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1.
BMC Med ; 21(1): 506, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124088

RESUMO

BACKGROUND: Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations. METHODS: Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort's distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial's intervention was targeted (national). RESULTS: Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p < 0.001) were over- and under-represented relative to the regional reference, while the UK featured higher regional and national SES bias with over-representation and under-representation from the least-deprived and most-deprived quintiles (p < 0.0001). CONCLUSIONS: Significant national differences in trial participation of low SES participants were observed, highlighting limitations in access to clinical research and the importance of reporting sociodemographic representation in diabetes clinical trials. TRIAL REGISTRATION: NCT01581476. Registered on 20 April 2012.


Assuntos
Diabetes Mellitus Tipo 1 , Adolescente , Humanos , Austrália/epidemiologia , Canadá/epidemiologia , Ensaios Clínicos como Assunto , Estudos Transversais , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/terapia , Estudos Retrospectivos , Fatores Socioeconômicos
2.
N Engl J Med ; 377(18): 1733-1745, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-29091568

RESUMO

BACKGROUND: Among adolescents with type 1 diabetes, rapid increases in albumin excretion during puberty precede the development of microalbuminuria and macroalbuminuria, long-term risk factors for renal and cardiovascular disease. We hypothesized that adolescents with high levels of albumin excretion might benefit from angiotensin-converting-enzyme (ACE) inhibitors and statins, drugs that have not been fully evaluated in adolescents. METHODS: We screened 4407 adolescents with type 1 diabetes between the ages of 10 and 16 years of age and identified 1287 with values in the upper third of the albumin-to-creatinine ratios; 443 were randomly assigned in a placebo-controlled trial of an ACE inhibitor and a statin with the use of a 2-by-2 factorial design minimizing differences in baseline characteristics such as age, sex, and duration of diabetes. The primary outcome for both interventions was the change in albumin excretion, assessed according to the albumin-to-creatinine ratio calculated from three early-morning urine samples obtained every 6 months over 2 to 4 years, and expressed as the area under the curve. Key secondary outcomes included the development of microalbuminuria, progression of retinopathy, changes in the glomerular filtration rate, lipid levels, and measures of cardiovascular risk (carotid intima-media thickness and levels of high-sensitivity C-reactive protein and asymmetric dimethylarginine). RESULTS: The primary outcome was not affected by ACE inhibitor therapy, statin therapy, or the combination of the two. The use of an ACE inhibitor was associated with a lower incidence of microalbuminuria than the use of placebo; in the context of negative findings for the primary outcome and statistical analysis plan, this lower incidence was not considered significant (hazard ratio, 0.57; 95% confidence interval, 0.35 to 0.94). Statin use resulted in significant reductions in total, low-density lipoprotein, and non-high-density lipoprotein cholesterol levels, in triglyceride levels, and in the ratio of apolipoprotein B to apolipoprotein A1, whereas neither drug had significant effects on carotid intima-media thickness, other cardiovascular markers, the glomerular filtration rate, or progression of retinopathy. Overall adherence to the drug regimen was 75%, and serious adverse events were similar across the groups. CONCLUSIONS: The use of an ACE inhibitor and a statin did not change the albumin-to-creatinine ratio over time. (Funded by the Juvenile Diabetes Research Foundation and others; AdDIT ClinicalTrials.gov number, NCT01581476 .).


Assuntos
Albuminúria/prevenção & controle , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Creatinina/urina , Diabetes Mellitus Tipo 1/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Adolescente , Albuminúria/etiologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Área Sob a Curva , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/urina , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Lipídeos/sangue , Masculino , Adesão à Medicação
3.
Pediatr Diabetes ; 21(7): 1322-1332, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32783254

