Dissertations / Theses on the topic 'Diabetes – Prevention'

Background: Diabetes is a common and costly disease that is expected to continue even to grow in prevalence and health expenditures over the coming decades. Type 2 diabetes is the most common diabetes type and is characterized by insulin resistance and relative insulin deficiency. Type 2 diabetes develops over a long period and is often undetected over years. During this time, people almost always first develop any of the pre-diabetic states, i.e. impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or a combination of both (IFG&IGT). This thesis focuses on type 2 diabetes only. In the following, the term diabetes is used to refer to type 2 diabetes only. Diabetes is associated with a sedentary lifestyle and obesity. While those are not the only factors contributing to the development and maintenance of diabetes, several studies have shown that prevention of diabetes among individuals at high risk through lifestyle change is possible, effective and cost-effective, especially targeting diet and exercise to reduce weight. No previous study had, however, estimated the cost-effectiveness of diabetes prevention strategies from a population-based perspective including healthy individuals and also considered IFG and IGT as two distinct pre-diabetic states. Objective: The overall objective of this thesis was to establish, describe and evaluate a model that can assess the cost-effectiveness of lifestyle intervention programs to prevent diabetes. Methods: First, a Markov Model was established using data from the literature. The cost of a German diabetes prevention program was estimated. Second, risk equations for change to worsened glucose states were estimated using factor analysis and logistic regression based on consecutive data from the Västerbotten Intervention Program (VIP). The risk equations described transition probabilities in the final model and were based on several risk factors such as age, sex, physical activity and smoking status. Third, information on the Short-Form 36 questionnaire from the VIP population was transformed into Short-Form 6D. Health utility weights (HUW) by glucose group and four risk factors were estimated using beta regression. Fourth, an updated Markov model was established using an updated model structure compared to the one in Paper I, program costs of Paper I, risk equations of Paper II, health utility weights of Paper III and updated cost and mortality estimates. Results: The first model in Paper I showed that lifestyle intervention programs have the potential to be cost-effective with a high degree of uncertainty. The risk equations in Paper II indicated that the impact of each risk factor depended on the starting and ending pre-diabetes state, where high levels of triglyceride, hypertension, and high body mass index were the strongest risk factors to transit to a worsened glucose state. The overall mean HUW in Paper III was 0.764 with healthy individuals having the highest HUW, those with diabetes the lowest and those in pre-diabetic states ranging in between. The intervention described in Paper IV was cost-effective for all sex and age scenarios ranging from 3,833 EUR/QALY gained (women, 30 years) to 9,215 EUR/QALY gained (men, 70 years). The probability that the intervention is cost-effective was high (85.0-91.1%). Conclusion: We established a model that can estimate the cost-effectiveness of different scenarios of initiatives to prevent diabetes. The prevention or the delay of the onset of diabetes is feasible and cost-effective. A small investment in a healthy lifestyle with the change in physical activity and diet together with weight loss can have a decent, cost-effective result. The full range of possibilities this model offers has not been evaluated so far. We have, however, shown that implementing a lifestyle intervention program like the Västerbotten Intervention Programme would be cost-effective.

Established IDDM in the BB/E rat was associated with severe disturbance in the development of the pre-implantation embryo, as indicated by (1) a five fold increase in the number of unfertilised oocytes, (2) a reduced percentage of expanded blastocytes, and (3) a -20% inner cell mass (ICM) cellular deficit in embryos which reached the expanded blastocyst stage. Data obtained from pregnant Diabetes Prone (DP) BB/E rats during the pre-diabetic period (when the maternal metabolic profile was normal), showed that the full complement of IDDM susceptibility genes was not in itself, sufficient to disturb early embryo development and/or give rise to an ICM cell deficit. In addition, experiments involving the transfer of two-cell embryos showed that the oviductal/uterine environment of a Diabetic DP-BB/E recipient could induce not only an ICM deficit but also a TE cell accretion in embryos from Non-Diabetic Diabetes Resistant (DR) BB/E donor rats. However, transfer of two-cell embryos from Diabetic DP- into Non-Diabetic DR-BB/E mothers did not prevent the development of an ICM cellular deficit or a TE cell accretion - implying earlier damage to the germ cells. Greatly improved metabolic control was achieved in Diabetic DP-BB/E rats before and over the period of conception using sustained release insulin implants. This resulted in a reduction in the number of unfertilised oocytes, an increase in the percentage of expanded blastocysts but no change in ICM cellular deficit. A sensitive and accurate quantitative RT-PCR method was developed and used to determine the ratio of bcl-2 (a cell death agonist gene) to bax (a cell death antagonist gene) expression in single blastocysts from Diabetic DP- and Non-Diabetic DR-BB/E rats. Although the bcl-2 to bax ratio was not significantly increased in blastocytes from diabetic rats, these data demonstrate for the first time that bax and bcl-2 mRNA is present in the pre-implantation embryo.

Pancreatic β cells are selectively destroyed by the host immune system in type 1 diabetes, which results in the inability to regulate glucose homeostasis due to loss of insulin production capacity. Drugs that preserve β cell mass and function therefore have the potential to prevent or slow the progression of this disease. It was recently reported by our group that the use-dependent sodium channel blocker, carbamazepine, protects pancreatic β cells from inflammatory cytokines in vitro. Subsequent experiments found carbamazepine increased insulin gene expression, which corroborated with an increase in insulin content in islets from mice lacking the Nav1.7 voltage gated sodium channel, which was shown to be a target of carbamazepine in β cells. While these in vitro results were promising, it was unclear whether carbamazepine would protect β cells in vivo against a complete immune system. Therefore, we tested the effects of oral treatment in female non-obese diabetic (NOD) mice, achieving serum carbamazepine levels of 14.98 ± 3.19 μM. Remarkably, diabetes incidence over 25 weeks was ~50% lower in carbamazepine treated animals. Partial protection from diabetes in carbamazepine-fed NOD mice was also associated with improved glucose tolerance at 6 weeks of age, prior to the onset of diabetes in our colony. Insulitis was improved in carbamazepine treated NOD mice at 6 weeks of age, but we did not observe differences in CD4⁺ and CD8⁺ T cell composition in the pancreatic lymph node, as well as circulating markers of inflammation. Taken together, our results demonstrate that carbamazepine reduces the development of type 1 diabetes in NOD mice.
Medicine, Faculty of
Graduate

Background: The aim of this paper was to create an updated Australian guideline on footwear for people with diabetes. Methods: We reviewed new footwear publications, (international guidelines, and consensus expert opinion alongside the 2013 Australian footwear guideline to formulate updated recommendations. Result: We recommend health professionals managing people with diabetes should: (1) Advise people with diabetes to wear footwear that fits, protects and accommodates the shape of their feet. (2) Advise people with diabetes to always wear socks within their footwear, in order to reduce shear and friction. (3) Educate people with diabetes, their relatives and caregivers on the importance of wearing appropriate footwear to prevent foot ulceration. (4) Instruct people with diabetes at intermediate-or high-risk of foot ulceration to obtain footwear from an appropriately trained professional to ensure it fits, protects and accommodates the shape of their feet. (5) Motivate people with diabetes at intermediate-or high-risk of foot ulceration to wear their footwear at all times, both indoors and outdoors. (6) Motivate people with diabetes at intermediate-or high-risk of foot ulceration (or their relatives and caregivers) to check their footwear, each time before wearing, to ensure that there are no foreign objects in, or penetrating, the footwear; and check their feet, each time their footwear is removed, to ensure there are no signs of abnormal pressure, trauma or ulceration. (7) For people with a foot deformity or pre-ulcerative lesion, consider prescribing medical grade footwear, which may include custom-made in-shoe orthoses or insoles. (8) For people with a healed plantar foot ulcer, prescribe medical grade footwear with custom-made in-shoe orthoses or insoles with a demonstrated plantar pressure relieving effect at high-risk areas. (9) Review prescribed footwear every three months to ensure it still fits adequately, protects, and supports the foot. (10) For people with a plantar diabetic foot ulcer, footwear is not specifically recommended for treatment; prescribe appropriate offloading devices to heal these ulcers. Conclusions: This guideline contains 10 key recommendations to guide health professionals in selecting the most appropriate footwear to meet the specific foot risk needs of an individual with diabetes.

The phosphodiesterase (PDE) inhibitors Pentoxifylline (PTX), a general inhibitor, and Rolipram (ROL), a type 4 inhibitor, have been shown to have anti-inflammatory effects. They elevate intracellular CAMP levels and suppress the production of inflammatory cytokines such as tumor necrosis factor (TNF)alpha, interferon (IFN)gamma, and interleukin-12 (IL-12). These drugs have also been reported to modulate the immune response in favor of Th2 responses and to be therapeutically effective in various models of autoimmune and/or inflammatory disorders. Their effects on nitric oxide (NO) production are not well studied. Inflammatory cytokines and NO are important mediators implicated in islet beta-cell destruction.
In the first part of the study, we examined the effect of PTX and ROL in preventing insulitis and diabetes in non-obese diabetes-prone (NOD) mice as a spontaneous model of insulin-dependent diabetes (IDDM). We found that a 4 week treatment with either PTX or ROL had a strong protective effect, that was still apparent 11 weeks after withdrawing the drugs. Both drugs were equally effective at optimal doses in preventing mstiulitis and diabetes in NOD mice.
In the second part of the study, we examined the effects of PDE inhibitors on NO production by peritoneal macrophages and RAW 246.7 cells. We also correlated these effects with elevated cAMP levels. We found that both PTX and ROL suppress NO production by IFNgamma and lipopolysaccharide (LPS)-activated macrophages. The inhibitory effects correlated with elevated CAMP levels and were mimicked by other agents which elevate CAMP levels such as dibutyryl cAMP, 8-bromo cAMP, and Forskolin. This suppression was found to be at the transcriptional level. In vivo, ROL treatment prevented macrophage activation by staphylococcal enterotoxin B (SEB) and suppressed NO production by these macrophages in ex vivo culture.
In the third part of the study, we examined the effects of PDE inhibitors on NO production by insulin-producing NIT-1 insulinoma cells and normal islet cells. It has been reported that islet beta-cells express PDE3 and PDE4. We found that inhibitors of PDE4 (ROL), PDE3 (Cilostamide; CIL), or a general inhibitor (PTX), suppressed NO production by islet cells. A combination of ROL and CIL appeared to have more than an additive effect, suggesting synergism. Like in macrophages, the suppression was at the transcriptional level and mimicked by other agents which elevate cAMP levels. In vivo, ROL treatment suppress iNOS expression in the islets of NOD mice with cyclophosphamide-accelerated disease, as determined by immunohistochemistry.
These studies establish for the first time that PDE inhibitors have a therapeutic potential in IDDM and other NO-and/or cytokine-mediated inflammatory disorders.

