Type 2 Diabetes Mellitus (T2DM), a metabolic disorder denoted by elevated blood glucose levels and insufficient insulin action, is growing in prevalence worldwide . Barriers to improving disease outcome resolve primarily around identifying and intervening during the preliminary stages of insulin resistance, a state clinically referred to as pre-diabetes. Emerging evidence suggests that mitochondrial dysfunction may underlie , and potentially precede, progressive insulin resistance, suggesting that biomarkers indicative of mitochondrial dysfunction could predict disease risk and status. In this study, we examined epigenetic modifications, in the form of DNA methylation, in the promoter region of peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α), a known regulator of mitochondrial biogenesis. Following the initiation of a high fat diet, we observed significant genotypic (DNA methylation) and phenotypic (mitochondrial copy number) alterations in C57/BL6 rodent models. These changes preceded overt disease onset, as classified by clinically utilized indices, which included the homeostatic model assessment for insulin resistance (HOMA-IR), the homeostatic model assessment for β-cell dysfunction (HOMA- β), and the quantitative insulin-sensitivity check index (QUICKI). Our data indicate that methylation analysis may serve as an effective clinical parameter to use in conjunction with physiological criterion for the diagnosis of pre-diabetes and the assessment of T2DM disease risk, and adds to the growing body of work seeking to elucidate the role. / Doctor of Philosophy / High blood glucose, referred to as type 2 diabetes (T2DM), increases the risk for heart and kidney disease, blindness, stroke, and death. Efforts to prevent T2DM have centered primarily around behavioral interventions, which include increased physical activity and decreased caloric intake. Importantly, the interventions are most effective when implemented early on in disease progression. In this study, we sought to examine the effects of a high fat diet on the epigenetic profile of PGC-1α, a gene responsible for maintaining mitochondrial biogenesis. The mitochondria, the powerhouse of the cell, is responsible for maintaining the energy systems in the body. Therefore, we examined how increasing in caloric intake resulted in changes in the epigenetic profile of the PGC-1α promoter, and how these changes impacted mitochondrial number. Further, we sought to examine how hypermethylation of PGC-1α led to changes in gene and protein expression in the mitochondria. Results from our study indicate that DNA methylation changes preceded disease onset, as characterized by the homeostatic model assessment for insulin resistance (HOMA-IR), the homeostatic model assessment for β-cell dysfunction (HOMA- β), and the quantitative insulin-sensitivity check index (QUICKI). Our data indicate that methylation analysis may serve as diagnostic and risk assessment tool for pre-diabetes and T2DM in conjunction with physiological measures.

Yes / Individuals with type 2 diabetes play a pivotal role in their health. Enhancing the self-management of diabetes can improve blood glucose control, and quality of life, and reduce diabetes-related complications. We have identified factors influencing the self-management of type 2 diabetes to inform strategies that may be applied in the long-term management of blood glucose control. Methods: We conducted a systematic literature review of recent studies published between January 2010 to December 2020 to identify the available evidence on effective self-management strategies for type 2 diabetes. The databases used for the searchers were Scopus, PubMed, Science Direct, CINAHL, and Google Scholar. We assessed English language publications only. The screening of titles was duplicated by two researchers. We then conducted a thematic analysis of the key findings from eligible publications to identify reoccurring messages that may augment or abate self-management strategies. Results: We identified 49 relevant publications involving 90,857 participants. Four key themes were identified from these publications: Individual drive, social capital, Knowledge base, and Insufficient health care. High motivation and self-efficacy enabled greater self-management. The importance of family, friends, and the health care professional was salient, as were the negative effects of stigma and labelling. Enablers to good self-management were the level of support provided and its affordability. Finally, the accessibility and adequacy of the health care services emerged as fundamental to permit diabetes self-management. Conclusions: Self-management of type 2 diabetes is an essential strategy given its global presence and impact, and the current resource constraints in health care. Individuals with type 2 diabetes should be empowered and supported to self-manage. This includes awareness raising on their role in self-health, engaging broader support networks, and the pivotal role of health care professionals to inform and support. Further research is needed into the capacity assessment of healthcare systems in diabetes medicine, targeted low-cost resources for self-management, and the financial requirements that enable self-management advice to be enacted. / While this research did not receive any specific project funding, KRB is funded by a University of Otago Pacific Ph.D. Scholarship. ANR is funded as a Research Fellow by the National Heart Foundation.

