Quantitative Differences in the Urinary Proteome of Siblings Discordant for Type 1 Diabetes Include Lysosomal Enzymes.

Individuals with type 1 diabetes (T1D) often have higher than normal blood glucose levels, causing advanced glycation end product formation and inflammation and increasing the risk of vascular complications years or decades later. To examine the urinary proteome in juveniles with T1D for signatures indicative of inflammatory consequences of hyperglycemia, we profiled the proteome of 40 T1D patients with an average of 6.3 years after disease onset and normal or elevated HbA1C levels, in comparison with a cohort of 41 healthy siblings. Using shotgun proteomics, 1036 proteins were identified, on average, per experiment, and 50 proteins showed significant abundance differences using a Wilcoxon signed-rank test (FDR q-value ≤ 0.05). Thirteen lysosomal proteins were increased in abundance in the T1D versus control cohort. Fifteen proteins with functional roles in vascular permeability and adhesion were quantitatively changed, including CD166 antigen and angiotensin-converting enzyme 2. α-N-Acetyl-galactosaminidase and α-fucosidase 2, two differentially abundant lysosomal enzymes, were detected in western blots with often elevated quantities in the T1D versus control cohort. Increased release of proteins derived from lysosomes and vascular epithelium into urine may result from hyperglycemia-associated inflammation in the kidney vasculature.

Effects of Low-Calorie Sweetener Restriction on Glycemic Variability and Cardiometabolic Health in Children with Type 1 Diabetes: Findings of a Pilot and Feasibility Study.

Low-calorie sweeteners (LCS) are commonly consumed by children with type 1 diabetes (T1D), yet their role in cardiometabolic health is unclear. This study examined the feasibility, acceptability, and preliminary effects of 12 weeks of LCS restriction among children with T1D. Children (n = 31) with T1D completed a two-week run-in (n = 28) and were randomly assigned to avoid LCS (LCS restriction, n = 15) or continue their usual LCS intake (n = 13). Feasibility was assessed using recruitment, retention, and adherence rates percentages. Acceptability was assessed through parents completing a qualitative interview (subset, n = 15) and a satisfaction survey at follow-up. Preliminary outcomes were between-group differences in change in average daily time-in-range (TIR) over 12 weeks (primary), and other measures of glycemic variability, lipids, inflammatory biomarkers, visceral adiposity, and dietary intake (secondary). Linear regression, unadjusted and adjusted for age, sex, race, and change in BMI, was used to compare mean changes in all outcomes between groups. LCS restriction was feasible and acceptable. No between-group differences in change in TIR or other measures of glycemic variability were observed. However, significant decreases in TNF-alpha (-0.23 ± 0.08 pg/mL) and improvements in cholesterol (-0.31 ± 0.18 mmol/L) and LDL (-0.60 ± 0.39 mmol/L) were observed with usual LCS intake, compared with LCS restriction. Those randomized to LCS restriction did not report increases in total or added sugar intake, and lower energy intake was reported in both groups (-190.8 ± 106.40 kcal LCS restriction, -245.3 ± 112.90 kcal usual LCS intake group). Decreases in percent energy from carbohydrates (-8.5 ± 2.61) and increases in percent energy from protein (3.2 ± 1.16) and fat (5.2 ± 2.02) were reported with usual LCS intake compared with LCS restriction. Twelve weeks of LCS restriction did not compromise glycemic variability or cardiometabolic outcomes in this small sample of youth with T1D. Further examination of LCS restriction among children with T1D is warranted.

Authoritative parenting, parenting stress, and self-care in pre-adolescents with type 1 diabetes.

Parent involvement in type 1 diabetes (T1DM) care leads to improved adherence; however, the manner in which parents approach illness management interactions with children must also be considered. It was hypothesized that greater use of an authoritative parenting style and less parenting stress would be associated with greater behavioral adherence and better metabolic control. Ninety-five primary caregivers of preadolescents (ages 8-11) with T1DM completed questionnaires assessing parenting style, pediatric parenting stress, and child behavioral adherence. Caregivers primarily self-identified as using an authoritative parenting style. Greater authoritative parenting was associated with greater behavioral adherence and less difficulty with pediatric parenting stress; no differences in metabolic control were observed. Greater engagement in authoritative parenting behaviors may contribute to increased age-appropriate child behavioral adherence and less pediatric parenting stress. Interventions highlighting diabetes-specific authoritative parenting techniques may enhance health outcomes and improve overall family functioning.

