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1.
Horm Res Paediatr ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38663372

RESUMO

Teplizumab (TzieldTM, Provention Bio), a monoclonal antibody directed at t-cell marker CD3, is the first medication approved by the FDA to delay progression from Stage 2 to Stage 3 type 1 diabetes (T1D). To date, the overwhelming majority of pediatric endocrinologists do not have experience using immunotherapeutics and seek guidance the use of teplizumab in clinical practice. To address this need, the Pediatric Endocrine Society (PES) Diabetes Special Interest Group (Diabetes SIG) and Drug and Therapeutics Committee assembled a task force to review clinical trial data and solicit expert recommendations on the approach to teplizumab infusions. We present considerations on all aspects of teplizumab administration, utilizing evidence where possible and providing a spectrum of expert opinions on unknown aspects. We discuss patient selection and prescreening, highlighting the safety and considerations for monitoring and treatment of side effects. We propose a schedule of events, a protocol for administration and discuss practice management aspects. We advocate for the need for further long-term systematic surveillance studies to continue evaluating the efficacy and safety of teplizumab.

2.
BMJ Open Diabetes Res Care ; 12(2)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631820

RESUMO

INTRODUCTION: Among youth with type 1 diabetes (T1D), longitudinal poor glycemic control is associated with adverse socioeconomic conditions at the neighborhood level. Child Opportunity Index (COI), which encompasses measures of education, health, environment, social, and economic factors, is associated with obesity in youth but has not been evaluated in youth with new-onset T1D or type 2 diabetes (T2D). We hypothesized that lower COI would be associated with adverse clinical outcomes at diabetes diagnosis, and due to differing risk factors and pathophysiology, that youth with new-onset T2D would have lower COI than youth with T1D. RESEARCH DESIGN AND METHODS: Retrospective cohort of youth with new-onset diabetes admitted to a large academic pediatric hospital. COI was compared by diabetes type using t-tests and Χ2 tests. Multivariable linear and logistic regression analyses were used to evaluate associations between COI and clinical characteristics, stratified by diabetes type and adjusted for age and sex. RESULTS: The cohort (n=484) differed in race and age by diabetes type (T1D: n=389; 10.0% black, 81.2% white; age 9.6±0.2 years; T2D: n=95; 44.2% black, 48.4% white; age 14.8±0.3 years). Youth with T2D had lower COI (p<0.001). Low COI was associated with diabetic ketoacidosis in T1D and T2D. Black youth with low COI had the highest hemoglobin A1c among youth with T2D and the highest obesity prevalence among youth with T1D. CONCLUSIONS: COI is associated with differing characteristics at diagnosis in youth-onset T1D and T2D but is worse among youth with T2D overall. These findings underscore the need to address socioeconomic adversity when designing interventions to reduce T2D risk and to improve outcomes at diabetes diagnosis in youth.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Criança , Humanos , Adolescente , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Obesidade/complicações
3.
Health Psychol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635187

RESUMO

OBJECTIVE: We examined the links of supportive and conflictual peer interactions to mood and self-care via ecological momentary assessment. METHOD: Adolescents with Type 1 diabetes (n = 167, 49% female) recruited between 2018 and 2021 were prompted 8 times a day for 8 days to complete brief surveys that measured perceived social interactions, affect, and self-care. RESULTS: Cross-sectional analyses revealed between- and within-person (WP) links of peer support to positive mood and conflict to negative mood. Between-person peer support was linked to healthy self-care, but WP support was not. Lagged analyses showed conflictual interactions were associated with self-care decline. There was some evidence that females did not benefit as much from support and were more bothered by conflict than others. CONCLUSIONS: Results underscore differences in between- and WP links of social interactions to health. Individual differences in support were more influential than conflict, but conflictual interactions had more momentary effects than supportive interactions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

