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Type 2 diabetes mellitus (T2DM) is characterised by the hormonal imbalance of insulin and glucagon, leading to dysfunctional glucose homeostasis. Glucagon-like peptide 1 (GLP-1), which is an incretin hormone, activates the predominantly Gαs-coupled glucagon-like peptide 1 receptor (GLP-1R), which is a class B G protein-coupled receptor (GPCR), to mediate glucose homeostasis. It does so by promoting glucose stimulated insulin secretion (GSIS) in the pancreatic β cells and inhibiting glucagon secretion in the pancreatic α cells. Given its proven clinical efficacy in reducing long term blood glucose level, GLP-1-based treatments, such as exenatide and liraglutide, have been widely used in T2DM patients. However, in contrast to the well-studied phenomenon of how GLP-1 enhances GSIS, the mechanism of how GLP-1 regulates glucagon secretion is still unclear. Therefore, the aim of this work is to shed new lights on how GLP-1 mediates its glucagonostatic action. To do so, the signalling properties of GLP-1 and its closely-related peptide hormones, namely oxyntomodulin (OXM), glucagon (GCG), glucose-dependent insulinotropic polypeptide (GIP), and its metabolite, GLP-1(9-36)NH2, were examined in recombinant cell lines and rodent clonal α and β cell lines using cAMP functional assaying technique. It was demonstrated that these glucagon-like peptides, including GLP-1(9-36)NH2 yet except GIP, can activate both GLP-1R and glucagon receptor (GCGR), which is struc- turally analogous to GLP-1R. Furthermore, GLP-1R, despite its very low expression in the mouse αTC1.6 cell line detected through semi-quantitative RT-PCR studies, is found to play a critical role in directly inhibiting glucagon secretion upon GLP-1 activation through performing glucagon secretion antagonism studies. More importantly, the physiologically abundant GLP-1 metabolite is discovered to play a glucagonostatic role in the mouse glucagonoma cell line via the direct actions of GLP-1R and GCGR, an observation that has not yet been documented. Therefore, this thesis provides evidence of how GLP-1 and its metabolite are actively involved in their glucagonostatic actions via direct activations of GLP-1R and GCGR. Another aim of this work is to identify viable pharmacological regulator of GLP-1- mediated glucose homeostasis through the action of positive allosteric modulator (PAM). Here, compound 249, which was identified previously as a small molecule GLP-1R PAM, was further pharmacologically validated using various signal transduction assaying techniques in recombinant cell lines. It was also demonstrated that compound 249 works independent of the cysteine-347 residue on the GLP-1R, an amino acid residue which has been previously shown to be instrumental for the actions of another GLP-1R agonist-PAMs. More importantly, compound 249 demonstrates robust potentiation of GLP-1 and OXM-augmented GSIS in the rat INS-1 832/3 insulinoma cell line and ex vivo isolated mouse islets, substantiating the potential of compound 249 to be further developed as a novel T2DM treatment. Overall this thesis presents new evidence on the direct involvement of GLP-1R on GLP-1-regulated glucagon secretion in the pancreatic α cells and illustrates compound 249 as a PAM to promote GLP-1 mediated GSIS. The findings in this thesis will be used for future design of safer and more efficacious T2DM treatments.

The diminished incretin effect is a pathological characteristic of type 2 diabetes mellitus (T2DM), caused by reduced secretion of glucagon-like-peptide-1 (GLP-1) and blunted biological actions of glucose-dependent insulinotropic polypeptide (GIP). Presently, clinically approved GLP-1 analogues, targeting the GLP-1 arm of the incretin axis, help to overcome the diminished GLP-1 secretion. However, currently there is no clinically approved therapeutic agent to potentiate the biological actions of GIP. Furthermore, established pharmacological agents currently fail to replicate the benefits of bariatric surgery, which along with increasing prevalence increases both health and socio-economic burdens. Likewise, due to the multifactorial characteristics, current monotherapies fail to elicit persistent effective management. Therefore, novel, more-effective treatment paradigms are required to address these unmet needs. The gut hormone xenin has been reported to potentiate biological actions of GIP, with truncated analogues of xenin displaying more potent antidiabetic effects. This thesis characterised the GIP-potentiating effects of xenin-based therapies, along with their therapeutic applicability for diabetes and/or obesity. This included xenin-8-Gln, as part of a hybrid agent- (DAla2)GIP/xenin-8-Gln, multiple novel xenin hexapeptides, as well as TNP-470, an angiogenesis inhibitor shown to increase xenin concentrations. Importantly, in all therapies assessed, there was clear augmentation of GIP action, resulting in enhanced metabolic effects. (DAla2)GIP/xenin-8-Gln administered in combination with exendin-4 demonstrated metabolic benefits that were persistent in nature, which is highly favourable in such a progressive disease. Further characterisation of truncated xenin peptides showed that ψ-xenin-6 was the most potent truncated hexapeptide assessed, with GIP-potentiating and satiety effects shown, along with biological effects evident up to 8 hours. Furthermore, repeated administration of ψ-xenin-6 in combination with sitagliptin further augmented the efficacy of sitagliptin, with effects more prominent and rapid with combined modulation. Additionally, beneficial efficacy of sitagliptin was augmented through combined administration with TNP-470, displaying improvements in glucose tolerance, insulin sensitivity and significant anti-obesity effects. Together, these findings provide reinforcing evidence for development of novel xenin-based therapies, which act to potentiate biological actions of GIP, and the need for combinational therapeutic approaches to target multiple pathways to help alleviate hyperglycaemia in T2DM, with potential for translation to the clinic.

