Diabetes mellitus is one of the leading causes of death in the United States, contributing to rising health care costs and increased morbidity and mortality rates. Researchers demonstrated that aggressive heath measures involving ongoing diabetes self-management education are paramount in minimizing associated complications of diabetes. The management and prevention of diabetes is not standardized and providers within a health clinic in Illinois reported challenges in providing self-management education during scheduled patient appointments due to limited resources and time. The purpose of this DNP project was to develop a clinical practice guideline to be used by all providers within the health care clinic for the management of Type 2 diabetes. The goal of the developed guideline was to optimize the time providers spend with patients diagnosed with diabetes and improve the consistency and quality of education and care. The health promotion model provided a guide for the development of the practice guideline. The method and design of this DNP project involved extensive research, literature review, evidence grading, and development of an evidence-based practice guideline for Type 2 diabetes management. A selected team of 3 diabetes experts appraised the developed guideline using the AGREE II instrument, and guideline usability was evaluated by 3 nurse practitioners within the medical clinic using a 10-item questionnaire. Results of the appraisal confirmed the high quality, feasibility, and usability of the developed guideline for diabetes self-management education and support. Improving the delivery of care can bring about positive social change by improving health outcomes in individuals with Type 2 diabetes and reducing morbidity and mortality rates.

Type 2 diabetes mellitus (T2DM) is a disease that affects the body's ability to metabolize glucose effectively. The disease is predicted to be prevalent in over 300 million people by the year 2030. African Americans (AA) have the highest prevalence rates in the United States. Lifestyle modification and awareness of risk factors, including family history, are important aspects for prevention of developing T2DM. The purpose of this study was to understand if a family history of T2DM played an influential role in individuals making positive health behavior changes for T2DM prevention. The phenomenological study was grounded in the health belief model. Participants selected for this study were at least 18 years of age, self-identified as AA, self-reported a family history of T2DM, and were not diagnosed with the disease themselves. Transcriptions of 20 face-to-face interviews were stored and organized via a qualitative research software NVivo Version 12 for Mac and later analyzed for data outcome. Participants demonstrated a strong awareness of T2DM with an accurate definition of T2DM and explanation of signs, symptoms, and prevention. Participants recognized family history as a risk factor in only 55% of the responses. However, family history played a major role in prevention in the lives of the participants. The participants reflected on personal barriers to health behavior changes and were encouraged to incorporate better life choices in their own lives. This research offers communities, healthcare providers, and stakeholders a better understanding of the importance of family history as a risk factor to T2DM as programs are developed to mitigate health disparities in the AA community.

Nondiabetic immigrants from Cameroon who migrate to Minnesota lack knowledge of risk factors associated with type 2 diabetes and face challenges accessing health care services. Nondiabetic immigrants from Cameroon lack culturally appropriate health care services and therefore find it difficult to follow providers' recommendations. This phenomenological study explored the perceptions and experiences of nondiabetic immigrants from Cameroon regarding access to affordable, quality health care services as well as their behaviors, beliefs, and knowledge of type 2 diabetes self-management. Bronfenbrenner's social ecological model provided the theoretical framework. Research questions addressed access to affordable health care services, knowledge, and perception of type 2 diabetes, dietary and activity behaviors, and awareness of diabetes self-management. A purposive sample of 13 nondiabetic Cameroonian immigrants participated in the study. Data were collected through in-depth personal interviews. Interviews were hand-coded, and NVivo was used to identify emerging themes. A key finding for this study is that participants leave their appointments without adequate information and continue living in poor health because they lack understanding of medical recommendations. The participants expressed concerns that their health care providers did not address their psychosocial needs in conjunction with physical needs. They also expressed interest in learning about healthy eating. Participants prefer to learn how to count carbohydrates and nutritional values of traditional food to help manage portion size. The social change implications indicate further training for health care professionals in physical and emotional needs of immigrant population from Cameroon.