4.
JAMA Netw Open ; 7(4): e245656, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38578636

RESUMO

Importance: Youths with type 2 diabetes are at higher risk for complications compared with peers with type 1 diabetes, though few studies have evaluated differences in access to specialty care. Objective: To compare claims with diabetes specialists for youths with type 1 vs type 2 diabetes and the association between specialist claims with multidisciplinary and acute care utilization. Design, Setting, and Participants: This cross-sectional study used Optum Clinformatics Data Mart commercial claims. Individuals included in the study were youths younger than 19 years with type 1 or 2 diabetes as determined by a validated algorithm and prescription claims. Data were collected for youths with at least 80% enrollment in a commercial health plan from December 1, 2018, to December 31, 2019. Statistical analysis was performed from September 2022 to January 2024. Main Outcomes and Measures: The primary outcome was the number of ambulatory claims from an endocrine and/or diabetes physician or advanced practice clinician associated with a diabetes diagnosis code; secondary outcomes included multidisciplinary and acute care claims. Results: Claims were analyzed for 4772 youths (mean [SD] age, 13.6 [3.7] years; 4300 [90.1%] type 1 diabetes; 472 [9.9%] type 2 diabetes; 2465 [51.7%] male; 128 [2.7%] Asian, 303 [6.4] Black or African American, 429 [9.0%] Hispanic or Latino, 3366 [70.5%] non-Hispanic White, and 546 [11.4%] unknown race and ethnicity). Specialist claims were lower in type 2 compared with type 1 diabetes (incidence rate ratio [IRR], 0.61 [95% CI, 0.52-0.72]; P < .001) in propensity score-weighted analyses. The presence of a comorbidity was associated with increased specialist claims for type 1 diabetes (IRR, 1.07 [95% CI, 1.03-1.10]) and decreased claims for type 2 diabetes (IRR, 0.77 [95% CI, 0.67-0.87]). Pooling diagnosis groups and adjusted for covariates, each additional specialist claim was associated with increased odds of a claim with a diabetes care and education specialist (odds ratio [OR], 1.31 [95% CI, 1.25-1.36]), dietitian (OR, 1.14 [95% CI, 1.09-1.19]), and behavioral health clinician (OR, 1.16 [95% CI, 1.12-1.20]). For acute care claims, each additional specialist claim was associated with increased odds of admission (OR, 1.17 [95% CI, 1.11-1.24]) but not for emergency claims (OR, 1.03 [95% CI, 0.98-1.82]). Conclusions and Relevance: This cross-sectional study found that youths with type 2 diabetes were significantly less likely to have specialist claims despite insurance coverage, indicating other barriers to care, which may include medical complexity. Access to diabetes specialists influences engagement with multidisciplinary services. The association between increasing ambulatory clinician services and admissions suggests high utilization by a subgroup of patients at greater risk for poor outcomes.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Adolescente , Feminino , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/complicações , Estudos Transversais , Estudos Retrospectivos , Etnicidade
5.
Diabetologia ; 67(2): 290-300, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37914981

RESUMO

AIM/HYPOTHESIS: We assessed whether HOMA-IR and the Matsuda Index are associated with transitions through stages of type 1 diabetes. METHODS: Autoantibody (AAb)-positive relatives of individuals with type 1 diabetes (n=6256) from the TrialNet Pathway to Prevention were studied. Associations of indicators of insulin resistance (HOMA-IR) and insulin sensitivity (Matsuda Index) with BMI percentile (BMIp) and age were assessed with adjustments for measures of insulin secretion, Index60 and insulinogenic index (IGI). Cox regression was used to determine if tertiles of HOMA-IR and Matsuda Index predicted transitions from Not Staged (<2 AAbs) to Stage 1 (≥2 AAbs and normoglycaemia), from Stage 1 to Stage 2 (≥2 AAbs with dysglycaemia), and progression to Stage 3 (diabetes as defined by WHO/ADA criteria). RESULTS: There were strong associations of HOMA-IR (positive) and Matsuda Index (inverse) with baseline age and BMIp (p<0.0001). After adjustments for Index60, transitioning from Stage 1 to Stage 2 was associated with higher HOMA-IR and lower Matsuda Index (HOMA-IR: HR=1.71, p<0.0001; Matsuda Index, HR=0.40, p<0.0001), as with progressing from Stages 1 or 2 to Stage 3 (HOMA-IR: HR=1.98, p<0.0001; Matsuda Index: HR=0.46, p<0.0001). Without adjustments, associations of progression to Stage 3 were inverse for HOMA-IR and positive for Matsuda Index, opposite in directionality with adjustments. When IGI was used in place of Index60, the findings were similar. CONCLUSIONS/INTERPRETATION: Progression to Stages 2 and 3 of type 1 diabetes increases with HOMA-IR and decreases with the Matsuda Index after adjustments for insulin secretion. Indicators of insulin secretion appear helpful for interpreting associations of progression to type 1 diabetes with HOMA-IR or the Matsuda Index in AAb-positive relatives.


