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1.
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
2.
PLoS One ; 15(8): e0237305, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822421

RESUMO

Diabetes can elicit direct deleterious effects on the myocardium, independent of coronary artery disease or hypertension. These cardiac disturbances are termed diabetic cardiomyopathy showing increased risk of heart failure with or without reduced ejection fraction. Presently, there is no specific treatment for this type of cardiomyopathy and in the case of type I diabetes, it may start in early childhood independent of glycemic control. We hypothesized that alterations in isolated myocyte contractility and cardiac function are present in the early stages of experimental diabetes in rats before overt changes in myocardium structure occur. Diabetes was induced by single-dose injection of streptozotocin (STZ) in rats with data collected from control and diabetic animals 3 weeks after injection. Left ventricle myocyte contractility was measured by single-cell length variation under electrical stimulation. Cardiac function and morphology were studied by high-resolution echocardiography with pulsed-wave tissue Doppler imaging (TDI) measurements and three-lead surface electrocardiogram. Triglycerides, cholesterol and liver enzyme levels were measured from plasma samples obtained from both groups. Myocardial collagen content and perivascular fibrosis of atria and ventricle were studied by histological analysis after picrosirius red staining. Diabetes resulted in altered contractility of isolated cardiac myocytes with increased contraction and relaxation time intervals. Echocardiography showed left atrium dilation, increased end-diastolic LV and posterior wall thickness, with reduced longitudinal systolic peak velocity (S') of the septum mitral annulus at the apical four-chamber view obtained by TDI. Triglycerides, aspartate aminotransferase and alkaline phosphatase were elevated in diabetic animals. Intertitial collagen content was higher in atria of both groups and did not differ among control and diabetic animals. Perivascular intramyocardial arterioles collagen did not differ between groups. These results suggest that alterations in cardiac function are present in the early phase in this model of diabetes type 1 and occur before overt changes in myocardium structure appear as evaluated by intersticial collagen deposition and perivascular fibrosis of intramyocardial arterioles.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Cardiomiopatias Diabéticas/fisiopatologia , Contração Miocárdica , Miócitos Cardíacos/patologia , Animais , Células Cultivadas , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/patologia , Cardiomiopatias Diabéticas/induzido quimicamente , Cardiomiopatias Diabéticas/patologia , Ratos , Estreptozocina
3.
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
4.
Diabetes Res Clin Pract ; 166: 108297, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32623042

RESUMO

AIMS: Coronavirus disease (Covid-19) could lead persons with pre-existing medical conditions to severe respiratory infections. The Italian Government introduced quarantine to limit viral transmission. This measure could lead people with type 1 diabetes (PWT1D) to disrupt daily care routine including PA practice with difficulties in glycemia management. This study aims to explore PA level in PWT1D before and during quarantine and to describe variation in glycemia values. METHODS: An online survey investigating medical factors and the perceived and PA level in pre-established period before and after the introduction of quarantine was developed. Comparison between pre and post quarantine was assessed by Wilcoxon Signed Ranks test for continuous variables. RESULTS: A total of 154 subjects satisfied the eligibility criteria (54.5% males, 44.8 ± 12.5 years). We found a decrease of PA level (Godin Scale Score 25 ± 1.7vs38.6 ± 1.7 points), steps number and minutes of exercise (respectively 12.606 ± 5026vs4.760 ± 3.145 and 66±4 vs 38±3) and an increase of glycemia values (142.1 ± 25.4 mg/dLvs150.8 ± 29.4 mg/dL). CONCLUSIONS: PWT1D reported a decrease in exercise and worst glycemia. Although PWT1D tried to remain active, their PA level was inadequate to prevent glycemia rising. The difficult to maintain a glycemic control could expose patients to diabetes complications and to an higher risk to counteract infections.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/prevenção & controle , Diabetes Mellitus Tipo 1/terapia , Exercício Físico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adulto , Glicemia/análise , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/virologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Quarentena , Inquéritos e Questionários
5.
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
6.
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
7.
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
8.
Am J Physiol Regul Integr Comp Physiol ; 319(3): R358-R365, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726156