This thesis is an evaluation of the effectiveness of a community-wide diabetes prevention program conducted in three Divisions of General Practice in Sydney, Australia. The aims were to assess whether translation of diabetes prevention programs was feasible in real-life settings and whether results achieved were comparable with those of randomised trials on which this intervention was based. Its primary goals were to assess whether the lifestyle intervention could increase participation in moderate-to-vigorous physical activity to 210 minutes per week, reduce total fat and saturated fat consumption to 30% and 10% of total daily energy intake, increase fibre consumption to 15 g/1,000 kcal/day, and lead to 5% weight loss over one year. The background section covers the physiopathology of type 2 diabetes, its risk factors, and the available population screening tools to identify people at risk. The growing morbidity and mortality burden, the economic implications of this public health problem, and the importance and feasibility of preventing or delaying the onset by intervening in the precursor stages are then summarised. Evidence for preventability is examined through a literature review of lifestyle interventions in research settings comprising highly structured and closely monitored physical activity and dietary programs under controlled conditions. Examples of the effectiveness of translation of randomised controlled trials (RCTs) into less stringent programs in community settings such as workplaces, churches, indigenous communities and whole-of-country initiatives are presented. A systematic review and meta-analysis of effectiveness of the lifestyle approaches in routine clinical practice supplements the evidence for application of prevention principles in real-life settings. The main chapters of the thesis centre on process and impact evaluation of the semi-structured Sydney-based intervention, which recruited 1,250 participants from the mainstream Australian 29 public using general practitioner services in the study area, who were followed for 12 months. The intervention’s goals aligned with those of the Finnish Diabetes Prevention Program but with less stringent entry criteria and less intensive intervention components delivered by purpose-trained lifestyle officers. The Program included an initial individual assessment and coaching session, three subsequent group sessions in the following three months, then three follow-up coaching calls at three, six and nine months. A final assessment at one year, using the same objective and self-reported measures as in the initial assessment, captured changes in body weight, physical activity and dietary habits. The process evaluation showed that it is feasible and effective to use targeted screening to identify and recruit high-risk individuals into a free-of-charge program in the general practice setting, however a quarter of participants were lost to follow-up by one year. While minor variations in aspects of the Program were required to meet local need, Program fidelity in delivering components, and self-reported adherence to diet and physical activity was high. Using a before-after study design, the impact evaluation measured 1-year changes in key Program parameters in relation to baseline. These comprised: measured weight, waist circumference, BMI, and glycaemia measurements; and self-reported dietary intake and structured physical activity, using a 3-day food record and the Physical Activity Scale for the Elderly (PASE) questionnaire, respectively. The main findings at 12 months for the 586 completers as at December 2010 were: a mean weight loss of 2.1 kg; waist circumference reduction of 2.5 cm; no significant change in glycaemia; 3% reduction of fat and saturated fat intake; 16% increase in fibre intake; and mean increase in moderate-to-vigorous physical activity of 13.7 minutes/week. All these changes were smaller than those achieved by the RCTs in research settings, most likely due to the lower intensity and monitoring of the Sydney intervention. Weight loss and waist circumference reductions were similar for participants in 30 group session and those who received telephone-only coaching. Diabetes incidence was 1% at the end of the first year. An economic appraisal of the Program implementation completes the evaluation. A cost of A$400 per kg lost among people achieving the weight goal was estimated on Program completion, but the cost was double for the overall group that included non weight losers. The cost of achieving the physical activity goal and the dietary goals was not feasible or sustainable with resources available in routine clinical settings. The costs per outcome were similar for participants not attending group sessions, who received only telephone coaching. Hence it is worth exploring this less labour-intensive modality if a general practice based Program were to be delivered as routine preventive care. In sum, the evaluation of this community-wide diabetes prevention program showed that translation of diabetes prevention programs into routine practice, while feasible at less intensive levels than in RCTs, has a somewhat lower effect on diabetes risk reduction and it can still be a financial burden in clinical settings. However, given the potential for population-wide benefit, the effectiveness of alternative delivery modes, number and duration of program components and more targeted patient sub-groups should be investigated.
The Sydney Diabetes Prevention Program was funded by New South Wales Health as part of the Australian Better Health Initiative. Financial contribution and other in-kind support were provided by the Sydney South West Area Health Service and the Australian Diabetes Council -NSW.

OBJECTIVES: In Australia, diabetes causes significant morbidity and mortality. Whilst the need to prevent diabetes and its complications has been widely recognised, the capacity of health care systems - which organise diabetes care - to facilitate prevention has not been fully established. METHODS: A series of seven population-based case-control studies were used to examine the effectiveness of the Australian health care system and its capacity to manage diabetes. Six of the studies compared the patterns of care of patients who had developed advanced diabetes complications in 2000 (cases), to similar patients who remained free of the condition (controls) across Australia and for various risk groups. A secondary study investigated the role of treating GPs in the development of the outcome. RESULTS: A strong relationship between the patterns of care and the development of advanced diabetes complications was found and is described in Chapter 4. In Chapter 5, this same relationship was investigated for each Australian state and territory, and similar findings were made. The study in Chapter 6 investigated whether late diagnosis or the patterns of care was the stronger risk factor for advanced diabetes complications, finding that the greatest risk was associated with the latter. In Chapter 7 the influence of medical care during the pre-diagnosis period was explored, and a strong relationship between care obtained in this period and the development of advanced complications was found. In Chapter 8, which investigated the role of socio-economic status in the development of advanced complications, found that the risk of advanced diabetes complications was higher in low socio-economic groups. Chapter 9 investigated geographic isolation and the development of advanced diabetes complications and found that the risk of advanced complications was higher in geographically isolated populations. Finally, Chapter 10, which utilised a provider database, found that some GP characteristics were associated with the development of advanced diabetes complications in patients. CONCLUSION: A number of major risk factors for the development of advanced complications in Australia was found. These related to poorer diabetes management, later diagnosis, low socioeconomic status and geographic isolation. Strategies must be devised to promote effective diabetes management and the early diagnosis of diabetes across the Australian population.

Master of Public Health
OBJECTIVES: In Australia, diabetes causes significant morbidity and mortality. Whilst the need to prevent diabetes and its complications has been widely recognised, the capacity of health care systems - which organise diabetes care - to facilitate prevention has not been fully established. METHODS: A series of seven population-based case-control studies were used to examine the effectiveness of the Australian health care system and its capacity to manage diabetes. Six of the studies compared the patterns of care of patients who had developed advanced diabetes complications in 2000 (cases), to similar patients who remained free of the condition (controls) across Australia and for various risk groups. A secondary study investigated the role of treating GPs in the development of the outcome. RESULTS: A strong relationship between the patterns of care and the development of advanced diabetes complications was found and is described in Chapter 4. In Chapter 5, this same relationship was investigated for each Australian state and territory, and similar findings were made. The study in Chapter 6 investigated whether late diagnosis or the patterns of care was the stronger risk factor for advanced diabetes complications, finding that the greatest risk was associated with the latter. In Chapter 7 the influence of medical care during the pre-diagnosis period was explored, and a strong relationship between care obtained in this period and the development of advanced complications was found. In Chapter 8, which investigated the role of socio-economic status in the development of advanced complications, found that the risk of advanced diabetes complications was higher in low socio-economic groups. Chapter 9 investigated geographic isolation and the development of advanced diabetes complications and found that the risk of advanced complications was higher in geographically isolated populations. Finally, Chapter 10, which utilised a provider database, found that some GP characteristics were associated with the development of advanced diabetes complications in patients. CONCLUSION: A number of major risk factors for the development of advanced complications in Australia was found. These related to poorer diabetes management, later diagnosis, low socioeconomic status and geographic isolation. Strategies must be devised to promote effective diabetes management and the early diagnosis of diabetes across the Australian population.

Thesis (Ph.D. in Molecular Biology) -- University of Colorado Denver, 2007.
Typescript. Includes bibliographical references (leaves 162-196). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

The socio-economic and political inequities stemming from colonialism have adversely affected the health of Canadian Aboriginal people. In particular, type 2 diabetes affects these populations in disproportionately high rates. As a result, there have been calls for policy-makers, program designers and practitioners to create culturally appropriate health education programming. However, few programs have been successful. It has been argued that this is because traditional approaches to diabetes education programming do not address the unique history and lived experiences of Aboriginal people. This project explored the experiences of participants, staff, facilitators and stakeholders with an Aboriginal Diabetes Awareness Prevention and Teaching Program (ADAPT) located in a major Western Canadian city. A total of 14 people were interviewed. The primary goals were to identify how the program activities and messaging were perceived, understood and acted upon by participants; to describe how the staff and facilitators envisioned their roles with the program; and to gain insight into how ADAPT fit with the lives of participants. Critical theoretical perspectives, and in particular, postcolonial theory served as the primary paradigm for this project. Data analysis was guided by interpretive description. Program participants’ that were interviewed for this project described their experiences within two main themes: building relationships and building knowledge. Staff, facilitators and stakeholder’s experiences also centered around two main themes: building relationships with participants and facilitating change. ADAPT participants, staff, facilitators and stakeholders all described the program as a place that recognizes the impacts of that colonialism has had on people’s lives and health. The program was seen as a safe and supportive place to build relationships with others and to learn about diabetes. The findings of this project can help to inform the design of Aboriginal-focused diabetes education programs.

The challenge of diabetes prevention is to reduce the financial and human costs of diabetes by preventing new cases and enacting social change. African Americans and Hispanics Americans have a high incidence of Type 2 diabetes because of factors that place them at risk for prediabetes. The purpose of this project was to plan the implementation and evaluation of a Type 2 diabetes prevention program in a medical office clinical setting. The clinic of interest was located in the downtown area of the city and provided care mostly to African American population. The Iowa model of evidence-based practice formed the theoretical framework for the study. The goal was to decrease the number of African Americans patients who will convert from prediabetes to Type 2 diabetes in the medical office clinic. The program was planned using the information from the Center for Disease Control and Prevention Road to Health toolkit. The outline covered a 6-week program. A pretest will be given to assess baseline knowledge of diabetes and diabetes prevention. The same test will be given after the implementation to evaluate if the program enhanced diabetes and diabetes prevention knowledge. Six months after the implementation of the program, nurses will complete a chart review to evaluate how many patients converted from pre-diabetes to Type 2 diabetes since the implementation of the project. The project will lead to the integration of a Type 2 diabetes prevention program in a medical clinic. It will increase the number of African Americans with prediabetes who will engage in lifestyle modification behavior. The project will also decrease the incidence of Type 2 diabetes among African Americans and reduce the health disparity of diabetes among the population.