Impacts of the COVID-19 Pandemic on Pediatric Type 1 Diabetes Management: A Qualitative Study.

PURPOSE: The purpose of this study was to understand impacts of the coronavirus (COVID-19) pandemic on pediatric type 1 diabetes management. METHODS: In-depth qualitative interviews were conducted with 15 parents of children (age 6-12 years) with type 1 diabetes. Parents responded to 8 open-ended questions about their experiences managing their children's type 1 diabetes during the COVID-19 pandemic. All interviews were transcribed, coded, and analyzed using qualitative thematic methods. RESULTS: Parents reported both positive and negative aspects of managing their children's type 1 diabetes during the COVID-19 pandemic. Facilitators of diabetes management included spending more time together at home and enhanced convenience of telehealth appointments and online supply ordering. Parents also described difficulties managing their children's type 1 diabetes during the COVID-19 pandemic, including a lack of structure in their child's daily routine, which led to increases in sedentary behavior. Furthermore, they reported psychosocial challenges of type 1 diabetes management, which were exacerbated by the pandemic. CONCLUSION: While the COVID-19 pandemic was described as having overall positive impacts on pediatric type 1 diabetes management, efforts to support parents in increasing children's physical activity and reducing screen time are needed, along with readily accessible mental health resources for both parents and their children with type 1 diabetes.

Rationale and design of DRINK-T1D: A randomized clinical trial of effects of low-calorie sweetener restriction in children with type 1 diabetes.

BACKGROUND: Low-calorie sweeteners (LCSs) provide sweetness without sugar or calories and are used to replace added sugars by many children with type 1 diabetes (T1D). However, the role of LCSs in diabetes management and cardiometabolic health is unclear. OBJECTIVE: The Diabetes Research in Kids Study (DRINK-T1D) aims to investigate effects of LCS restriction on glycemic variability, visceral adiposity, lipid profiles, and systemic inflammation among children 6-12 years old with T1D. METHODS: Children with T1D, who report habitual consumption of foods and beverages containing LCSs, are recruited from the Washington Nationals Diabetes Care Complex (DCC) at Children's National Hospital (CNH) in Washington, DC. Following a phone screening and two-week run-in period involving continuation of usual LCS intake, children are randomized to 12 weeks of LCS restriction (replacement of diet beverages with still or sparkling water and avoidance of other sources of LCSs) or continued usual LCS intake (control). The primary outcome is the difference in change in glycemic variability in the LCS restriction group versus the control group. Change in glycemic variability will be assessed as the difference in daily average time-in-range (TIR), measured using continuous glucose monitoring (CGM) during two weeks at the end of the 12-week intervention, compared with during the two-week run-in period prior to randomization. Participants also complete a variety of anthropometric, metabolic, dietary, and behavioral assessments throughout the 14-week study. CONCLUSIONS: DRINK-T1D is an innovative, randomized controlled trial, evaluating effects of LCS restriction on glycemic variability and cardiometabolic health in children with T1D. Findings of DRINK-T1D will support or challenge the common practice of recommending LCS use in this patient population and will have clinically relevant implications for pediatric T1D management. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04385888.

Substance Use Among Adolescents and Young Adults With Type 1 Diabetes: Discussions in Routine Diabetes Care.

Pediatric health care providers are in a unique position to discuss the health implications of alcohol, tobacco, and drug use with adolescents and young adults (AYAs) with type 1 diabetes (T1D). This study evaluated the frequency of self-reported substance use and associated demographic and clinical characteristics in a sample of AYAs with T1D and patient-provider discussions of substance use in T1D care. Sixty-four AYAs completed questions about substance use from the Youth Risk Behavior Survey (YRBS). Corresponding diabetes clinic visits were audio-recorded, transcribed, and reviewed to examine substance use discussions. A total of 56.3% of AYAs reported ever engaging in substance use; 40.6% reported substance use within the past 30 days. Five AYAs had discussions about substance use during their most recent diabetes clinic visit. Substance use should be proactively addressed by pediatric health care providers and AYAs should be encouraged to raise questions related to substance use during clinic visits.

