenças Transmissíveis , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Monitorização Ambulatorial , Pneumonia Viral/epidemiologia , Adulto , Betacoronavirus , Glicemia , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Humanos , Injeções , Insulina de Ação Prolongada/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Espanha/epidemiologia , Medicina Estatal
12.
Cochrane Database Syst Rev ; 8: CD009966, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32803882

RESUMO

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


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Adamantano/efeitos adversos , Adamantano/análogos & derivados , Adamantano/uso terapêutico , Viés , Causas de Morte , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Jejum/sangue , Hemoglobina A Glicada/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Insulina/uso terapêutico , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Nitrilos/efeitos adversos , Nitrilos/uso terapêutico , Pioglitazona , Complicações Pós-Operatórias/etiologia , Pirrolidinas/efeitos adversos , Pirrolidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fosfato de Sitagliptina/efeitos adversos , Fosfato de Sitagliptina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico , Transplantados , Vildagliptina
13.
Diabetes Res Clin Pract ; 166: 108302, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32623034

RESUMO

INTRODUCTION: Management of Type 1 Diabetes (T1D) poses numerous challenges, especially for young children and their families. Parental care positively influencesthe outcomesofchildren with T1D, while there are often criticisms in school environment. The COVID-19 pandemic has forced children and parents to spend many hours at home and diabetes care has returned mainly in the hands of parents. AIM OF THE STUDY: To evaluate the effectiveness of exclusive return to parental care in pre-school and school children with T1D treated with Tandem Basal IQ system during the COVID-19 pandemic. PATIENTS AND METHODS: 22 children (M:F = 14:8) with T1D have been evaluated. We compared insulin and CGM data (TIR, TBR and TAR) of two periods: PRE-COV and IN-COV, in which children have transitioned from normal school attendance to the exclusive care of their parents. RESULTS: During the IN-COV period a significantly (p < 0.001) higher median value of TIR (66,41%) was observed as compared to PRE-COV period (61,45%). Patients also showed a statistically significant difference (p < 0.002) between the IN-COV period and the PRE-COV period as concerning the TAR metric: respectively 29,86 ± 10,6% vs 34,73 ± 12,8%. The difference between the bolus insulin doses was statistically significant (PRE-COV 5,3 IU/day, IN-COV 7,9 IU/day - p < 0.05). CONCLUSION: Our observational real-life study confirms the positive effect of parental care in T1D very young children and demonstrates that during the COVID-19 pandemic it was possible to obtain a good glycometabolic compensation despite the significant change in lifestyle.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Pandemias/prevenção & controle , Pais/psicologia , Pneumonia Viral/prevenção & controle , Quarentena/métodos , Adolescente , Criança , Pré-Escolar , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos
14.
Diabetes Res Clin Pract ; 166: 108307, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32650036

RESUMO

AIMS: On the 10th of March, Greece imposed the closure of schools and universities and a full lockdown a few days later in order to counter the spread of the coronavirus outbreak. Our aim was to monitor the effect of the coronavirus lockdown in diabetes management in children with Type 1 Diabetes Mellitus (T1DM) wearing insulin pump equipped with continuous glucose monitoring system. METHODS: In 34 children with T1DM on Medtronic 640G insulin pump equipped with the Enlite Sensor uploaded CareLink data were categorized in 2 three-week periods before and after the 10th of March. RESULTS: Mean time in range (TIR) did not significantly differ between the two periods. However, a significantly higher Coefficient of Variation (CV) indicating an increased glucose variability in the pre-lockdown period was observed (39.52% versus 37.40%, p = 0.011). Blood glucose readings were significantly fewer during the lockdown period (7.91 versus 7.41, p = 0.001). No significant difference was recorded regarding the total daily dose of insulin and the reported carbohydrates consumed. However, the meal schedule has changed dramatically as the percentage of breakfast consumed before 10.00 a.m. has fallen from 80.67% to 41.46% (p < 0.001) during the lockdown. Correspondingly, the percentage of dinner consumption before 10.00 p.m. significantly fell during the lockdown period (60.22% versus 53.78%, p = 0.019). CONCLUSIONS: Glycemic control during the coronavirus lockdown can be adequately achieved and be comparable to the pre-lockdown period in children with type 1 diabetes mellitus wearing insulin pump equipped with sensor.


Assuntos
Betacoronavirus/isolamento & purificação , Automonitorização da Glicemia/métodos , Glicemia/análise , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina/estatística & dados numéricos , Insulina/uso terapêutico , Pneumonia Viral/complicações , Adolescente , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/virologia , Feminino , Grécia/epidemiologia , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico
15.
Diabetes Res Clin Pract ; 166: 108344, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32710997

RESUMO

AIMS: To assess knowledge, attitude, and practices (KAP) of young adults with type 1 diabetes mellitus (T1DM) towards COVID-19 amid nationwide lockdown in India. METHODS: We conducted a cross-sectional web-based survey among young adults with T1DM (aged 18-30 years) in the North, Central, South, and West zones of India. It consisted of fifteen, five and eight questions pertaining to knowledge, attitude, and practices towards COVID-19, respectively. Certain questions relevant to T1DM were also incorporated. RESULTS: After exclusion, 212 participants were included (mean age = 25.1 ± 4.3 years; M:F = 10:11). The overall correct rate of the knowledge questionnaire was 83% (mean total knowledge score = 12.4 ± 1.9). Most (74%) had an average knowledge score (mean ± 1SD). Higher educational status, urban residence, and being married were associated with better knowledge scores; however, only urban residence was found to be statistically significant on multinomial logistic regression. Most (88%) felt that being a patient of T1DM, they were at higher risk of getting infected with COVID-19. At the same time, 98% were confident about self-protection. Fifty-one percent of respondents had left home amid lockdown mostly to procure insulin/injection needles/syringes/glucometer strips from the pharmacy. However, all were maintaining proper hand hygiene and majority were following routine dietary advice (95%) and administering prescribed insulin doses (99%). Seventy-two participants (34%) had experienced one or more episodes of hypoglycemia since the commencement of lockdown. CONCLUSIONS: Young adults with T1DM have average knowledge, positive attitude, and healthy preventive practices towards COVID-19. Awareness campaigns targeted towards rural communities and providing doorstep delivery of insulin/needles/syringes may be more rewarding.