Background: Decisions regarding the management of Type 2 Diabetes mellitus (T2DM) are complex as the management of this chronic illness requires a multifaceted approach. Shared decision-making is a patient-centred care approach in which the patients and their healthcare professionals (HCPs) collaboratively make a health decision, not only using the best available evidence, but also reflecting patients' needs, preferences and values. While there is growing evidence of the effectiveness of shared decision-making in supporting T2DM patients' involvement in the decisions across the world, potentially contributing to the improvement of their overall well-being, little is actually known about patient involvement in the decisions and particularly about shared decision-making in the Malaysian context. Aims: This study explores the experiences and perspectives of patients and HCPs on patient involvement in decision-making in the management of T2DM in Malaysia. Methods: A qualitative research design is employed in this study. Data were collected in the outpatient setting of three health facilities in the urban area of Malaysia. Face-to-face in-depth interviews were conducted, over a period of six months, with 19 HCPs (including three specialists, five medical officers, five diabetes educators/nurses, four dietitians/nutritionist and two pharmacists) and 24 T2DM patients. Thematic analysis and constant comparative method were used to analyse the data. Findings: The data highlighted a range of interpretations of shared decision-making. While patients described shared decision-making as a way for their concerns, preferences and values to be heard and addressed by their HCPs, the HCPs emphasised their patients' agreement and compliance with their recommendations. The types of decisions made, despite professed patient involvement would seem to remain largely in the hands of the HCPs. The extent to which patients are generally involved is subtle, whereby the decision is not necessarily shared and the decision-making for T2DM extends outside the face-to-face clinical encounter. This study also highlights that patient involvement in their decision is mainly influenced by patients and HCPs characteristics, values, beliefs, culture and past experience; their interpersonal relationship and communication; and role expectations in the healthcare field. Using Bourdieu's work to shape analysis showed that these factors intersect with each other and create a multifaceted patient-HCP power dynamic in making the decision. By including different groups of HCPs, this study also has provided valuable insight into the struggle among the non-physicians, who perceived to have limited decision-making power in managing patients with T2DM despite being the HCPs who were found to be more encouraging of patient involvement in the decisions. This is an addition to the struggles that are generally faced by all groups of HCPs, including their dilemma to balance their ethical foundation of beneficence and respecting patients' autonomy; their limited opportunity for involving patients due to constraints on the resources available at their facilities; and the language barrier. Conclusion: In conclusion, this study highlights the benefit of integrating the shared decision-making approach with some additional emphases on facilitating patient involvement in the decisions. These emphases include (1) inclusion of problem identification as one of the element of shared decision-making; (2) reducing the power gap and struggle by explicitly addressing the power issue and improving patients' cultural health capital; (3) strengthening of patient-HCP interpersonal relationship and communication skills; (4) allowing experimentation of different options that suit patients' condition; (5) integration of other approaches including motivational interviewing, support for self-management and interprofessional collaboration.

The rising epidemic of diabetes mellitus is likely to result in increased morbidity and mortality in the future. The chronic hyperglycaemia leading to diabetic microvascular and macrovascular sequelae affects multiple organs and an understanding of the mechanisms involved will help find solutions for many diabetic complications. Endothelial dysfunction is an independent predictor of cardiovascular disease, particularly in patients with type 2 diabetes. Testosterone deficiency is being increasingly recognized as an association of type 2 diabetes mellitus, in particular. Several studies have investigated the effects of testosterone replacement on metabolic dysfunction in hypogonadic men with type 2 diabetes, but there have been no studies specifically looking at endothelial dysfunction and the microcirculation in patients with diabetes and hypogonadism. This preliminary study aimed to investigate the effects of TRT (intramuscular testosterone undecanoate-Nebido, 1gm/ 4ml every 3 months for 12 months) on endothelial dysfunction in 24 men, aged 40 to 80 years, mean age 61.2 ± 8 years, with type 2 diabetes and hypogonadism. At week 30, significant improvements were noted from baseline following TRT, namely in endothelial vasodilatation, which was significant for SNP-mediated vasodilation [baseline: 47.14 ± 25.7 % vs week 30: 75.8 ± 40%, p < 0.003] and waist circumference [baseline: 117.3 ± 14 cm vs. week 30: 112 ± 13 cm, p < 0.03], but not in any of the metabolic parameters. Further large, well-controlled, long-term studies are warranted to investigate the potential favourable effects of TRT on the microcirculation and biochemical components of MetS in T2DM. Patients with type 2 DM are known to have impaired bone turnover despite having normal or high BMD and are at an increased risk of developing diabetic foot disorders, such as foot ulcers and deformities (Charcot neuroarthropathy), probably related to the microvascular disturbances. In an observational-comparative study, we investigated bone metabolism and microvascular function in T2DM patients (n=21) and controls (n=10). SNP-mediated vasodilation but not Ach-mediated vasodilation was more pronounced in controls than T2DM patients [SNP %change: 47.72% (14.13 to 106.6) vs. 32.9% (-1.64 to 61.4), p=0.12]. Serum osteopontin, a bone marker that is suggested to be a predictor of diabetic neuropathy, was higher in T2DM patients than controls [Controls: 2.8 (0.8 to 7.5) vs T2DM: 5 (0.05 to 16.3) ng/ml, (p = 0.345)]. Various vascular growth factors and bone proteins are commonly expressed in both diabetic osteopathy and microvascular disease, which highlights the molecular crosstalk between bone and vasculature. CN is a rare but life-threatening medical challenge that is usually associated with a poor prognosis that may be attributed to CN-related sequelae such as foot deformities, ulceration and amputation. A retrospective clinical audit, involving 70 patients with T1DM or T2DM and CN, was performed to assess current practice in the management of CN against pre-defined standards to find means to improve care in these patients and examine the level of adherence with national guidance. This audit reported certain deficiencies in documentation of critical findings (temperature difference, site of CN, details of offloading) that could impact on the management and natural course of CN.

