Este trabalho teve como objetivo conhecer como se dão as interações familiares de adolescentes com diabetes tipo 1 desde o diagnóstico da doença.Utilizou-se como referencial metodológico a História Oral .Os dados coletados mediante entrevistas gravadas com sete adolescentes foram analisados à luz do Modelo Calgary para Avaliação da Família de Wright e Leahey.As narrativas demonstraram que apesar do acréscimo de atividades na rotina diária do adolescente e da família, relacionadas à manutenção e controle do diabetes, as interações familiares sofrem poucas modificações com a chegada da doença e que os conflitos entre os pais e o adolescente com diabetes não diferem tanto daqueles ocorridos entre os pais e adolescentes saudáveis.A superproteção foi um sentimento percebido pelos adolescentes após o surgimento da doença,pois os pais têm preocupações com complicações imediatas e em longo prazo. O principal vínculo demonstrado pelos adolescentes entrevistados com a suas famílias foi o vínculo de confiança. Para eles é muito importante saber que conquistaram a confiança de seus pais de que podem ter certa autonomia em relação ao manejo do diabetes.Com os irmãos compartilham superficialmente o diabetes,mesmo aqueles que mantêm relações mais estreitas.A família extensa também oferece contribuições em diferentes fases da doença. Os adolescentes entrevistados forneceram dados de que sua comunicação verbal com sua família é ampla e direta. Sentem-se livres e confiantes em falar abertamente sobre assuntos diversos com os pais e os outros membros que coabitam, relatando também com quem se relacionam melhor em casa. Percebe-se também que a família tenta de alguma maneira moldar-se de acordo com as necessidades da pessoa que tem diabetes,na organização e funcionamento.Sentimentos de gratidão são demonstrados pela associação especializada em educação em diabetes, citada como a responsável por todo ou grande parte do conhecimento adquirido,principalmente pelas atividades oferecidas no acampamento para jovens, e também como fonte de solução de problemas oriundos do diagnóstico do diabetes para os pais e para os próprios adolescentes. / This study aimed to understand how to give the family interactions of adolescents with type 1 diabetes since diagnosis of illness. The method used was Oral History y. Data collected through recorded interviews with seven adolescents were examined in the light of Wright e Leaheys Calgary Family Evaluation Model .Narratives demonstrated that despite the increased activities in the daily routine of the adolescent and family for care and control of diabetes, family interactions experience little change with the arrival of the illness and that conflicts between parents and adolescents with diabetes do not differ from those that occurred between parents and healthy adolescents. Overprotection was a sentiment felt by the teenagers after the onset of the disease because parents have concerns about immediate complications and long term. The main bond shown by the adolescents interviewed with their families was the bond of trust. Adolescents share the diabetes management with brothers superficially, even those who maintain more closed. Extended family also offers contributions in different stages of the disease. The adolescents interviewed communicate with your family is extensive and direct, feeling confident to talk about various issues with parents and other members, also reporting to whom they relate better at home. Family tries shape up according to the needs of the person who has diabetes, the organization and function.