RESUMO

OBJECTIVES: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D. METHODS: Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/min/1.73m2 /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource. RESULTS: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10-7 ; -0.18 [-0.26, -0.11], P = 5.1 × 10-6 ; -0.12 [-0.20, -0.05], P = 1.6 × 10-3 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10-8 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10-6 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10-6 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10-4 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR. CONCLUSIONS: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Adolescente , Adulto , Fatores Etários , Biomarcadores/sangue , Criança , Estudos de Coortes , Cistatina C/sangue , Nefropatias Diabéticas/diagnóstico , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular , Humanos , Pessoa de Meia-Idade , Osteopontina/sangue , Fator Trefoil-3/sangue , Adulto Jovem , Microglobulina beta-2/sangue
4.
Eur Heart J ; 40(43): 3559-3566, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30863865

RESUMO

AIMS: High-density lipoprotein (HDL) function may be altered in patients with chronic disease, transforming the particle from a beneficial vasoprotective molecule to a noxious pro-inflammatory equivalent. Adolescents with Type 1 diabetes often have elevated HDL, but its vasoprotective properties and relationship to endothelial function have not been assessed. METHODS AND RESULTS: Seventy adolescents with Type 1 diabetes (age 10-17 years) and 30 age-matched healthy controls supplied urine samples for the measurement of early renal dysfunction (albumin:creatinine ratio; ACR), blood samples for the assessment of cardiovascular risk factors (lipid profiles, HDL functionality, glycaemic control, and inflammatory risk score), and had their conduit artery endothelial function tested using flow-mediated dilation (FMD). HDL-c levels (1.69 ± 0.41 vs. 1.44 ± 0.29mmol/L; P < 0.001), and glycated haemoglobin (HbA1c) (8.4 ± 1.2 vs. 5.4 ± 0.2%; P < 0.001) were increased in all patients compared with controls. However, increased inflammation and HDL dysfunction were evident only in patients who also had evidence of early renal dysfunction (mean ± standard deviation for high-ACR vs. low-ACR and healthy controls: inflammatory risk score 11.3 ± 2.5 vs. 9.5 ± 2.4 and 9.2 ± 2.4, P < 0.01; HDL-mediated nitric-oxide bioavailability 38.0 ± 8.9 vs. 33.3 ± 7.3 and 25.0 ± 7.7%, P < 0.001; HDL-mediated superoxide production 3.71 ± 3.57 vs. 2.11 ± 3.49 and 1.91 ± 2.47nmol O2 per 250 000 cells, P < 0.05). Endothelial function (FMD) was impaired only in those who had both a high inflammatory risk score and high levels of HDL-c (P < 0.05). CONCLUSION: Increased levels of HDL-c commonly observed in individuals with Type 1 diabetes may be detrimental to endothelial function when accompanied by renal dysfunction and chronic inflammation.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Endotélio Vascular/fisiopatologia , Hiperlipidemias/etiologia , Inflamação/etiologia , Lipoproteínas HDL/sangue , Adolescente , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Doença Crônica , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/fisiopatologia , Inflamação/sangue , Inflamação/fisiopatologia , Masculino , Insuficiência Renal/sangue , Insuficiência Renal/etiologia , Insuficiência Renal/fisiopatologia
5.
Am J Physiol Renal Physiol ; 314(4): F667-F674, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29357443

RESUMO

Adolescents with Type 1 diabetes mellitus (T1DM) are at risk for hyperfiltration and elevated urinary albumin-to-creatinine ratio (ACR), which are early indicators of diabetic nephropathy. Adolescents with T1DM also develop early changes in blood pressure, cardiovascular structure, and function. Our aims were to define the relationships between hyperfiltration, ACR, and 24-h ambulatory blood pressure over time in adolescents with T1DM. Normotensive, normoalbuminuric adolescents ( n = 98) with T1DM underwent baseline and 2-yr 24-h ambulatory blood pressure monitoring, glomerular filtration rate (eGFR) estimated by cystatin C (Larsson equation), and ACR measurements. Linear regression models adjusted for diabetes duration, sex, and HbA1c were used to determine associations. Hyperfiltration (eGFR ≥ 133 ml/min) was present in 31% at baseline and 21% at 2-yr follow-up. Hyperfiltration was associated with greater odds of rapid GFR decline (>3 ml·min-1·yr-1) [OR: 5.33, 95%; CI: 1.87-15.17; P = 0.002] over 2 yr. Natural log of ACR at baseline was associated with greater odds of hyperfiltration (OR: 1.71, 95% CI: 1.00-2.92; P = 0.049) and 2-yr follow-up (OR: 2.14, 95%; CI: 1.09-4.19; P = 0.03). One SD increase in eGFR, but not ln ACR, at 2-yr follow-up conferred greater odds of nighttime nondipping pattern (OR: 1.96, 95% CI: 1.06-3.63; P = 0.03). Hyperfiltration was prevalent at baseline and at 2-yr follow-up, predicted rapid decline in GFR, and was related to ACR. Elevated GFR at 2-yr follow-up was associated with nighttime nondipping pattern. More work is needed to better understand early relationships between renal hemodynamic and systemic hemodynamic changes in adolescents with T1DM to reduce future cardiorenal complications.