Approximately 8.3% of the U. S. population has type 2 diabetes. Preventing the onset and improving the management type 2 diabetes are crucial for health care professionals. The purpose of this project was to develop and evaluate a type 2 diabetes prevention and management education program in a primary care setting using group medical appointments (GMAs). The chronic care model provided the framework for the study. The education program consisted of information from the Centers for Disease Control on the management of type 2 diabetes to be delivered by clinic staff using a GMA approach, a timeline for implementing the education program, and evaluation strategies for assessing patient health outcomes. Staff participants included 9 females and 1 male. One week after the presentation, staff responded to open-ended questions addressing the plan for prevention and management of type 2 diabetes. Findings indicated that staff unanimously approved the content of the program, thought the program could realistically be implemented, thought the proposed evaluation methods were appropriate, and thought the program would have a positive influence on patient health outcomes. Prevention and management education programs using a GMA approach may be used to reduce incidence and improve management of type 2 diabetes.

Diabetes is a group of metabolic diseases characterized by hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. Several models have been developed for describing the glucose-insulin system. Silber and Jauslin developed a semi-mechanistic integrated glucose insulin (IGI) model which simultaneously describe glucose and insulin profiles in either healthy subjects or type 2 diabetis mellitus (T2DM) patients. The model was developed for describing the basal system, i.e. when no drugs are present in the body. In this thesis the IGI model was extended to also include the effects of anti-diabetic drugs on glucose homeostasis. The model was extended to describe postprandial glucose and insulin excursions in T2DM patients treated with either biphasic insulin aspart or the GLP-1 receptor agonist liraglutide. These extensions make the model a useful tool in drug development as it can be used for elucidating the effects of new products as well as for clinical trial simulation. In this thesis several modelling tasks were also performed to get a more mechanistic description of the glucose-insulin system. A model was developed which describes the release of the incretin hormones glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 following the ingestion of various glucose doses. The effects of these hormones on the beta cell function were incorporated in a model describing both the C-peptide and insulin concentrations in healthy subjects and T2DM patients during either an oral glucose tolerance test or an isoglycaemic intravenous glucose infusion. By including measurements of both C-peptide and insulin concentrations in the model it could also be used to characterize the hepatic extraction of insulin.

Sustainable Built Environments Senior Capstone Project / For over a century, Pima Indians living just south of Phoenix, Arizona on the Gila River Indian Reservation have suffered from an epidemic of type 2 Diabetes Mellitus. Over half of the Pima population living on the reservation is diagnosed with diabetes while the socioeconomic conditions of the tribal community are in an unstable and dilapidated state (Unnatural Causes 2008). Fifty percent of the Pimas living on the Gila River Indian Community live below the poverty level (Unnatural Causes 2008). Displacement from traditional customs and neglect from the U.S. federal government are just some of the detrimental impacts the people have faced over the last century (Unnatural Causes 2008). The discussions within this paper will attempt to address how and why the Pima Indians have experienced such severe changes in lifestyle and economy over the last century and what affect this has had on the physical health of the people in the community. By addressing these overarching issues, one should find that socioeconomics and conditions of physical health are strongly connected. Looking even closer though, specifically at the epidemic of type 2 diabetes and the contributing risk factors that this population suffers from, one will begin to question how within just a matter of 3 decades the number of diagnosed cases of type 2 diabetes doubled among the Pima and how the rates are some of the highest recorded in the entire world. Moreover, the underlying issue is not simply a cause of poor diet, change in activity levels and unfavorable genetics, rather - being robbed of a critical natural resource, forced to adapt to unfavorable economic changes and in the end, the U.S. government failure to intervene – are truly the underlying causes that have impacted the health of the Pima Indians of Southern Arizona. The Pimas are people of their natural environment. Having a long history of living along the Gila River, the Pima were water irrigation engineers (Unnatural Causes 2008). Cultivating local crops, living off the land and providing for themselves using waters of the Gila River in an arid climate is as much a part of their culture as is their ancestral bloodline. The research presented in these discussions will look at the identical ancestry of Pima Indians living in Southwestern Sonora, Mexico in the Sierra Madre Mountains of Maycoba in order to evaluate the Pima tribe’s predisposition to the disease. The significance of looking at these groups is that their genetic history is the same based upon linguistic and genealogy studies (Schulz, Bennett, Ravussin, Kidd, Kidd, Esparza, Valencia, 2006). However, the Pima living in Sonora have not seen the same ever-increasing rates of type 2 diabetes or even obesity, as their northern counterparts have. Notably, the Mexican Pima have not experienced the same environmental changes (i.e. drought) either. Subsequently, the Pima of Sonora have been able to continue their traditional ways of life including subsistence farming and healthy diet and exercise. A historical background of the Arizona Pimas will be provided, from their cultural traditions as irrigation engineers to their participation in federal subsidy programs and their current economic state. In-depth historical accounts will also be made for the history of water law in the Southwestern United States, including what drove white settlers’ demand for water west of the Mississippi over the course of two centuries, to the attempts to mitigate the severity of drought on Native American reservations through multiple legislative acts. Information regarding the Mexican Pima’s current economy, levels of physical activity and typical diet will be presented in comparison to the present health and economic conditions of the Arizona Pima.