RESUMO

Studies have shown that early-stage type 1 diabetes mellitus (T1DM) leads to an exaggerated reflex pressor response to both static muscle contraction and tendon stretch. However, whether similar responses are present during dynamic exercise (i.e., intermittent contraction) is not known. Therefore, the purpose of this study was to determine whether T1DM leads to an exaggerated reflex pressor response to intermittent muscle contraction. We measured the exercise pressor reflex in unanesthetized, decerebrated T1DM (50 mg/kg streptozotocin; STZ) and healthy control (CTL) Sprague-Dawley rats by intermittently contracting the hindlimb muscles for 30 s while measuring mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). Intermittently contracting the hindlimb muscles evoked exaggerated mean RSNA (STZ: Δ109 ± 21%, n = 4 rats; CTL: Δ61 ± 8%, n = 5 rats, P < 0.05), peak MAP (STZ: Δ32 ± 2 mmHg, n = 9 rats; CTL: Δ12 ± 2 mmHg, n = 6 rats, P < 0.05), blood pressure index (STZ: Δ625 ± 60 mmHg/s, n = 9 rats; CTL: Δ241 ± 46 mmHg/s, n = 6 rats, P < 0.05), and HR (STZ: Δ24 ± 3 beats/min, n = 9 rats; CTL: Δ9 ± 3 beats/min, n = 6 rats, P < 0.05) responses to similar developed tensions (P > 0.05) in T1DM compared with CTL rats. T1DM rats also exhibited exaggerated early-onset sympathetic (onset: 1 s) and pressor (onset: 5 s) responses. These data show that early-stage T1DM leads to an exaggerated pressor reflex evoked by intermittent muscle contraction. The early onset and greater blood pressure index suggest that cardiovascular strain during dynamic exercise may be significantly higher in individuals with T1DM.NEW & NOTEWORTHY This is the first study to provide evidence that early-stage type 1 diabetes mellitus (T1DM) leads to an exaggerated exercise pressor reflex evoked by intermittent muscle contraction, resulting in substantially higher cardiovascular strain. These findings are significant as they indicate that interventions targeting the exercise pressor reflex may work to alleviate the increased cardiovascular strain and overall burden during exercise in T1DM.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Diabetes Mellitus Tipo 1/fisiopatologia , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Sistema Cardiovascular , Ratos Sprague-Dawley , Reflexo/fisiologia , Sistema Nervoso Simpático/fisiopatologia
9.
Diabetes Metab Syndr ; 14(5): 1213-1216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32679527

RESUMO

BACKGROUND AND AIMS: COVID 19 is a novel pandemic affecting globally. Although no reliable data suggests that patients of well controlled Type 1 Diabetes Mellitus (T1DM) being at increased risk of becoming severely ill with SARS-CoV2, but lockdown may impact patients with T1DM requiring regular medications and follow up. Hence this study was planned to see the impact of lockdown on glycemic control in patients with T1DM. METHODS: A cross sectional study was done in T1DM patients in whom a structured questionnaire was administered on follow up within 15 days after lockdown. Data regarding hypoglycemic and hyperglycemic episodes, Diabetic ketoacidosis (DKA), insulin dose missed, regular glucose monitoring, dietary compliance, physical activity, hospitalization during the phase of lockdown was taken. Average blood glucose and HbA1C of lockdown phase was compared with the readings of prelockdown phase. RESULTS: Out of 52 patients, 36.5% had hyperglycemic and 15.3% had hypoglycemic episodes. Insulin dose was missed in 26.9%, glucose monitoring not done routinely in 36.5% and 17.4% were not diet compliant during lockdown. Average blood glucose during lockdown phase was 276.9 ± 64.7 mg/dl as compared to 212.3 ± 57.9 mg/dl during prelockdown phase. Mean HbA1c value of lockdown (10 ± 1.5%) which was much higher that of pre lockdown (8.8 ± 1.3%) and the difference was statistically significant (p < 0.05). CONCLUSION: Glycemic control of T1DM patients has worsened mainly due to non availability of insulin/glucostrips during lockdown period. There is a need for preparedness in future so that complications can be minimised.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Hiperglicemia/epidemiologia , Hipoglicemia/epidemiologia , Pneumonia Viral/complicações , Quarentena/estatística & dados numéricos , Adolescente , Adulto , Biomarcadores/análise , Glicemia/análise , Criança , Pré-Escolar , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Estudos Transversais , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/virologia , Hipoglicemia/virologia , Incidência , Índia/epidemiologia , Lactente , Masculino , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico , Adulto Jovem
10.
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
11.
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
12.
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
13.
Diab Vasc Dis Res ; 17(3): 1479164120928303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32538145