Bakgrund: Diabetiska fotsår, ”Diabetes foot ulcer” (DFU) är ett globalt hot mot personer med diabetes på grund av de komplikationer som kan uppkomma som en efterföljd av diabetes. Neuropati är en vanlig följdsjukdom till diabetes vilket medför risken för DFU. Neuropati orsakar nedsatt känsel i underben och fötter vilket kan medföra att patienten inte känner föremål i skorna som skaver och trycker mot fötterna som kan orsaka DFU. Syfte: Syftet med litteraturstudien var att beskriva sjuksköterskors preventionsstrategier för att reducera utvecklingen av fotsår hos patienter med diabetes. Metod: Denna studie genomfördes som en beskrivande litteraturstudie baserat på 12 vetenskapliga artiklar som bestod av fyra kvalitativa och åtta kvantitativa artiklar. Huvudresultat: Resultatet visade att sjuksköterskor är i behov av ökad kunskap genom sårvårdsutbildning efter kandidatexamen. Det framkommer att sjuksköterskornas kunskaper har en stor roll i behandlingen av DFU varav patienternas egenvårdsförmåga lyfts fram för att tillsammans finna de rätta strategierna för varje patient i sin DFU behandling. Slutsats: Fördjupad kunskap inom preventionsstrategier att reducera utvecklingen av DFU hos patienter med diabetes skulle kunna komma både patienter, sjuksköterskor och svensk hälso- och sjukvård till nytta. Kunskapen om preventionsstrategier hos sjuksköterskor i arbetet av DFU varierade inom hälso-ochsjukvårdsverksamheter världen över. Det finns flera strategier att arbeta vidare med som sjuksköterska i förebyggandet av DFU. Två viktiga aspekter inom preventionsstrategier är ökad utbildning för grundutbildade sjuksköterskor inom sårvård av DFU.Patientutbildning inom egenvård i förebyggande av komplikationer av DFU är en viktigstrategi i sjuksköterskans yrkesroll för att kunna bidra med goda förutsättningar och hälsofrämjande vård.
Abstract Background: Diabetic foot ulcer (DFU) is a global threat to people with diabetes due tothe complications that can arise as a result of diabetes. Neuropathy is a common secondary result of diabetes which carries the risk of DFU. Neuropathy causes decreased sensation in the lower legs and feet which can cause the patient not to feel objects in the shoes rubbing and pressing against the feet which can cause DFU. Aim:The purpose of the literature study was to describe nurses' prevention strategies for reducing the development of foot ulcers in patients with diabetes. Method: This study was conducted as a descriptive literature study based on 12 scientific articles consisting of four qualitative and eight quantitative articles. Main results: The results showed that nurses are in need of increased knowledge through wound care training after thebachelor's degree. It appears that the nurses 'knowledge has a major role in the treatmentof DFU, of which the patients' self-care ability is highlighted in order to jointly find theright strategies for each patient in their DFU treatment. Conclusion: Advanced knowledge of prevention strategies to reduce the development of DFU in patients with diabetes could benefit both patients, nurses and Swedish health care. The knowledge of prevention strategies among nurses in the work of DFU varied in health care activitiesworldwide. There are several strategies to continue working with as a nurse in the prevention of DFU. Two important aspects in prevention strategies are increased training for undergraduate nurses in wound care at DFU. Patient education in self-care in the prevention of complications of DFU is an important strategy in the nurse'sprofessional role in order to be able to contribute with good conditions and health promoting care.

The objectives of this research were to determine the impact of 4 different bedtime snack compositions on prevention of nocturnal hypoglycemia and to determine whether optimized titration and delivery of bedtime insulin using multiple daily injections of insulin (MDI) or continuous subcutaneous insulin infusion (CSII) could prevent nocturnal hypoglycemia in the absence of bedtime snacks. We also sought to determine whether 3 months of CSII therapy would improve catecholamine response and symptom awareness to experimentally-induced hypoglycemia. The need for and the most appropriate composition of bedtime snacks were dependent on the glycemic level at bedtime. No bedtime snacks were necessary at bedtime glycemic levels > 10 mmol/L. At bedtime glycemic levels between 7-10 mmol/L , a standard snack and cornstarch-containing snack worked best and at bedtime glycemic levels < 7mmol/L, a standard and protein-rich snack were most effective. Despite optimized titration and delivery of bedtime insulin, including the use of CSII, "the gold standard" of nocturnal insulin replacement, the incidence of nocturnal hypoglycemia over 181 nights was 54 episodes per 100 patientnights. However, there was a substantial reduction, by 36% (p=0.17), in the incidence of nocturnal hypoglycemia with the use of bedtime snacks. Therefore bedtime snacks, tailored to the bedtime glycemic level, are recommended for ail adults undergoing intensive management with MDI or CSII. Although, 3 months of CSII therapy did not improve catecholamine response and symptom awareness to experimentally-induced hypoglycemia, it did not deteriorate the responses either. Therefore, CSII therapy is a viable option in intensive management of adults with type 1 diabetes.

The objective of this literature study was to describe the nurse’s preventive actions to prevent diabetes type 2 among children and adolescents in school age. It emerged from the analysis that the nurse is working according to three pillars; screening, lifestyle changes and counselling/education. This result showed that what often increase difficulties when working with screening are: undefined guidelines, lack of time and resources. Overweight/obesity is one of many indicators to develop diabetes type 2, therefore it is important that both BMI and waist are measured. The nurse was working actively with education and intervention, for example engaging schools to make diet changes and increase physical activity. She/he was also giving counselling to children, adolescents and their families about the disease diabetes type 2 and how it could be prevented. Barriers often experienced by the nurse in her/his preventive work were the families’ attitudes and lifestyles. There were often an expressed wish from nurses to receive guidance in their work on motivating to lifestyle changes.

The Monterey School Diabetes Prevention Project's (MSDPP) ENERGY Club is a pilot project for school-based health prevention curriculum targeting students with risk factors for diabetes. ENERGY is an acronym for Exercise 'n Eating Right is Good for You.

Aldose reductase inhibitors (ARI's) have been shown to attenuate or prevent several complications of diabetes in animals. Tolrestat is a potent and unique ARI from Ayerst Laboratories, New York, NY. The efficacy and toxicology of tolrestat via topical ocular administration was examined. Tolrestat effectively enhanced corneal reepithelialization and was efficacious in the prevention of cataracts in the streptozotocin-diabetic rat. Ocular tissues were examined by slit lamp biomicroscopy, scanning and transmission electron microscopy, and light microscopy. Liver and kidney tissue was also examined. The presence of tolrestat was confirmed in urine, feces, and eye specimens, and quantitated in serum. There was no evidence of local or systemic tolrestat induced toxicity. Tolrestat prevented cataract formation at less than one-third the reported oral dose and at approximately one-fiftieth the associated serum concentration in rats. ED-50 and TD-50 calculations indicate that tolrestat is a relatively safe drug by topical ocular administration.

Bakgrund: Förändringar i vår livsstil har lett till att diabetes typ 2 har blivit en global epidemi. Att försöka förändra beteendet och motivera patienter med diabetes typ 2 till egenvård är en central del av diabetesvården. Syfte: Beskriva olika tillvägagångssätt för sjuksköterskan att motivera patienter med diabetes typ 2 till livsstilsförändringar. Metod: En litteraturstudie baserad på 13 artiklar har gjorts. Artiklarna hittades via databaserna CINAHL och PubMed samt via manuell sökning varpå de analyserades och kvalitetsgranskades. Resultat: Patienter med diabetes typ 2 kan motiveras till livsstilförändringar genom individuell utbildning, gruppbaserad utbildning samt genom användning av motiverande samtal (MI). Vid individuell utbildning är det viktigt med ett personligt anpassat samtal. MI gjorde att patienterna förändrade sitt beteende men däremot påvisades ingen effekt på HbA1c, det långsiktiga blodsockret. Vid gruppbaserad utbildning höjdes motivationen genom stödet från gruppmedlemmarna vilket resulterade i goda livsstilsval. Slutsats: Gruppbaserad utbildning bör användas av sjuksköterskan som motivation för patienter med diabetes typ 2 till livsstilförändringar. Även individuell utbildning kan användas om fokus ligger på personligt anpassat samtal, men däremot behövs mer forskning på MI.

Background: Changes in our lifestyle have resulted in a global epidemic of the type 2 diabetes. Essential issues for the diabetes care are to try to change the behaviour as well as motivate patients with type 2 diabetes. Aim: To describe different approaches for nurses to motivate patients with type 2 diabetes to lifestyle changes. Method: A literature review based on 13 articles, found through the database CINAHL and PubMed and through manual search, has been analyzed and quality assessed. Results: Patients with type 2 diabetes can be motivated to lifestyle changes through individual education, group education as well as through motivational interviewing (MI). In the individual education it’s important to have a personal adapted conversation. MI resulted in changes in the patients’ behaviour, but no effects have been shown on HbA1c, which is the long-term blood glucose level. Results show that the motivation increased in the group education, due to the support from other group members, and which resulted in good choices of lifestyle. Conclusion: Group education should be adopted by nurses as a method to work with motivation of patients with type 2 diabetes in order to lifestyle changes. Individual education can as well be used if the focus lies on personal adapted conversations, but however, more research is needed on the method MI.