Published research on diabetes in Ghana is quite limited and relates mainly to incidence and prevalence of the disease with little research on the patients experiences of coping with the diabetes. It is estimated that diabetes affects 6.3% of the Ghanaian population with type 2 diabetes accounting for 90-95% of all cases of diabetes. In Ghana, individuals diagnosed with type 2 diabetes mellitus are confronted with difficulties including the high cost of treatment of the condition, stigmatization, and interruptions to normal physiological processes. In addition, the patients experience, limited clinic accessibility, inadequate drug availability, inadequate numbers of trained staff, as well as limited availability of equipment needed for adequate care of the condition. The review of literature for this current thesis also showed that none of the studies on coping were undertaken in Ghana, but were conducted in the western world where socio-cultural factors are quite diverse from the Ghanaian situation. In the light of the challenges facing diabetic patients as well as the gap observed in literature, the study set out to explore the coping strategies of patients with type 2 diabetes mellitus at a hospital in Ghana. A hermeneutic phenomenological approach to qualitative research was utilized. Twenty seven (27) in-depth interviews carried out with newly diagnosed patients with type 2 diabetes, between August and October 2009 at a hospital in Ghana. Interviews were conducted in the local Ghanaian Twi language and English. Participants who could not speak English were interviewed in Twi language and later translated into English by the researcher. Data analysis used Creswell (1998) approach to qualitative data analysis, which provided a rich description of the essential structures of the phenomenon under study. The study identified patients’ perceptions as to the causes of diabetes mellitus, the social meanings attributed to diabetes (with particular attention paid to the language by Ghanaian people to describe disease condition), and subsequently reactions and resolutions to diagnosis. Patients discussed treatment options, while at the same time remaining hopeful of finding a cure. All patients had a firm spiritual belief system that underpinned their understanding of the causation and treatment of their illness. This combined with various degrees of understanding and acceptance of western explanations of illness influenced the coping strategies employed by patients, which variously reported as positive, negative, and alternative strategies. The study establishes a platform upon which health providers can develop educational programmes for diabetic patients in Ghana, which will address misconceptions about diabetes mellitus in Ghana and the importance of programmes of care, which take account of and build upon the cultural context of ‘being Ghanaian’. Diabetes, at least for Ghanaian patients is more than a biomedical disease. In this sense a biomedical framework in and of itself will not enable healthcare providers to effectively manage this chronic disease in the Ghanaian population, but through the inclusion of an understanding of their spiritual beliefs, healthcare providers can understand the realities of what it is like for Ghanaian diabetes patients to live with diabetes. It is argued that a stronger collaboration and integration between traditional healthcare systems and orthodox healthcare systems will provide the optimum opportunity to maximize patient care in Ghana. Future research should concentrate on better understanding how lay knowledge and health related attitudes, beliefs and behaviours are associated with diabetes in Ghana.

