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1.
Nat Commun ; 11(1): 5162, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33056984

RESUMO

Bioactive natural C-glycosides are rare and chemical C-glycosylation faces challenges while enzymatic C-glycosylation catalyzed by C-glycosyltransferases provides an alternative way. However, only a small number of C-glycosyltransferases have been found, and most of the discovered C-glycosyltransferases prefer to glycosylate phenols with an acyl side chain. Here, a promiscuous C-glycosyltransferase, AbCGT, which is capable of C-glycosylating scaffolds lacking acyl groups, is identified from Aloe barbadensis. Based on the substrate promiscuity of AbCGT, 16 C-glycosides with inhibitory activity against sodium-dependent glucose transporters 2 are chemo-enzymatically synthesized. The C-glycoside 46a shows hypoglycemic activity in diabetic mice and is biosynthesized with a cumulative yield on the 3.95 g L‒1 scale. In addition, the key residues involved in the catalytic selectivity of AbCGT are explored. These findings suggest that AbCGT is a powerful tool in the synthesis of lead compounds for drug discovery and an example for engineering the catalytic selectivity of C-glycosyltransferases.


Assuntos
Aloe/enzimologia , Glicosídeos/biossíntese , Glicosiltransferases/metabolismo , Proteínas de Plantas/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo , Aloxano/toxicidade , Aloe/genética , Animais , Biocatálise , Glicemia/análise , Glicemia/efeitos dos fármacos , Clonagem Molecular , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Descoberta de Drogas/métodos , Feminino , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Glicosilação , Glicosiltransferases/genética , Glicosiltransferases/isolamento & purificação , Humanos , Masculino , Camundongos , Proteínas de Plantas/genética , Proteínas de Plantas/isolamento & purificação , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Especificidade por Substrato
2.
PLoS One ; 15(10): e0237843, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031385

RESUMO

OJECTIVES: Thrombotic and antifibrinolytic influence of Diabetes mellitus type 1 (T1DM) on haemostasis have been well demonstrated. There has been no research assessing the influence of poor glycemic control on thrombus formation under flow conditions in vitro or in pregnant type 1 diabetic women to date. PATIENTS/METHODS: This study compared singleton pregnant T1DM women (n = 21) and control pregnant subjects without any metabolic disease (n = 15). The T1DM group was divided into two subgroups of sufficient (SGC-DM; HbA1c ≤6,5%,n = 15) and poor glycaemic control (PGC-DM; HbA1c >6,5%,n = 6). Evaluation of the whole blood thrombogenicity we assessed using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan). RESULTS: Blood clot formation initiation time (T10) was significantly shortened in PGC-DM subgroup when compared to SGC-DM subgroup (p = 0,03). The area under the curve (AUC30) of blood clot time formation and the MPV (mean platelet volume) values were substantially higher in the PGC-DM subgroup in comparison to the SGC-DM group (p = 0,03). Negative correlations were noted between HbA1c and T10 values (p = 0,02) and between T10 and MPV values in the T1DM group (p = 0,04). CONCLUSIONS: Poor glycaemic control in T1DM subjects triggers a shift towards a prothrombotic and antifibrinolytic state. This phenomenon can be detected using the novel system for quantitative assessment of the platelet thrombus formation process under flow conditions in vitro. The alteration of T-TAS values in PGC-DM subgroup proves that a poor glycemic control-related shift of the equilibrium toward thrombogenesis occurs in this group of patients. Our findings need a further elucidation in research on more massive data sets to be confirmed.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Gravidez em Diabéticas/sangue , Adulto , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Feminino , Fibrinólise , Humanos , Polônia , Gravidez , Trombose/sangue , Trombose/etiologia , Adulto Jovem
3.
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
4.
Diab Vasc Dis Res ; 17(5): 1479164120952321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32883101