Assuntos
Diabetes Mellitus Tipo 1 , Resistência à Insulina , Humanos , Insulina/metabolismo , Autoanticorpos/metabolismo , Secreção de Insulina , Glicemia
6.
Pediatr Diabetes ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37929230

RESUMO

Objectives: To understand the practices, attitudes, and beliefs of type 1 diabetes (T1D) providers towards school-based diabetes care (SBDC), including counseling families and communicating with schools, and explore the barriers and facilitators which affect their support of SBDC. Research Design and Methods: We conducted a national survey of pediatric T1D providers about their perceived support of SBDC, including family counseling and school communication. We used descriptive statistics to analyze results and explored differences by practice size (<500, 500-999, and ≥1000 patients) and environment (academic vs non-academic). Results: A total of 149 providers completed the survey. Nearly all (95%) indicated SBDC was very important. Though most (63%) reported counseling families about SBDC multiple times per year, few (19%) spoke with school staff routinely, reporting that was a shared responsibility among different providers. Close to 90% agreed school feedback on T1D management plans would be helpful, yet only 31% routinely requested this input. Moderate to extremely significant barriers to SBDC communication included internal factors, such as staff resources (67%) and time (82%), and external factors, such as school nurse education needs (62%) and differing school district policies (70%). Individuals from large or academic practices reported more barriers in their knowledge of SBDC, including federal/state laws. Desired facilitators for SBDC included a designated school liaison (84%), electronic transmission for school forms (90%), and accessible school staff education (95%). Conclusions: Though providers universally agree that SBDC is important, there are multilevel internal (practice) and external (policy) barriers to facilitating a bidirectional relationship between schools and health teams.


Assuntos
Diabetes Mellitus Tipo 1 , Criança , Humanos , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/terapia , Inquéritos e Questionários , Instituições Acadêmicas
7.
Pediatr Diabetes ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37929232

RESUMO

Objective: The Diabetes Device Confidence Scale (DDCS) is a new scale designed to evaluate school nurse confidence with diabetes devices. We hypothesized that DDCS score would be associated with related constructs of school nurse diabetes knowledge, experience, and training. Research Design and Methods: In a cross-sectional study, we co-administered the DDCS and Diabetes Knowledge Test 2 (DKT2) questionnaires to school nurses in Pennsylvania. We summarized DDCS scores (range 1-5) descriptively. We evaluated the relationship between DKT2 percent score and DDCS mean score with the Spearman correlation coefficient. Simple linear regression examined school nurse characteristics as predictors of DDCS score. Results: A total of 271 completed surveys were received. Mean DDCS score was 3.16±0.94, indicating moderate confidence with devices overall. School nurses frequently reported low confidence in items representing specific skills, including suspending insulin delivery (40%), giving a manual bolus (42%), knowing when to calibrate a continuous glucose monitor (48%), changing an insulin pump site (54%), and setting a temporary basal rate (58%). Mean DKT2 score was 89.5±0.1%, which was weakly but not significantly correlated with DDCS score (r=0.12, p=0.06). Formal device training (p<0.001), assisting ≥5 students with diabetes devices in the past 5 years (p<0.01), and a student caseload between 1000-1500 students (p<0.001) were associated with higher mean DDCS score. Conclusions: DDCS score is related to prior training and experience, providing evidence for the scale's convergent validity. The DDCS may be a useful tool for assessing school nurse readiness to use devices and identify areas to enhance knowledge and practical skills.