Introduction: Diabetes is a global and rapidly increasing disease that in 2014 affected morethan 422 million people, and takes 1,2 million lives per year. The importance of identifyingnew ways to manage and prevent the disease has led science to a new area – modulation ofthe gut microbiota. It is well known that the composition of gut microbiota differs betweennon-diabetic and diabetic adults, and that nutrition is the main way to modulate gutmicrobiota composition. Food and lifestyle are of great importance for the development andtreatment of type 2 diabetes and pre-diabetes, but less is known about whether gut microbiotamodulation is mediating that link. Aim: The aim is to examine whether there is a scientifically well-supported link between diet,gut microbiota and the development or treatment of type 2 diabetes or pre-diabetes in humans. Methods: Systematic review with literature search via PubMed and Cochrane, following themanual from the Swedish Agency for Health Technology Assessment and Assessment ofSocial Services (SBU). Results: Of 12 articles finally included, two studies found a strong impact of diet on diabetesrelatedvariables via modulation of gut microbiota. Another four studies did not find anassociation, and six studies lacked sufficient data to be able to draw a conclusion. Dietinterventions and study design differed between studies, which led to heterogeneous results. Conclusions: This review demonstrates a large knowledge gap in how dietary modificationscan prevent or treat type 2 diabetes or pre-diabetes via changes in gut microbiota.

Beta-cell failure is a key step in the progression from metabolic disorder to overt type 2 diabetes (T2D). This failure is characterised by both secretory defects and loss of beta-cell mass, the latter most likely through increases in the rate of apoptosis. Although the mechanisms underlying these beta-cell defects are unclear, evidence suggests that chronic exposure of beta-cells to elevated fatty acid (FA) plays a role in disease development in genetically susceptible individuals. Furthermore, it has been postulated that endoplasmic reticulum (ER) stress signalling pathways (the unfolded protein response; UPR) play a role in FA-induced beta-cell dysfunction. The broad aim of this thesis was to explore the nature of these relationships. Experiments detailed in this thesis demonstrate that MIN6 beta-cells mount a comprehensive ER stress response with exposure to elevated saturated fatty acid palmitate, but not the unsaturated fatty acid, oleate, within the low elevated physiological range. This response was time-dependent and involved both transcriptional and translational changes in UPR transducers and targets. The differential activation of ER stress in MIN6 beta-cells by saturated, but not unsaturated FA species may represent a mechanism of differential beta-cell death described in many studies with these FA. Furthermore, these experiments describe defects in ER to Golgi trafficking with chronic palmitate treatment, but not oleate or thapsigagin treatment, identifying this as a potential mechanism by which palmitate treatment induces ER stress. Moreover, these studies have shown the relevance to ER stress to a whole body model of T2D by demonstrating UPR activation in the islets of the db/db mouse. In conclusion, studies detailed in this thesis have demonstrated that ER stress occurs in in vitro and in vivo models of beta-cell lipotoxicity and apoptosis. In addition, these studies have identified defects in ER to Golgi trafficking as a mechanism by which palmitate treatment induces ER stress. These studies highlight the importance of ER stress in the development of T2D.