People with type 2 diabetes are at increased risk of age-related cognitive impairment. Previous literature has focused on case-control studies comparing rates of cognitive impairment in patients with and without diabetes. Investigations of potential risk factors for cognitive impairment (including those with increased prevalence in diabetes, such as macrovascular disease, and diabetes-specific factors such as hypoglycaemia) in study populations consisting exclusively of patients with type 2 diabetes have been largely neglected. Moreover, previous studies have failed to take advantage of the extensive characterisation and prospective nature of longitudinal cohort studies to investigate the relative predictive ability of a wider range of potential risk factors for cognitive decline. Using data from the prospective Edinburgh Type 2 Diabetes Study (ET2DS) the present thesis aimed (i) to determine associations of cognitive decline with macrovascular disease and with severe hypoglycaemia, and (ii) to compare a wider range of potential risk factors in their ability to predict cognitive decline. In 2006/2007, 1066 patients with type 2 diabetes (aged 60 to 75 years) attended the baseline ET2DS clinic and 831 returned for the follow-up at year 4. Subjects were extensively characterised for risk factor profiles at baseline, and at year 4 for incidence of severe hypoglycaemia. Socioeconomic status was estimated using postcode data. Scores on seven tests of age-sensitive ‘fluid’ cognitive function, which were administered at baseline and at year 4, were used to derive a general cognitive component (‘g’). A vocabulary-based test, administered at baseline, estimated pre-morbid ability. Findings are reported in three parts. 1.) Macrovascular disease and cognition: Subjects with higher levels of biomarkers indicative of subclinical macrovascular disease, including plasma N-terminal pro-brain natriuretic peptide and carotid intima-media thickness, had significantly steeper four-year cognitive decline, independent of traditional cardiovascular risk factors, stroke, socioeconomic status and estimated pre-morbid cognitive ability. For ankle-brachial pressure index, the association fell just short of statistical significance. Effect sizes were overall modest, with fully adjusted standardised beta coefficients ranging from 0.06 to -0.12. Little evidence was found for associations of the symptomatic markers of macrovascular disease with four-year change in cognitive function that was independent of participants’ pre-morbid ability and socioeconomic status. 2.) Severe hypoglycaemia and cognition: Subjects with lower cognitive ability at baseline were at two-fold increased risk of experiencing their first-ever incident severe hypoglycaemia during follow-up. The rate of four-year cognitive decline was significantly steeper in those exposed to hypoglycaemia compared with hypoglycaemia-free participants, independently of cardiovascular risk factors, microand macrovascular disease and of estimated pre-morbid cognitive ability. Effect sizes again were overall modest (Cohen’s d = 0.2 to 0.3 for statistically significant differences in four-year cognitive decline between subjects with and those without hypoglycaemia, following multivariable adjustment) 3.) Consideration of a wider range of risk factors and cognition: A stepwise linear regression model including a total of 15 metabolic and vascular risk factors identified inflammation, smoking and poorer glycaemic control (in addition to some of the subclinical markers of macrovascular disease) as predictive of a steeper four-year cognitive decline. Other traditional cardiovascular risk factors, diabetic retinopathy, clinical macrovascular disease and a baseline history of severe hypoglycaemia were not included in this model. The interpretation of the latter finding is limited, however, by the fact that the stepwise regression procedure may exclude true predictors from a model when they correlate with already included risk factors. This thesis has demonstrated associations of later-life cognitive decline in people with type 2 diabetes with markers of subclinical macrovascular disease and poor glycaemic control (including hypoglycaemia) as well as other cardiometabolic risk factors (inflammation, smoking). Findings suggest that associations are relatively weak and complex due to inter-relationships amongst risk factors, and indicate a role of pre-morbid ability and socioeconomic status (which as risk factors are difficult to modify) in the relationships of risk factors with cognitive decline. Future research including case-control studies to compare risk factor associations between people with type 2 diabetes and non-diabetic older adults and randomised controlled trials to evaluate potential causal effects of individual modifiable risk factors on cognitive decline, will help to evaluate the mechanisms underlying the observation that people with type 2 diabetes are at risk of cognitive impairment in later life.

Type 2 Diabetes Mellitus (T2DM) was once a disease process found only in the adult population. However, incidence rates of T2DM in children and adolescents are increasing at alarming rates and becoming a grave public health concern. As many as 5,089 individuals under the age of 20 are newly diagnosed with T2DM each year. The military community is not immune to these national trends and T2DM among military dependents is growing at similar rates to that of the civilian population. The primary aim of this DNP project was to investigate if barriers exist with regard to pediatric military dependents, ages 10-17 years, receiving appropriate diagnosis, and treatment of T2DM. Previously published literature has identified health disparities exist within the Military Health System (MHS), despite beneficiaries having equal access to care. This project also sought to assess providers' use of Evidence Based Practice (EBP) and Clinical Practice Guidelines (CPGs) in the treatment of pediatric patients' ages 10-17 with T2DM, as it has been indicated that use of evidence based guidelines for management of T2DM vary among military treatment facilities. Results of the DNP Project reflected information found in previous evidence based literature. Fifty percent of providers felt there is "probably" a health disparity among Type 2 Diabetic youth who seek care at a Military Treatment Facility (MTF). Diverse responses were received regarding applicable health disparity indicators among MHS beneficiaries, indicating these disparities may be multifactorial. Routine incorporation of EBP and CPGs into clinical practice also appeared to vary among participants. It is evident that further research may positively contribute to current understanding of health disparities among MHS beneficiaries.