Assuntos
Albuminúria/etiologia , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/etiologia , Taxa de Filtração Glomerular , Rim/fisiopatologia , Adolescente , Fatores Etários , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Biomarcadores , Monitorização Ambulatorial da Pressão Arterial , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Criança , Ritmo Circadiano , Creatinina/sangue , Cistatina C/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Lipoproteínas LDL/sangue , Masculino , Prognóstico , Fatores de Risco , Fatores de Tempo
6.
J Pediatr ; 198: 247-253.e1, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29752172

RESUMO

OBJECTIVE: To examine the relationship between the social determinants of health and markers of early renal injury in adolescent patients with type 1 diabetes (T1D). STUDY DESIGN: Renal outcomes included estimated glomerular filtration rate (eGFR) and albumin-creatinine excretion ratio (ACR). Differences in urinary and serum inflammatory markers also were assessed in relation to social determinants of health. Regression analysis was used to evaluate the association between the Ontario Marginalization Index (ON-Marg) as a measure of the social determinants of health, patient characteristics, ACR, eGFR, and renal filtration status (hyperfiltration vs normofiltration). RESULTS: Participants with T1D (n = 199) with a mean age of 14.4 ± 1.7 years and diabetes duration of 7.2 ± 3.1 years were studied. Mean eGFR was 122.0 ± 19.4 mL/min/1.73 m2. Increasing marginalization was positively associated with eGFR (P < .0001) but not with ACR (P = .605). Greater marginalization was associated with greater median levels of urinary interleukin (IL)-2, IL-12 (p40), macrophage-derived chemokine, monocyte chemoattractant protein-3, and tumor necrosis factor-ß and serum IL-2. ON-Marg was significantly associated with eGFR after we controlled for age, sex, body mass index z score, ethnicity, serum glucose, and hemoglobin A1c in linear regression. A similar association between hyperfiltration and ON-Marg score was observed in multivariable logistic regression. CONCLUSION: Increasing marginalization is significantly associated with both eGFR and hyperfiltration in adolescents with T1D and is associated with significant changes in urinary inflammatory biomarkers. These findings highlight a potentially important interaction between social and biological determinants of health in adolescents with T1D.


Assuntos
Injúria Renal Aguda/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/psicologia , Determinantes Sociais da Saúde , Injúria Renal Aguda/diagnóstico , Adolescente , Biomarcadores/metabolismo , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Mediadores da Inflamação/metabolismo , Modelos Logísticos , Masculino , Albumina Sérica Humana/metabolismo , Marginalização Social
7.
Am J Physiol Renal Physiol ; 312(2): F335-F342, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27733369

RESUMO

The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess 1) levels of urinary RAAS components and 2) the association between RAAS components and HbA1c, the urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and blood pressure (BP) in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). Urinary angiotensinogen and angtionsin-converting enzyme (ACE) 2 levels, activity of ACE and ACE2, BP, HbA1c, ACR, and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). Urinary levels of all RAAS components were higher in T1D vs. HC (P < 0.0001). Higher HbA1c was associated with higher urinary angiotensinogen, ACE2, and higher activity of ACE and ACE2 (P < 0.0001, P = 0.0003, P = 0.003, and P = 0.007 respectively) in T1D. Higher ACR (within the normal range) was associated with higher urinary angiotensinogen (P < 0.0001) and ACE activity (P = 0.007), but not with urinary ACE2 activity or ACE2 levels. These observations were absent in HC. Urinary RAAS components were not associated with BP or eGFR in T1D or HC. Otherwise healthy adolescents with T1D exhibit higher levels of urinary RAAS components compared with HC. While levels of all urinary RAAS components correlate with HbA1c in T1D, only urinary angiotensinogen and ACE activity correlate with ACR, suggesting that these factors reflect an intermediary pathogenic link between hyperglycemia and albuminuria within the normal range.