The ability of insulin to stimulate glucose uptake into muscle and adipose tissue is central to the maintenance of whole-body glucose homeostasis. Deregulation of insulin action manifests itself as insulin resistance, a key component of type 2 diabetes. Insulin resistance is also observed in HIV patients receiving protease inhibitors. An agent that can reversibly induce an insulin-resistant state would be a very useful tool in developing model systems that mimic the pathogenesis of type 2 diabetes. Insulin resistance can arise from defects in insulin signal transduction, changes in the expression of proteins or genes that are targets of insulin action, cross talk from other hormonal systems or metabolic abnormalities. Deterioration of the insulin-receptor-signalling pathway at different levels leading to decreased levels of signalling pathway intermediates and/or decreased activation through phosphorylation accounts for the evolution from an insulin-resistant state to type 2 diabetes. In addition, defects in GLUT4 glucose transporter translocation are observed, further fuelling impairments in skeletal muscle glucose uptake. Levels of insulin-induced GLUT4 translocation in the skeletal muscle of type 2 diabetic patients are typically reduced by 90%. Many cellular pathways & their intermediates are in some way or another linked to insulin signalling. This study focused on three of these namely the PI3-kinase/Akt pathway, the Mitogen Activated Protein Kinase (MAPK) cascade and the AMP Kinase pathway, with successful monitoring of the PI3-K pathway. Investigations involved observing and evaluating the effects of various compounds as well as an indigenous medicinal plant, Sutherlandia frutescens on the activities of key insulin signalling pathway intermediates within the three fore mentioned pathways including Akt, AMPK and MEK1/2 as well as membrane surface GLUT4 levels. Scientific research has in the past leant heavily on Western blotting as the method of choice for gaining vital information relating to signal transduction pathways, however for research into cellular mechanisms the negatives of this method outweigh the positives. The drawbacks include a need for large amount of cells, multiple washing steps which may be disadvantageous to any weak and transient interactions as well as lysing of cells which may interfere with the maintenance of the subcellular localisation of a specific signalling event. Based on these, the need for a better method in terms of speed & reliability to monitor phosphorylation states of signal transduction pathway intermediates & GLUT4 translocation was evident and was one VII of the main aims & successes of this study. The method created used the mouse muscle cell line C2C12 in conjunction with the quick, sensitive method of flow cytometry which allowed us to monitor these processes in these cells through immune-labelling. Adherent cell cultures such as the C2C12 cell line pose the problem of possible damage to plasma membrane receptors (including insulin receptors) during harvesting to obtain a cell suspension for flow cytometry. We however used C2C12 mouse myocytes to optimize a method yielding insulin responsive cells in suspension that were successfully used for flow cytometry after immunelabelling of insulin signalling intermediates. Insulin (0.1μM) significantly raised the levels of both P-Akt and GLUT4 above basal levels. This effect was shown to be dose dependent. At a concentration of 50μg/ml, Sutherlandia frutescens was able to act as an insulin-mimetic in terms of its ability to increase P-Akt levels, GLUT4 translocation and glucose utilisation in an acute manner. These increases could be reduced with the addition of wortmannin, a PI3-K inhibitor. Therefore, these results suggest the mechanism of the plant extract’s insulin-like activity may be in part due to the activation of the insulin signalling pathway leading to GLUT4 translocation, which involves the phosphorylation of insulin receptor- and subsequent PI3-K activity, leading to P-Akt activity. These results provide further evidence of this plant extract’s anti-diabetic potential. The effect of Sutherlandia frutescens on insulin secretion, calcium signalling and proliferation in INS-1 rat pancreatic cells was also investigated and it was found to increase the activities of all of these processes. However no change in the levels of GLUT2 glucose transporter was seen. Ritonavir is prescribed by the South African Department of Health in co-formulation with other protease inhibitors within its second regime in the treatment of HIV and AIDS. Using C2C12 cells, ritonavir decreased glucose uptake acutely and had no effect on GLUT4 translocation however surprisingly increased P-Akt levels. In conclusion, it was found that Sutherlandia frutescens has antidiabetic benefits, diverse in nature depending on tissue type as well as length of time administered. The establishment of novel flow cytometry techniques to assess antidiabetic properties using in vitro cell culture was achieved. These methods will be useful in the future for the assessment of insulin sensitivity and in the identification of novel compounds that stimulate the insulin signalling pathways.

Health coaching is a promising approach to support self-management of chronic conditions like type 2 diabetes; however, there aren’t enough coaching practitioners to support those in need. Advances in Artificial Intelligence (AI) and Machine Learning (ML) have the potential to enable innovative, automated health coaching interventions, but important gaps remain in applying AI and ML to coaching interventions. This thesis aims to identify computational approaches and interactive technologies that enable automated health coaching systems. First, I utilized computational approaches that leverage individuals’ self-tracking and health data and used an expert system to translate ML inferences into personalized nutrition goal recommendations. The system, GlucoGoalie, was evaluated in multiple studies including a 4-week deployment study which demonstrated the feasibility of the approach. Second, I compared human-powered and automated/chatbot approaches to health coaching in a 3-week study which found that t2.coach — a scripted, theoretically-grounded chatbot designed through an iterative, user-centered process — cultivated a coach-like experience that had many similarities to the experience of messaging with actual health coaches, and outlined directions for automated, conversational coaching interventions. Third, I examined multiple AI approaches to enable micro-coaching dialogs — brief coaching conversations related to specific meals, to support achievement of nutrition goals — including a knowledge-based system for natural language understanding, and a data-driven, reinforcement learning approach for dialog management. Together, the results of these studies contribute methods and insights that take steps towards more intelligent conversational coaching systems, with resonance to research in informatics, human-computer interaction, and health coaching.

The pathophysiology of cytokines released by infiltrating white blood cells upon pancreatic beta cells is not fully understood. Early growth response gene-1 (Egr-1) expression is specifically and transiently up regulated in pancreatic beta cells in response to glucose. We hypothesized that interleukin-1 beta (IL-1▀) induction of nitric oxide alters glucose induced Egr-1 transcription levels. Egr-1 levels were assessed via western blot, nitric oxide was measured with a Griess Reagent kit and insulin levels via ELISA. Glucose induced both insulin and Egr-1 production in INS-1 cells. IL-1▀ dose dependently increased nitric oxide production over time and significantly attenuated glucose induced Egr-1 expression. Sodium nitroprusside dose dependently reduced glucose induced Egr-1 production. The data suggest a strong relationship between IL-1▀ induced nitric oxide production and the reduction of glucose stimulated Egr-1 production. The pathways altered by this cytokine could provide a better understanding of the pathophysiology leading to pancreatic beta cell death.