RESUMO

AIM: The aim of this study was to investigate the correlation between skin microvascular reactivity and clinical microangiopathy in patients with type 1 diabetes. METHODS: We included 61 patients with type 1 diabetes, that is, 31 patients with and 30 without clinical microangiopathy, and 31 healthy controls. A microangiopathy scoring system was introduced for comparison of data between patients with microangiopathy. Responses to iontophoresis of acetylcholine and sodium nitroprusside were assessed by laser Doppler imaging. RESULTS: Patients with microangiopathy had reduced acetylcholine- and sodium nitroprusside-mediated flux in forearm skin microcirculation compared to healthy controls (p = 0.03 and p < 0.001, respectively, repeated measures analysis of variance), whereas no significant differences were found between patients without microangiopathy and controls. Skin reactivity was reduced in patients with microangiopathy compared to patients without microangiopathy: 1.43 ± 0.38 versus 1.59 ± 0.39 arbitrary units for acetylcholine-mediated peak flux and 1.44 ± 0.46 versus 1.74 ± 0.34 arbitrary units for sodium nitroprusside-mediated peak flux (p < 0.05 for both). A tendency of gradual decrease in acetylcholine and sodium nitroprusside responses was found in patients with increasing microangiopathy scores. CONCLUSION: We conclude that skin microvascular reactivity is associated with clinical microangiopathy in patients with type 1 diabetes. Impaired skin microvascular function in type 1 diabetes seems to be multifactorial and involves both endothelial-dependent and endothelial-independent pathways. We introduce a novel microangiopathy score that could easily be used in a clinical setting for comparison of patients with various degrees of microangiopathy.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Microcirculação , Pele/irrigação sanguínea , Vasodilatação , Administração Cutânea , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/fisiopatologia , Feminino , Antebraço , Humanos , Iontoforese , Fluxometria por Laser-Doppler , Masculino , Microcirculação/efeitos dos fármacos , Angioscopia Microscópica , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Fatores de Risco , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem
14.
Life Sci ; 255: 117724, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32360624

RESUMO

AIMS: Type 1 diabetes (T1D) is the most common autoimmune disease that affects a global scale. Accumulating evidence has indicated, nuclear factor kappa B (NF-κB) and some microRNAs (miRNAs) as important biomarkers participating in the development of T1D. Thus, we aimed to determine the role of NF-κB and miR-150 in the development of T1D and to unravel the molecular mechanism. MAIN METHODS: Non-obese diabetic mice were used for the T1D model establishment by injecting with streptozotocin. Besides, pancreatic islet ß cells, separated from T1D mice, were induced by interferon-γ and tumor necrosis factor-α for 3 days to mimic T1D damage. The expression of NF-κB p65, miR-150, and p53 up-regulated modulator of apoptosis (PUMA) was evaluated by RT-qPCR, while the expression of PUMA, p65, and apoptotic proteins in pancreatic islet ß cells were determined by western blot analysis. Besides, inflammatory factors IL-17A, IL-2, IFN-γ, and IL-4 were detected by ELISA. The relationship among NF-κB, miR-150, and PUMA was analyzed by the dual-luciferase reporter gene, chromatin- and RNA-immunoprecipitation assays, respectively. KEY FINDINGS: Restoration of NF-κB reduced the incidence of T1D in mice. Over-expressed NF-κB inhibited the release of inflammatory factors and apoptosis in pancreatic islet ß cells. PUMA was confirmed to be a potential target gene of miR-150. miR-150 suppressed PUMA to inhibit the T1D-induced inflammation and ß cell apoptosis whereas NF-κB activated the miR-150 expression by binding to the miR-150 promoter, thereby preventing the T1D-induced inflammation and ß cell apoptosis. SIGNIFICANCE: NF-κB/miR-150/PUMA may serve as potential therapeutic targets for T1D.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , MicroRNAs/genética , NF-kappa B/genética , Proteínas Supressoras de Tumor/genética , Animais , Apoptose/genética , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 1/genética , Inflamação/genética , Inflamação/patologia , Células Secretoras de Insulina/patologia , Camundongos , Camundongos Endogâmicos NOD , Regulação para Cima
15.
Rev Assoc Med Bras (1992) ; 66(2): 216-221, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32428158