Predictors of diabetes-related quality of life after transitioning to the insulin pump.

OBJECTIVE: To examine family and individual psychosocial, medical, and demographic factors associated with improved diabetes-related quality of life (QOL) after transitioning to the insulin pump among youth with type 1 diabetes. METHOD: Fifty-three parent-child dyads completed questionnaires on four occasions prior to and following this medical regimen change, assessing QOL, family environment, depressive and anxiety symptoms, and medical and demographic information. Trajectories of change in QOL were analyzed using multilevel modeling. RESULT: Psychosocial, medical, and demographic characteristics were associated with QOL prior to pump-start. Elements of children's QOL significantly improved after the transition, and improvement was predicted by psychosocial, medical, and demographic characteristics. CONCLUSION: Results indicate that individual and contextual factors may play a role in QOL as children transition to the insulin pump. Findings may guide efforts to support families through this challenging time and potentially inform candidacy for transition to the pump.

Nighttime caregiving behaviors among parents of young children with Type 1 diabetes: associations with illness characteristics and parent functioning.

Parents of young children with Type 1 diabetes describe daily management as relentless. Nighttime caregiving, including nocturnal blood glucose monitoring (NBGM), occurs and may increase parents' anxiety and stress. The goal of this study was to examine the frequency of NBGM among parents of young children with Type 1 diabetes, and to identify children's illness characteristics and parents' fear of hypoglycemia, anxiety, and parenting stress associated with nighttime monitoring. Parents (N = 71) of children with Type 1 diabetes ages 2 to 6 completed questionnaires to assess frequency of NBGM, illness characteristics and health outcomes, and parent concern. Approximately one third of parents reported regularly monitoring their child's blood glucose level after their child was asleep. Frequency of NBGM was positively associated with basal-bolus regimen, longer illness duration, and increased parent-reported anxiety and parenting stress (p < .05). NBGM is prevalent among parents of young children with Type 1 diabetes, suggesting that parents' nighttime caregiving practices and resulting sleep disruption should be routinely addressed in clinical practice. Further investigations of NBGM, child health outcomes, and parent quality of life are warranted.

Stress among fathers of young children with type 1 diabetes.

Although fathers' stress has been shown to have important implications for children's health and well-being, few studies of children with Type 1 diabetes have considered paternal parenting stress. The current study contributes to the literature by exploring correlates of fathers' pediatric parenting stress in a sample of young children with Type 1 diabetes. Forty-three fathers of children 2-6 years old with Type 1 diabetes completed self-report questionnaires examining pediatric parenting stress, child behavior, participation in diabetes management tasks, and parental psychological resources. Results of multiple regression show that fathers' pediatric parenting stress is positively associated with state anxiety and mother-reported difficult child behavior. These findings suggest that fathers may experience parenting stress differently than mothers, and that their experiences may have implications not only for their own level of anxiety, but also for their children's behavior.

Diabetes-specific family conflict and responsibility among emerging adults with type 1 diabetes.

Emerging adulthood is a transitional period for type 1 diabetes management, and aspects of family functioning such as family conflict and responsibility for diabetes management likely change following high school graduation. This study examined changes in diabetes-specific family conflict, family responsibility for diabetes management tasks, and associations with glycemic control up to 1 year after high school. Seventy-nine emerging adults with type 1 diabetes (M age = 18.09 ± .43 years; 51% female; 71% Caucasian) and their parents (73% female) completed self-report measures on diabetes-specific family conflict and family responsibility at 3 consecutive clinic visits, beginning in the spring of their senior year of high school. Hemoglobin A1c (HbA1c) was obtained from medical records. Diabetes-specific family conflict was relatively low; scores did not significantly change from baseline to Time 3. Parent responsibility for diabetes care decreased from baseline to Time 3. Higher parent- and emerging adult-reported family conflict and higher parent responsibility for diabetes care were associated with worse glycemic control (ps < .05). Parent-reported family conflict and the interaction between parent-reported family conflict and responsibility predicted HbA1c 1 year after high school. Conversely, HbA1c did not predict diabetes-specific family conflict or responsibility 1 year after high school. Findings indicate that diabetes-specific family conflict is associated with glycemic control after high school, even when emerging adults assume greater responsibility for diabetes self-care. Diabetes-specific family conflict levels were generally low and did not change over time despite this transitional period. If diabetes-specific conflict is present, it should be an important avenue for potential intervention for emerging adults with type 1 diabetes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Diagnosis and treatment of neonatal diabetes: a United States experience.