Assuntos
Betacoronavirus/isolamento & purificação , Automonitorização da Glicemia/métodos , Infecções por Coronavirus/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Insulina/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Quarentena/métodos , Adolescente , Adulto , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/virologia , Feminino , Educação em Saúde , Humanos , Hipoglicemiantes/uso terapêutico , Índia/epidemiologia , Masculino , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Inquéritos e Questionários , Adulto Jovem
16.
Diabetes Res Clin Pract ; 166: 108348, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32711000

RESUMO

INTRODUCTION: The COVID-19 pandemic has forced governments to take exceptional measures to minimize its spread, imposing lockdown policies. The aim of this study was to evaluate the impact of lockdown on type 1 diabetes (T1D) glycemic control. MATERIAL AND METHODS: People with T1D using flash glucose monitoring were included. Data from the 14 days before lockdown were compared with data from the last 14 days after 8 weeks of lockdown. RESULTS: A total of 307 patients were included (age 45.8 ± 12.6 years, 50.2% male, diabetes duration 21.1 ± 12.3 years). Only one patient had COVID-19 infection. Mean glucose decreased from 166.89 ± 29.4 to 158.0 ± 29.0 mg/dL and estimated HbA1c declined from 7.4 ± 1.0 to 7.1 ± 1.0% (54 ± 10.9 vs 57 ± 10.9 mmol/mol; p < 0.001). Time in range increased from 57.8 ± 15.8 to 62.46 ± 16.1%. Time in hyperglycemia > 180 mg/dL and >250 mg/dL decreased from 37.3 ± 1.9% to 32.0 ± 17.1% and from 13.0 ± 11.3 to 10.3 ± 10.6%, respectively; (p < 0.001). Time in hypoglycaemia <70 mg/dL increased from 4.9 ± 4.0% to 5.5 ± 4.4% (p < 0.001). No differences in time <54 mg/dl, coefficient of variation (CV%) or number of scans per day were found. CONCLUSION: Despite the limitations of lockdown, glycemic control improved in patients with T1D. These results suggest that having more time for self-management may help improve glycemic control in the short term.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Insulina/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Quarentena/métodos , Automonitorização da Glicemia/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/virologia , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Espanha/epidemiologia
18.
Rev Med Suisse ; 16(697): 1191-1196, 2020 Jun 10.
Artigo em Francês | MEDLINE | ID: mdl-32520457

RESUMO

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


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Insulina/uso terapêutico , Pacientes Ambulatoriais , Cetoacidose Diabética/etiologia , Cetoacidose Diabética/prevenção & controle , Cetoacidose Diabética/terapia , Humanos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos
19.
South Med J ; 113(6): 320-324, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32483643

RESUMO

OBJECTIVE: To evaluate pharmacist involvement in the inpatient transition of care (TOC) process for patients hospitalized with type 1 diabetes mellitus, type 2 diabetes mellitus, or chronic obstructive pulmonary disease. METHODS: A pharmacist screened patients admitted with one or more of the qualifying conditions within 48 hours of admission to perform medication reconciliation. During medication reconciliation, the pharmacist removed any duplicate or nonindicated medications and added any omitted medications. The pharmacist also reviewed the discharge summary to ensure medication optimization upon discharge. RESULTS: Pharmacist involvement in the admission and discharge reconciliation processes of the 50 identified patients was 100% and 44%, respectively. A medication-related problem was identified in 96% (n = 48) of patients, representing 338 pharmacist-mediated interventions with an average of 6.8 ± 4.0 (range 0-16) interventions per patient. Of those 338 interventions, 298 drug discrepancies were identified and corrected, with an average of 6.0 ± 3.7 (range 0-15) discrepancies per patient. Average time spent was 66 ± 22 (range 30-130) minutes with each patient. Of the 50 patients enrolled, 12 were readmitted within 30 days. CONCLUSIONS: This pilot study demonstrated an improved medication reconciliation process with pharmacist involvement, expanding the body of evidence that pharmacists can enhance TOC management in an inpatient setting. These results highlight the utility of a pharmacist in the implementation and refinement of TOC services and provides impetus for a team-based approach when patients experience a TOC.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hospitalização , Reconciliação de Medicamentos , Transferência de Pacientes , Serviço de Farmácia Hospitalar , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Redução de Custos , Registros Eletrônicos de Saúde , Feminino , Humanos , Ciência da Implementação , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Readmissão do Paciente , Farmacêuticos , Projetos Piloto , Papel Profissional , Adulto Jovem
20.
N Engl J Med ; 382(26): 2493-2503, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579810

RESUMO

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Inibidores Enzimáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Adulto , Idoso , Alopurinol/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina , Falha de Tratamento
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