Assuntos
Diabetes Mellitus , Humanos , Estudos Transversais , Diabetes Mellitus/terapia , Insulina , Inquéritos e Questionários , Estudantes
8.
Pediatr Diabetes ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37929231

RESUMO

Objective: Using continuous glucose monitoring (CGM), we examined patterns in glycemia during school hours for children with type 1 diabetes, exploring differences between school and non-school time. Methods: We conducted a retrospective analysis of CGM metrics in children 7-12 years (n=217, diabetes duration 3.5±2.5 years, hemoglobin A1c 7.5±0.8%). Metrics were obtained for weekday school hours (8 AM to 3 PM) during four weeks in fall 2019. Two comparison settings included weekend (fall 2019) and weekday (spring 2020) data when children had transitioned to virtual school due to COVID-19. We used multilevel mixed models to examine factors associated with time in range (TIR) and compare glycemia between in-school, weekends, and virtual school. Results: Though CGM metrics were clinically similar across settings, TIR was statistically higher, and time above range (TAR), mean glucose, and standard deviation (SD) lower, for weekends and virtual school (p<0.001). Hour and setting exhibited a significant interaction for several metrics (p<0.001). TIR in-school improved from a mean of 40.9% at the start of the school day to 58.0% later in school, with a corresponding decrease in TAR. TIR decreased on weekends (60.8 to 50.7%) and virtual school (62.2 to 47.8%) during the same interval. Mean glucose exhibited a similar pattern, though there was little change in SD. Younger age (p=0.006), lower hemoglobin A1c (p<0.001), and insulin pump use (p=0.02) were associated with higher TIR in-school. Conclusion: Although TIR was higher for weekends and virtual school, glycemic metrics improve while in-school, possibly related to beneficial school day routines.


Assuntos
Diabetes Mellitus Tipo 1 , Humanos , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas , Glicemia/análise , Automonitorização da Glicemia , Estudos Retrospectivos
9.
Diabetes Care ; 46(11): 2035-2043, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37708415

RESUMO

OBJECTIVE: Innate immune responses may be involved in the earliest phases of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: To test whether blocking innate immaune cells modulated progression of the disease, we randomly assigned 273 individuals with stage 1 T1D to treatment with hydroxychloroquine (n = 183; 5 mg/kg per day to a maximum of 400 mg) or placebo (n = 90) and assessed whether hydroxychloroquine treatment delayed or prevented progression to stage 2 T1D (i.e., two or more islet autoantibodies with abnormal glucose tolerance). RESULTS: After a median follow-up of 23.3 months, the trial was stopped prematurely by the data safety monitoring board because of futility. There were no safety concerns in the hydroxychloroquine arm, including in annual ophthalmologic examinations. Preplanned secondary analyses showed a transient decrease in the glucose average area under the curve to oral glucose in the hydroxychloroquine-treated arm at month 6 and reduced titers of anti-GAD and anti-insulin autoantibodies and acquisition of positive autoantibodies in the hydroxychloroquine arm (P = 0.032). CONCLUSIONS: We conclude that hydroxychloroquine does not delay progression to stage 2 T1D in individuals with stage 1 disease. Drug treatment reduces the acquisition of additional autoantibodies and the titers of autoantibodies to GAD and insulin.


Assuntos
Diabetes Mellitus Tipo 1 , Hidroxicloroquina , Humanos , Hidroxicloroquina/uso terapêutico , Autoanticorpos , Insulina , Glucose
10.
J Pediatr Psychol ; 48(11): 940-951, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37740947

RESUMO

OBJECTIVE: The goal of the study was to examine the relations of general and diabetes-specific friend support and conflict to psychological and diabetes health among youth with type 1 diabetes. We examined gender as a moderator of these relations, and friend responsiveness and information-sharing as potential mediators. METHODS: Youth with type 1 diabetes (n = 167; M age 15.83 [SD = 0.78]; 50% female) were interviewed once in the Fall and once in the following Spring of the school year. Using multiple regression analysis, general friend support, general friend conflict, diabetes-specific support, and diabetes-specific conflict were investigated as simultaneous predictors of psychological and diabetes outcomes cross-sectionally and longitudinally over four months. RESULTS: Cross-sectionally friend conflict, including both general and diabetes-specific, was more predictive of outcomes than friend support. In cross-sectional and longitudinal analyses, gender was a significant moderator, such that several relations of general friend conflict to outcomes were significant for females but not nonfemales. Friend support revealed mixed relations to outcomes across cross-sectional and longitudinal analyses. Although we found links of friend relationship variables to mediators (perceived responsiveness; information sharing), we found little evidence of mediation. CONCLUSIONS: These findings show stronger evidence that conflictual friend relationships than supportive friend relationships are linked to health. Findings suggest that problematic friend relationships may have a stronger impact on the health of females than nonfemales. These results underscore the need to better understand the conditions under which friend support is helpful versus harmful and the reasons underlying these links.