Type 2 diabetes (T2D) is a health problem throughout the world. In 2010, there were nearly 230 million individuals with diabetes worldwide and it is estimated that in the economically advanced countries the cases will increase about 50% in the next twenty years. Insulin resistance is one of major features in T2D, which is also a risk factor for metabolic and cardiovascular complications. Epidemiological and animal studies have shown that the consumption of vegetables and fruits can delay or prevent the development of the disease, although the underlying mechanisms of these effects are still unclear. Brassica species such as broccoli (Brassica oleracea var. italica) and nasturtium (Tropaeolum majus) possess high content of bioactive phytochemicals, e.g. nitrogen sulfur compounds (glucosinolates and isothiocyanates) and polyphenols largely associated with the prevention of cancer. Isothiocyanates (ITCs) display their anti-carcinogenic potential by inducing detoxicating phase II enzymes and increasing glutathione (GSH) levels in tissues. In T2D diabetes an increase in gluconeogenesis and triglyceride synthesis, and a reduction in fatty acid oxidation accompanied by the presence of reactive oxygen species (ROS) are observed; altogether is the result of an inappropriate response to insulin. Forkhead box O (FOXO) transcription factors play a crucial role in the regulation of insulin effects on gene expression and metabolism, and alterations in FOXO function could contribute to metabolic disorders in diabetes. In this study using stably transfected human osteosarcoma cells (U-2 OS) with constitutive expression of FOXO1 protein labeled with GFP (green fluorescent protein) and human hepatoma cells HepG2 cell cultures, the ability of benzylisothiocyanate (BITC) deriving from benzylglucosinolate, extracted from nasturtium to modulate, i) the insulin-signaling pathway, ii) the intracellular localization of FOXO1 and iii) the expression of proteins involved in glucose metabolism, ROS detoxification, cell cycle arrest and DNA repair was evaluated. BITC promoted oxidative stress and in response to that induced FOXO1 translocation from cytoplasm into the nucleus antagonizing the insulin effect. BITC stimulus was able to down-regulate gluconeogenic enzymes, which can be considered as an anti-diabetic effect; to promote antioxidant resistance expressed by the up-regulation in manganese superoxide dismutase (MnSOD) and detoxification enzymes; to modulate autophagy by induction of BECLIN1 and down-regulation of the mammalian target of rapamycin complex 1 (mTORC1) pathway; and to promote cell cycle arrest and DNA damage repair by up-regulation of the cyclin-dependent kinase inhibitor (p21CIP) and Growth Arrest / DNA Damage Repair (GADD45). Except for the nuclear factor (erythroid derived)-like2 (NRF2) and its influence in the detoxification enzymes gene expression, all the observed effects were independent from FOXO1, protein kinase B (AKT/PKB) and NAD-dependent deacetylase sirtuin-1 (SIRT1). The current study provides evidence that besides of the anticarcinogenic potential, isothiocyanates might have a role in T2D prevention. BITC stimulus mimics the fasting state, in which insulin signaling is not triggered and FOXO proteins remain in the nucleus modulating gene expression of their target genes, with the advantage of a down-regulation of gluconeogenesis instead of its increase. These effects suggest that BITC might be considered as a promising substance in the prevention or treatment of T2D, therefore the factors behind of its modulatory effects need further investigation.
Diabetes mellitus Typ 2 stellt auf der ganzen Welt ein Gesundheitsproblem dar. Im Jahr 2010 waren annähernd 230 Millionen Personen weltweit an Diabetes erkrankt und innerhalb der nächsten 20 Jahre wird in industrialisierten Ländern eine Steigerung der Fälle um 50% erwartet. Eines der Hauptmerkmale des Typ 2 Diabetes ist die Insulinresistenz, die auch als Risikofaktor für metabolische und kardio-vaskuläre Komplikationen gilt. Epidemiologische Studien und Tierversuche haben ergeben, dass durch Verzehr von Gemüse und Obst eine Prävention oder Verzögerung der Entwicklung dieser Krankheit erreicht werden kann, jedoch sind die zugrunde liegenden Mechanismen dieser Effekte noch nicht aufgeklärt. Brassica Spezies wie Broccoli (Brassica oleracea var. italica) und Nasturtium (Tropaeolum majus) enthalten einen hohen Anteil an bioaktiven Pflanzen-inhaltsstoffen, wie z. B. stickstoff- und schwefelhaltige Verbindungen (Glukosinolate und Isothiocyanate) und Polyphenole, die bisher hauptsächlich mit der Prävention von Krebs assoziiert wurden. Isothiocyanate (ITCs) erreichen ihr antikanzerogenes Potential durch die Induktion von entgiftenden Phase II Enzymen und eine Anhebung der Glutathion (GSH)-Spiegel im Gewebe. Diabetes Typ2 geht einher mit einem Anstieg der Glukoneogenese und Triglycerid-Synthese, sowie einer Reduktion der Fettsäure-Oxidation in Verbindung mit erhöhten Spiegeln an reaktiven Sauerstoffspezies (ROS) insgesamt als Resultat einer unangemessenen Insulinantwort. Forkhead box O (FOXO) Transkriptionsfaktoren spielen eine wesentliche Rolle in der Regulation der Insulineffekte in Bezug auf die vermittelte Genexpression und den Metabolismus, wobei Veränderungen in der Funktion von FOXO zu metabolischen Entgleisungen im Diabetes beitragen können. In dieser Studie wurde unter Verwendung von stabil transfizierten humanen Osteosarkoma-Zellen (U-2 OS) mit konstitutiver Expression von GFP (grün fluoreszierendes Protein)-markiertem FOXO1 und humanen Hepatoma-Zellen (HepG2) die Wirkung von Benzylisothiocyanat (BITC), dessen Vorstufe Benzylglukosinolat aus Nasturtium isoliert wurde, in Zellkulturen evaluiert wie Modulationen der i) Insulin-Signal-Kaskade, ii) intrazellulären Lokalisation von FOXO1 und iii) Expression beteiligter Proteine am Glucose Metabolismus, der ROS Detoxifikation, Zellzyklus-Fixierung und DNA-Reparatur. BITC erzeugte oxidativen Stress und induzierte als Antwort darauf eine Translokation von FOXO1 aus dem Zytoplasma in den Zellkern antagonisierend zum Insulin-Effekt. Eine Stimultion mit BITC war in der Lage, die Expression von Enzymen der Gluconeogenese herunter zu regulieren, was als antidiabetogener Effekt betrachtet werden kann, eine antioxidative Resistenz durch Induktion der Mangan-Superoxid-Dismutase (MnSOD) und entgiftender Enzyme zu erzeugen, Autophagie zu modulieren durch Induktion von BECLIN1 und Herunterregulation des „mammalian target of rapamycin complex1 (mTORC1)-Stoffwechselwegs, den Zellzyklus zu fixieren und DNA-Reparatur zu induzieren durch Hochregulation des Cyclin- abhängigen Kinase- Inhibitors p21CIP und GADD45 (growth arrest and DNA damage repair). Mit Ausnahme des nuklearen Faktors (erythroid derived)-like2 (NRF2) und dessen Einfluss auf die Genexpression von Entgiftungsenzymen waren alle beobachteten Effekte unabhängig von FOXO1, Proteinkinase B (PKB/AKT) und der NAD-abhängigen Deacetylase Sirtuin-1 (SIRT1). Die gegenwärtige Studie liefert Anhaltspunkte dafür, dass Isothiocayanate neben dem antikanzerogenen Potential eine Rolle bei der Prävention von Typ 2 Diabetes spielen könnten. BITC-Stimulationen ahmen einen Fastenzustand nach, in dem kein Insulin-Signal ausgelöst wird, FOXO Proteine im Zellkern verbleiben und die Expression von Target-Genen modulieren, mit dem Vorteil einer Herunterregulation der Glukoneogenese anstelle seiner Zunahme. Diese Effekte legen nahe, dass BITC als vielversprechende Substanz zur Prävention und Behandlung von Typ 2 Diabetes angesehen werden könnte. Deshalb benötigen die Faktoren, die dessen modulatorische Effekte hervorrufen, weitere Untersuchungen.

Type 2 diabetes is a chronic metabolic disorder and the seventh leading cause of death in the United States. Type 2 diabetes is linked to many chronic diseases, including cardiovascular disease, stroke, and chronic kidney failure. African American adults have a high prevalence of Type 2 diabetes with early onset of diabetes complications. Poor dietary behavior is the primary cause of Type 2 diabetes and its complications, changing dietary behaviors can prevent the onset of diabetes complications or impede existing ones. The purpose of this phenomenological study was to explore patients’ perceptions of diet-only therapy in the prevention of diabetes complications. Face-to-face interviews were conducted with six African American adults with Type 2 diabetes between 40 to 64 years using purposeful sampling method. Health belief model formed the conceptual framework of the study. I applied inductive coding process and manually analyze data for themes. Participants expressed fear of diabetes complications, acknowledged effectiveness of dietary therapy, physician communication and strong family support in Type 2 diabetes management. Findings can produce positive social change among African American adults with type 2 diabetes. Patients can be motivated to change their dietary behaviors to prevent disability and death from diabetes complications. Adherence to diet can reduce medical costs associated with Type 2 diabetes and its complications at the individual, family, community, and government levels. Health care providers can apply the findings in their interactions with patients to provide a more patient-centered education that integrates patients’ cultural and dietary preferences to facilitate adoption of dietary interventions and long-term adherence.

Several viral infections have been associated with human type 1 diabetes (T1D), although it has proven difficult to unequivocally establish them as causative agents. In rodent models, however, viruses have definitely been established to cause T1D. The treatment of weanling BBDR rats with the combination of a TLR3 ligand, pIC, and an ssDNA parvovirus, KRV, precipitates T1D in nearly 100% of rats within a short, predictable timeframe. In this dissertation, we utilized the BBDR rat model to (1) identify early serum biomarkers that could predict T1D precipitated by viral induction and (2) test the efficacy of leptin, a therapeutic agent, which may have the ability to prevent diabetes onset, reverse new onset diabetes and prevent autoimmune recurrence of diabetes in rats transplanted with syngeneic islet grafts. Identification of biomarkers has long served as an invaluable tool for disease prediction. In BBDR rats, we identified an acute phase response protein, haptoglobin, as a potential biomarker for pIC + KRV induced T1D using the global proteomic profiling techniques, 2D gel analysis and iTRAQ. Upon validating this biomarker, we determined that haptoglobin was sensitive in predicting T1D in the pIC + KRV model, in which nearly 100% of the rats become diabetic, but not in models where diabetes expression was variable (KRV only or RCMV only models). However, analysis of the serum kinetics of haptoglobin and its functional capacity in the blood has given us insights into the potential role of early phase reactants in modulating virally mediated T1D. An alternative means of regulating T1D pathogenesis is through leptin. Leptin is a hormone with pleotropic roles in the body, particularly affecting energy metabolism and immune regulation. These characteristics make leptin an intriguing candidate for therapeutic testing in T1D models. Our studies have determined that high doses of leptin delivered via an adenovirus (AdLeptin) or alzet pump delivery system can prevent diabetes in > 90% of rats treated with pIC + KRV. We further showed that serum hyperleptinemia was associated with decreased body weight, decreased non-fasting serum insulin levels and lack of islet insulitis in pIC + KRV treated rats pretreated with AdLeptin compared with those pretreated with PBS. We discovered that hyperleptinemia induced a profound decrease in splenic weight and splenic cellularity, including reductions in CD4+ and CD8+ T cells, DC/MACs and B cells. These findings indicate a potential mechanism whereby hyperleptinemia protects rats from virally induced T1D through the promotion of peripheral immunosuppression. Among pIC + KRV treated rats, we have also found that leptin therapy can reverse hyperglycemia in a subset of new onset diabetics for up to 20 days. In the absence of exogenous insulin, leptin treatment of new onset diabetics prevented the rapid weight loss associated with osmotic diuresis, as well as the ketosis observed in vehicle treated diabetic rats. Overall, these findings point to the therapeutic value of leptin in maintaining glycemic control and preventing ketosis in an insulin deficient state, in the absence of exogenous insulin therapy. Additionally, we have also determined that AdLeptin treatment can prolong the survival of syngeneic islets transplanted into diabetic BBDR rats for up to 50 days post transplant. Although hyperleptinemia generated by AdLeptin was unable to prevent insulitis into islet grafts, this insulitis did not appear to be destructive as islet grafts continued to stain positively for insulin when compared with control rats whose grafts succumbed to recurrent autoimmunity. In the various therapeutic settings in which we have tested leptin treatment, we have found this hormone to have significant beneficial effects. These findings merit further evaluation of leptin as a therapeutic agent in human T1D.

