Lower performance on measures of neuropsychological and academic ability has been noted in adolescents with either Type I Diabetes Mellitus (T1DM) or exposure to traumatic life events. This present study looked to gather information on trauma exposure and symptoms in adolescents with T1DM. The first aim was to compare the neuropsychological and academic achievement performance of Type I Diabetes Mellitus positive adolescents who had experienced a traumatic event with those who had not. Second, the study explored if T1DM positive adolescent’s performance on neuropsychological and academic achievement could be predicted by the number and severity of traumatic stress symptoms they experienced. Finally, the study aimed to explore the nature of trauma exposure of its T1DM positive adolescent participants. Results found limited evidence participants who self-reported trauma exposure performed worse than those who did not on a measure of perceptual reasoning; those with parent-reported trauma exposure scored lower on a measure of visual perception and reasoning as well as an assessment of calculation ability than those whose parents did not. As trauma symptoms scores as reported by either self- or parent-report increased, participant scores on measures of general cognitive ability and attention decreased. As self-reported trauma symptoms increased, performance on perceptual reasoning and psychomotor ability decreased. As parent-reported trauma symptoms increased, vocabulary and verbal abilities decreased. In addition to the results noted for trauma symptom scores, the as the number of self-reported symptoms increased, executive functioning, vocabulary, and verbal abilities decreased. While parent-reported trauma symptoms were not associated with decreased performance on any academic measure, as self-reported trauma symptoms scores increased math calculation, reading comprehension, and writing fluency scores decreased.

Youth with type 1 diabetes (T1D) from single-parent families are more likely to be in poorer glycemic control (HbA1c). Demographic trends indicate more households are composed of unmarried adults and fewer youths. Family density, or a youth: adult ratio, may be a more salient factor than single-parent status in the association with glycemic control. Data from 257 adolescents aged 11-14 years (M = 12.84) at two different sites were collected as part of a randomized control trial of a treatment intervention designed to increase parent involvement and prevent deterioration of adolescent diabetes disease care. Single-parent status was determined by parental report of a sole caregiving adult in a youth’s household. A family density ratio was calculated via parental report of the number of youths to adults in a home. A youth: adult ratio greater than two was considered “high family density” (Liaw & Brooks-Gun, 1994). Diabetes-related risk and protective factors of parental monitoring, youth adherence to disease care behaviors, parental stress, and diabetes-related conflict were measured using parent and youth report questionnaires. Glycemic control was determined via a DCA2000 analyzer with results abstracted from medical chart review. Consistent with the literature, single-parent status was correlated with higher HbA1c (r = .19, p = .01) or poorer glycemic control. Similarly, higher family density also was related to higher HbA1c (r = .32, p < .001). An overall multiple regression model including family structure constructs (single-parent status and density), socioeconomic status, and ethnicity accounted for 18% of the variance in glycemic control. However, family density, β = .22, and SES, β = -.29, were the only significant correlates of glycemic control in the model when considered simultaneously with single-parent status and ethnicity. Although single-parent families have youths in poorer metabolic control, higher family density appears to be a more potent correlate of youth glycemic control perhaps because it might be a more sensitive indicator of available parental time and resources. Family density is significantly related to poorer adherence and greater diabetes-related conflict. Further, poorer adherence and more diabetes-related conflict partially explained the relation between high family density and poorer glycemic control. Family density appears to be an important family structure factor for adolescents with T1D and the identification of risk factors for poorer glycemic control has both clinical and research implications.

Person-oriented and variable-oriented analyses were conducted to investigate sociodemographic differences in biological, psychosocial and disease care factors in youth with type 1 diabetes. Additionally, diabetes knowledge was evaluated as a potential mediator of SES effects on HbA1c and disease care. The sample included 349 youth, age 9-17 years (79.9% Caucasian, 71.3% lived with two biological parents, M SES = 46.24). Person-oriented t-tests confirmed commonly reported ethnic differences in HbA1c and disease care behaviors. However, variable-oriented analyses controlling for confounding sociodemographic influences showed most disease care effects attributed to ethnicity were better explained by SES. While diabetes knowledge was not a significant mediator of meal composition, it appeared to suppress the effect of social class on carbohydrate and fat consumption, such that more diabetes knowledge minimized the negative effect of lower SES on optimal carbohydrate and fat consumption. Results may inform future interventions for youth at risk of poor metabolic control.