Objectives: To explore how adjustment to type 2 diabetes mellitus (T2DM) can be understood using psychological (in)flexibility, the theoretical model underlying acceptance and commitment therapy (ACT). The specific research questions are: (a) what are participant experiences of adjustment and coping in T2DM? and (b) how can participant experiences be understood in terms of the processes underlying the model of psychological (in)flexibility? Design: This interview study utilised a cross-case qualitative methodology. Methods: Semi-structured interviews were conducted with 11 purposively recruited individuals with a diagnosis of T2DM. Interview transcripts were subjected to an interpretative phenomenological analysis (IPA) methodology. Results: Three primary themes were identified from the IPA: (a) ‘Eating myself into diabetes’: Managing the self in relation to perceived diabetes stigma; (b) My other illness is the real problem: diabetes minimised in the context of co-morbid diagnoses; and (c) Knowledge reduces attachment to the patient-role self-story. Conclusion The interpretation of the qualitative data generated suggests that adjustment to a diagnosis of T2DM is a complex process incorporating intra-individual and systemic factors. Whilst psychological flexibility may be a useful model for understanding and supporting adjustment, interventions are required that also address wider systemic issues such as the integration of care, health-related stigma and relationships with health professionals.

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

The IL-6 system is key in the development of chronic low-grade inflammation. It is known to be upregulated in response to acute exercise and lowered at rest after exercise training. IL-6 has both anti- and pro-inflammatory properties and moderation of this cytokine could alleviate chronic low-grade inflammation which is associated with obesity and Type 2 diabetes mellitus (T2DM). This thesis investigated the interplay between inflammation, glycaemic control and high intensity intermittent training (HIIT) - an exercise regimen that has been shown to yield many health benefits. There was a greater increase in IL-6 after an acute bout of HIIT than continuous moderate intensity exercise, where external work was matched (Chapter 4). Although sIL-6R and the IL-6/sIL-6R complex were both significantly increased after acute exercise there were no differences between HIIT and moderate intensity exercise. In response to 2 weeks HIIT there was a significant reduction in IL-6 and increase in IL-6R in adipose tissue in overweight and obese males (Chapter 5). It was also determined that IL-6R present in adipose tissue is at least partly composed of the membrane-bound IL-6R isoform (Chapter 6). Reductions in circulating sIL-6R, the IL-6/sIL-6R complex, MCP-1 and adiponectin, as well as a decrease in waist circumference and increase in peak oxygen uptake during exercise were also induced after 2 weeks HIIT (Chapter 5). Young adults with T2DM (< 40 y) displayed elevated levels of inflammatory proteins in comparison to lean controls, however there were no significant differences in comparison to obese controls (Chapter 7). In conclusion, the findings of this thesis demonstrate that acute and repeated bouts of HIIT have positive effects on the inflammatory profile in the circulation and adipose tissue, particularly in relation to the IL-6 system. It should be determined if HIIT is an achievable mode of exercise for patient populations, including T2DM patients, in order to downregulate the inflammatory profile.

Coronary artery disease (CAD), Hypertension (Ht) and Type 2 Diabetes Mellitus (T2DM) are all global health problems. This is particularly evident amongst South Asian population groups. The conventional risk factors do not fully explain the higher prevalence of these diseases among South Asians. The endothelial Nitric Oxide Synthase (eNOS) gene is responsible for the production of Nitric Oxide (NO), which may contribute to the physiology of all three disease states. Endothelial dysfunction (which is characterised by a reduction in basal NO) has been shown to be present in, or prior to all three diseases. Numerous variations exist within the eNOS gene, of these variations three have been shown to have a possible functional effect. The first is the Glu298Asp polymorphism within the exon region of the gene, resulting in an amino acid substitution of Glutamate (Glu) to Aspartate (Asp). The second, known as the T-786C polymorphism, is a thymine to cytosine mutation at position -786 in the promoter region. Finally a VNTR polymorphism in Intron 4 causes either a 4 27bp repeat or a 5 27bp repeat. It is hypothesised that these variations could have an effect on the ability of eNOS to produce NO and thus may increase the risk or contribute to the development of the diseases. Previous studies on these variants have shown conflicting results and further studies are warranted to understand and confirm the role of eNOS gene polymorphisms in cardio-metabolic diseases. There is very limited research into the distributions of these genetic variants and their interaction in diseases processes in North Indian populations. Objectives: 1. To analyse through a case control study three different polymorphisms of the eNOS gene for possible association with Coronary Artery Disease (CAD), Hypertension (Ht) and Type 2 Diabetes Mellitus (T2DM) in North Indian population groups. 2. To statistically evaluate descriptive statistics including; age, gender, smoking, dietary behaviours and lipid parameters for possible influence on disease and potential interaction with genetic polymorphisms. 3. To evaluate linkage disequilibrium between the three eNOS variants and carryout haplotype analysis to work out haplotype risk in different diseases. 4. To analyse through a case control study the deletion variant of the Angiotensin-converting enzyme (ACE) gene for possible association with Coronary Artery Disease (CAD), Hypertension (Ht) and Type 2 Diabetes Mellitus (T2DM) in North Indian population groups. 5. To determine a possible interactive effect of the eNOS polymorphisms with the ACE polymorphism. Subjects and Methods: The Glu298Asp and Intron 4 variants were genotyped using a PCR-RFLP technique, the T-786C variant was genotyped using a real time-PCR technique. The ACE deletion variant was also genotyped using a standard PCR technique. The genotyping was undertaken in a total of 457 CAD patients and 220 matched controls from Lucknow, Uttar Pradesh in North India, 319 T2DM patients and 307 matched controls from Punjab, North India and 210 Ht and 162 matched controls, also from Punjab, North India. Results: CAD: The Glu298Asp was significantly associated with CAD among smokers (TT+GT vs. GG OR=2.84 (CI: 1.61-5.0), p<0.001). The Intron 4 variant was also significantly associated with CAD in a smoking dependent manner (4aa+4ab vs. 4bb OR=0.56 (CI: 0.33-0.96). The T-786C variant showed no overall influence on CAD risk. There was also evidence for both synergistic and haplotypic effects of the eNOS gene on CAD status (haplotype G-C-4b OR=4.76 (CI: 1.43-15.78), p<0.001). The ACE genetic variant was confirmed to be a strong independent risk factor for CAD under a dominant model (OR=2.18 (CI: 1.46-3.25), p<0.001). There was no evidence for an interactive effect between the ACE deletion and any of the three eNOS variants incorporated in the current study. Ht: The Glu298Asp variant was not shown to increase Ht risk, with a reduced risk association found under a recessive model (OR=0.316 (CI:0.089-1.116)), p=0.061). The T-786C variant s role in disease remained unclear with the findings showing a non significant increased risk. The Intron 4 variant was also shown to increase Ht risk, in a non significant manner. Sufficiently powered studies would be required to clarify these possible associations. The combined analysis, using logistic regression and haplotype analysis revealed no significant associations, but there was a possible protective effect of the T-C-4b haplotype (OR=0.46 (CI: 0.21-1.01), p=0.054). The ACE gene variant was confirmed to be a strong independent risk factor for Ht under a recessive model (OR=1.81 (CI: 1.20-2.74), p=0.01). Again there was no evidence for an interactive effect between the ACE deletion and any of the three eNOS variants in hypertension. T2DM: The Glu298Asp variant was found to be associated with T2DM under a dominant model, the protective effect remained significant following adjustment for conventional risk factors and other gene variants (OR=0.407 (CI: 0.231-0.717), p=0.002). The T-786C variant showed no overall influence on T2DM risk. The Intron 4 variant also found no overall influence. Haplotype analysis found the T-T-4b was found to be significantly protective for T2DM (OR=0.41 (CI: 0.26-0.65), p=0.0002). Finally the ACE gene variant was confirmed to be a risk factor for T2DM under a dominant model (OR=2.62 (CI: 1.51-4.54), p=0.001). Overall Conclusions: To conclude, this study successfully identified the frequency of three eNOS gene variants and the ACE deletion variant in three complex diseases within north Indian populations. There is a clear role of the eNOS gene in all three diseases and consequently the genetic variants have susceptible/protective associations. The association with disease was found to be present at an individual level, in association with risk factors and at a haplotypic level. These findings warrant further studies to confirm and untangle the genetics of complex diseases and genetic risk profiles calculations which will contribute to the field of medical genomics/personalised medicare and interventions among North Indian populations.