Type 2 diabetes is a chronic metabolic disorder and the seventh leading cause of death in the United States. Type 2 diabetes is linked to many chronic diseases, including cardiovascular disease, stroke, and chronic kidney failure. African American adults have a high prevalence of Type 2 diabetes with early onset of diabetes complications. Poor dietary behavior is the primary cause of Type 2 diabetes and its complications, changing dietary behaviors can prevent the onset of diabetes complications or impede existing ones. The purpose of this phenomenological study was to explore patients' perceptions of diet-only therapy in the prevention of diabetes complications. Face-to-face interviews were conducted with six African American adults with Type 2 diabetes between 40 to 64 years using purposeful sampling method. Health belief model formed the conceptual framework of the study. I applied inductive coding process and manually analyze data for themes. Participants expressed fear of diabetes complications, acknowledged effectiveness of dietary therapy, physician communication and strong family support in Type 2 diabetes management. Findings can produce positive social change among African American adults with type 2 diabetes. Patients can be motivated to change their dietary behaviors to prevent disability and death from diabetes complications. Adherence to diet can reduce medical costs associated with Type 2 diabetes and its complications at the individual, family, community, and government levels. Health care providers can apply the findings in their interactions with patients to provide a more patient-centered education that integrates patients' cultural and dietary preferences to facilitate adoption of dietary interventions and long-term adherence.

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 mellitus typ 2 är en sjukdom som ökar i västvärlden. I Sverige är det uppskattningsvis fyra procent av befolkningen som har sjukdomen. Att få diabetes typ 2, innebär en riskökning att drabbas av för tidig död, komplikationer såsom stroke, hjärtinfarkt, njursvikt, nervskador och allvarlig synnedsättning. Att befinna sig i ett prediabetestillstånd ger upp till 70 % risk att utveckla diabetes typ 2 på sikt. De kvinnor som haft graviditetsdiabetes tillhör denna grupp. Att som kvinna drabbas av graviditetsdiabetes och sedan ha en förhöjd risk att utveckla typ 2 diabetes går att förhindra eller fördröja med livsstilsförändringar. Att förändra sin livsstil är en utmaning för de flesta och för nyblivna mammor ska detta införlivas i den nya rollen som förälder. Syftet med studien är att undersöka hur kvinnor med graviditetsdiabetes som riskerar att få typ 2 diabetes upplever sin situation och vilket stöd de efterfrågar. En litteraturstudie har genomförts med kvalitativ innehållsanalys av åtta artiklar. Analysen resulterade i att två huvudteman: 1) behov av kunskap och 2) kontroll av livssituationen och fyra underteman: 1) livsstilsförändringar, 2) motivation, 3) stöd från närstående och andra samt 4) stöd från vården kunde identifieras. Studien visar att det finns hinder att komma förbi för de nyblivna mammorna även efter det att de fångats upp av vården. Kvinnornas behov av kunskap beskrivs som en förutsättning för att göra nödvändiga livsstilsförändringar liksom det bristande stödet från närstående och vården. Den redovisar också de möjligheter som finns för att identifiera förebyggande insatser samt att ge dessa kvinnor det stöd de efterfrågar och behöver.

Type 2 diabetes mellitus (DM) is a progressive disease characterised by hyperglycaemia caused by defects in insulin secretion and insulin action. In early stages of type 2 DM, dietary and lifestyle changes are often sufficient to control blood glucose levels. However, over time, many patients experience β cell dysfunction and require insulin therapy, either alone or in combination with oral agents. There are guidelines available to structure the management of this disease state, including both the use of oral hypoglycaemic agents and or insulin. Besides health complications, there are economic burdens associated with the management of type 2 diabetes mellitus. The aim of this study was to determine the management of type 2 DM in a South African sample group of patients drawn from a large medical aid database. The objectives of the study were: to establish the prevalence of type 2 DM relative to age, examine the nature of chronic comorbid disease states, establish trends in the prescribing of insulin relative to other oral hypoglycaemic agents, investigate cost implications, and determine trends in the use of blood and urine monitoring materials by patients. The study was quantitative and retrospective and descriptive statistics were used in the analysis. DM was found to be most prevalent amongst patients between 50 and 59 years old. Results also demonstrated that 83% of DM patients also suffered from other chronic comorbid diseases, with cardiovascular diseases, especially hypertension and hypercholesterolaemia being the most prominent. This study also revealed that DM is predominantly managed with oral hypoglycaemic agents. Changes in drug prescribing, for chronic disease states such as DM may have medical, social and economic implications both for individual patients and for society and it is envisaged that the results of this study can be used to influence future management of DM. Keywords: Pharmacoepidemiology, management, type 2 diabetes mellitus

Preeclampsia is a multi-system disorder that affects approximately 3-5% of all pregnancies and is one of the leading causes of maternal and neonatal morbidity and mortality globally. At present, there remain many facets of preeclampsia lacking data and comprehensive understanding. This thesis presents a number of studies investigating various aspects of prediction, prevention and long-term sequelae of preeclampsia. Women with pre-existing diabetes mellitus (DM) form a unique cohort of women with significantly increased risk of developing preeclampsia in pregnancy compared to the general population. Despite this, there is minimal data on serum predictive markers and no data on urinary predictive markers for the development of preeclampsia in this cohort. This thesis explored both urinary and serum predictive markers for preeclampsia throughout pregnancy, in women with pre-existing DM. We described urinary protein excretion as pregnancy progresses in women with pre-existing DM. For total protein excretion measured via spot urine protein-to-creatinine ratio (uPCR), results were in keeping with the literature within the general obstetric population, with increments as pregnancy progressed. However, unlike the general population, in our population of women with pre-existing DM, spot urinary albumin-to-creatinine ratio (uACR) remained stable until late trimester 3. We additionally found that for our population, in each trimester of pregnancy, spot uACR outperformed spot uPCR with respect to its association with the outcome of preeclampsia. Additionally, placental growth factor (PlGF) is known to play a key role in placental angiogenesis in pregnancy - we found that preeclampsia is associated with an anti-angiogenic state, with reduced levels of serum PlGF and increased levels of soluble fms-like protein kinase 1 (sFlt1). We demonstrated correlation between urinary and serum levels of PlGF throughout pregnancy and in contrast to the literature within the general obstetric population, we found that for our women with DM, serum PlGF alone performed as a better predictor of preeclampsia than the serum sFlt1-to-PlGF ratio, at all gestations sampled throughout pregnancy. Due to their increased preeclampsia risk, there is clear consensus that women with pre-existing DM would benefit from aspirin prophylaxis for preeclampsia risk reduction. These recommendations appear to stem from data obtained in the general population. However, there is evidence suggesting potentially reduced aspirin effectiveness in those with pre-existing DM. We reviewed the current literature of preeclampsia risk reduction with aspirin prophylaxis within women with pre-existing DM. Our systematic review is the first published review exploring the available data around the use of antenatal aspirin for the prevention of preeclampsia specifically in women with pre-existing DM. Our findings revealed a great void of available data surrounding aspirin prophylaxis for preeclampsia risk reduction in this cohort, with results suggesting no difference in preeclampsia outcome with aspirin use, a finding likely a consequence of lack of power due to insufficient data available for our cohort of interest. Preeclampsia not only poses immediate risk to the mother and neonate during the peripartum period, but it is now understood that it has long-term implications for both the mother and offspring. A wealth of evidence now exists demonstrating women with a history of preeclampsia have increased long term risk of cardiovascular morbidity and mortality. It appears that preeclampsia history may be a gender specific cardiovascular risk factor akin to traditional cardiovascular risk factors such as hypertension or obesity. It is known that those with increased cardiovascular risk are also at increased cardiovascular morbidity and mortality post-surgery. However, no data exists regarding postoperative cardiovascular risk in women with a history of preeclampsia. We aimed to explore this association in the PREECLAMPSIA-VISION study, a sub-study including all female participants with a positive pregnancy history from the original Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, a large international prospective cohort study of a representative sample of adults aged 45 years and older who underwent non-cardiac surgery. Our primary outcome was Myocardial Injury after Non-cardiac Surgery (MINS) within 30 days after surgery. We found that a positive preeclampsia history was an independent risk factor for MINS, with 26% relative increase in the hazard of MINS in the first 30 post-operative days when compared to women whose previous pregnancies were not complicated by preeclampsia. In addition to long-term implications for the woman, epidemiological evidence also supports an association between maternal preeclampsia and long-term neurocognitive function in the offspring. However, the available literature is conflicting and there is often incomplete consideration of confounding factors. We explored this association, taking into account important confounding and mediating factors, via a population-based cohort study using record-linkage of New South Wales birth, hospitalization and education data. Our outcome of measure for neurocognitive function was offspring school performance as assessed by the Grade 3 National Assessment Program–Literacy and Numeracy (NAPLAN), a standardised national test, which assesses children in 5 domains: reading, writing, spelling, grammar and punctuation, and numeracy. Our outcome of interest was a score below the national minimal standard (BNMS) in any of the 5 NAPLAN domains. In children exposed to preeclampsia in utero, crude univariate analysis demonstrated an increased risk of scoring BNMS in all 5 NAPLAN domains compared to children of unaffected pregnancies. Interestingly, once perinatal and child factors were accounted for, these differences were completely attenuated. The perinatal factors had a greater mediating effect than child factors, with gestational age at birth being the primary contributor, accounting for up to 21% of the association between preeclampsia and scoring BNMS. All the studies presented within this thesis have either direct clinical implication or translational potential to clinical practice and have laid the foundation for further research. We suggest that women with pre-existing DM form a unique high-risk cohort of women with respect to the outcome of preeclampsia, and screening with uACR instead of the current clinically used uPCR would provide improved risk stratification for this cohort. Our results also suggest that the implementation of current clinically used algorithm-based screening, particularly those that include serum sFlt1-to-PlGF ratio may not be appropriate for women with pre-existing DM and screening within this cohort cannot be based on extrapolation of data obtained from the general obstetric population. Additionally, urinary PlGF holds promise for preeclampsia screening within this cohort and possibly the general obstetric population, however more sensitive commercially available kits are required. Further, we suggest caution before extrapolating currently available data for preeclampsia risk reduction with aspirin prophylaxis to women with pre-existing DM. Our PREECLAMPSIA-VISION study underscores the distinct requirement for enhancement in our overall understanding of gender differences in perioperative cardiovascular outcomes and overall long-term cardiovascular risk and suggests benefit in the incorporation of preeclampsia history into current perioperative risk predictive models for female patients. Lastly, to reduce the risk of poorer long-term offspring educational outcomes associated with preeclampsia, we support the implementation of strategies to safely prolong pregnancy and increase gestational age at birth in women whose pregnancies are complicated by preeclampsia.