RESUMO

BACKGROUND: Estimated glucose disposal rate (eGDR) is a practical measure of Insulin Resistance (IR) which can be easily incorporated into clinical practice. We profiled eGDR in younger adults with type 1 diabetes mellitus (T1DM) by their demographic and clinical characteristics. METHODS: In this single centre study, medical records of TIDM were assessed and eGDR tertiles correlated with demographic and clinical variables. RESULTS: Of 175 T1DM individuals, 108 (61.7%) were males. Mean age (±SD) was 22.0 ± 1.6 years and median time from diagnosis 11.0 years (range 1-23). Individuals were predominantly Caucasian (81.7%), with 27.4% being overweight (BMI: 25-30 kg/m2) and 13.7% obese (BMI > 30 kg/m2). Mean total cholesterol (TC) levels were significantly lower in high and middle eGDR tertiles (4.4 ± 1 and 4.3 ± 0.8 mmol/l, respectively) compared with low eGDR tertile (4.8 ± 1, p < 0.05 for both). Triglyceride (TG) levels showed a similar trend at 1.1 ± 0.5 and 1.1 ± 0.5 mmol/l for high and middle eGDR tertile compared to low eGDR tertile (1.5 ± 1 mmol/l, p < 0.05 for both). Renal function was similar across eGDR tertiles and no difference in retinopathy was detected. CONCLUSION: TC and TG are altered in individuals with T1DM and low eGDR, suggesting that this subgroup requires optimal lipid management to ameliorate their vascular risk.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Resistência à Insulina , Fatores Etários , Biomarcadores/sangue , Colesterol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Retrospectivos , Fatores de Tempo , Triglicerídeos/sangue , Adulto Jovem
5.
PLoS One ; 15(9): e0239091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915897

RESUMO

INTRODUCTION: To investigate the glycaemic response, macronutrient intake and insulin management in people with type 1 diabetes (T1D) compared to healthy individuals around a running competition. MATERIAL AND METHODS: This was a single-centre, prospective, controlled observational study performed in individuals with T1D and healthy people. 24 people (12 T1D) were included in this study (age: T1D 41±12 vs. healthy 38±6 years, females: 3 vs. 6, BMI: 25.53.0 vs. 22.9±2.8 kg/m2). Both groups received an intermittently scanned continuous glucose monitoring (isCGM; FreeStyle Libre 1, Abbott, USA) system to assess glycaemia 24 hours before, during and 24 hours after a running competition. During this period, participants recorded their food intake and insulin administration. Data were analysed via ANOVA and mixed model analyses with post-hoc testing (p≤0.05). RESULTS: For overall glycaemic ranges in comparison of groups, significant differences were found for time in range (T1D 63±21% vs. healthy 89±13%, p = 0.001), time above range (TAR) 1 (T1D 21±15% vs. healthy 0±0%, p<0.001) and TAR 2 (T1D 8 [0-16%] vs. healthy 0±0%, p<0.001). When glycaemic variability was assessed, people with T1D had a higher glycaemic variability compared to healthy individuals (p<0.0001). Basal insulin dose was significantly reduced when compared against the regular pre-study basal insulin dose (pre-study 22±6 vs. pre-competition day 11±9 (-50±41%), p = 0.02; competition day 15±5 (-32± 1%)). CONCLUSION: People with T1D have impaired glucose responses around a running competition compared to healthy individuals. However, basal insulin dose reductions were sufficient to prevent further dysglycaemia. CLINICAL TRIAL ID: drks.de; DRKS00019886.


Assuntos
Glicemia/fisiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Ingestão de Alimentos/fisiologia , Insulina/administração & dosagem , Corrida/fisiologia , Adolescente , Adulto , Idoso , Glicemia/análise , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia/estatística & dados numéricos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
7.
J Adolesc Health ; 67(4): 615-617, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32798101

RESUMO

Amidst the unprecedented global pandemic of COVID-19, attending to the needs of adolescents with diabetes mellitus became more challenging. They faced the uncertainty of access to care and the attendant problems of a lockdown. We present the nurse-led telehealth initiative for adolescents with diabetes mellitus, leveraging on existing infrastructure and resources with the aim of addressing the anticipated challenges that many of the adolescents might face. The initiative was well received among those who participated, and there were no significant adverse effects noted.


Assuntos
Diabetes Mellitus Tipo 1/enfermagem , Telemedicina , Adolescente , Betacoronavirus , Infecções por Coronavirus , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/terapia , Hemoglobina A Glicada/análise , Humanos , Pandemias , Satisfação do Paciente , Pneumonia Viral , Singapura , Inquéritos e Questionários
8.
PLoS One ; 15(8): e0237667, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833960

RESUMO

BACKGROUND AND AIMS: This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when ß-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early ß-cell damage. MATERIALS AND METHODS: We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. RESULTS: We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early ß-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. CONCLUSIONS: RIAO level increases as the number of complications rises; RIAOs > 3.35 µg/ml is a predictor of changes in the current indicators of ß-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.