Background: Type 2 diabetes mellitus (T2DM) is a rising global health concern that requires long-term treatment and close monitoring. As a behaviour-directed intervention, telemonitoring has shown promising results in facilitating patient-physician interaction and improving treatment adherence among patients with chronic disease. However, there is lack of evidence about its use in T2DM. This thesis aims to address this gap by analysing the impact of treatment adherence, which is a key self-care behaviour in patients with a chronic illness, on glycaemic control and the overall effectiveness of telemonitoring in T2DM management. [...]

Background: Type 2 diabetes mellitus (T2DM) is the most common type of diabetes mellitus (DM) and its prevalence in China has increased rapidly. Poor control of DM leads to a series of complications, which seriously impair patients' quality of life. Importantly, the proportion of T2DM patients who meet the diagnostic criteria for metabolic syndrome (MS) is very high. The coexistence of the two diseases increases DM complications and the incidence of cardiovascular and cerebrovascular diseases. Individuals that have T2DM and MS experience a higher incidence of depression and anxiety symptoms than the general population. These negative emotions create obstacles in effectively managing blood glucose levels. In addition, T2DM and MS patients commonly display suboptimal self-care behaviors, which can be attributed to negative emotions, insufficient knowledge about diabetes, or cognitive biases linked to the disease. Cognitive behavioral therapy (CBT) aims to change the non-adaptive cognitions and behaviors of patients by developing therapeutic alliances, psychological education, cognitive reconstruction, and behavioral activation. Previous studies have applied it to the prevention and treatment of DM and MS and found positive effects. However, there have been few studies on the coexistence of two or more conditions. To address this gap, this study aimed to conduct a randomized controlled trial (RCT) to explore the effectiveness of CBT on the improvement of health outcomes in T2DM patients who have comorbid MS. This study represents the pioneering effort to explore the effectiveness of CBT in diabetes patients with coexisting MS. Additionally, the innovative integration of both face-to-face and remote intervention methods adds a novel dimension to this research. Furthermore, the study encompasses a diverse array of health outcome, including physiological indicators, psychological indicators, behavioral indicators, quality of life, and sleep quality. Aims: This study had three primary objectives: (1) to evaluate the effectiveness of CBT in improving health outcomes for patients who have diabetes, hypertension, and coronary heart disease (CHD) using existing published studies, (2) to use baseline data to identify the variables that may be related to emotions, behaviors, and cognition in patients who have T2DM and comorbid MS to design targeted CBT intervention programs for the cohort of patients who have T2DM and comorbid MS, and (3) to investigate the impact of the CBT intervention program designed for this study on physiological, psychological, and behavioral indicators as well as its influence on sleep quality and the overall quality of life of patients who have T2DM and comorbid MS.

Gestational diabetes mellitus, among the most frequent complications occurring during pregnancy, affects approximately 8% 10% of pregnant women. These women are at a much higher risk of developing type 2 diabetes mellitus later in life. Concerningly, during the transition from obstetrical care to primary care, women with gestational diabetes often miss the required follow-up testing, preventive care, and education on lifestyle changes that could prevent or delay the development of type 2 diabetes mellitus. This integrative review analyzed current evidence on detecting and preventing type 2 diabetes mellitus in women with a history of gestational diabetes. Four essential themes appeared in the literature that highlighted the fact that women with a history of gestational diabetes have a 60% higher risk of developing type 2 diabetes in their lifetime. There is good evidence to support that to minimize the risk and possibly delay the development of this disease, screening is essential, and lifestyle modifications, medications, and breastfeeding can all be helpful for these patients. Women need to be educated on the importance of follow-up after a diagnosis of gestational diabetes, and they need to be encouraged to become partners with a primary care provider to ensure that the proper testing and care is received. It is also crucial that primary care providers integrate the evidence and guidelines for postpartum gestational diabetes care into their practice.