Recently the development of Patient-specific models (PSMs) tailored to patient-specific data, has gained more and more attention in clinical applications. PSMs could represent a solution to the growing awareness of personalized medicine which allow the realization of more effective rehabilitation treatments designed on the subject capabilities. PSMs have the potential of improving diagnosis and optimizing clinical treatments by predicting and comparing the outcomes of different approaches of intervention. Furthermore they can provide information that cannot be directly measured, such as muscle forces or internal stresses and strains of the bones. Given the considerable amount of diseases affecting motor ability, PSMs of the lower limbs have been broadly addressed in literature. Two techniques are mostly used in this area: musculoskeletal (MS) modeling and finite element (FE) analysis. (MS) models represent a valuable tool, as they can provide important information about the unique anatomical and functional characteristics of different subjects, through the computation of human internal variables, such as muscle activations and forces and joint contact forces. The flexibility and adaptability of FE analysis makes it a perfect solution to model biological geometries and materials and to simulate complicated boundary and loading conditions. Accurate and descriptive FE models would serve as an excellent tool for scientific and medical research. Furthermore they could be used in clinical settings if combined with medical imaging, in order to improve patient care. Several 3-dimensional (3D) foot FE models were recently developed to analyze the biomechanical behavior of the human foot and ankle complex that is commonly studied with experimental techniques like stereophotogrammetry, force and plantar pressure plates. In this context, many gait analysis protocols have been proposed to assess the 3D kinetics, kinematics and plantar pressure distribution. This evaluation has shown to be useful in characterizing the foot biomechanics in different pathologies like the diabetic foot. Diabetic foot is an invalidating complication of diabetes mellitus, a chronic disease frequently encountered in the aging population. It is characterize by the development of ulcers which can lead to amputation. Models for simulations of deformations and stresses in the diabetic plantar pad are required to predict high risk areas on the plantar surface and can be used to investigate the performance of different insoles design for optimal pressure relief. This work represents a first effort towards the definition of a more complete PSM which combining both a MS model and a FE model, can increase the understanding of the diabetic foot pathology. To achieve this objective, several limitations and issues have been addressed. As first, MS models of diabetic and control subjects were developed using OpenSim, to estimate muscle forces. The objective was to evaluate whether the diabetic population exhibit lower limb muscle strength deficits compared to the healthy one. Subjects routine gait analysis was performed and lower limb joints kinematics, kinetics, time and space parameters estimated by means of a modified version of the IORgait protocol. 3D lower limb joints kinematics and kinetics was also calculated with OpenSim. Both methodologies were able to highlight differences in joint kinematics and kinetics between the two populations. Furthermore MS models showed significant differences in healthy muscle forces with respect to the diabetic ones, in some of the muscles. This knowledge can help the planning of specific training in order to improve gait speed, balance, muscle strength and joint mobility. After the use of MS models proved to be applicable in the diabetic population, the next step was to combine them with foot FE models. This was done in two phases. At first the impact of applying the foot joints contact forces (JCFs) obtained from MS models as boundary condition on the foot FE models was verified. Subject specific geometries from MRI were used for the development of the foot FE models while the experimental plantar pressures acquired during gait were used in the validation process. A better agreement was found between experimentally measured and simulated plantar pressure obtained with JCFs than with the experimentally measured ground reaction forces as boundary conditions. Afterwards the use of muscles forces as boundary condition in the FE simulations was evaluated. Subject-specific integrated and synchronized kinematic-kinetic data acquired during gait analysis were used for the development of the MS models and for the computation of the muscle forces. Muscle insertions were then located in the MRI and correspondent connectors were created in the FE model. FE subject-specific simulations were subsequently run with Abaqus by conducting a quasi-static analysis on 4 gait cycle phases and adopting 2 conditions: one including the muscle forces and one without. Once again the validation of the FE simulations was done by means of a comparison between simulated and experimentally measured plantar pressures. Results showed a marked improvement in the estimation of the peak pressure for the model that included the muscles. Finally, an attempt towards the definition of a parametric foot finite element model was done. In fact, despite the recent developments, patient-specific models are not yet successfully applied in a clinical setting. One of the challenges is the time required for mesh creation, which is difficult to automate. The development of parametric models by means of the Principle Component Analysis (PCA) can represent an appealing solution. In this study PCA was applied to the feet of a small cohort of diabetic and healthy subjects in order to evaluate the possibility of developing parametric foot models and to use them to identify variations and similarities between the two populations. The limitations of the use of models have also been analyzed. Their adoption is indeed limited by the lack of verification and validation standards. Even using subjects’ MRI or CT data for the development of FEM together with experimentally acquired motion analysis data for the boundary and loading conditions, the subject specifity is still not reached for what regards all the material properties. Furthermore it should be considered that everything relies on algorithm and models that would never be perfectly representing the reality. Overall, the work presented in this thesis represents an extended evaluation of the possible uses of modeling techniques in the diabetic foot prevention, by considering all the limitations introduced as well as the potential benefits of their use in a clinical context. The research is organized in six chapters: Chapter 1 - provides a background on the modeling techniques, both FE modeling and MS modeling. Furthermore it also describes the gait analysis, its instrumentation and some of the protocols used in the evaluation of the biomechanics of the lower limbs; Chapter 2 - gives a detailed overview of the biomechanics of the foot. It particularly focuses on the diabetes and the diabetic foot; Chapter 3 - introduces the application of MSs for the diabetic foot prevention after a brief background on the techniques usually chosen for the evaluation of the motor impairments caused by the disease. Aim, material and methods, results and discussion are presented. The complete work flow is described, and the chapter ends with a discussion on new key findings and limitations. Chapter 4 – reports the work done to combine the use of musculoskeletal models with foot FEMs. At first the impact of applying the foot joints contact forces obtained from MS models as boundary condition on the foot FEMs is verified. Then the use of muscles forces (again obtained from MS models) as boundary condition in the FE simulations is evaluated. For both studies a brief background is presented together with the methods applied, the results obtained and a discussion of novelties and drawbacks. Chapter 5 – explores the possibility of defining a parametric foot FEM applying the Principle Component Analysis (PCA) on the feet of a small cohort of diabetic and healthy subjects. A background on the importance of patient specific models is presented followed by material and methods, results and discussion of what obtained with this study. Chapter 6 - summarizes the results and the novelty of the thesis, delineating the conclusions and the future research paths.
Recentemente lo sviluppo di modelli specifici di un paziente (PSM), cioè creati a partire dai suoi dati, ha guadagnato sempre più attenzione per le possibili applicazioni cliniche. Questi modelli potrebbero, infatti, rappresentare una soluzione alla crescente consapevolezza che la medicina deve essere personalizzata al fine di ottenere un trattamento riabilitativo più efficace e disegnato ad hoc sulle capacità soggetto. Gli PSM hanno il potenziale di migliorare la diagnosi e di ottimizzare la terapia riabilitativa, data la loro capacità di prevedere e di confrontare i risultati di diversi approcci d’intervento. Inoltre essi sono in grado di fornire informazioni che non possono essere direttamente misurate, quali forze muscolari o tensioni interne alle ossa. Data la notevole quantità di malattie che causano deficit motori, gli PSM sono stati ampiamente affrontati in letteratura. Le due tecniche per lo più utilizzate in questo settore sono la modellazione muscoloscheletrica (MS) e la modellazione agli elementi finiti (FE). I modelli MS rappresentano uno strumento prezioso, poiché possono fornire importanti informazioni sulle caratteristiche anatomiche e funzionali dei diversi soggetti, attraverso il calcolo di variabili interne come attivazioni muscolari e forze di contatto alle articolazioni. La flessibilità e l'adattabilità dell'analisi FE la rende una soluzione ideale per modellare geometrie e materiali biologici e per simulare condizioni al contorno e di carico complicate. Modelli FE (FEM) precisi e descrittivi potrebbero dimostrarsi un ottimo strumento per la ricerca scientifica e medica. Inoltre, potrebbero essere utilizzati in ambito clinico se combinati con l'imaging medico, al fine di migliorare la cura del paziente. Diversi FEM a 3 dimensioni (3D) del piede sono stati recentemente sviluppati per analizzare il comportamento biomeccanico del complesso piede-caviglia che è comunemente studiato con tecniche sperimentali come la stereofotogrammetria, le piattaforme di forza e di pressione. In questo contesto, sono stati proposti molti protocolli per l'analisi del cammino al fine di valutare la cinematica, la cinetica e la distribuzione della pressione plantare in 3D. Questa valutazione si è dimostrata utile per caratterizzare la biomeccanica del piede in diverse patologie come il piede diabetico. Il piede diabetico è una complicanza invalidante del diabete mellito, una malattia cronica sempre più frequente nella popolazione anziana. Esso è caratterizzato dallo sviluppo di ulcere che possono portare all'amputazione. Modelli per la simulazione di deformazioni e sollecitazioni nel tessuto plantare diabetico devono essere in grado di prevedere quali sono le zone ad alto rischio per la formazione di ulcere sulla superficie plantare e possono essere usati per studiare le prestazioni di diverse solette nell'alleviare la pressione. Questo lavoro rappresenta un primo sforzo verso lo sviluppo di uno PSM più completo che combinando un modello MS a un FEM, può aumentare la comprensione della patologia del piede diabetico. Per raggiungere quest’obiettivo, numerose limitazioni e problematiche sono state analizzate e risolte. Innanzitutto, modelli MS di soggetti sani e diabetici sono stati sviluppati usando OpenSim al fine di stimare le forze muscolari. L'obiettivo era di valutare se la popolazione malata presenta deficit di forza muscolare negli arti inferiori rispetto a quella sana. I soggetti sono stati sottoposti a un'analisi del cammino e la cinematica e la cinetica degli arti inferiori sono state stimate per mezzo di una versione modificata del protocollo IORgait. La cinematica e la cinetica 3D delle articolazioni degli arti inferiori sono state calcolate anche con OpenSim. Entrambe le metodologie sono state in grado di evidenziare alcune differenze di cinematica e cinetica articolare tra le due popolazioni. I modelli MS hanno inoltre evidenziato differenze nelle forze muscolari dei soggetti sani rispetto a quelli diabetici. Questa conoscenza può aiutare nella pianificazione di terapie riabilitative specifiche per i pazienti diabetici al fine di migliorare la velocità, l'equilibrio, la forza muscolare, l’andatura e la mobilità articolare. Dopo aver dimostrato l'applicabilità dei modelli MS nella popolazione diabetica, il passo successivo è stato quello di combinarli con FEM del piede. Ciò è stato fatto in due fasi. In un primo momento l'impatto dell'applicazione delle forze di reazione dell'articolazione del piede, ottenute dai modelli MS, come condizione al contorno per modelli FE del piede è stata verificata. Le geometrie specifiche del soggetto, ricavate da MRI, sono state utilizzate per lo sviluppo dei FEM del piede mentre le pressioni plantari sperimentalmente acquisite durante la deambulazione sono state utilizzate nel processo di validazione. Un miglior accordo tra pressione misurata sperimentalmente e pressione simulata è stato ottenuto utilizzando, come condizioni al contorno, le forze di reazione alla caviglia rispetto alle forze di reazione del suolo sperimentalmente simulate. Dopodiché l'uso di forze muscolari come condizione al contorno nelle simulazioni FE è stata valutata. Dati di cinematica e cinetica acquisiti in sincrono durante l'analisi del cammino sono stati utilizzati per lo sviluppo di modelli MS e per il calcolo delle forze muscolari. Le inserzioni muscolari sono state poi trovate nelle immagini di risonanza magnetica e i connettori corrispondenti sono stati creati nel FEM. Le simulazioni FE specifiche del soggetto sono state in seguito eseguite con il software Abaqus conducendo un'analisi quasi statica su quattro fasi del ciclo del passo e adottando due condizioni di carico: una che comprendeva le forze muscolari e una senza. Ancora una volta la validazione delle simulazioni FE è stata fatta per mezzo di un confronto tra le pressioni plantari simulate e misurate sperimentalmente. I risultati hanno mostrato un miglioramento marcato nella stima del picco di pressione nel modello che includeva i muscoli. Infine è stato fatto un tentativo per la definizione di un modello agli elementi finiti del piede parametrico. Infatti, nonostante i recenti sviluppi, gli PSM non sono ancora stati applicati con successo in un ambiente clinico. Una delle possibili spiegazioni è il tempo necessario per la creazione della mesh, operazione che è di difficile automatizzazione. Lo sviluppo di modelli parametrici mediante l'analisi in componenti principali (PCA) può rappresentare una soluzione accattivante. In questo studio la PCA è stata applicata alla geometria dei piedi di una piccola coorte di soggetti diabetici e sani per valutare la possibilità di sviluppare modelli parametrici del piede e di utilizzarli per identificare varianti e analogie tra le due popolazioni. Anche i limiti imposti dall'uso di modelli sono stati analizzati. La loro adozione è, infatti, limitata dalla mancanza di standard di verifica e validazione. Anche utilizzando l'MRI per lo sviluppo di un FEM, e dati sperimentali di analisi del movimento per le condizioni al contorno e di carico, la specificità del soggetto non è mai perfettamente raggiunta ad esempio per quanto riguarda le proprietà dei materiali. Inoltre bisognerebbe considerare che tutto si appoggia su algoritmi e modelli che non saranno mai in grado di rappresentare perfettamente la realtà. Nel complesso, il lavoro presentato in questa tesi rappresenta una valutazione estesa dei possibili usi di tecniche di modellazione nella prevenzione del piede diabetico, considerando tutte le limitazioni introdotte e i potenziali vantaggi del loro utilizzo in un contesto clinico. La ricerca si articola in sei capitoli: Capitolo 1 - fornisce uno sguardo generale sulle tecniche di modellazione, sia modellazione agli elementi finiti sia modellazione muscoloscheletrica. Inoltre descrive l'analisi del cammino, la strumentazione richiesta e i protocolli sviluppati per l'analisi degli arti inferiori. Capitolo 2 - fornisce una panoramica dettagliata della biomeccanica del piede concentrandosi in particolare sul diabete e il piede diabetico; Capitolo 3 - introduce l'applicazione dei modelli MS per la prevenzione del piede diabetico dopo una breve introduzione sulle tecniche più comuni utilizzate nella valutazione dei deficit motori causati dalla malattia. Obiettivi, materiali e metodi, risultati e discussione finale sono presentati. Il flusso di lavoro completo è descritto, e il capitolo si finisce con una discussione sulle nuove scoperte e sulle limitazioni. Capitolo 4 - riporta il lavoro fatto per combinare l'uso di modelli muscoloscheletrici con FEM del piede. In un primo momento è verificato l'impatto dell'applicazione delle forze di contatto all'articolazione del piede, ottenute dai modelli MS, come condizione al contorno nei FEM del piede. Di seguito è valutato l'uso delle forze muscolari (ancora una volta ottenute dai modelli MS) come condizione al contorno nelle simulazioni FE. Per entrambi gli studi è presentata una breve introduzione insieme ai metodi applicati, ai risultati ottenuti e a una discussione sulle novità introdotte e sui limiti. Capitolo 5 - esplora la possibilità di definire un FEM del piede parametrico applicando l' analisi delle componenti principali (PCA) ai piedi di una piccola coorte di soggetti diabetici e sani. Una panoramica sull'importanza di modelli specifici dei pazienti è presentata seguita da materiali e metodi, risultati e discussione di ciò che è stato ottenuto con questo studio. Capitolo 6 - riassume i risultati e la novità della tesi, delineando le conclusioni e i percorsi di ricerca futuri.