Assuntos
Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Células Secretoras de Insulina/patologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Obesidade/patologia , Estrutura Quaternária de Proteína , Adolescente , Animais , Linhagem Celular , Sobrevivência Celular , Células Cultivadas , Criança , Pré-Escolar , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/sangue , Polipeptídeo Amiloide das Ilhotas Pancreáticas/toxicidade , Polipeptídeo Amiloide das Ilhotas Pancreáticas/ultraestrutura , Microscopia Eletrônica de Transmissão , Neurônios/efeitos dos fármacos , Obesidade/sangue , Obesidade/complicações , Projetos Piloto , Cultura Primária de Células , Multimerização Proteica , Ratos , Testes de Toxicidade Aguda
9.
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
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.
Nat Med ; 26(8): 1247-1255, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770166

RESUMO

Type 1 diabetes (T1D)-an autoimmune disease that destroys the pancreatic islets, resulting in insulin deficiency-often begins early in life when islet autoantibody appearance signals high risk1. However, clinical diabetes can follow in weeks or only after decades, and is very difficult to predict. Ketoacidosis at onset remains common2,3 and is most severe in the very young4,5, in whom it can be life threatening and difficult to treat6-9. Autoantibody surveillance programs effectively prevent most ketoacidosis10-12 but require frequent evaluations whose expense limits public health adoption13. Prevention therapies applied before onset, when greater islet mass remains, have rarely been feasible14 because individuals at greatest risk of impending T1D are difficult to identify. To remedy this, we sought accurate, cost-effective estimation of future T1D risk by developing a combined risk score incorporating both fixed and variable factors (genetic, clinical and immunological) in 7,798 high-risk children followed closely from birth for 9.3 years. Compared with autoantibodies alone, the combined model dramatically improves T1D prediction at ≥2 years of age over horizons up to 8 years of age (area under the receiver operating characteristic curve ≥ 0.9), doubles the estimated efficiency of population-based newborn screening to prevent ketoacidosis, and enables individualized risk estimates for better prevention trial selection.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Cetose/sangue , Medição de Risco , Autoanticorpos/imunologia , Autoimunidade/genética , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Insulina/deficiência , Insulina/imunologia , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/patologia , Cetose/imunologia , Masculino , Triagem Neonatal , Fatores de Risco
12.
Nutr Metab Cardiovasc Dis ; 30(10): 1800-1805, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32669240

RESUMO

BACKGROUND AND AIMS: Self-monitoring blood glucose (SMBG) remains a widespread tool to monitor blood glucose. The development of diabetes management systems (DMS) allows SMBG to provide additional information as time spent in target range (TIR). This study evaluates the association between HbA1c and TIR, evaluated through DMS, over 2 months, and 2 weeks. METHODS AND RESULTS: Type 1 (T1D) and Type 2 (T2D) insulin-treated patients with diabetes were enrolled. We used the term PIR (Points in Range) instead of TIR, since SMBG provides point-in-time glucose values rather than a continuous trend over time. PIR was calculated in 2-month and 2-week time ranges before available HbA1c measurement. One-hundred ninety-seven patients with T1D and 36 with T2D were recruited. HbA1c and PIR were inversely associated (2 months: R -0.72, 2 weeks R -0.70; p < 0.0001) in all subjects. The relationship did not change when T1D and T2D patients were analyzed separately. For every 10% change of PIR, there was a change of HbA1c by 0.4%. CONCLUSIONS: Our study, for the first time, demonstrates a significant correlation between HbA1c and PIR calculated by DMS. DMS offers additional information useful in disease management of patients with T1D and T2D performing SMBG.


Assuntos
Automonitorização da Glicemia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
Cardiovasc Diabetol ; 19(1): 102, 2020 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-32622354

RESUMO

Glycemic variability (GV), defined as an integral component of glucose homoeostasis, is emerging as an important metric to consider when assessing glycemic control in clinical practice. Although it remains yet no consensus, accumulating evidence has suggested that GV, representing either short-term (with-day and between-day variability) or long-term GV, was associated with an increased risk of diabetic macrovascular and microvascular complications, hypoglycemia, mortality rates and other adverse clinical outcomes. In this review, we summarize the adverse clinical outcomes of GV and discuss the beneficial measures, including continuous glucose monitoring, drugs, dietary interventions and exercise training, to improve it, aiming at better addressing the challenging aspect of blood glucose management.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Estilo de Vida Saudável , Hipoglicemiantes/uso terapêutico , Comportamento de Redução do Risco , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Dieta Saudável , Exercício Físico , Homeostase , Humanos , Hipoglicemiantes/efeitos adversos , Valor Nutritivo , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
Diabetes Res Clin Pract ; 166: 108281, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32628980

