Type 1 diabetes is one of the most common pediatric chronic illnesses. Adolescents are at risk for poorer glycemic control; however, youth whose parents remain involved in diabetes care are in better control. The current study examined parental involvement (PI) using a multi-method, multi-source approach in a sample of 255 youth (Age M = 12.83). The Diabetes Family Responsibility Questionnaire, Parental Monitoring of Diabetes Care Scale, and 24-Hour Diabetes Interview assessed two types of PI, parental responsibility and parental monitoring. Global and specific assessment served to cross-corroborate indicators of PI related to HbA1c. Higher levels of monitoring related to lower HbA1c for both parent- and youth-report; however, the effect decreased after controlling for socioeconomic status (SES). Additionally, monitoring mediated the relation between age and HbA1c. Controlling for SES, youth whose parents demonstrated higher levels of monitoring were in better glycemic control. Both research and clinical implications are discussed.

Objectives: The rate and impact of depressive symptoms were examined with two models based on known effects of depression on variables related to diabetes management, parental involvement and diabetes conflict. The proposed models will measure potential effects high maternal depressive symptoms may have on parental monitoring and involvement and diabetes specific conflict and how these variables may in turn relate to poor regimen adherence. Methods: Participants included 225 mothers and young adolescents (aged 11-14) with T1D. Diabetes self-care behaviors were measured with the 24 Hour Recall Interview, parental involvement and monitoring were measured with the Parent Management of Diabetes Scale, and diabetes specific conflict was measured with the Diabetes Family Conflict Scale. Results: A significant portion of mothers (21%) reported clinically elevated levels of depressive symptoms. These high levels of depressive symptoms were related to low levels of parental involvement with diabetes care (r = -.19, p < .01). Depressive symptoms were indirectly related to lower frequency of blood glucose monitoring (C.95 = -.03, -.002), insulin use (C.95 = -.01, -.0007), and meals (C.95 = -.02, -.002) through low levels of parental involvement. Higher levels of depressive symptoms were also related to higher levels of diabetes specific conflict (r = .16, p < .01), however, this relationship did not have a significant indirect effect on frequency of self-care behaviors. Conclusions: A significant portion of mothers in the current sample reported symptoms of depression above the clinical cutoff. Mothers that reported higher levels of depressive symptoms also reported lower levels of parental involvement in management of disease-care behaviors. Low levels of parental involvement mediated a significant relation between depressive symptoms and less frequent disease-care behaviors. Diabetes conflict did not mediate a relation between depressive symptoms and disease-care behaviors. These findings suggest that the reported high levels of maternal depressive symptoms among mothers of children with T1D may interfere with good diabetes management through low parental involvement. Individual treatment for depressive symptoms and interventions targeted at increasing parental involvement without increasing diabetes conflict could help improve regimen adherence.

The aim of the current study was to examine the associations among youth diabetes self-efficacy, family conflict, disease care and glycemic control via a comprehensive path model. Data were from a baseline assessment of a longitudinal RCT of 257 adolescent/parent dyads (adolescents aged 11–14). Each member of the dyad separately completed the Self-efficacy for Diabetes Self-Management Scale, Family Environment Conflict subscale, Diabetes Family Conflict Scale, Diabetes Behavior Rating Scale, and 24-hr Diabetes Interview Blood Glucose Frequency subscale. Additionally, a biological marker of glycemic control, or HbA1c, and relevant demographic variables were collected. A mediation model found higher youth diabetes self-efficacy mediated the link between lower family conflict and better disease care (β = -.08, p <.01) to glycemic control (β = .05, p <.05.). Further, the relation of higher self-efficacy to better glycemic control was mediated by better disease care (β = -.06, p <.05). Higher youth diabetes self-efficacy (β = -.16, p <.05), lower family conflict (β = .19, p <.001), and better disease care (β = -.17, p <.01) each were directly related to better glycemic control. The overall model with relevant demographic factors fit the data well [χ² (2) = .50, p = .78, CFI = 1.00, RMSEA= .00] and accounted for 13% of the variance in self-efficacy, 32% of the variance for disease care, and 25% of the variance in glycemic control. Interventions that target better youth diabetes self-efficacy and lower family conflict concurrently may promote better disease care and glycemic control.