Although considered a substanially preventable disease, Type 2 diabetes is reaching epidemic status within the Maori population. This study sought to investigate factors that positively and negatively influenced levels of physical activity for Maori within Otepoti/Dunedin, and to discuss ideas and potential initiatives that could increase levels of physical activity and aid in the prevention of Type 2 diabetes. Eighteen Maori (9 males; 9 females) from this rohe (area) participated in a four hour focus group interview (groups of three) and were also invited to attend an evaluation hui. A Maori-centered research orientation was used throughout the research process. Individual transcripts from focus groups, debriefing discussion and content from the evaluation hui were inductively analysed to identify the main themes. The 'active' participants were physically active because of the benefits they attained for health and longevity, and to undertake task-oriented activity such as gathering kai. Barriers to physical activity (i.e., family, work), a contemporary societal shift towards inactivity, and negative personal attitudes and perceptions towards physical activity detrimentally affected levels of physical activity. Initiatives to increase levels of physical activity included community, educational and work-based initiatives. A key element of each proposed initiative was a 'by Maori for Maori' approach, with a focus on strengthening whānau and iwi networks, a comfortable environment and social support. While education was believed to be a key component for Type 2 diabetes prevention, an avoidance barrier and fatalistic attitudes could negatively affect any attempt to prevent Type 2 diabetes and increase levels of physical activity. The results indicated that to strengthen Maori identity, increase levels of physical activity and prevent Type 2 diabetes, positive changes (taking responsibility for health), cultural changes (a shift towards a stronger identity and belief in the taonga [treasure] of being Maori), societal changes ( a more positive view of Maori, better role models and education), and social economic changes (better access to exercise facilities, healthy food and education for those in the lower deprivation indices) were needed.

This thesis begins with a background chapter which explores the current diabetes epidemic and examines the role of obesity and oxidative stress as causative factors. Current dietary recommendations for prevention of type 2 diabetes are critically evaluated. A systematic review and meta-analysis was conducted to determine the independent role of fruit and vegetables in preventing diabetes. Convincing benefit for greater consumption of green leafy vegetables was demonstrated. An insignificant trend towards benefit was observed for fruit and vegetables. The Fruit and Vegetable Intake and Glucose Control Study (FIVE) is a sub study of the Let’s Prevent Diabetes Study. FIVE includes cross sectional analysis of baseline plasma vitamin C, (a biomarker for fruit and vegetable intake) from 2101 participants. FIVE further includes 12 months analysis of individuals with impaired glucose regulation, randomised to receive group education or usual care. Results demonstrate 29% of the population consumed at least 5 portions of fruit and vegetables a day. Fewer South Asian individuals met the recommendation compared to White Europeans (21% vs. 30% p = 0.003). Each additional piece of fruit or vegetable consumed (21.8μmol/l plasma vitamin C) was associated with a reduction of 0.04% in HbA1c, 0.05mmol/l in fasting and 0.22mol/l in 2 hour blood glucose. Participants who consumed 5 portions a day compared to those who did not, had a 24% associated reduced risk of being diagnosed with impaired glucose regulation (OR = 0.76, 95% CI: 0.59 to 0.98). At 12 months follow up those receiving lifestyle education had greater levels of plasma vitamin C compared to those in the usual care arm (36.1μmol/l (SD 20.7) vs.29.9μmol/l (SD 20.3)). No statistical difference in mean change between intervention arms was seen. The thesis provides novel, robust nutritional biomarker data from a large at risk, multi ethnic population. Results support recommendations to promote fruit and vegetables in the diet to prevent diabetes. The potential for tailored advice on increasing green leafy vegetables among those at risk of diabetes should be investigated further.