Type 2 diabetes mellitus (T2DM) disproportionality affects under-represented groups, specifically Asian Americans. Asian Americans are less likely to receive proper diabetes mellitus screening compared to other racial and ethnic groups, potentially due to improper screening guidelines by clinicians, and Asian Americans being unaware of their increased risk for diabetes mellitus. There are differences in the etiology of T2DM in Asian Americans compared to White Americans. Due to the increasing rates of T2DM among Asian Americans, new approaches in the screening of T2DM should be tailored based on race and ethnicity. The aging process is frequently associated with decreased muscle mass and increased adipose tissue, which can contribute to insulin resistance and lead to elevated hemoglobin A1c (HbA1c) percentages. Although sex has not been classified as an independent risk factor for T2DM, it is important to consider sex-specific conditions in the context of the disease. Body mass index (BMI) alone is insufficient to properly evaluate adiposity in Asian-American adults due to Asian Americans having a lower BMI with a higher body fat percentage. Waist circumference, waist-to-height ratio (WHtR), and visceral adiposity index (VAI) may be better for screening Asian Americans for T2DM. Multiple modifiable risk factors, such as sedentary behavior, and dietary intake (specifically dietary magnesium intake) can increase the risk for T2DM. Lack of physical activity can result in insulin resistance and impaired glucose metabolism as a result of muscle disuse and decreased lean body mass. Half of the Asian-American population is not consuming the recommended amounts of magnesium from foods, drinks, and dietary supplements. There is an inverse relationship between increased dietary magnesium intake and the risk of T2DM. In addition, the main language spoken in the household may influence lifestyle and risk of T2DM. The overarching goal of the present study was to establish which independent variables (age, sex, BMI, waist circumference, WHtR, VAI, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language) were the strongest predictors of HbA1c percentage (a measure of blood glucose control) in Asian-American adults using the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2020. The present study also evaluated the relationship among multiple predictors of HbA1c percentage, including age, sex, body composition, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language among Asian-American adults, 18 years of age and older, using the NHANES data from 2011 to 2020.

Diabetes mellitus type 2 (T2DM) is a growing epidemic that affects millions of people throughout the world. The recent COVID-19 pandemic has created many new challenges, including access to health care for treatment of chronic diseases, such as diabetes (Robson & Hosseinzadeh, 2021). Telehealth has offered a promising approach to improve the management of diabetes(Bellman, 2021). People with diabetes are less likely to manage their diabetes through the usual care because of risk of contracting COVID-19 (CDC, 2022). The purpose of this EBP project was to evaluate the effectiveness of T2DM management through a telehealth approach. This project has addressed the following PICOT question: In patients with diabetes mellitus type 2 who have difficulty with medical visit compliance (P), will the telehealth platform (I), compared to patient's previous face-to-face visit HgbA1c (C) improve future HgbA1c diagnostic marker readings (O) over a 12-week period(T)? This EBP project took place in a private practice located in the suburbs of Chicago. Twenty-one patients participated in this quality improvement project with an average age of age of the patients was 53 years of age (SD-11.6). Two-thirds of the participants were self-identified as female (67%, n=14) and one-third were self-identified as being male (33%, n=7). The mean pre-intervention HbA1c 7.9% (SD=1.04%). The median HBA1c was 7.5% (IQR=1.4%). The minimum HbA1c was 6.7% and the maximum pre-intervention HbA1c was 10. The average post-intervention HbA1c was 7.0% (SD=.79%). The median post-intervention HBA1c was 6.9% (IQR=1.3%). A paired t-test was utilized and showed that there was statistical significance in the outcome. The statistical findings indicated that the post-intervention HbA1c was less then pre-intervention HbA1c (p

Diabetes self-management education and support (DSMES) programs have been shown to improve patient outcomes and lower hemoglobin A1c (Hgb A1c) levels in those who are diagnosed with type two diabetes mellitus (T2DM). However, these programs are often underutilized and have low referral rates, despite the known benefits (Powers et al., 2020). The purpose of this patient-centered EBP project was to evaluate the effectiveness of a patient-driven questionnaire, completed by patients with T2DM during routine office visits, in increasing the percentage of patients referred to DSMES by their provider. Specifically, this project addressed the following PICOT question: In adults who have T2DM (P), how does the implementation of a screening tool (I) compared to current practice (C) impact the number of patient referrals to the DSMES (O) over a 12-week period (T)? This EBP project took place at an internal medicine clinic in northern Indiana. There are two providers at this clinic and four medical assistants (MA). After eligibility was determined, the patient was given the screening tool for completion. Any “yes” or concerning answer triggered the provider to submit the DSMES referral. A total of 54 screening tools were administered and 22 patients were referred to the program. Data between groups were analyzed using odds ratio. It was found that patients seen during the time period in which the screening tool was used were 2.3 times as likely to be referred than those during the same period in the previous year (p =.039), 95% CI [1.07, 5.37]. These findings indicate that a patient-driven screening tool streamlines the referral process to the DMSES and assists in provider understanding of when the patient with T2DM requires referral.