Assuntos
Diabetes Mellitus Tipo 1 , Amigos , Humanos , Feminino , Adolescente , Masculino , Amigos/psicologia , Diabetes Mellitus Tipo 1/psicologia , Estudos Transversais , Instituições Acadêmicas , Relações Interpessoais
12.
Diabetes Care ; 46(5): 1005-1013, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36920087

RESUMO

OBJECTIVE: Previous studies showed that inhibiting lymphocyte costimulation reduces declining ß-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses. RESEARCH DESIGN AND METHODS: We conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests. RESULTS: A total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline. CONCLUSIONS: Although abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Humanos , Abatacepte/uso terapêutico , Abatacepte/farmacologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Imunossupressores , Linfócitos T Reguladores , Glucose/uso terapêutico
13.
J Endocr Soc ; 7(3): bvad003, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36741943

RESUMO

Context: Participants with stage 1 or 2 type 1 diabetes (T1D) qualify for prevention trials, but factors involved in screening for such trials are largely unknown. Objective: To identify factors associated with screening for T1D prevention trials. Methods: This study included TrialNet Pathway to Prevention participants who were eligible for a prevention trial: oral insulin (TN-07, TN-20), teplizumab (TN-10), abatacept (TN-18), and oral hydroxychloroquine (TN-22). Univariate and multivariate logistic regression models were used to examine participant, site, and study factors at the time of prevention trial accrual. Results: Screening rates for trials were: 50% for TN-07 (584 screened/1172 eligible), 9% for TN-10 (106/1249), 24% for TN-18 (313/1285), 17% for TN-20 (113/667), and 28% for TN-22 (371/1336). Younger age and male sex were associated with higher screening rates for prevention trials overall and for oral therapies. Participants with an offspring with T1D showed lower rates of screening for all trials and oral drug trials compared with participants with other first-degree relatives as probands. Site factors, including larger monitoring volume and US site vs international site, were associated with higher prevention trial screening rates. Conclusions: Clear differences exist between participants who screen for prevention trials and those who do not screen and between the research sites involved in prevention trial screening. Participant age, sex, and relationship to proband are significantly associated with prevention trial screening in addition to key site factors. Identifying these factors can facilitate strategic recruitment planning to support rapid and successful enrollment into prevention trials.

15.
Horm Res Paediatr ; 95(6): 593-607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36446320

RESUMO

The past 200 years have brought an understanding of diabetes and its pathogenesis, as well as the development of treatments that could not have been predicted when the disorder was first clinically described 2000 years ago. Beginning in the late 19th century, the initial descriptions of the microscopic anatomy of the pancreatic islets by Langerhans led to recognition of pancreatic endocrine function. Many investigators attempted to isolate the hypoglycemic factor produced by the pancreas, but Banting, Best, Macleod, and Collip were able to extract and purify "isletin" to treat human diabetes in 1921. Rapid scientific progress over the next 100 years led to an understanding of insulin synthesis, structure and function, production of modified synthetic insulins, and the physiopathology that permitted classification of diabetes subtypes. Improvements in control of diabetes have reduced the risks of complications. In less than two hundred years, we have gone from being unable to measure glucose in blood to being able to offer people with diabetes continuous blood glucose monitoring, linked to continuous subcutaneous insulin infusion. We come ever closer with new drugs and treatments to repair the biochemical defects in type 2 diabetes and to biologically replace islets and their function in type 1 diabetes. This review addresses the history of continuing progress in diabetes care.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Automonitorização da Glicemia , Glicemia , Insulina , Diabetes Mellitus Tipo 1/terapia
16.
Front Endocrinol (Lausanne) ; 13: 937093, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992154