This thesis explores the impact of type 2 diabetes among Indian and Pakistani migrants. Indians and Pakistanis living in the UK have a high incidence of type 2 diabetes and associated complications. Research is needed in order to understand factors that make it difficult to adhere to lifestyle advice about diet, exercise and medication. Drawing on data collected during a sixteen-month ethnographic investigation, this thesis explores Indians’ and Pakistanis’ perceptions of diabetes. The research revealed that Indians and Pakistanis related the onset of diabetes to processes of migration and settling in the UK as well as to stress and depression. In particular, holding on to negative thoughts and worries, were perceived by respondents as directly affecting the body by causing stress, depression and eventually illness. Struggles over diabetes control were also perceived as to cause distress. Specifically, respondents struggled to adhere to a healthy diet regime, since food, especially taste, played a crucial role in forming, reinforcing and demarcating social relations and in ensuring cultural continuity. In addition, respondents struggled to ‘adhere’ to their prescriptions of diabetes medications due to the uncomfortable side effects that they experienced, particularly in the stomach. Respondents, however, counteracted side effects by turning to alternative medications which were perceived to facilitate flow within the circulatory and digestive system. Thus, in spite of the difficulties that Indians and Pakistanis experienced in following biomedical recommendations for diabetes control, they still actively engaged in searching and using different treatments available to them in order to control the disease.

New Zealand is currently in the midst of a diabetes epidemic and it has become clear that the increasing prevalence of obesity and a sedentary lifestyle are inextricably linked to this escalating health crisis. Extensive research has long made clear that people of all ages can enhance their health by incorporating moderate levels of physical activity as part of their normal daily routine and physical activity is now recognised as a major therapeutic modality for type 2 diabetes. Despite such evidence, most people in the western world do not engage in sufficient regular physical activity and there remains a paucity of evidence that elucidates effective methods of achieving the required behaviour change over time. This study set out to demonstrate meaningful correlations between the psychosocial constructs optimism, exercise self-efficacy, goal-directness, stage of change, anxiety and depression, the biochemical measures HbA1c and BMI and also the behavioural outcomes of general physical activity and physical exercise participation, all within a newly diagnosed type 2 diabetic population. Participants (n=30, newly diagnosed adults with type 2 diabetes; mean age 61.46 years; BMI 31.43 Kg/m²[range 18.8-50.95 Kg/m²]) were recruited from attendees of the Christchurch Diabetes Centre's education seminars. The recruitment strategy was designed to search out diabetic patients as near as practicable to the point in time when they first became cognisant of their disease state. A battery of instruments was assembled into a researcher-administered retrospective questionnaire and this was completed with all subjects at baseline and again at six month follow-up. Additional data comprised subject's demographics and selected bio-chemical measures (subject height, weight, and blood Haemoglobin A1c). Descriptive, correlational and qualitative statistics were evaluated. The level of physical activity reported was significantly less than is required to facilitate the biochemical and psychological changes that are generally considered necessary to support optimal health. On average, study participants did not perform their planned physical activity tasks as well as they might have, despite being relatively optimistic and goal-directed at baseline. Many participants clearly indicated an inadequate understanding of exercise modalities and the intensity, duration and frequency of physical activity required to support optimal health. Generally, participants tended to overestimate their physical activity levels. Exercise self-efficacy emerged as an especially important psychological construct, and one that appeared to be among those central to the participants' relationships with physical activity and exercise. The study group demonstrated a relatively high prevalence of low level anxiety and depression, and even at these sub-clinical levels, anxiety and depression were significantly inversely related to optimism, goal-directness, goal-attainment, exercise self-efficacy and stage of change. The study findings illuminate the wide contextual variability among patients who are suffering from the same chronic condition. Further, the implications of conducting detailed pre-assessments of patients' personal characteristics and their psychological profiles, in order to guide intervention tailoring, are also outlined and discussed. Areas for future research are highlighted. In conclusion, meso and macro-level policy implications are discussed, with reference to an array of the broader determinants of health.