PrediXcan, an imputed gene expression-trait association method, was compared to multiple linear regressions (MLR) of single nucleotide polymorphisms (SNPs) using the quantitative phenotypes serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglycerides (TG). The gene expression prediction models were trained using transcriptome- and genome-wide data from Depression Genes and Networks (DGN whole blood) and Genotype-Tissue Expression (GTEx) Project (GTEx whole blood, GTEx pancreas and GTEx liver). Linear combinations of the effect sizes derived using elastic net or least absolute shrinkage and selection operator (LASSO) with genotypes from 1304 European patients from the Diabetes Control and Complications Trial (DCCT) were used to estimate the genetically regulated expression (GReX) for genes. Different gene expression predictors were present in each training set. The 10-fold cross-validated predictive performance, estimated GReX, and p values from associations for matched genes were weakly correlated across training sets and strongly correlated for models derived using elastic net and LASSO. MLR models had more significant associations than PrediXcan models and larger inflation factors for p values. A comparison of p values for matched genes between PrediXcan and MLR models showed weak correlations but strong evidence for LDL and HDL associations with genes at locus 1p13.3 and 16q13, respectively. / Thesis / Master of Science (MSc)

Objective: To identify whether perceived stress is a risk-factor for higher cortisol levels and greater insulin resistance in Type 2 diabetic patients, using data from participants with and without diabetes in the National Survey of Midlife Development in the United States (MIDUS), specifically MIDUS II, Project 4. The following hypotheses were tested: (H1a) greater perceived stress would be associated with higher cortisol for Type 2 diabetic participants, (H1b) the perceived stress/cortisol relationship would be stronger for people with Type 2 diabetes than for those without it, (H2) greater perceived stress would be associated with higher Homeostatic Model Assessment-Insulin Resistance (HOMA-IR, insulin-resistance) for Type 2 diabetic participants, (H3a) subjective well-being would moderate the perceived stress/insulin resistance relationship for Type 2 diabetic participants, and (H3b) depression would moderate the perceived stress/insulin resistance relationship for Type 2 diabetic participants. Method: MIDUS, a longitudinal study of over 7,000 American adults, explores biopsychosocial factors that could contribute to variance in mental/physical health. Only complete data were utilized. Type 2 participants (n=115) consisted of 54 males and 62 females ranging in age from 36 to 81 years. Non-diabetic participants (n=1097) consisted of 470 males and 627 females ranging in age from 34 to 84 years. Results: None of the predicted relationships were statistically significant. Waist to hip ratio was significantly related to insulin resistance (r = .31, p = .001). Conclusions: Future studies should collect information about the type and duration of stressors in addition to perceptions about stress for those with Type 2 diabetes.

Dados prévios ja demostram que o controle intensivo da glicemia diminui o risco de eventos microvasculares em pacientes com diabetes mellitus. No entanto, seu efeito cardiovascular é incerto. Nós sumarizamos os dados de estudos das principais bases de dados. 2 revisores extraíram dados de estudos randomizados de pacientes com diabetes tipo 2, que visavam 2 níveis de intensidade da glicemia. Investigou-se as retinopatia, neuropatias, nefropatias, mortalidade cardiocascular e total, infarto do miocárdio (IAM), acidente vascular cerebral, amputação de membros e episódios de hipoglicemia. Realizamos a meta-análise para obter o risco relativo (RR). Foram incluídos 7 estudos com 27.814 pacientes. O controle intensivo reduziu o RR de IAM e amputação, além progressão da retinopatia, incidência de neuropatia periférica, incidência e progressão de nefropatia e microalbuminúria. Entretanto, dobrou o risco de episódios de hipoglicemia. Não houve diferenças quanto à mortalidade e outros resultados. Conclui-se que controle intensivo reduziu o risco de alguns eventos, sem reduzir a mortalidade, porém as custas do dobro da incidência de de hipoglicemia. / Previous data already show that intensive glucose control reduces the risk of microvascular events in patients with diabetes mellitus. However, its cardiovascular effect is uncertain. We summarize data from studies of the major databases. 2 reviewers extracted data from randomized studies of patients with type 2 diabetes, aimed at two intensity levels of blood glucose. We investigated the retinopathy, neuropathy, nephropathy, and total mortality cardiocascular, myocardial infarction (IAM), stroke, limb amputation and episodes of hypoglycemia. We conducted a meta-analysis to obtain the relative risk (RR). We included seven studies with 27.814 patients. The intensive control reduced the RR of IAM, and amputation, and progression of retinopathy, incidence of peripheral neuropathy, incidence and progression of nephropathy and microalbuminuria. However, it doubled the risk of hypoglycemia. There were no differences in mortality and other outcomes. We conclude that intensive control reduced the risk of some events without reducing mortality, but the expense of twice the incidence of hypoglycemia.

Fan, Rongrong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 130-150). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Kwan, Yee Mei. / Thesis (D.Nurs.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 152-171). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; appendixes includes Chinese.

Cheng, Suosuo. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 159-173). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts aslo in English.