It has long been known that in addition to disruptions in glucose homeostasis, individuals with insulin resistance have a breakdown in lipid dynamics, often manifested by elevated levels of circulating fatty acids (FA) together with accumulation of lipids in insulin-sensitive tissues, including skeletal muscle. However, little is known about how common therapies used to treat insulin resistant individuals (such as Rosiglitazone and exercise training) improve skeletal muscle lipid and glucose metabolism. Thus, the primary aim of the studies undertaken for this thesis was to enhance our understanding of the mechanisms by which Rosiglitazone and exercise training improve skeletal muscle lipid metabolism and insulin sensitivity in two distinct models of insulin resistance. The first investigation determined the effect of chronic Rosiglitazone treatment on the accumulation of lipid metabolites and enzymatic regulators of lipid metabolism in the skeletal muscle of obese Zucker rats. The observation that Rosiglitazone treatment exacerbated the accumulation of muscle ceramide and diacylglycerol in skeletal muscle, while improving glucose tolerance led to the conclusion that this insulin sensitising drug improves insulin sensitivity by mechanisms other than reduction of fatty acid metabolites in this tissue. Accordingly, the second investigation sought to identify an alternative mechanism by which Rosiglitazone treatment may improve skeletal muscle insulin sensitivity. It was found that Rosiglitazone restored AMP-activated protein kinase (AMPK) á2 activity in the skeletal muscle of obese Zucker rats, providing a potential peroxisome proliferator activated receptor (PPAR) ã-independent mechanism by which this drug may mediate its insulinsensitising actions. The final experiment undertaken for this thesis determined the independent and interactive effects on Rosiglitazone and exercise training on various aspects of skeletal muscle glucose and lipid metabolism in a model of diet-induced insulin resistance, the high-fat fed rat. Exercise training, but not Rosiglitazone treatment restored skeletal muscle insulin sensitivity in high-fat fed rats. Improvements in insulin sensitivity with exercise training were associated with increased FA oxidation, increased AMPK activity and a normalisation of the expression of the Akt substrate, AS160. In contrast, Rosiglitazone treatment was associated with increased FA uptake and decreased insulin-stimulated glucose uptake in skeletal muscle. Exercise prevented the accumulation of skeletal muscle lipids in Rosiglitazone-treated animals when the two treatments were combined. In summary, the results from the studies undertaken for this thesis provide novel information regarding the mechanisms by which two insulinsensitising therapies, exercise training and Rosiglitazone treatment, act to improve glucose and lipid metabolism in skeletal muscle.It has long been known that in addition to disruptions in glucose homeostasis, individuals with insulin resistance have a breakdown in lipid dynamics, often manifested by elevated levels of circulating fatty acids (FA) together with accumulation of lipids in insulin-sensitive tissues, including skeletal muscle. However, little is known about how common therapies used to treat insulin resistant individuals (such as Rosiglitazone and exercise training) improve skeletal muscle lipid and glucose metabolism. Thus, the primary aim of the studies undertaken for this thesis was to enhance our understanding of the mechanisms by which Rosiglitazone and exercise training improve skeletal muscle lipid metabolism and insulin sensitivity in two distinct models of insulin resistance. The first investigation determined the effect of chronic Rosiglitazone treatment on the accumulation of lipid metabolites and enzymatic regulators of lipid metabolism in the skeletal muscle of obese Zucker rats. The observation that Rosiglitazone treatment exacerbated the accumulation of muscle ceramide and diacylglycerol in skeletal muscle, while improving glucose tolerance led to the conclusion that this insulin sensitising drug improves insulin sensitivity by mechanisms other than reduction of fatty acid metabolites in this tissue. Accordingly, the second investigation sought to identify an alternative mechanism by which Rosiglitazone treatment may improve skeletal muscle insulin sensitivity. It was found that Rosiglitazone restored AMP-activated protein kinase (AMPK) á2 activity in the skeletal muscle of obese Zucker rats, providing a potential peroxisome proliferator activated receptor (PPAR) ã-independent mechanism by which this drug may mediate its insulinsensitising actions. The final experiment undertaken for this thesis determined the independent and interactive effects on Rosiglitazone and exercise training on various aspects of skeletal muscle glucose and lipid metabolism in a model of diet-induced insulin resistance, the high-fat fed rat. Exercise training, but not Rosiglitazone treatment restored skeletal muscle insulin sensitivity in high-fat fed rats. Improvements in insulin sensitivity with exercise training were associated with increased FA oxidation, increased AMPK activity and a normalisation of the expression of the Akt substrate, AS160. In contrast, Rosiglitazone treatment was associated with increased FA uptake and decreased insulin-stimulated glucose uptake in skeletal muscle. Exercise prevented the accumulation of skeletal muscle lipids in Rosiglitazone-treated animals when the two treatments were combined. In summary, the results from the studies undertaken for this thesis provide novel information regarding the mechanisms by which two insulinsensitising therapies, exercise training and Rosiglitazone treatment, act to improve glucose and lipid metabolism in skeletal muscle.