Assuntos
Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Rim/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Adolescente , Albuminúria/metabolismo , Angiotensinogênio/urina , Biomarcadores/metabolismo , Creatinina/urina , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/metabolismo , Masculino , Peptidil Dipeptidase A/urina
8.
Pediatr Diabetes ; 18(1): 33-44, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26748950

RESUMO

OBJECTIVE: To describe insulin pump use by youth since introduction of universal funding in Ontario, Canada and to explore the relationship between pump use and pediatric diabetes center characteristics and the relationship between discontinuation and center and patient characteristics. RESEARCH DESIGN AND METHODS: Observational, population-based cohort study of youth with type 1 diabetes (<19 yr) who received pump funding from 2006 to 2013 (n = 3700). We linked 2012 survey data from 33 pediatric diabetes centers to health administrative databases. We tested the relationship between center-level pump uptake and center characteristics (center type, physician model, and availability of 24-h support) using an adjusted negative binomial model; we studied center- and patient-level factors (socioeconomic status and baseline glycemic control) associated with discontinuation using a Cox proportional hazards model with generalized estimating equations. RESULTS: Pump users were more likely to be in the highest income quintile than non-pump users (29.6 vs. 19.1%, p < 0.0001). In 2012, mean percent pump use was 38.0% with variability across centers. There was no association between uptake and center characteristics. Discontinuation was low (0.42/100 person-yr) and was associated with being followed at a small community center [hazard ratio (HR): 2.24 (1.05-4.76)] and being more deprived [HR: 2.36 (1.14-1.48)]. Older age was associated with a lower rate of discontinuation [HR: 0.31 (0.14-0.66)]. CONCLUSIONS: Rates of pump use have increased since 2006 and discontinuation is rare. Large variation in uptake across centers was not explained by the factors we examined but may reflect variation in patient populations or practice patterns, and should be further explored.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Sistemas de Infusão de Insulina/estatística & dados numéricos , Masculino , Ontário/epidemiologia , Classe Social
9.
Healthc Q ; 19(4): 6-9, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28130944

RESUMO

We evaluated the universal funding program for pediatric insulin pumps in Ontario by examining the dynamics underlying patterns of pump use and adverse events using population-based health administrative data available at the Institute for Clinical Evaluative Sciences (ICES), supplemented by other data. We found that (1) pump use has increased steadily since 2006 with variation across centres and disparity in use by socioeconomic status; (2) pump discontinuation is uncommon; (3) physicians value pump therapy in numerous ways that provide important insights into patterns of uptake; and (4) the safety profile of pump therapy is, in general, very good; however, individuals of lower socioeconomic status are at an increased risk of acute diabetes complications, most frequently diabetic ketoacidosis. This comprehensive mixed-methods evaluation reveals the need to understand and intervene to reduce social disparities in the use and adverse outcomes of technologies used for diabetes management.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina/efeitos adversos , Sistemas de Infusão de Insulina/economia , Adolescente , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/epidemiologia , Disparidades em Assistência à Saúde , Humanos , Insulina/administração & dosagem , Sistemas de Infusão de Insulina/estatística & dados numéricos , Ontário
10.
J Pediatr ; 177: 167-172, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27476636