5 Abstract Type 1 diabetes (T1D) is a serious organ-specific autoimmune disease characterised by irreversible destruction of pancreatic β-cells by immune system. This process results in an absolute insulin deficiency. Both genetical predisposition and environmental factors influence the development of the disease. β-cell destruction is mediated by cellular components of an immune system. Proinflammatory Th1 response is considered as most pathological. Autoimmune destruction of β-cells can be identified by the detection of specific serum autoantibodies a long time before the T1D clinical onset. Currently, there is no efficient cure available to prevent or at least to delay the destructive insulitis. This diploma thesis describes the influence of synthetic diabetogenic autoantigens GAD65 and IA2 on the cytokine response of peripheral blood mononuclear cells (PBMC) obtained from T1D patients with regards to their antibody profile. The study has been carried out on patients with confirmed T1D diagnosis who tested positive for anti-GAD65 and/or anti-IA2 autoantibodies. By using flow cytometry we measured the cell type ratio in PBMC samples. The cells have been stimulated by three different concentrations of antigens and their IFNγ and IL-17 production has been detected by ELISPOT assay. In the case of both...

Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2006. / Objectives. Autoantibodies to the 65kDa isoform of glutamic acid decarboxylase (GAD65Abs) are accepted markers for type 1 diabetes and, together with autoantibodies to insulin (IAA) and a protein tyrosine phosphatase-like islet cell antigen (IA-2), predict the disease. IAA are often the first autoantibodies detected in type 1 diabetics and can be present before the onset of clinical diabetes. These autoantibodies and their epitopes are however not well characterized. We explored the use of monoclonal antibodies and their recombinant Fab (rFab) as reagents for epitope analysis. Methods and Results. Four rFab specific for insulin were cloned from murine monoclonal antibodies (mAbs) 1E2, HB-126, HB-123, HB-127, and one rFab specific for GAD65 was cloned from human mAb IgG antibody DP-D (derived from autoimmune disease patients), to characterise insulin and GAD65 autoantibodies present in the sera of patients with type 1 diabetes. Only rFab 126 and DP-D showed insulin and GAD65 specific binding, respectively in radiobinding assays. In competition experiments with sera positive for autoantibodies to insulin the rFab 126 significantly reduced the binding to 125I-insulin by sera of type 1 (n=35) and type 1.5 diabetes (or LADA) (n=14) patients (p<0.0001). There was no difference in the competition pattern in IAA positive type 1 diabetes patients (n=35) and IAA positive type 1.5 diabetes patients (n=14). The insulin epitope that the rFab binds to was mapped using competitive radiobinding assays with two monoclonal antibodies (mAb 1 and mAb 125) whose epitopes are on the B chain and A chain loop of insulin, respectively. We found the epitope of this recombinant antibody to be located on the A chain loop of the insulin molecule. The 3-dimensional structure of rFab 123, 126 and DP-D were determined using an automated homology modelling programme. Using the computer programme ‘PatchDock’ we attempted to further map the epitope that rFab 126 binds to on insulin. Of the three models generated, only one supported our findings that rFab 126 binds to the A chain loop of insulin. The binding of GAD65Ab in 61 type 1 diabetes patients to GAD65 was analyzed by competitive radioimmunoassays with rFab DP-D to ascertain disease-specific GAD65Ab binding specificities. The median binding was reduced significantly by rFab DP-D (80%) (p<0.0001). The competition pattern in type 1 diabetes patients was different from that in GAD65Ab-positive type 1.5 diabetes patients (n=44), first degree relatives (n=38), and healthy individuals (n=14) (Padoa et al., 2003). Conclusions. We have shown that rFab specific for insulin and GAD65 can be generated using PCR technology and that such agents can be used to determine the insulin/GAD65 epitopes recognized by autoantibodies from type 1 and 1.5 diabetics. These novel findings with GAD65- and insulin-specific rFab support the view that type 1 diabetes is associated with disease- and epitope-specific GAD65- and insulin-autoantibodies and supports the notion that the middle epitope of GAD65 is disease-specific. These GAD65-specific rFab should prove useful in predicting type 1 diabetes. Furthermore, rFabs may be a novel method for blocking autoimmune responses against β cell autoantigens in type 1 diabetics.