Objective: Type 1 diabetes is one of the most common pediatric chronic illnesses. Adolescents are at risk for poorer adherence and in turn, poorer glycemic control; however, youth whose parents remain involved in diabetes care are in better control. A parent’s level of involvement is dependent in part upon his or her own social and emotional functioning. Much is known about the link between separate aspects of parent psychosocial functioning (e.g., depressive symptoms, parental stress) and parent involvement in diabetes care, adherence, and glycemic control. However, no study to our knowledge has examined these constructs simultaneously as they interrelate to one another and to youth diabetes status. Given the complexity of human behavior, use of multiple indicators of parent psychosocial status should provide a comprehensive portrayal of precursors to parental monitoring. Methods: The current study used structural equation modeling (SEM) in a sample of 257 parent-youth (aged 11-14) dyads (91% mothers) to examine comprehensive parent psychosocial functioning including parental distress, authoritative parenting, and parental self-efficacy for diabetes management as related to parental monitoring, youth adherence and glycemic control. Results: The SEM model fit the data well [χ2 (121) = 209.24, p < .001, CFI = .93, TLI = .91, RMSEA = .06, SRMR = .08]. Overall, the model accounted for 30% of the variance in parental monitoring, 27% of the variance in adherence, and 22% of the variance in glycemic control. Specifically, lower levels of parental distress (i.e., depressive symptoms, parenting stress, and hypoglycemic fear) related to higher parental self-efficacy for diabetes management and more authoritative parenting, each of which in turn related to more parental monitoring. Further, higher parental self-efficacy related directly to better youth adherence. Conclusions: The current study shows interrelated paths of parent psychosocial functioning associated with parental monitoring of youth diabetes care and ultimately, youth adherence and glycemic control. Interventions that target diabetes adherence in adolescents with T1D should consider screening for and treatment of parental distress.

The Test of Diabetes Knowledge (TDK) was studied to determine its appropriateness for children. Early onset diabetes was examined for residual effects on poorer adolescent understanding of diabetes and problem solving that could affect self-care behaviors. Participant groups were created as children (<12) and adolescents (≥12). A second division created a group of adolescents with early onset disease (EOD < 12 years) and with late onset disease (LOD >12 years). Participants were predominantly Caucasian and from middle class families. 51% were boys with an average age of 12.95 years, disease duration of 4.35 years and onset age of 8.58 years. Children scored significantly lower and responded “I don’t know” significantly more often for all levels of knowledge when compared to adolescents. EOD and LOD group differences in problem-solving knowledge were not found for adolescents, although duration accounted for a significant amount of variance in the model. Post-hoc regression indicated a significant negative relationship between duration and knowledge. EOD and LOD group differences were not found in self-care behaviors. The TDK does not appear to be developmentally appropriate for children. EOD adolescents do not differ from LOD adolescents on problem solving questions; mean scores indicate the lack of abstract knowledge seen in children may be resolved with the transition into adolescence. Results indicate the longer a child has diabetes the less knowledge they appear to retain.

Better disease care behaviors in youth with type 1 diabetes (T1D) are strongly related to better metabolic control (HbA1c). However, HbA1c results are only available, on average, every three months, and may not accurately capture intricacies of blood glucose fluctuations. Youth then must rely on blood glucose levels obtained throughout the day to determine which disease care behaviors to perform to maintain optimal metabolic control. Youth may have difficulty performing these disease care behaviors properly or consistently, which makes parental monitoring a crucial aspect of the diabetes regimen. Additionally, youth who experience frequent or severe hypoglycemia may develop a fear of hypoglycemia, which may impact their disease care behaviors and blood glucose levels directly. Average blood glucose levels strongly related to HbA1c which verifies HbA1c as a good indicator of average blood glucose levels. The Average Daily Risk Range (ADRR) index had a stronger relation to HbA1c than Mean Amplitude of Glycemic Excursions (MAGE) index; however, the percentage of blood glucose levels below, within, and above range may be the best indicator of glycemic variability, as it is more easily calculated and understood. More parental monitoring related to more diabetes prevention behaviors but not intervention behaviors or less glycemic variability.

The psychometric properties of two measures of diabetes disease care, the Diabetes Behavior Rating Scale (DBRS) and the 24-hr Diabetes Interview (24-hr) were evaluated. The 24-hr is a widely used, structured interview while the DBRS is a self-administered, fixed-choice questionnaire. Both measures were administered to 250 youth with Type 1 Diabetes (aged 11–14 years) and their parents. Overall, both measures demonstrate adequate psychometric properties. The DBRS and the 24-hr demonstrated good incremental validity and low convergent validity with each adding significant additive value. Both measures demonstrated good concurrent validity with HbA1c. As expected, scores on the 24-hr demonstrated less than adequate test-retest reliability and both measures demonstrated low parent/youth agreement. Interestingly, external validity analyses demonstrated DBRS scores were moderately related to HbA1c in non-pump but not pump regimens, while the 24-hr displayed acceptable external validity. Only three subscales significantly contributed to HbA1c suggesting a more parsimonious assessment measure. This novel, brief combination could prove efficacious for clinical practice.