Type 2 Diabetes Mellitus (T2DM) is a significant public health concern with high morbidity and mortality burden. Maladaptive food behaviors contribute to poor glycemic outcomes for persons with Type 2 Diabetes Mellitus (T2DM). Factors which may contribute to poor T2DM dietary behaviors include food addiction (FA; overconsumption to the point there are similar symptoms to substance use addiction) and impulsivity (lack of control in food consumption). FA and impulsivity behaviors can be reflected by differences in brain tissue integrity, but the relationships between FA, impulsivity, and brain tissue changes in persons with T2DM are unclear. To date, little is known about FA and impulsivity in association with A1c levels (indication of poor glycemic control) among T2DM patients. While studies indicate associations between brain injury and A1c levels in T2DM patients, it is also unclear if FA and brain injury can independently predict glycemic control in T2DM. An examination of the brain associated with these behaviors has not been assessed in persons with T2DM. The overarching purpose of this dissertation study is to offer valuable insights into the link between brain tissue integrity, food behaviors, and glycemic control in T2DM patients. Manuscript one compares the relationships between FA, impulsivity, and glycemic outcome (hemoglobin A1c) between 32 T2DM and 32 healthy patients between the ages 40-65 years. Participants completed the Yale Food Addiction Scale 2.0 (YFAS) and Barratt Impulsiveness Scale-11 (BIS) online questionnaires and A1c was measured with a fingerstick test. Between T2DM and healthy patients, there were no group differences in the prevalence of FA diagnosis, YFAS 2.0 scores, BIS-11 scores, or severity classification of FA diagnosis. There were positive correlations between two FA symptomatologies with higher A1c: food tolerance and food use in physically hazardous situations (r= 0.254, r= 0.417, P

In dit onderzoek hebben we de rol van thromboinflammatie onderzocht in verschillende hoog-risico populaties, zoals mensen met type 2 diabetes mellitus (T2DM) en patiënten met ernstige COVID-19, als ook naar verhoogd risico bij vrouwen in de Nederlandse samenleving. Thromboinflammatie is de verbinding tussen de gelijktijdige activatie van de stollingsroute en immuunrespons welke een belangrijke trigger vormt voor bloedvat schade, prominent in microvasculaire gezondheid. Als eerste laten we zien dat er genderspecifieke associaties zijn tussen het activatie potentieel van de stollingsroute en microvasculaire gezondheid met betrekking tot eventueel ontwikkelen van hartfalen. Het mechanisme van T2DM progressie varieert bij verschillende etniciteiten en we hebben aangetoond dat veranderingen in cholesterol functie (HDL) en lipiden profiel in het bloed een van de onderliggende mechanismen kunnen zijn die leiden tot versnelde ziekte progressie bij Zuid-Aziaten van Nederlandse afkomst met T2DM in vergelijk met Nederlandse blanke Europeanen met T2DM. Met nieuwe geavanceerde technieken vonden we ook dat bij patiënten met ernstige COVID-19 factoren in het bloed aanwezig zijn die schade aan de kleine bloedvaten en verhoogde stollingsactiviteit teweegbrengen. Ook bij deze patiënten zagen we dat veranderingen in HDL compositie een belangrijke rol in de ernst van de ziekte speelt. Samen geven de resultaten het belang aan van thromboinflammatie in verhoogd-risico populaties in versneld ontwikkelen van hartfalen, T2DM en COVID-19. Het onderzoek laat de noodzaak zien van vroege detectie in het proces, waarbij vroegtijdige interventies kunnen lijden tot preventie of het beter managen van het thromboinflammatoire ziekteproces.*************************************************************************In this study, we investigated the role of thromboinflammation in various high-risk populations, including individuals with type 2 diabetes mellitus (T2DM) and patients with severe COVID-19, as well as the increased risk in women in Dutch society. Thromboinflammation refers to the simultaneous activation of the clotting pathway and immune response, which is a significant trigger for vascular damage, particularly in microvascular health.Firstly, we demonstrated sex-specific associations between coagulation parameters and microvascular health. The mechanism of T2DM progression varies among different ethnicities, and we found that changes in cholesterol function (HDL) and lipid profiles in the blood could be underlying mechanisms leading to accelerated disease progression in South Asians of Dutch descent with T2DM compared to Dutch white Caucasian with T2DM.Using advanced techniques, we also identified factors in the blood of patients with severe COVID-19 that contribute to small blood vessel damage and increased clotting activity. We observed that changes in HDL composition played an important role in the severity of the disease in these patients.Overall, our results highlight the importance of thromboinflammation in high-risk populations in the accelerated development of heart failure, T2DM, and COVID-19. The research emphasizes the need for early detection in the process, where timely interventions can lead to prevention or better management of the thromboinflammatory disease process.

ABSTRACT Purpose: The purpose of this article is to provide an understanding of negative health effects of adverse childhood experiences (ACEs) on Type II Diabetes Mellitus and the role of primary healthcare providers in decreasing morbidity and mortality through screening and intervention. Method: A literature search was conducted through PubMed, EBSCO, ProQuest Education and PLOS ONE using keywords such as: adverse childhood experiences (ACEs), type 2 diabetes mellitus, primary care intervention. The most relevant articles were selected with additional selectivity based on the publication year as the basis for this piece. Results: Currently, minimal information exists on the role of primary care providers in screening ACEs and early intervention in relation to type 2 diabetes. Conclusion: Ultimately, more research needs to be conducted in assessing the benefits and risks of early intervention of children with ACEs to analyze the change in trajectory of type 2 diabetes mellitus in their adult life.

In 2018, 34.2 million Americans had diabetes and there continues to be 1.5 million Americans diagnosed with diabetes every year (ADA, 2018). Due to this increasing prevalence, self-management of type 2 diabetes mellitus (T2DM) is essential to disease management. The PICOT question for this project was: In adults with T2DM with a hemoglobin A1C (HbA1C) greater than 8% in a diabetes specialty clinic (P), what is the effect of a multimodal smartphone application (I) compared to prior nonuse of the application (C) on average blood glucose readings (O) over an 8-week period (T)? The project was completed in a large, metropolitan area located in southcentral Wisconsin. There was a total of 11 participants, comprised mostly of males with a range from 46-76 years of age. The Johns Hopkins Nursing Evidence-Based Practice (JHNEBP) Model was utilized to guide the development and implementation of this project. The project used a within-group design that evaluated the effect of a multimodal smartphone application on average blood glucose levels. Data were collected through patient-owned glucometers that were connected via Bluetooth to the mySugr© application. Pre-intervention and post-intervention blood glucose level data were analyzed using a paired sample t-test. Secondary outcomes included time in range (TIR), estimated HbA1C, and DES-SF scores. Statistically significant differences were found for average blood glucose levels (p = .008), TIR (p = .0025), estimated HbA1C (p = .00048), and DES-SF scores (p =.007). Findings from this project demonstrated that the use of a multimodal smartphone application can lower average blood glucose levels.