Abstract Type 2 diabetes is one of the fastest increasing lifestyle diseases globally. Its cure is not yet possible, but there is firm evidence from scientific studies that it can effectively be prevented by lifestyle changes. There is limited evidence-based information on the prevention of diabetes in practice. This dissertation offers new desirable information on the issue. The aim of this dissertation study was to describe the prevalence of risk factors for type 2 diabetes and hidden glucose disorders predicting the development of diabetes in the Finnish adult population, and to analyse whether the risk for developing diabetes could be reduced by simple lifestyle counselling. Furthermore, the ability of the Finnish Diabetes Risk Score (FINDRISC) to detect glucose disorders leading to diabetes and undiagnosed diabetes was analysed. In the dissertation data from large Finnish population surveys (the FINRISK 2002 glucose tolerance survey and the FIN-D2D 2004−2005 survey) were analysed. In addition, a prospective design and large-scale intervention were included. We found that obesity and glucose disorders are very common in the Finnish middle-aged population. Prevalence of obesity was 24% for men and 28% for women, that of abnormal glucose metabolism 42% for men and 33% for women, and that of undiagnosed diabetes 9% for men and 7% for men. One quarter of individuals aged 45−64 years were at high risk for diabetes. Lifestyle interventions were offered to more than 10,000 high-risk individuals, 3,379 men and 6,770 women. Of the men, 43% were also at high risk for cardiovascular morbidity and 42% at high risk for cardiovascular mortality estimated through the FRAMINGHAM and SCORE risk engines, respectively. The FINDRISC, originally developed for predicting the risk of development of type 2 diabetes, also predicted the prevalence of diabetes in the population. The effect of lifestyle interventions on weight and its association with glucose tolerance was evaluated in individuals at high risk for diabetes in a one-year follow-up. In total 17.5% of them lost ≥ 5% weight. Their relative risk for diabetes decreased 69% compared with the group that maintained their weight. This study shows that FINDRISC predicts prevalent type 2 diabetes. A significant proportion of middle-aged Finnish population has a glucose disorder including undiagnosed type 2 diabetes. Lifestyle interventions in primary health care may promote weight loss, which decreases the risk of diabetes
Tiivistelmä Diabetes on yksi nopeimmin lisääntyvistä elintapasairauksista maailmassa. Sitä ei vielä voida parantaa, mutta tieteellisissä tutkimuksissa on kiistattomasti osoitettu, että sitä voidaan tehokkaasti ehkäistä elintapamuutoksilla. Diabeteksen ehkäisystä käytännössä on hyvin niukasti tutkimustietoa. Tämä väitöskirja tuo kaivattua lisätietoa aiheesta. Väitöstutkimuksen päätavoitteena oli selvittää diabeteksen riskitekijöiden ja piilevien diabetesta ennakoivien sokerihäiriöiden yleisyyttä suomalaisessa aikuisväestössä. Tämän ohella tavoitteena oli selvittää voidaanko yksinkertaisella elintapaneuvonnalla vähentää sellaisten henkilöiden sairastumisvaaraa, joilla oli suuri riski sairastua diabetekseen. Lisäksi arvioitiin diabetesriskitestin kykyä tunnistaa ennakoivat sokerihäiriöt ja aiemmin tunnistamaton diabetes. Tutkimuksessa käytettiin laajoja suomalaisia väestötutkimusaineistoja: FINRISKI-2002 -tutkimusta, sen alaotosta ja D2D-väestötutkimusta 2004–2005. Mukana oli myös pitkittäisasetelma ja laajamittainen interventio. Tutkimuksen perusteella huomasimme, että lihavuus ja sokerihäiriöt ovat hyvin yleisiä keski-ikäisillä suomalaisilla. Merkittävästi lihavia (BMI ≥ 30 kg/m2) oli 24 % miehistä ja 28 % naisista ja poikkeava sokeriaineenvaihdunta oli 42 %:lla miehistä ja 33 %:lla naisista. Tunnistamaton diabetes oli 9 %:lla miehistä ja 7 %:lla naisista. Suuressa diabetekseen sairastumisvaarassa oli neljäsosa 45−64-vuotiaista. Interventioon otettiin yli 10 000 suuressa diabeteksen sairastumisriskissä olevaa henkilöä, 3 379 miestä ja 6 770 naista. Miehistä 43 % oli suuressa sairastumisvaarassa myös sydän- ja verisuonisairauteen ja 42 % suuressa kuolemanvaarassa Framingham- ja SCORE-riskilaskureilla arvioituna. Tyypin 2 diabeteksen sairastumisriskin arviointiin kehitetty Riskitesti ennusti hyvin myös diabeteksen esiintymistä väestössä. Elintapainterventioiden vaikutusta painoon ja sokeriaineenvaihduntaan analysoitiin vuoden seurannassa sellaisilla henkilöillä, joilla oli suuri diabetesriski. Paino laski 5 % tai enemmän 17,5 %:lla, jolloin sairastumisriski diabetekseen väheni 69 % verrattuna ryhmään, jonka paino ei muuttunut. Tutkimuksen perusteella lihavuus, sokerihäiriöt ja tunnistamaton diabetes ovat yleisiä keski-ikäisessä väestössä. Riskitesti on hyvä työkalu myös diabeteksen seulonnassa. Perusterveydenhuollossa tarjottavalla elintapaneuvonnalla voidaan saada aikaan laihtuminen, joka vähentää sairastumisvaaraa diabetekseen

This thesis addressed gaps in the literature regarding the effects of Mindfulness-based interventions (MBIs) for Type 2 diabetes (T2D) and sought to investigate the acceptability and feasibility of an MBI for a group at high risk for T2D, South Asians. A mixed-methods approach was utilised to produce four studies: 1) a systematic review evaluating the psychological and physiological effects of MBIs applied to T2D; 2) a modelling phase to gauge interest in, and cultural considerations for, a modified MBI for young adult South Asians as a diabetes prevention strategy; 3) an examination of the acceptability and feasibility of a modified MBI; and 4) a comparison of the perceived and objective effects of the modified MBI. The review found evidence for psychological benefits and mixed results for physiological effects. The modelling phase indicated that Mindfulness is acceptable to young South Asians pending minor adaptations. The subsequent feasibility study found the modified MBI to be acceptable and feasible, warranting a future full-scale trial. Across these studies, Mindfulness bore psychological benefits, and to a lesser degree physiological and behavioural benefits. The final study’s triangulation approach (using quantitative and qualitative methods) suggests the intervention has a potential positive impact on stress, anxiety, energy levels, emotional wellbeing, and systolic blood pressure in this sample.

The primary aim of this thesis was to contribute to the evidence base guiding the prevention and treatment of type 2 diabetes (T2DM) in children and adolescents, specifically through lifestyle intervention. This thesis presents four research studies examining strategies aimed at preventing T2DM in high-risk youth and one study aimed at optimising treatment for youth with T2DM. The four prevention studies focus on the effect of lifestyle interventions, incorporating a dietary and/or exercise component, to lead to sustainable improvements in weight status, cardio-metabolic risk factors and cardiorespiratory fitness, all of which are risk factors for the development of T2DM. For the treatment of T2DM, one study examined whether an intensive very low energy diet (VLED) intervention can lead to rapid weight loss and reversal of T2DM in young people. The key findings of this thesis are: 1. Weight loss can be achieved in children and adolescents with obesity irrespective of the macronutrient distribution of a reduced-energy diet 2. A 12 week exercise program is associated with sustainable improvements in aerobic fitness and anaerobic threshold 3. Prescriptive dietary advice is safe and is associated with long-term improvements in insulin sensitivity and body composition but not weight loss 4. Early weight loss is a strong predictor of long-term obesity treatment outcome 5. Adherence to a VLED can lead to the reversal of T2DM in youth Findings from this thesis provide an improved understanding of the impact of lifestyle interventions in the prevention and treatment of T2DM in children and adolescents. Not only are these findings of immediate benefit to the clinician and patient but they will also be useful in guiding future research in this area.

Abstract Background: Shifts in the gastrointestinal microbiome have been shown to contribute to the progression of metabolic diseases including prediabetes and type 2 diabetes mellitus. Research suggests that in vivo modulation of the gut microbiome by specific probiotic microorganisms may improve insulin sensitivity and blood sugar management, preventing or delaying the development of type 2 diabetes mellitus. However, further research is needed to understand the effect of probiotics as a therapy for the treatment of metabolic diseases. The overall aim of this thesis was to develop and assess the efficacy of an evidence-based multi-strain probiotic in vitro and in vivo. This probiotic was developed to encourage a shift in the gastrointestinal microbial cohort from a disease-prone to a balanced state with the aim of improving metabolic markers associated with type 2 diabetes mellitus. Methods: Three studies were conducted to assess this aim. Study 1 (Chapter 2) is a systematic review of randomised clinical trials to identify the probiotics with the greatest anti-obesity and anti-diabetic effects and consequently develop a multi-strain probiotic. Study 2 (Chapter 3) describes a series of in vitro experiments that investigate the effect of metabolites in the supernatant from the multi-strain probiotic on glucose uptake and lipid accumulation in muscle cells and adipocytes. Study 3 (Chapter 4) describes a double-blind, placebo-controlled pilot study aimed to assess the effect of the multi-strain probiotic on metabolic and inflammatory markers and the intestinal microbial profile of participants with obesity, prediabetes and recently diagnosed with type 2 diabetes mellitus. Results and discussion: Study 1 found that a multi-strain probiotic containing L. bulgaricus, L. gasseri, L. plantarum, B. breve, B. bifidum, B. lactis, S. thermophilus and Saccharomyces boulardii might have anti-obesity, anti-diabetic and anti-inflammatory effects. Study 2 found the supernatant from this probiotic decreased lipid accumulation in adipocytes and partially restored glucose uptake in insulin resistant skeletal muscle cells. Study 3 found the multi-strain probiotic did not decrease blood glucose levels, however it did improve insulin sensitivity, gut permeability and the production of gut microbial-derived metabolites in participants recently diagnosed with type 2 diabetes mellitus and produced a beneficial shift in the intestinal microbial profile of those taking metformin. Conclusion: Intentional manipulation of beneficial microbes and microbial-derived metabolites in the intestine using an evidence-based multi-strain probiotic may be useful in managing insulin resistance.

Despite a vast amount of epidemiological data documenting the ‘epidemic’ of type 2 diabetes and extensive randomised controlled trials evidence of effective interventions, there is a contrast between this wealth of quantitative research and the relatively underdeveloped qualitative understanding of how type 2 diabetes impacts upon patients and health care professionals. We therefore seem no closer to understanding how to effectively tackle the massive burden this represents for both patients and the health service. The publications discussed here represent a body of work consisting of five first author publications (2005-2012) that explore interventions and patient and health professional perspectives regarding the prevention of and care management for type 2 diabetes. Two main methods are used in the studies represented by the papers. These are primary qualitative research (three publications) and evidence synthesis (two publications) for public health guidance. The qualitative methods used in two primary studies and one evidence synthesis allow the perspectives of service users and professionals to be assessed in relation to public health interventions and health care. The remaining evidence synthesis examines how large scale diabetes prevention interventions can be tailored for use in the community. A major theme that links the publications is transferability of care management and prevention ideals to life in the real world. The Chronic Care Model (CCM) provides an optimum framework for such adaptations. However, whilst NHS policies and the CCM focus on patient engagement, it is clear that much needs to be done in recognising and addressing the feasibility of prevention and care strategies in practice. The thesis discusses how disparities between idealism and the ‘life world’ of patients might be addressed, adding to current debates about shared understanding and the importance of taking into account behavioural influences that might undermine or enhance the achievement of shared goals.

AN ABSTRACT OF THE THESIS OF Sarah Sheffer, for the Master of Science degree in Food and Nutrition, presented on September 3, 2009, at Southern Illinois University Carbondale. TITLE: "R. U. A. HEALTHY KID?"- NON-INVASIVE SCREENING FOR RISK FACTORS FOR TYPE 2 DIABETES AT VIENNA GRADE SCHOOL MAJOR PROFESSOR: Dr. Sharon Peterson It is estimated that 1 in 3 children born after the year 2000 will develop some form of diabetes (CDC, 2007). Through Public Act 92-0703, the state of Illinois has started requiring screening for T2DM at the 6th and 9th grade school physicals following the ADA guidelines (IDHS, 2006). The ADA recommends screening children ten and older with a BMI ≥ 85th percentile for two additional risk factors for T2DM (ethnic minority, positive family history of T2DM, hypertension, acanthosis nigricans) (ADA, 2000). While much research has been done, few studies in the U.S. have looked at traditionally "low risk" populations (Sinha 2002, Whitaker 2004, Arslanian 2005). Our study sought to further understand the prevalence of risk factors in a predominantly Caucasian elementary school (K-8 grade). Our study (N=299) found approximately 67% of students to have 1 or more risk factors for T2DM and classified 17 students "at risk" for T2DM. Following Illinois Public Act 92-0703, only 1 student would have been identified "at risk" for T2DM. When comparing "at risk" status, all risk factors except ethnicity were found statistically significant (p< 0.001). Hypertensive "at risk" students were more likely to be morbidly obese (p< 0.001). Our study also found more risk factors as BMI increased.