Individual growth curve (IGC) modeling evaluated longitudinal trajectories of glycemic control and diabetes care of youth with Type 1 Diabetes (T1D) over three years. IGC modeling allowed comparison of confounded sociodemographic predictors of disease outcomes that included ethnicity, SES, parent marital status, family structure, as well as disease duration, to determine the relative impact of these factors in the evolution of HbA1c and diabetes care throughout adolescence. At baseline, participants recruited from two pediatric endocrinology clinics included 198 youth, ages 9-15 (M age = 12.65, 77% Caucasian, 74% lived with married biological parents, M SES = 45.70) with average HbA1c of 8.43% and reported diabetes care behaviors consistent with ADA recommendations. Glycemic control did not deteriorate significantly, but IGC modeling detected a trend of a steady decline in HbA1c of .01% each year. Youth with married biological parents had HbA1c levels approximately 1.23% lower than youth with alternative parent marital status throughout adolescence, t = 4.03, p < .001, although an age by marital status interaction, t = -2.34, p < .05, indicated the impact of parent marital status on HbA1c decreased at age 17. Analyses revealed significant annual declines in blood glucose monitoring frequency, t = -7.61, p < .001, eating frequency, t = -9.04, p < .001, and exercise frequency, t = -7.87, p < .001. Alternatively, the consumption of carbohydrates and fats remained relatively stable throughout adolescence. Consideration of sociodemographic predictors and disease duration further clarified trajectories of disease care behaviors. Throughout adolescence, African American youth reported lower blood glucose monitoring frequency than Caucasian youth. Youth with lower SES exercised less frequently and demonstrated poorer dietary consumption than youth with higher SES. Youth from families with alternative parent marital status ate and exercised less frequently compared to youth from married biological families. However, youth from single-parent homes exercised more frequently than those from two-parent homes. Longer disease duration related to declines in blood glucose monitoring frequency, yet better dietary consumption. Results may inform development of interventions for youth at risk of poor glycemic control and diabetes management across ethnicity, SES, and parent marital status groups.

L’action physiologique des glucocorticoïdes (GC) est de mobiliser certaines ressources de l’organisme pour s’adapter à des changements d’origine endogène ou exogène susceptibles de perturber l’homéostasie de l’organisme. Des facteurs métaboliques/nutritionnels modifient l’intensité d’action des GC. Ils agissent au niveau i) de l’activation de l’axe corticotrope, ii) de leur biodisponibilité des GC (régulation « pré-récepteur »), iii) de l’activation transcriptionnelle des récepteurs des GC (régulation « post-récepteur »). L’objectif général de ce travail repose sur l’exploration du rôle de certains facteurs métaboliques/nutritionnels dans la modulation pré- et post-récepteur de l’action des GC sur l’organisme. Dans une approche clinique, notre attention s’est tout d’abord focalisée sur le rôle de l’équilibre diabétique et/ou l’état inflammatoire des patients atteints de diabète de type I et le métabolisme pré-récepteur du cortisol. Par l’étude en spectrométrie de masse des métabolites du cortisol, nous montrons une augmentation significative de l’activité de la hydroxystéroïde-déshydrogenase 1, principale enzyme de régénération intracellulaire du cortisol. Cette augmentation est corrélée à des marqueurs de l’inflammation chez les enfants diabétiques. Ces résultats suggèrent un lien entre le diabète et l’existence d’une inflammation à bas bruit et l’augmentation de l’exposition cellulaire aux GC. Dans une approche expérimentale, nous nous sommes ensuite intéressés à l’action de l’acide rétinoïque all trans (atAR), métabolite actif de la vitamine A, sur l’activité transcriptionnelle des GC. Nous avons choisi un modèle in vitro de cellules hippocampiques en raison d’effets contrastés de l’atAR et des GC sur les fonctions mnésiques in vivo. Nous observons une interaction entre les voies de signalisation transcriptionnelle de l’atAR et des GC sur leurs propres récepteurs et sur des protéines de la plasticité synaptique. Par ailleurs, l’atAR est responsable de modifications de la phosphorylation du récepteur aux GC altérant ainsi ses fonctions transcriptionnelles. Enfin atAR et GC modifient différemment l’organisation du cytosquelette d’actine sans modification transcriptionnelle ou traductionnelle. La compréhension du rôle de certains facteurs environnementaux dans la signalisation des GC pourrait permettre de réduire certains des effets délétères du stress. L’utilisation de certains nutriments, vitamine A par exemple, pourrait atténuer certaines conséquences d’un tonus glucocorticoïde excessivement prolongé. / Rôles to mobilize body resources and to adapt to endogenous or exogenous changes that might disrupt the homeostasis of the body. Nutritional & metabolic factors may modify the intensity of GC action in: i) the activation of the corticotrope axis and their secretion by the adrenals, ii) their bioavailability ("pre-receptor" regulation), iii) the transcriptional activation of their receptors ("post-receptor" regulation). The main target of this work is to explore the role of some metabolic/nutritional endogenous or exogenous factors in modulating pre- and post-receptor action of GC. Our attention first focused on the role of diabetes and the related inflammation in patients with type I diabetes, and pre-receptor metabolism of cortisol. We showed that a significant increase in the activity of hydroxysteroid dehydrogenase 1, the main enzyme of intracellular cortisol regeneration, is correlated with markers of inflammation in diabetic children. This suggests a link between diabetes and the low-level chronic inflammation and increased cellular exposure to GC . Then, we focused on the action of all-trans retinoic acid (atRA), the active metabolite of vitamin A on the transcriptional activity of GC. We used an in vitro model of hippocampal cells as GC and atRA have contrasted effects on mnesic processes in vivo. We observed a transcriptional interaction between the GC and retinoic pathways targeting their receptors and genes involved in neuronal plasticity. atRA also affects the phosphorylation of the GC receptor and modifies its transcriptional activity. Lastly, both atRA and GC affect cellular organisation of actin cytoskeleton. The knowledge acquired by studying the action of nutritional molecules on GC action could be used to easily reduce the deleterious effects of GC in chronic stress. Clinical studies have started in this direction.