Type 2 diabetes mellitus and coronavirus disease 2019 independently are not only highly prevalent diseases with enormous impact on individual morbidity and mortality, but they pose a severe burden on the broader healthcare system as well. And when the patient suffers from both conditions, the deleterious health effects multiply manifold. For example, the systemic inflammation induced by both conditions can in combination lead to severe lung injury and endothelial damage, increased risk of cardiovascular events, immune dysfunction, and poorer glucose control; the resulting hyperglycemia can worsen the viral inflammation, and the systemic inflammation can in turn exacerbate the hyperglycemia. Fortunately for type 2 diabetes, biguanides like metformin are highly effective at lowering blood glucose levels, as shown through decades of preclinical, experimental, and observational studies. Given metformin’s well-known pleiotropic effects in protecting against aging, cancer, and cardiovascular and neurological diseases, the goal of this thesis is to assess the clinical epidemiological evidence surrounding the efficacy of metformin in mitigating COVID-19-related morbidity and mortality. The thesis then explores the specific physiological mechanisms through which metformin exerts its wide-ranging protective effects against thrombosis, cardiovascular events, pulmonary fibrosis and dysfunction as well as its anti-inflammatory and anti-viral effects. Finally, the thesis explores the drawbacks and risks of metformin, in particular investigating the impact of lactic acidosis (a well-known side effect of metformin treatment) in patients with COVID-19.

The purpose of this research is to assess the efficacy of employing telemedicine (TM) technology compared to traditional face-to-face (F2F) visits as an alternative healthcare delivery service for managing diabetes in populations residing in urban medically underserved areas (UMUPA). Researchers investigating public health and healthcare systems fully grasp the enormous challenges encountered by vulnerable populations as a result of healthcare access barriers.1 Prior to the COVID-19 pandemic, F2F visits were most often utilized for healthcare delivery service, which frequently posed barriers for vulnerable populations. When marginalized people, encounter healthcare access barriers, a cascade of events generally occur leading to forestalling or avoiding healthcare services entirely, complicating disease management, resulting in negative health outcomes. This was a novel study examining the hemoglobin A1c (HbA1c) values of 111 patients with uncontrolled type 2 diabetes mellitus (T2DM) and 81 patients with prediabetes. Retrospective electronic patient health records (PHR) from a medical clinic were examined from January 1st, 2019, to June 30th, 2021. The results indicate that lowering HbA1c values for T2DM patients through utilizing TM is similar to outcomes from traditional visits, suggesting that TM may be an alternative mode of healthcare delivery for vulnerable populations. Results for patients with prediabetes were not statistically significant. Patients with uncontrolled diabetes and prediabetes shared a number of similar characteristics; they were predominantly Black, non-Hispanic, females, with a median age of 57 years; and resided in locations with inadequate access to healthcare services in an UMUPA. The majority of patients with uncontrolled diabetes who reside in an UMUPA completed appointments utilized TM technology, lending credence to its potential as an alternative healthcare delivery service for underserved populations. TM technology supports PH and the healthcare system with a viable, alternative strategy for expanding healthcare access where chronic illness and disease pose a significant threat to the health and wellbeing of vulnerable groups. Optimal treatment for patients with diabetes necessitates a proactive, coordinated, systems-thinking team approach. This research supports PH’s endeavors in tackling the long-standing healthcare access barrier challenges in underserved populations.

Objectives: To standardize health education about low carbohydrate diets, portion size control, and nutritional label literacy in an outpatient setting to increase patient’s knowledge and facilitate behavior change as a means to better manage Type 2 Diabetes Mellitus. Background: Type 2 diabetes mellitus (T2DM) is a growing public health concern that affects nearly 29 million and now is the seventh leading cause of death in U.S. residents; 10% of U.S. residents were T2DM-affected in 2017, as many as 33% may be affected by 2025. Standardization of nutritional education for diabetes management can improve health outcomes and achieve glycemic control. Nutritional interventions focused on calorie reduction, and minimal carbohydrate intake are recognized to be the basis of treatment. Methods: Participants (n=14) received standardized evidence-based nutrition education intervention focused on a low carbohydrate diet, portion size control, and nutrition label literacy within a primary care setting. Participants had an eight-week follow up visit with the same provider to reinforce subject matter and collect data. The primary outcome of the intervention was HgbA1c, and secondary outcomes were knowledge retention, improved BMI, and improved TTM stage of change which were measured at the baseline and eight-week follow-up visit. Patient satisfaction were also measured at eight-week follow up. Results: Of the 14 participants, nine showed lower HgbA1c at the post-intervention visit, one showed no change, and four showed a higher measurement; with mean and median measures of 7.53% (SD 0.90) and 7.2%, respectively. Changes in knowledge score between the pre and post intervention visits were positive, meaning participants either scored the same or higher of up to six points increase on their post-intervention score. Specifically, the mean of the pre- and post-intervention knowledge scores were 5.7 (SD 1.48) and 7.3 (SD 2.02), respectively, and the difference in knowledge across individuals was 1.64 (SD=1.5). No statistical significance in pre and post intervention for BMI. Overall, positive feedback was received on the patient satisfaction survey. Conclusions and Implications: Implementing a standardized, low-cost approach to include nutritional education focusing on portion size control, nutrition label literacy, and low carbohydrate in primary care may help achieve glycemic control. Focusing on preventive care may sustain potential return of investment through limited expenditures on specialty care services.