Globally the diabetes epidemic is a major health challenge. Associated with the diagnosis of diabetes is the morbidity and premature mortality stemming from the complications of the disease. It was identified that approximately 50% of clients who attended a diabetes centre in an outer western metropolitan region of Sydney were not completing diabetes education. A strategy employed to overcome this was the introduction of a 2 ½ hour group diabetes education program called the Ongoing Education System (OES), for persons with Type 2 diabetes, that enabled completion of education at this one session. However, debate occurred among health professionals at the Wentworth Diabetes Service (WDS) as to the effectiveness of the OES as compared to the traditional individual education sessions. (one-on-one education). The purpose of this study was to compare the outcomes of two modes of diabetes education for completing education for clients with Type 2 diabetes , namely individual education (Treatment A) and the OES group education (Treatment B). The findings overall revealed no difference in the outcomes of participants who received individual education and those who received the OES at completion of education as well as at 6 and 12 month post education. A secondary finding of this study was the significant influence gender and age exerted on the outcomes of the education programs. One significant implication from the findings for both the person diagnosed with Type 2 diabetes and the health care organisation is that the OES provides a cost effective alternative to individual education that encourages clients to complete diabetes education thereby enabling the person to achieve an optimal quality of life. In addition this study provides research evidence for the benefit of current practice in diabetes education. / Doctor of Philosophy (PhD)

Adult Oral Health Programme: The Effect of Periodontal Treatment and the Use of a Triclosan Containing Toothpaste on Glycaemic Control in Diabetics Abstract Aim: The aim of the research study is to establish an adult oral health programme for diabetics in Majuro, Republic of the Marshall Islands in order to determine the impact of non-surgical periodontal treatment followed by the use of a triclosan containing dentifrice on the maintenance of periodontal health and glycaemic control in type 2 diabetic patients. Hypothesis: Non-surgical periodontal treatment results in improved periodontal health and better glycaemic control in diabetics and use of a triclosan containing toothpaste is effective in maintaining this improvement in diabetics. Methods: An adult oral health programme was created, within which was conducted a two-group randomised clinical trial to address the hypothesis that non-surgical periodontal treatment results in improved periodontal health and better glycaemic control in type 2 diabetics and that the use of a triclosan containing toothpaste is effective in maintaining this improvement in diabetics. In this double blind controlled trial, sixty adult patients (aged 35 to 65 years) with type 2 diabetes mellitus having a minimum of 16 teeth received non-surgical periodontal treatment. Half of the patients were randomly assigned to use a triclosan containing toothpaste, Colgate Total, and the other group a non-triclosan toothpaste, Colgate Fluoriguard. The study evaluated the improvement in periodontal health by recording Probing Pocket Depth (PPD) on 6 sites of each tooth, and the number of sites bleeding on probing (BOP) at baseline, and at 6 months and 12 months after treatment. The second part of the study evaluated the impact of improvement of periodontal health on glycaemic control in type 2 diabetics by measuring HbA1c and RBS, and also assessing the levels of C-Peptides and CRP at baseline, and at 6 months and 12 months after treatment. The study also evaluated the effectiveness of a triclosan containing toothpaste in maintaining the improvement in periodontal health after non-surgical periodontal treatment. Results: The results showed that it was feasible to establish an oral health programme for the diabetics and could improve their periodontal health, and that toothpaste containing triclosan is effective in maintaining the improved periodontal heath in type 2 diabetics. Mean PPD dropped from 2.35mm to 1.95mm in the triclosan group and from 2.49mm to 2.24 mm in the non-triclosan group and the mean number of BOP sites dropped from 4.9 to 2.8 in the triclosan group and from 4.7 to 3.2 in the fluoriguard at 12 month visits. However, the results did not show improvement of HbA1c nor RBS levels in either group. C-Peptide levels increased and C-Reactive Protein levels decreased in both groups, however, not to significant levels at 12 month visits. Conclusion: The results of this research study lead to the conclusion that treating periodontal infection has effect of periodontal health of type 2 diabetic patients and following-up with simple personal oral hygiene of regular tooth-brushing helps maintain their periodontal health. This programme also proved that this type of oral health programme is feasible and valuable for diabetics in isolated places like the Marshall Islands, where infrastructure, personnel and resources are limited to treat microvascular and macrovascular complications of diabetes. As for the effectiveness of treating periodontal infections on glycaemic control of diabetics, this study failed to support the hypothesis that non-surgical treatment plus triclosan containing toothpaste would lead to better glycaemic management through improved periodontal health.