RESUMO

AIMS: To evaluate the effect of continuous subcutaneous insulin infusion (CSII) on glycaemic control, hypoglycaemia and emotional distress in adults with type 1 diabetes (T1D) during the first 12 months. METHODS: 47 patients were started on CSII as per NICE guidelines. Anthropometric, clinical and biochemical parameters, hypoglycaemia rates and emotional distress measured by Problem Areas in Diabetes questionnaires (PAID) were recorded at baseline and during follow up at 3-6 months and 6-12 months. RESULTS: Mean HbA1c dropped by 1.1% (11.8 mmol/mol; p < 0.0001) at 3-6 months and by 0.8% (8.6 mmol/mol; p = 0.008) at 6-12 months. Most patients had improved HbA1c between 6.5 and 8.5% (48-69 mmol/mol) during these follow ups (68.3% and 71.5% respectively). Frequency of hypoglycaemia reduced from 338.2 to 187.2 and 155.3 per 100 patient years during follow ups. Severe hypoglycaemia also decreased from 48.9 to 8.5 and 6.3 per 100 patient years respectively. PAID scores improved from 29.8 ± 18.5 to 17.2 ± 14.0 (p = 0.0002) at 3-6 months and to 12.8 ± 11.7 (p < 0.00001) at 6-12 months. Reduction in HbA1c, insulin dose and PAID scores was more significant in group with HbA1c > 8.5% (69 mmol/mol) at baseline whereas improvement in episodes of hypoglycaemia and severe hypoglycaemic was more in patients who had HbA1c ≤ 8.5% before commencement of CSII therapy. CONCLUSIONS: CSII therapy led to early improvement in glycaemic control, rates of hypoglycaemia and diabetes specific emotional distress. As beneficial effects are recorded within the first few months, CSII therapy should be started more proactively in T1D.


Assuntos
Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 1/terapia , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Angústia Psicológica , Estresse Psicológico/etiologia , Adulto , Glicemia/análise , Glicemia/metabolismo , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Seguimentos , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estresse Psicológico/epidemiologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
N Engl J Med ; 382(26): 2504-2513, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579811

RESUMO

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Supressores da Gota/uso terapêutico , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Idoso , Alopurinol/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina , Falha de Tratamento
17.
Acta Diabetol ; 57(10): 1245-1253, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32488499

RESUMO

AIMS: To compare diabetes patients with hyperglycaemic hyperosmolar state (HHS), diabetic ketoacidosis (DKA), and patients without decompensation (ND). METHODS: In total, 500,973 patients with type 1 or type 2 diabetes of all ages registered in the diabetes patient follow-up (DPV) were included. Analysis was stratified by age (≤ / > 20 years) and by manifestation/follow-up. Patients were categorized into three groups: HHS or DKA-during follow-up according to the most recent episode-or ND. RESULTS: At onset of diabetes, HHS criteria were met by 345 (68.4% T1D) and DKA by 9824 (97.6% T1D) patients. DKA patients had a lower BMI(-SDS) in both diabetes types compared to ND. HbA1c was higher in HHS/DKA. During follow-up, HHS occurred in 1451 (42.2% T1D) and DKA in 8389 patients (76.7% T1D). In paediatric T1D, HHS/DKA was associated with younger age, depression, and dyslipidemia. Pump usage was less frequent in DKA patients. In adult T1D/T2D subjects, metabolic control was worse in patients with HHS/DKA. HHS and DKA were also associated with excessive alcohol intake, dementia, stroke, chronic kidney disease, and depression. CONCLUSIONS: HHS/DKA occurred mostly in T1D and younger patients. However, both also occurred in T2D, which is of great importance in the treatment of diabetes. Better education programmes are necessary to prevent decompensation and comorbidities.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Cetoacidose Diabética/epidemiologia , Hiperglicemia/epidemiologia , Coma Hiperglicêmico Hiperosmolar não Cetótico/epidemiologia , Adolescente , Adulto , Idoso , Áustria/epidemiologia , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Cetoacidose Diabética/sangue , Cetoacidose Diabética/complicações , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Hiperglicemia/sangue , Hiperglicemia/complicações , Coma Hiperglicêmico Hiperosmolar não Cetótico/sangue , Coma Hiperglicêmico Hiperosmolar não Cetótico/complicações , Luxemburgo/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Suíça/epidemiologia , Adulto Jovem
18.
Arch Endocrinol Metab ; 64(3): 312-318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555999