RESUMO

OBJECTIVE: To evaluate the relationship between social determinants of health (SDH) and cardiovascular disease (CVD) risk factors as well as a measure of arterial stiffness in adolescents with type 1 diabetes (T1D). STUDY DESIGN: SDH were measured with the validated Ontario Marginalization Index, derived from deidentified postal code data and stratified by quintile (first = least deprived; fifth = most deprived). SDH dimensions included material deprivation; ethnic concentration; and measures of dependency and residential instability. Metabolic control (hemoglobin A1c), cardiovascular risk metrics, and pulse wave velocity, as a measure of arterial stiffness, were related to SDH. Data were evaluated from a cohort of Canadian adolescents within the Adolescent Diabetes Cardiorenal Intervention Trial, a T1D clinical trial RESULTS: A total of 704 participants were evaluated, and significant differences in hemoglobin A1c were evident at the extremes of material deprivation (8.4% vs 9.1% for least vs most deprived, P < .01). CVD risk factors were analyzed in 199 participants, with the most deprived reporting significantly less exercise (P = .004) and increased rates of smoking (P = .008). Increased material deprivation was associated with fewer metrics of "ideal" cardiovascular health attained. Arterial stiffness, as measured by pulse wave velocity, was associated positively with age, body mass index z score, and material deprivation. CONCLUSION: Increased material deprivation was associated with poorer glycemic control. Modifiable, lifestyle-related risk factors for CVD and early arterial wall change are associated with SDH and represent a target for clinical intervention to reduce future CVD burden in adolescents with T1D.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/etiologia , Determinantes Sociais da Saúde , Rigidez Vascular , Adolescente , Feminino , Humanos , Masculino , Análise de Onda de Pulso , Fatores de Risco
11.
Paediatr Child Health ; 25(7): 399-400, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33173549
12.
Diabetologia ; 56(10): 2308-17, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23893332

RESUMO

AIMS/HYPOTHESIS: Acute clamped hyperglycaemia activates the renin-angiotensin-aldosterone system (RAAS) and increases the urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus. Our objective was to determine whether blockade of the RAAS would blunt the effect of acute hyperglycaemia on urinary cytokine/chemokine excretion, thereby giving insights into potentially protective effects of these agents prior to the onset of clinical nephropathy. METHODS: Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances) and urinary cytokines/chemokines were measured after 6 h of clamped euglycaemia (4-6 mmol/l) and hyperglycaemia (9-11 mmol/l) on two consecutive days in patients with type 1 diabetes mellitus (n = 27) without overt nephropathy. Measurements were repeated after treatment with aliskiren (300 mg daily) for 30 days. RESULTS: Before aliskiren, clamped hyperglycaemia increased filtration fraction (from 0.188 ± 0.007 to 0.206 ± 0.007, p = 0.003) and urinary fibroblast growth factor-2 (FGF2), IFN-α2 and macrophage-derived chemokine (MDC) (p < 0.005). After aliskiren, the filtration fraction response to hyperglycaemia was abolished, resulting in a lower filtration fraction after aliskiren under clamped hyperglycaemic conditions (p = 0.004), and none of the biomarkers increased in response to hyperglycaemia. Aliskiren therapy also reduced levels of urinary eotaxin, FGF2, IFN-α2, IL-2 and MDC during clamped hyperglycaemia (p < 0.005). CONCLUSIONS/INTERPRETATION: The increased urinary excretion of inflammatory cytokines/chemokines in response to acute hyperglycaemia is blunted by RAAS blockade in humans with uncomplicated type 1 diabetes mellitus.


Assuntos
Amidas/uso terapêutico , Quimiocinas/urina , Citocinas/urina , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Fumaratos/uso terapêutico , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Adulto , Feminino , Humanos , Insulina/uso terapêutico , Masculino , Proteômica , Adulto Jovem , Ácido p-Aminoipúrico/uso terapêutico
13.
Pediatr Diabetes ; 14(5): 372-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23418901