<p>Type 2 diabetes mellitus (T2DM) is a heterogeneous disease affecting millions of people worldwide. Both genetic and environmental factors contribute to the pathogenesis. The disease is characterized by alterations in many genes and their products. Historically, genomic alterations have mainly been studied at the transcriptional level in diabetes research. However, transcriptional changes do not always lead to altered translation, which makes it important to measure changes at the protein level. Proteomic techniques offer the possibility of measuring multiple protein alterations simultaneously.</p><p>In this thesis, the proteomic technique surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) has been applied and evaluated in the context of T2DM research. Protocols for pancreatic islet and serum/plasma protein profiling and identification have been developed. In addition, the technique was used to analyze the influence of genetic background versus diabetic environment by determining serum protein profiles of individuals with normal glucose tolerance (NGT) and T2DM with or without family history of diabetes. In total thirteen serum proteins displayed different levels in serum from persons with NGT versus patients with T2DM. Among these proteins, apolipoprotein CIII, albumin and one yet unidentified protein could be classified as being changed because of different genetic backgrounds. On the other hand, ten proteins for instance transthyretin, differed as a result of the diabetic environment.</p><p>When plasma protein patterns of NGT and T2DM individuals characterized by differences in early insulin responses (EIR) were compared, nine proteins were found to be varying between the two groups. Of these proteins five were identified, namely two forms of transthyretin, hemoglobin α-chain, hemoglobin β-chain and apolipoprotein H. However no individual protein alone could explain the differences in EIR. In conclusion, SELDI-TOF MS has been successfully used in the context of T2DM research to identify proteins associated with family history of diabetes and β-bell function. </p>

Objective - To assess the relationship between schizophrenia and cardiovascular disease by evaluating metabolic risk associated with treatment for schizophrenia, prevalence of cardiovascular risk factors (CV-RF) and disease (CV-D), and health care utilization in people with schizophrenia compared to the non-schizophrenic population. Methods Four studies were completed to evaluate the dissertation objectives. A systematic review was completed to quantify the change in metabolic parameters associated with use of atypical antipsychotic agents. The second study utilized a period prevalence design to compare prevalence of CV-RF (diabetes, hypertension, dyslipidemia) and CV-D in people with and without schizophrenia using the administrative databases of Alberta Health and Wellness. General and cardiac specialist health care utilization was evaluated in people with schizophrenia using data from Alberta Health and Wellness. Lastly, results from the Canadian Community Health Survey were used to evaluate prevalence of CV-RF and CV-D while controlling for important lifestyle and demographic variables unavailable in the databases of Alberta Health and Wellness. Results Use of atypical agents, particularly clozapine, resulted in statistically significant weight gain and increases in total cholesterol and blood glucose compared to typical agents. Having schizophrenia was associated with a significantly higher prevalence of diabetes, obesity, smoking, and CV-D compared to people without schizophrenia. Individuals with schizophrenia visited a general practitioner and the emergency department more often, and were more likely to be hospitalized than those without schizophrenia. Despite having a higher prevalence of coronary artery disease, individuals with schizophrenia were significantly less likely to visit a cardiologist or undergo revascularization compared to people with coronary artery disease who did not have schizophrenia. Conclusion Individuals with schizophrenia have a considerable burden of cardiovascular disease compared to people without schizophrenia. This is likely a result of a number of factors, including medications used to treat schizophrenia, the increased prevalence of smoking and other unhealthy lifestyle factors, and the increased prevalence of cardiovascular risk factors in people with schizophrenia. Individuals with schizophrenia utilize the general health care system more frequently than their non-schizophrenic counterparts, therefore the opportunity exists for monitoring for and management of modifiable cardiovascular risk factors in this vulnerable population.