BACKGROUND/OBJECTIVE: Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a small fraction of those diagnosed between 6 and 12 months. The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age. METHODS: We used Oragene DNA Self-Collection kit to obtain a saliva sample for DNA. We sequenced the protein-coding regions of KCNJ11, ABCC8, and INS using standard methods. RESULTS: We enrolled 32 patients diagnosed with diabetes before 6 months of age and 45 patients diagnosed between 6 and 12 months. We identified a mutation in KCNJ11 in 14 patients from 12 families and in INS in 7 patients from 4 families. Three of the patients with an INS mutation were diagnosed with diabetes between 6 and 12 months of age. Finally, we found that two patients had an abnormality of chromosome 6q24 associated with transient neonatal diabetes mellitus. CONCLUSIONS: We were able to establish a genetic cause of diabetes in 63% of patients diagnosed with diabetes before 6 months of age and in 7% of patients diagnosed between 6 and 12 months. Genetic testing, which is critical for guiding appropriate management, should be considered in patients diagnosed with diabetes before 1 yr of age, especially if they are autoantibody negative, although the presence of autoantibodies does not rule out a monogenic cause.

Pediatric quality of life in transitioning to the insulin pump: does prior regimen make a difference?

A shift in conventional diabetes management has graduated to basal (glargine) and bolus (rapid-acting analogue) therapy via multiple daily injections or continuous subcutaneous insulin infusion (CSII). Continuous subcutaneous insulin infusion is considered the most intensive type of diabetes management, and before transitioning, consideration of regimen benefits should include lifestyle and quality-of-life issues in addition to medical benefits. Short-term and long-term changes in children's quality of life, as a function of their pre-CSII diabetes regimen, was assessed in 52 children before their transition to CSII from a conventional or multiple daily injection regimen. Results demonstrated significant improvement in quality of life only for those children transitioning to CSII from conventional vs multiple daily injection regimens; results were maintained at 6 months following pump initiation. Quality of life is an important consideration as children transition from more traditional to intensive regimens, and CSII devices may not necessarily improve satisfaction with diabetes control in all pediatric patients. Risks and benefits of both intensive regimens should be discussed before making the transition.

Self-Management Strategies in Emerging Adults With Type 1 Diabetes.

INTRODUCTION: We examined changes in self-management behaviors after high school graduation in a cohort of emerging adults with type 1 diabetes. METHODS: Sixty-four emerging adults reported on diabetes self-management behaviors at three time points over a 1-year period. Glycemic control and blood glucose monitoring frequency data were collected from the medical chart. RESULTS: Collaboration with parents decreased, diabetes problem-solving and communication increased, and glycemic control worsened during the first year after high school (p < .05). Problem solving appeared to be protective against worsening glycemic control; higher baseline diabetes problem solving significantly predicted better glycemic control at the 1-year follow-up. DISCUSSION: Emerging adults demonstrate increased independence in diabetes problem solving and communication with health care providers in the year after high school. Problem-solving skills may help emerging adults adapt type 1 diabetes self-care in response to unpredictable schedules after high-school, and promoting these skills may prevent deteriorations in glycemic control during this risky period.

Type 1 Diabetes: Urinary Proteomics and Protein Network Analysis Support Perturbation of Lysosomal Function.

While insulin replacement therapy restores the health and prevents the onset of diabetic complications (DC) for many decades, some T1D patients have elevated hemoglobin A1c values suggesting poor glycemic control, a risk factor of DC. We surveyed the stool microbiome and urinary proteome of a cohort of 220 adolescents and children, half of which had lived with T1D for an average of 7 years and half of which were healthy siblings. Phylogenetic analysis of the 16S rRNA gene did not reveal significant differences in gut microbial alpha-diversity comparing the two cohorts. The urinary proteome of T1D patients revealed increased abundances of several lysosomal proteins that correlated with elevated HbA1c values. In silico protein network analysis linked such proteins to extracellular matrix components and the glycoprotein LRG1. LRG1 is a prominent inflammation and neovascularization biomarker. We hypothesize that these changes implicate aberrant glycation of macromolecules that alter lysosomal function and metabolism in renal tubular epithelial cells, cells that line part of the upper urinary tract.