Autoimmunity develops over an extended period of time as the result of an amalgamation of genetic, environmental, and immunologic events. Though the precise etiological factors leading to most autoimmune disease are awaiting consensus, a common thread of the autoimmune paradigm is the inappropriate activation of tissue-specific immune cells by one or more autoantigen, which begins the destruction of the tissue. To prohibit immunopathology and fine-tune the immune responses in healthy individuals, the stimulatory activities of effector/memory T (Teffs) cells must be counteracted by the suppressive mechanisms of regulatory T cells (Tregs). Thus, the potential to modulate the ratio between Teff and Tregs in autoimmune patients has been widely investigated with high hopes to permanently cure certain autoimmune diseases such as type 1 diabetes militus (T1D). Autoantigen therapies, which attempt to induce Tregs to suppress pathogenic effector cells in an autoantigen-specific manner, have shown efficacy in preventing T1D in mice, but have largely failed in clinical trials. One approach to improve the effectiveness of islet autoantigen vaccinations is to combine them with an additional modulator of the T cell response which favors a regulatory phenotype. In the work presented here, we asked whether the addition of anti-interleukin-7 receptor-alpha (anti-IL-7Rα) monoclonal antibodies (mAbs) to islet autoantigen immunizations would modulate the T cell response and prevent T1D in non-obese diabetic (NOD) mice. It was found that anti-IL-7Rα mAbs reduced the absolute numbers of islet antigen-specific T cells when immunized with islet peptide in conjunction with the commonly used vaccine adjuvant alum. Such treatments were also observed to increase nonspecific IL-2, IFN-𝛾, and IL-10 cytokine production, resulting in no improvement of T1D onset prevention. In another approach, we generated a conjugate vaccine by conjugating islet autoantigens to the immunogenic carrier protein, Keyhole Limpet Hemocyanin (KLH). We found that islet antigen-KLH (Ag-KLH) vaccination resulted in significant expansion of the desirable antigen-specific Tregs. Further, Ag-KLH immunization successfully delayed, and in some cases entirely prevented, T1D onset in NOD mice. Indicating that KLH-conjugated vaccine may represent a promising approach for future autoantigen therapies against autoimmunity. Interestingly, administration of anti-IL-7Rα mAbs did not improve these outcomes. To the contrary, we again observed excessive nonspecific cytokine production induced by IL-7Rα blockade that inhibited the beneficial effects of Ag-KLH vaccination. Taken together, we concluded that the addition of anti-IL-7Rα mAbs did not improve the efficacy of autoantigen vaccinations to prevent T1D. Significant work still remains to better characterize and isolate the beneficial effects of anti-IL-7Rα mAbs to treat autoimmunity.