RESUMO

OBJECTIVE: In diabetics, foot deformities are risk factors that increase the risk of amputation as a result of developing ulcers. However, knowledge of the influence of plantar stiffness is still limited. The main objective was to describe connections between the degree of stiffness of the ankle, atypical amputation, and the Foot Posture Index (FPI). METHODS: 62 diabetic patients, 58 with type 2 and 4 with type 1 (average age 63.35 years) were included. Records of foot deformities were included; A range of motion test of the ankle joint was used to determine the degree of stiffness. An exploratory analysis of the association of foot position and the degree of rigidity was performed. RESULTS: The dorsal flexion range of the ankle was 9.6 ± 5.1 0, 13.8 ± 5.9 0 and 17.2 ± 6.5 0 and 20.5 ± 6.8 0 to 45, 67, 89 and 111 N respectively in the amputated feet., And 14 patients (22.58%) had a high level of pronation of IPF with an average value of 3.7 ± 2.629, CI (3.032.-4.367) in amputated feet compared to non-amputees. We use the device "Iowa ankle range of motion" (IAROM) to determine the differences in ankle stiffness. Proper IPF was associated with the presence of amputation and an increase in stiffness. CONCLUSIONS: There was an increase in the degree of limitation of movement of the ankle, as a greater force was applied. Comparing FPI between the groups, there was a higher frequency of prone feet in the group of amputees.


Assuntos
Amputação , Articulação do Tornozelo/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Amplitude de Movimento Articular/fisiologia , Idoso , Antropometria , Estudos Transversais , Feminino , Pé/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Postura/fisiologia , Valores de Referência , Estatísticas não Paramétricas
16.
Nat Rev Endocrinol ; 16(7): 349-362, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32398822

RESUMO

Loss of functional ß-cell mass is the key mechanism leading to the two main forms of diabetes mellitus - type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Understanding the mechanisms behind ß-cell failure is critical to prevent or revert disease. Basic pathogenic differences exist in the two forms of diabetes mellitus; T1DM is immune mediated and T2DM is mediated by metabolic mechanisms. These mechanisms differentially affect early ß-cell dysfunction and eventual fate. Over the past decade, major advances have been made in the field, mostly delivered by studies on ß-cells in human disease. These advances include studies of islet morphology and human ß-cell gene expression in T1DM and T2DM, the identification and characterization of the role of T1DM and T2DM candidate genes at the ß-cell level and the endoplasmic reticulum stress signalling that contributes to ß-cell failure in T1DM (mostly IRE1 driven) and T2DM (mostly PERK-eIF2α dependent). Here, we review these new findings, focusing on studies performed on human ß-cells or on samples obtained from patients with diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Pancreática Exócrina/etiologia , Células Secretoras de Insulina/fisiologia , Animais , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Insuficiência Pancreática Exócrina/fisiopatologia , Humanos , Células Secretoras de Insulina/patologia , Transdução de Sinais/fisiologia
17.
Health Qual Life Outcomes ; 18(1): 137, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398086