Background. Type 1 diabetes requires intensive management, including blood glucose monitoring, carbohydrate counting and dietary modification, and administering insulin. When a child is diagnosed with type 1 diabetes, family dynamics are often altered as family schedules revolve around care for the child with diabetes. In addition, siblings face unique challenges as they become involved in the care of the child with type 1 diabetes. Therefore, it is important to understand experiences of siblings of youth with type 1 diabetes. Aims and Objectives. To identify experiences of siblings of children with type 1 diabetes from their own perspectives. Sample. As part of a larger IRB approved study, 51 children and adolescents ages 8-18 years with diabetes (M = 13.18), who have a sibling ages 8-18 years (M = 12.6), were recruited from diabetes summer camps and the diabetes clinic at a regional medical center. Methods. A qualitative descriptive design was used to ascertain experiences of siblings of youth with T1DM using semi-structured, scripted interviews. Interviews were audio recorded, transcribed verbatim, and analyzed for common themes according to qualitative methodology. Results. Common themes emerging from the data are: (1) knowledge about type 1 diabetes – how it was obtained and what more siblings wanted to know; (2) feelings experienced; (3) sibling relationship – the impact of diabetes on the relationship; and (4) involvement in diabetic care. Implications. It is important for healthcare providers working with children with T1DM and their families need to be aware of and address the psychological effects of the disease on all family members. While providers cannot alleviate all challenges and fears experienced by siblings of a youth with T1DM, they can make the parents aware of the challenges siblings face, facilitate communication among family members, and help connect brothers/sisters with resources such as education, support groups, and counseling.

Föräldrar till barn med typ 1 diabetes mellitus (T1DM) genomgår en rad olika förändringar när deras barn insjuknar. Insjuknandet går fort och föräldrarna hinner inte bli förberedda på det som komma skall. De tvingas utan förvarning hantera de emotionella, psykologiska och fysiologiska förändringar som sjukdomen för med sig. Föräldrarna försöker hantera situationen och genomför på kort tid livsstilsförändringar kring kost, motion, läkemedelshantering, blodsockermätning och hantera medicinteknisk utrustning. Dessutom påverkas den sociala support de tidigare hade, deras egna arbetssituation kan komma att förändras. De ska fortsätta att se syskonen till det insjuknade barnet samtidigt som de ska vårda sitt sjuka barn dygnet runt, året ut och livet ut. Förändringarna och den nya livssituationen kan vara mycket ansträngande för föräldrarna och de riskerar sin egna hälsa för att vårda sitt barn. Syftet med studien var att belysa föräldrars upplevelser att leva med ett barn med typ 1 diabetes. Metoden i litteraturstudien bygger på 12 artiklar. Både kvalitativa och kvantitativa artiklar som belyser området vilka alla sammanställts och bildar resultatet. Tre huvudteman framkom i resultatet: Föräldrarnas tankar och känslor, Vikten av social support och Föräldrarnas egna hälsorisk. Subteman som kom fram under föräldrars tankar och känslor var normalisering, att ha kontroll, oro och rädsla, sorg, mödrar kontra fäder. Det framkom inom vikten av social support tre subteman: diabetsteam/ sjukvården, skola/ barnomsorg samt support från vänner och familj. Subteman under föräldrarnas egna hälsorisk berör sömnbrist och utbrändhet. I studiens resultat framkommer att föräldrarna är oroliga över den bristfälliga kunskap skolan har kring deras barns T1DM. Att föräldrarna saknar stöttning från sjukvården till att nå riktlinjerna för en bra metabol kontroll. Det framkom att sjukvården har en viktig uppgift att bidra med kunskap och information. Det framkom också att diabetesteam bör beakta vad som kan ligga bakom problemet till brister i egenvården. Egenvårdsbalansen bör upprättas på ett mer långsiktigt och konstruktivt sätt än om sjuksköterskan bara inriktar sig på att åtgärda problem. Sjuksköterskans roll bör vara av hjälpande, vägledande, lärande, motiverande, fysiskt eller psykologiskt stödjande funktion eller att bidra till ett sammanhang som stödjer utveckling för föräldrarna till barn med T1DM.