Changes in type 1 diabetes health indicators from high school to college.

OBJECTIVE: Evaluate trajectories of type 1 diabetes health indicators from high school through the first year of college. PARTICIPANTS: Seventy-four students with type 1 diabetes who maintained pediatric endocrinology care during the first year of college. METHODS: Hemoglobin A1c (HbA1c), blood glucose monitoring frequency, body mass index (BMI), and clinic attendance data were collected via retrospective medical chart review in spring 2012. Group-based trajectory models evaluated diabetes-related health indicators over time and identified distinct growth trajectory groups. RESULTS: BMI increased and clinic attendance decreased in the first year of college. Trajectories for other health indicators were heterogeneous and stable over time; 69% of students were classified as having stable good glycemic control. Racial minority youth and youth on conventional insulin regimens were disproportionally represented in higher-risk groups. CONCLUSIONS: Diabetes health indicators are stable or decline upon college entrance. Results signal the need for targeted support for college students with type 1 diabetes.

Outpatient Management of Pediatric Type 1 Diabetes.

The incidence of both type 1 and type 2 diabetes (T1DM and T2DM) continues to rise within the pediatric population. However, T1DM remains the most prevalent form diagnosed in children. It is critical that health-care professionals understand the types of diabetes diagnosed in pediatrics, especially the distinguishing features between T1DM and T2DM, to ensure proper treatment. Similar to all individuals with T1DM, lifelong administration of exogenous insulin is necessary for survival. However, children have very distinct needs and challenges compared to those in the adult diabetes population. Accordingly, treatment, goals, and age-appropriate requirements must be individually addressed. The main objectives for the treatment of pediatric T1DM include maintaining glucose levels as close to normal as possible, avoiding acute complications, and preventing long-term complications. In addition, unique to pediatrics, facilitating normal growth and development is important to comprehensive care. To achieve these goals, a careful balance of insulin therapy, medical nutrition therapy, and exercise or activity is necessary. Pharmacological treatment options consist of various insulin products aimed at mimicking prior endogenous insulin secretion while minimizing adverse effects. This review focuses on the management of pediatric T1DM in the outpatient environment, highlighting pharmacotherapy management strategies.

Mealtime behavior and diabetes-specific parent functioning in young children with type 1 diabetes.

OBJECTIVE: Management of meals and mealtime behavior is often challenging for parents of young children with Type 1 diabetes. Parent functioning related to diabetes care may directly affect mealtime behaviors and glycemic control. This study evaluated associations among diabetes-specific parent functioning, parent and child mealtime behaviors, and glycemic control. METHOD: Parents of young children with Type 1 diabetes (n = 134) completed self-report measures assessing diabetes-specific functioning (hypoglycemia fear, diabetes self-efficacy, diabetes-related quality of life) and child and parent mealtime behaviors. Hemoglobin A1c and percentage of blood glucose values out of range (<70 mg/dL or >200 mg/dL) over a 30-day period were abstracted from medical charts as indicators of glycemic control. Structural equation modeling was utilized to evaluate predictors and related outcomes of child and parent mealtime behavior. RESULTS: The proposed model fit the data very well. More frequent problematic child mealtime behaviors were associated with poorer glycemic control; however, more frequent problematic parent mealtime behaviors were marginally associated with better glycemic control. Poorer diabetes-specific parent functioning was associated with more frequent problematic child and parent mealtime behaviors. CONCLUSIONS: Problematic child mealtime behaviors, such as disruptive behavior, present a significant risk for poorer glycemic control. Parents may engage in ineffective mealtime management strategies in an effort to meet glycemic recommendations and avoid hyperglycemia and hypoglycemia. Future research will help to determine whether parents may benefit from specific, developmentally appropriate behavioral strategies to manage meals and snacks and promote optimal diabetes management.