RESUMO

Despite the wealth of information on biomarkers of diabetes complications in adults with type 1 diabetes, data in the pediatric population is limited. Diabetic nephropathy (DN), the leading cause of mortality in type 1 diabetes T1D), could be potentially missed in youth, as albuminuria, the current "gold" standard, may be transient and may not reflect permanent renal impairment. Soluble alpha KL has emerged as a potential marker of early diabetic nephropathy. Seventy-nine pediatric patients with type 1 diabetes meeting ISPAD criteria for nephropathy screening were consecutively recruited (90% Caucasian, 51% male, mean age 16.1 ± 3.1 years, duration of T1D 7.2 ± 3.9 years, 2-year average HbA1c 8.0 ± 1.3%, and serum and urine samples were collected for analysis. Serum Klotho (KL) and circulating miRNA levels of select miRNA involved in the pathogenesis of DN were estimated. KL had a strong inverse correlation with diabetes duration and HbA1c, two important risk factors in the development of diabetes complications. Serum miR-192 were negatively associated with KL among children with prolonged duration of diabetes (≥12 years) after adjustment for age and sex. In cell culture, overexpression of miR-192 significantly downregulated KL mRNA and protein levels, and reduced KL levels in the media. miR-192 mimic reduced luciferase activity in a reporter containing the KL 3' UTR (60% compared to controls, p<0.01), and the inhibitor rescued it. Deletion of a potential binding site for miR-192 in the KL 3'UTR completely abolished the effect of miR-192 in the reporter assay, suggesting that KL is a direct target gene of miR-192. Overexpression of miR-192 significantly increased oxidative stress (MDA) and expression of inflammatory and senescence markers IL-6 and p16. Inhibition of miR-192 significantly reduced levels of MDA, IL-6 and p16. In summary, we demonstrate an increase in miR-192 and a decrease in KL levels in children with prolonged duration of T1D. We demonstrate a novel role for miR-192 in directly regulating KL levels, and through that, senescence and oxidative stress, key pathological processes in the development of DN. miR-192 and/or KL levels are altered with severity and duration of diabetes and could serve as early biomarkers for DN.


Assuntos
Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , MicroRNAs , Adolescente , Adulto , Biomarcadores/urina , Criança , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/genética , Feminino , Hemoglobinas Glicadas , Humanos , Interleucina-6 , Proteínas Klotho , Masculino , Adulto Jovem
17.
Pediatr Diabetes ; 23(7): 926-943, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35821595

RESUMO

Diabetes is an increasingly common chronic metabolic disorder in children worldwide. The discovery of insulin in 1921 resulted in unprecedented advancements that improved the lives of children and youth with diabetes. The purpose of this article is to review the history of diabetes in children and youth over the last century and its implications for future developments in the field. We identified 68 relevant events between 1921 and 2021 through literature review and survey of pediatric endocrinologists. Basic research milestones led to the discovery of insulin and other regulatory hormones, established the normal physiology of carbohydrate metabolism and pathophysiology of diabetes, and provided insight into strategies for diabetes prevention. While landmark clinical studies were initially focused on adult diabetes populations, later studies assessed etiologic factors in birth cohort studies, evaluated technology use among children with diabetes, and investigated pharmacologic management of youth type 2 diabetes. Technological innovations culminated in the introduction of continuous glucose monitoring that enabled semi-automated insulin delivery systems. Finally, professional organizations collaborated with patient groups to advocate for the needs of children with diabetes and their families. Together, these advances transformed type 1 diabetes from a terminal illness to a manageable disease with near-normal life expectancy and increased our knowledge of type 2 diabetes and other forms of diabetes in the pediatric population. However, disparities in access to insulin, diabetes technology, education, and care support remain and disproportionately impact minority youth and communities with less resources. The overarching goal of diabetes management remains promoting a high quality of life and improving glycemic management without undermining the psychological health of children and youth living with diabetes.


Assuntos
Automonitorização da Glicemia , Diabetes Mellitus Tipo 2 , Adolescente , Adulto , Glicemia/metabolismo , Automonitorização da Glicemia/métodos , Criança , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Humanos , Insulina/uso terapêutico , Qualidade de Vida
18.
Pediatr Diabetes ; 23(6): 820-830, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35661517