RESUMO

BACKGROUND: Young adulthood is a challenging period for people with diabetes mellitus type 1 (T1DM) as they are facing multiple life transitions while managing a demanding disease. This poses a risk for impaired health-related quality of life (HRQOL). We assessed HRQOL in a cohort of young adults with T1DM in the Netherlands, and compared outcomes with those of Dutch norm groups of healthy young adults and young adults with a chronic disease. METHODS: We analyzed data collected in a larger evaluation study on transitional care for young adults with T1DM in a nationwide sample in the Netherlands, including twelve participating hospitals. These data had been obtained from online questionnaires completed by young adults with T1DM after they had transferred to adult care. HRQOL was self-reported with the Pediatric Quality of Life Inventory for young adults (PedsQL-YA). RESULTS: One hundred and sixty-five young adults with T1DM participated (44.2% response); and they scored significantly worse than did healthy peers on all domains of HRQOL, except social functioning. Particularly, functioning at school or work was worse than that of the norm group. The study group's HRQOL-scores were comparable to norm scores of young adults with chronic diseases, although the physical and social functioning of young people with T1DM was better. One quarter (26.1%) of all young adults with T1DM reported fatigue. CONCLUSIONS: During transition to adulthood, young adults with T1DM struggle to maintain a balance between the demands of managing a disease and their life. Many of them encounter problems at work or school, and suffer from fatigue. These findings underscore the need to regularly assess HRQOL, and to discuss work- and education-related issues in clinical practice.


Assuntos
Diabetes Mellitus Tipo 1/psicologia , Progressão da Doença , Qualidade de Vida , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 1/fisiopatologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Países Baixos , Autorrelato , Transição para Assistência do Adulto , Adulto Jovem
18.
Invest Ophthalmol Vis Sci ; 61(5): 36, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32437549

RESUMO

Purpose: Retinal vasomotor activity can be regulated by two major endothelial enzymes, nitric oxide synthase (NOS) and cyclooxygenase (COX). The vascular arginase also consumes a NOS substrate and thus impedes NOS-mediated vasodilation. Diabetes mellitus exhibits vascular complications in the retina with elevated oxidative stress and compromised NOS-mediated vasodilation. However, the underlying molecular mechanisms remain unclear, and the effect of diabetes on COX-mediated vasodilation is unknown. Herein, we examined the relative impact of diabetes on retinal arteriolar dilations to COX and NOS activation and the roles of arginase and superoxide in diabetes-induced vasomotor dysfunction. Methods: Retinal arterioles were isolated from streptozocin-induced diabetic pigs (2 weeks of hyperglycemia, 433 ± 27 mg/dL) or age-matched control pigs (97 ± 4 mg/dL). The vasodilations to bradykinin (NOS activator) and histamine (NOS/COX activator) were examined in vitro. Results: Retinal arteriolar dilations to histamine and bradykinin were significantly reduced after 2 weeks of diabetes. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the dilations of control vessels, but not diabetic vessels, to histamine. In the presence of L-NAME and COX inhibitor indomethacin, histamine-induced dilations of control and diabetic vessels were reduced similarly. Treatment of diabetic vessels with arginase inhibitor nor-NOHA, but not superoxide dismutase mimetic TEMPOL, preserved both histamine- and bradykinin-induced dilations in an L-NAME-sensitive manner. Conclusions: Arginase, rather than superoxide, impairs endothelium-dependent NOS-mediated dilation of retinal arterioles during diabetes, whereas vasodilation mediated by COX remains intact. Blockade of vascular arginase may improve endothelial function of retinal arterioles during early onset of diabetes.


Assuntos
Arginase/fisiologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Endotélio Vascular/enzimologia , Óxido Nítrico Sintase Tipo III/metabolismo , Artéria Retiniana/fisiologia , Vasodilatação/fisiologia , Animais , Arteríolas/fisiologia , Glicemia/metabolismo , Bradicinina/farmacologia , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Tipo 1/enzimologia , Inibidores Enzimáticos/farmacologia , Histamina/farmacologia , Hiperglicemia/fisiopatologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Sus scrofa
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