Many adolescents with type 1 diabetes (T1DM) have suboptimal glycaemic control, increasing the risk of diabetic complications. This thesis explores some of the causes, consequences and therapeutic options for adolescents with T1DM and poor glycaemic control. Insulin resistance occurs in T1DM and normal puberty and contributes to poor glycaemic control. The effect of rosiglitazone, an insulin sensitizer, in addition to insulin on the glycaemic control of adolescents with T1DM was tested using a randomized, double blind placebo controlled trial. Treatment with rosiglitazone did not improve HbA1c, however there was a significant reduction in insulin dose and adiponectin, suggesting improved in insulin sensitivity. Insulin sensitivity by euglycaemic hyperinsulinaemic clamp varied widely between individuals and there was no consistent pattern with rosiglitazone. Potential markers of insulin resistance in T1DM were examined. Total and high molecular weight (HMW) adiponectin levels were lower in children and adolescents with T1DM than controls. HMW adiponectin was significantly associated with other markers of insulin resistance, such as insulin dose, body mass index standard deviation score (BMI-SDS), age, pubertal stage and duration of diabetes. There is increasing evidence that insulin resistance may play a role in T1DM complications. The natural history and risk factors for the development of microalbuminuria was described using a retrospective cohort study of 972 children and adolescents. Most cases of microalbuminuria were transient. Apart from baseline albumin excretion rate, HbA1c and age at diagnosis, other predictors of subsequently developing persistent microalbuminuria included several markers of insulin resistance (higher cholesterol, BMI-SDS, and insulin dose). In addition to insulin resistance, there are many other factors that contribute to glycaemic control. The role of the variability in carbohydrate intake was assessed using questionnaires and food diaries. Although carbohydrate consumption varied by approximately 45grams each day, it had no significant correlation with HbA1c. The impact of socioeconomic status, quality of life and health care delivery is discussed by comparing glycaemic control of children with T1DM in three diabetes centres. A model for the factors associated with poor glycaemic control in adolescents with T1DM is proposed, and the challenges of research and clinical practice in this population are discussed.

The present study aimed to examine factors that predict glycemic control in Hispanic youths. Secondary aims included developing and evaluating Spanish translations of three measures commonly used in research with youths with type 1 diabetes and examining factors associated with diabetes self-management in this population. Data was collected at three sites through interviews, questionnaires, and medical chart review. Participants included 117 Hispanic diabetic youths (10 to 17 years old) and their caregiver. 15% of the youths who participated were born outside of the continental U.S. and 57% were first generation born in the U.S. Translations of the Diabetes Self-Management Profile, Diabetes Social Support Questionnaire-Family version, and the Family Environment Scale?s Organization subscale had adequate reliability and showed evidence of concurrent validity. Primary analyses indicated that parent education, occupation, and household income are all significant predictors of glycemic control in Hispanic youth. In addition, global ratings of diabetes self-management on the DSMP predicted control in this population. Family factors did not contribute directly to glycemic control after controlling for sociodemographic and disease variables. However, older age, more acculturation, and language barriers were associated with poorer self-management. Additionally, family support and organization significantly contributed to self-management.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 152-175).