RESUMO

BACKGROUND: School nurses need to be equipped to help students with diabetes devices. No existing tools assess school nurse self-efficacy in using devices. OBJECTIVE: To develop and evaluate the psychometric properties of a novel scale to measure school nurse confidence with diabetes devices. RESEARCH DESIGN AND METHODS: We generated a list of items with community partners and examined logical validity. We then revised and distributed the item set to school nurses in Pennsylvania to examine aspects of structural validity, convergent validity, and internal consistency reliability. We used item response theory to refine the scale. RESULTS: Facilitated discussion with collaborators generated an initial list of 50 potential items. Based upon the item-content validity index, we revised/eliminated 13 items. School nurses (n = 310) in Pennsylvania completed an updated 38-item scale; the majority had experience with insulin pumps or continuous glucose monitors. Exploratory factor analysis identified a one-factor solution, suggesting a unidimensional scale. We eliminated 13 additional items based upon significant inter-item correlation or skewed response patterns. Item response theory did not identify additional candidate items for removal. Despite a high degree of redundancy (Cronbach's alpha > 0.90), we retained all remaining items to maximize the future utility of the scale. CONCLUSION: The 25-item, unidimensional Diabetes Device Confidence Scale is a new tool to measure school nurse confidence with diabetes devices. This scale has future clinical, programmatic, and research applications. Combined with knowledge assessments, this scale can serve to evaluate school nurse device use readiness, assess training gaps, and tailor interventions.


Assuntos
Diabetes Mellitus , Análise Fatorial , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
19.
J Pediatr Psychol ; 47(10): 1135-1144, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-35713643

RESUMO

OBJECTIVE: There is evidence that youth with type 1 diabetes are at risk for depression, and depression is a significant risk factor for subsequent psychological and physical health problems. However, it is not clear if/when this depression risk emerges. The goal of this study was to determine if there are differences in levels of depressive symptoms between youth with and without type 1 diabetes that develop over the course of emerging adulthood. We also examined whether adolescent psychosocial variables predicted depressive symptoms during emerging adulthood. METHODS: Youth with (n = 132) and without (n = 131) type 1 diabetes were enrolled in the study at average age 12 and followed for 14 years. Depressive symptoms were measured throughout the study. Psychosocial variables of interest were measured during adolescence. RESULTS: Group differences in depressive symptoms emerged by study end at average age 26. Depressive symptoms appeared to decline over time for youth without diabetes and to increase over time for youth with diabetes. Parent relationship difficulties increased over adolescence as did peer conflict for the entire cohort. Supportive relationships with parent and peers predicted fewer end of study depressive symptoms (controlling for baseline depressive symptoms)-equally so for both groups. CONCLUSIONS: This study provides evidence that those with type 1 diabetes may be at risk for depressive symptoms many years after diagnosis and after adolescence. Although relational difficulties with parents and peers increase during adolescence, supportive relationships over the course of adolescence may help to mitigate depressive symptoms during young adulthood.


Assuntos
Comportamento do Adolescente , Diabetes Mellitus Tipo 1 , Adolescente , Humanos , Adulto Jovem , Adulto , Criança , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/psicologia , Depressão/psicologia , Grupo Associado , Comportamento do Adolescente/psicologia , Estudos de Coortes , Estudos Longitudinais
20.
Sci Diabetes Self Manag Care ; 47(6): 447-456, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34935539

RESUMO

PURPOSE: The purpose of this study is to survey parents of youth with type 1 diabetes during the COVID-19 pandemic with school closures to better understand the implications of the school day on health care behaviors. METHODS: A cross-sectional, online survey was distributed to parents of youth with type 1 diabetes ≤19 years of age in a large, academic diabetes center. Questions encompassed perceived changes in management behaviors and plans for return to school. Subgroup analysis compared parent responses by child's age, reported stressors, and socioeconomic markers. RESULTS: Parents reported a worsening in their child's diabetes health behaviors during school closures compared to what they perceived during a regular school day before the pandemic. More than half of parents reported feeling that their child was unable to maintain a normal routine, with particular implications for snacking between meals, daily physical activity, and sleep habits. Families with adolescents or those experiencing multiple pandemic-related stressors reported greater challenges. In open-ended responses, families highlighted difficulty in balancing school, work, and diabetes care and expressed concerns about the mental health repercussions of school closures for their children. Nearly half of parents reported being at least moderately worried about return to school, whereas only a minority reported seeking guidance from their diabetes provider. CONCLUSIONS: Parent-reported disruptions of school-day routines frequently had adverse consequences for diabetes management in this population. These findings highlight the importance of a school-day routine for children with type 1 diabetes; during closures, families may benefit from mitigating strategies to maintain effective habits.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Adolescente , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/epidemiologia , Comportamentos Relacionados com a Saúde , Humanos , Pandemias , Pais , SARS-CoV-2 , Instituições Acadêmicas
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