RESUMO

BACKGROUND: Depression and disturbed eating behavior (DEB) are more common in girls with type 1 diabetes (T1D) than in the general population, and may negatively affect metabolic control. OBJECTIVE: To examine the relationship among depression, DEB, and metabolic control in teenage girls with T1D. METHODS: Metabolic control, body mass index and interview-ascertained symptoms of depression, and DEB were assessed twice in 98 girls with T1D, 9-14 y at baseline and 5 yr later at 14-18 yr. RESULTS: At year 5, 12.2% of girls reported current depressive symptoms, 49.0% reported current DEB, and 13.3% had a full or subthreshold eating disorder (ED). Eating Disorder Examination score was higher in girls with depression (1.4 ± 1.3 vs. 0.5 ± 0.7; p = 0.03), and 75.0% of girls with depression also endorsed DEB vs. 45.3% of girls without depression (p = 0.05). Girls with an ED were at high risk for depressive symptoms; 69.2% reported depressive symptoms vs. 22.0% of girls with no DEB (p = 0.004). Metabolic control was not significantly associated with either depression or DEB in this cohort. A regression model using baseline and year 5 depression and DEB to predict year 5 hemoglobin A1c was not significant overall. CONCLUSIONS: Depression and DEB were common and frequently concurrent in this cohort. It was encouraging that poor metabolic control was not yet strongly associated with either depression or DEB. Early detection and treatment may help to prevent the development of entrenched difficulties in this triad of mood, eating behavior, and metabolic control in a vulnerable population.


Assuntos
Depressão/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Adolescente , Criança , Diabetes Mellitus Tipo 1/terapia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Estudos Longitudinais , Análise de Regressão
14.
Qual Life Res ; 22(2): 339-49, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22461136

RESUMO

PURPOSE: Quality of life (QoL) is a ubiquitous yet poorly defined concept; the precise determinants of QoL are rarely identified. We used pilot data from the GapS Questionnaire to investigate the most important determinants of QoL in children with chronic somatic illness. METHODS: We enrolled 92 participants including 60 parents and 32 of their children. The sample comprised rheumatology, diabetes, epilepsy, gastroenterology, cystic fibrosis, and day unit patients. Trained interviewers administered the GapS Questionnaire to parents, and to children if ≥ 10 years. We determined the relative importance of different items for QoL. RESULTS: Child participants had a mean age of 14.7 years. Children identified "having good friendships", "being happy most days", and "getting along with parents" as most important. Parents ranked most highly "being allowed to do all the things you like doing", "getting told you have done a good job at something", and "being physically able to do everything you enjoy doing". CONCLUSIONS: Physical health items were not as important as social and psychological determinants of QoL in our pilot sample.


Assuntos
Doença Crônica , Pais/psicologia , Qualidade de Vida/psicologia , Adolescente , Canadá , Criança , Pré-Escolar , Crianças com Deficiência , Feminino , Humanos , Lactente , Masculino , Relações Pais-Filho , Grupo Associado , Projetos Piloto , Reprodutibilidade dos Testes , Perfil de Impacto da Doença , Inquéritos e Questionários
15.
Pediatr Diabetes ; 13(2): 163-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21672108

RESUMO

BACKGROUND: Despite the advent of sensitive testing to detect celiac disease (CD), screening in type 1 diabetes (T1D) remains controversial. Many diabetes clinics are apprehensive about the prospect of introducing a second illness requiring intensive lifestyle changes in patients and families already managing a chronic condition, especially in asymptomatic patients. OBJECTIVE: To determine the impact of managing CD + T1D on quality of life in families, with attention to the effect of adherence with a gluten-free diet (GFD) and metabolic control. PATIENTS AND METHODS: Cross-sectional assessment using a validated self-reported quality of life measure: 28 children with biopsy-proven CD + T1D were compared with 40 subjects with T1D aged 8-18 yr. Parental and child reports were assessed as well as symptoms at the time of CD diagnosis and adherence with a GFD at the quality of life assessment. RESULTS: No significant differences in quality of life were observed between subjects with established CD + T1D and subjects with T1D alone. Parents of children with CD + T1D reported lower social functioning scores than parents of children with T1D (p = 0.03). In the CD + T1D group no differences in quality of life were observed with regard to age at CD diagnosis, CD duration, or on the basis of adherence with a GFD. CONCLUSIONS: The additional diagnosis of CD has minimal impact on quality of life in children with T1D; however, parents of CD + T1D children did express greater concern about their child's social functioning.