RESUMO

OBJECTIVE: To identify the level of physical activity and glycemic variability of adolescents with type 1 diabetes mellitus and to compare glycemic variability on days with different amounts of moderate to vigorous physical activity (MVPA). SUBJECTS AND METHODS: A sample of 34 subjects aged 10 to 15 years, 18 (52.94%) female; age: 13.04 ± 1.94; HbA1c: 9.76 ± 1.51. Physical activity was measured by wGT3X accelerometer. The glucose data were obtained using continuous glucose monitoring, and the following glycemic variability measures were calculated: standard deviation (SD), low blood glucose index (LBGI), high blood glucose index (HBGI), mean amplitude of glycemic excursions (MAGE), glycemic risk assessment in diabetes equation (GRADE) and coefficient of variation (CV). The most and least active days (the days with greater and lesser time dedicated to physical activities of moderate to vigorous intensity, respectively) were identified. In addition, based on the whole period of accelerometer use, daily means of time spent in MVPA were identified among participants, who were then divided into three groups: up to 100 minutes; from 101 to 200 minutes and above 201 minutes. Then, the measures of glycemic variability were compared among the most and least active days and among the groups too. RESULTS: The amount of MVPA was significantly different between the days evaluated (237.49 ± 93.29 vs. 125.21 ± 58.10 minutes), but glycemic variability measures did not present a significant difference. CONCLUSION: Despite the significant differences in the amount of MVPA between the two days evaluated, the glycemic variability did not change significantly. Arch Endocrinol Metab. 2020;64(3):312-8.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Exercício Físico/fisiologia , Adolescente , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Masculino
19.
JAMA ; 323(23): 2397-2406, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32543682

RESUMO

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes. Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes. Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100). Main Outcomes and Measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate. Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8). Conclusions and Relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT03240432.


Assuntos
Automonitorização da Glicemia/métodos , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Hemoglobina A Glicada/análise , Hipoglicemia/prevenção & controle , Idoso , Automonitorização da Glicemia/instrumentação , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Feminino , Humanos , Hiperglicemia/diagnóstico , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial/instrumentação , Medidas de Resultados Relatados pelo Paciente
20.
PLoS One ; 15(6): e0234319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542057

RESUMO

AIMS: Robust evidence supports intensive glucose control in those with recently diagnosed type 1 diabetes to reduce the risk of developing micro- and macrovascular complications. Data to support longitudinal glycaemic targets is lacking. We aimed to explore if longer duration of diabetes and greater age might reduce the impact of glycaemia on the risk of vascular complications. RESEARCH AND DESIGN METHODS: Data for adults age 20 years or more, was extracted from a clinical database of people with type 1 diabetes cared for at a London teaching hospital. The presence or absence of micro- and macro-vascular complications was recorded. Multivariable logistic regression analysis was performed using HbA1c as independent variable, diabetes duration and age as continuous variable and obesity, hypertension, hypercholesterolaemia, low HDL cholesterol and hypertriglyceridaemia as categorical variables. RESULTS: Data from 495 patients was used. HbA1c above 60 mmol/mol (7.6%) was associated with increased microvascular complications in patients aged 20-44 years, independent of age and duration of diabetes. In older people with T1DM duration of diabetes was the major risk factor. CONCLUSIONS: Our study suggests that increased age and greater duration of diabetes reduce the impact of glycaemia on the risk of vascular complications. Intensive blood glucose management in patients aged ≥45 years may have limited benefits in terms of reducing the risk of complications although this does not dismiss the benefits of good glycaemic control in older people with T1DM.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Angiopatias Diabéticas/sangue , Hemoglobina A Glicada/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/prevenção & controle , Feminino , Carga Glicêmica , Humanos , Hipoglicemiantes , Insulina/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Fatores de Risco , Adulto Jovem
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