Assuntos
Doença Celíaca/diagnóstico , Doença Celíaca/psicologia , Diabetes Mellitus Tipo 1/psicologia , Qualidade de Vida , Adolescente , Doença Celíaca/dietoterapia , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Dieta Livre de Glúten , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Cooperação do Paciente/psicologia
16.
Soc Work Health Care ; 51(9): 815-27, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23078013

RESUMO

The current study evaluated an online education and support website intervention for adolescents with Type 1 diabetes. Participants were enrolled in an 8-week, online program addressing diabetes-related issues for adolescents. The evaluation comprised an intervention trial in which participants were assigned to an intervention or control group, and pre- and post-intervention measures of social support were administered. Outcomes indicated interventional gains approaching significance in participants' quality of relationships with others external to their family. Post-intervention qualitative interviews with intervention group participants identified beneficial impacts of decreased isolation, knowledge gain, and normalization of experience. Findings suggest that online information and support is an important resource in augmenting clinical care. Implications and recommendations for clinical practice are discussed.


Assuntos
Diabetes Mellitus Tipo 1/psicologia , Educação de Pacientes como Assunto/métodos , Psicologia do Adolescente , Apoio Social , Adolescente , Criança , Humanos , Internet , Relações Interpessoais , Entrevistas como Assunto , Ontário , Satisfação do Paciente , Grupo Associado , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa , Estatísticas não Paramétricas
17.
Paediatr Child Health ; 22(8): 506-508, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29479267
19.
Healthc Q ; 14(1): 50-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21301240

RESUMO

Peer assessment has become an important component of physician evaluation. In an academic health sciences centre, in addition to clinical care there is a significant focus on education, training and research. The literature suggests that the use of a 360-degree evaluation can provide physicians with valuable information on many aspects of their practice and can inform both professional and personal development. We conducted a pilot study to determine the feasibility of using peer assessment as part of the evaluation of our academic physicians. To maintain anonymity, an outside company was engaged to conduct the study. Participants completed a self-assessment and provided the names of eight physician peers and eight non-physician peers who were then requested to complete an evaluation. In addition, 25 patients were asked to provide their feedback. All questionnaires were forwarded directly to the outside company, which then compiled the data and provided each participant with a final report. Results indicate that it is feasible to carry out peer assessment within an academic health sciences centre. Participants noted the value of the process for career development and quality improvement.


Assuntos
Centros Médicos Acadêmicos/normas , Avaliação de Desempenho Profissional/métodos , Grupo Associado , Médicos , Canadá , Estudos de Viabilidade , Humanos , Projetos Piloto , Inquéritos e Questionários , Recursos Humanos
20.
Front Psychol ; 12: 609639, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643137

RESUMO

BACKGROUND: Past research shows that physicians experience high ill-being (i.e., work-life conflict, stress, burnout) but also high well-being (i.e., job satisfaction, engagement). OBJECTIVE: To shed light on how medical faculty's experiences of their job demands and job resources might differentially affect their ill-being and their well-being with special attention to the role that the work-life interface plays in these processes. METHODS: Qualitative thematic analysis was used to analyze interviews from 30 medical faculty (19 women, 11 men, average tenure 13.36 years) at a top research hospital in Canada. FINDINGS: Medical faculty's experiences of work-life conflict were severe. Faculty's job demands had coalescing (i.e., interactive) effects on their stress, work-life conflict, and exhaustion. Although supportive job resources (e.g., coworker support) helped to mitigate the negative effects of job demands, stimulating job resources (e.g., challenging work) contributed to greater work-life conflict, stress, and exhaustion. Thus, for these medical faculty job resources play a dual-role for work-life conflict. Moreover, although faculty experienced high emotional exhaustion, they did not experience the other components of burnout (i.e., reduced self-efficacy, and depersonalization). Some faculty engaged in cognitive reappraisal strategies to mitigate their experiences of work-life conflict and its harmful consequences. CONCLUSION: This study suggests that the precise nature and effects of job demands and job resources may be more complex than current research suggests. Hospital leadership should work to lessen unnecessary job demands, increase supportive job resources, recognize all aspects of job performance, and, given faculty's high levels of work engagement, encourage a climate that fosters work-life balance.

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