Purpose: The purpose of this review is to explore whether plant-based (vegan) diets result in greater reductions in hemoglobin A1c (HbA1c) than high-fat carbohydrate-restricted (ketogenic) diets in adults with type 2 diabetes mellitus. Search Criteria: PubMed and Cochrane library databases were systematically searched for all relevant studies using MeSH terms (("diet, high fat" AND "diet, carbohydrate restricted") OR "diet, ketogenic" OR "diet, vegan") AND "diabetes mellitus, type 2/therapy". Limiting the research to meta-analyses and systematic reviews narrowed the results to six articles. One systematic review was excluded because it examined the effects of ketogenic diets on the quality of life of adults with chronic disease, not specifically glycemic control in patients with type 2 diabetes mellitus. Results: Eight randomized controlled trials reported a reduction of HbA1c between 0.3-1.4% after a vegan diet, but only two of the eight studies showed a statistically significant mean difference between the intervention and control groups. In a separate review, eight of thirteen studies showed a reduction of HbA1c ranging from 0.6-3.3% with a mean reduction of 1.07% following a ketogenic diet but offered no controls for comparison. A meta73 analysis of fourteen trials revealed that a ketogenic diet provided an average of 0.5% greater reduction in HbA1c compared to control (primarily low-fat) diets. The last two reviews agreed that vegan diets appear promising, but one included the benefits of ketogenic diets while the other found the studies on ketogenic diets inconclusive. Conclusion: While the results of some of the selected studies appear promising, the consensus among the systematic review and meta-analyses is that further research is needed to determine which eating patterns are most effective for improving glycemic control in type 2 diabetes.

Purpose In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. Methods This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. Results 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I-2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). Conclusion Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.

Abstract: Diabetes mellitus is one of the most common non-communicable diseases around the globe, with serious debilitating and life-threatening consequences. It is not just a mere disease, but a complex syndrome made up of several diseases with similar symptoms, signs, and complications when it is not adequately controlled. We aimed to investigate the relative validity of the dietary component of the Summary of Diabetes Self-Care Activities (SDSCA) measure against 3-day food records in individuals with type 2 diabetes mellitus and the relationship between dietary self-care behaviours and health care utilization in adults with type 2 diabetes after a decade of follow-up. Our results suggest that the self-reported dietary component of SDSCA measure was not strongly associated with 3-day food records. We also demonstrated that healthier diet patterns are associated with a protective effect on hospitalization in a population of people living with diabetes in our longitudinal study design, albeit primarily amongst females in the study cohort. Efforts to promote healthy diet should emphasize the clinical benefits. As the prevalence of diabetes continues to rise worldwide, promotion of better eating habit and self-care behaviors for managing type 2 diabetes is increasingly important in order to reduce the burden on the health care system.

Background: Type 2 diabetes mellitus (T2DM) is a significant health problem that imposes a large global economic and social burden on individuals, families and healthcare systems. It is the main cause of kidney insufficiency, blindness and non-traumatic amputations. T2DM is also a major risk factor for cardiovascular disease, which is the leading cause of mortality in people with T2DM. As T2DM is a metabolic disease, there is a large body of research around diet and diabetes. Human intervention studies have evaluated dietary components and dietary patterns for managing blood glucose levels in people with T2DM who have lost the ability to manage levels homeostatically. Through this body of work, there is clear evidence that sustained periods of high diet quality have positive effects on glycaemic control. However, surprisingly little is known about the diet quality of people with T2DM who are not participating in intervention studies, which is majority of the population with T2DM. Evaluating the usual dietary intake of certain groups is an important research activity that can help influence public health initiatives, inform dietary education materials and contribute to the development of targeted nutritional interventions. Improved, tailored care may lead to higher diet quality in people with T2DM, consequently reducing diabetes-related complications and healthcare costs. To enhance understandings of the natural course in adults’ diet quality with T2DM, the aims of this PhD were to: (i) synthesise evidence regarding the dietary intake of people diagnosed with T2DM; (ii) investigate how diet quality changes after diagnosis in people newly diagnosed with T2DM and (iii) identify the factors (demographic, physical and psychosocial) associated with changes in diet quality in people newly diagnosed with T2DM. These aims were addressed in three phases of research. Phase 1: A systematic literature review was conducted to investigate the dietary intake (by food group) in people with T2DM and compare these intakes to national and international dietary guidelines. Eleven studies met the inclusion criteria and were included in the final review. Findings (published in Diabetes Research and Clinical Practice, 2018) indicated that majority of people with T2DM were consuming less than the recommended serves of fruit, vegetables, grains and dairy and were meeting or exceeding the recommended serves for meat/meat alternatives. However, included studies only reported cross-sectional data and did not control for length of time with diabetes among participants. While cross-sectional analyses provide a snapshot of diet quality, there was no quantitative data on how people with T2DM change their diet quality over time, particularly from the point of diagnosis. This meant it was difficult to determine whether diet quality remains fixed once an individual is diagnosed or whether there are periods of marked dietary change. These findings went on to inform Phase 2 of this thesis. Phase 2: The systematic review findings informed the protocol for an observational, case-series study titled, “How does Diet change with a Diagnosis of Diabetes – The 3D study” (published in Nutrients, 2019). The 3D study was conducted in Australia between 2018-2020 and recruited 225 people newly diagnosed with T2DM (in the 6-months prior to recruitment) and monitored their dietary intake and demographic, health and psychosocial characteristics over 12-months. Diet quality was assessed using the Dietary Approaches to Stop Hypertension (DASH) dietary pattern scoring tool. The project was led by the candidate as the substantive work towards this thesis. Phase 3: Phase 3 involved the analysis of short and long-term outcomes from the 3D study (one paper published in Nutrition and Dietetics, 2020 and another under consideration with Public Health Nutrition) as well as a process evaluation (Chapter 8). The objective of the short-term outcome paper was to quantify short-term improvements in diet quality and to identify factors associated with improvements after T2DM diagnosis among participants in the 3D study. Participants were categorised into two groups: those who improved their DASH score by 3 or more points between baseline and 3-months and those who did not. Factors associated with change in DASH scores were clinically and statistically evaluated. Diet quality changes after diagnosis did not appear to be associated with demographic characteristics but were associated with some health factors. It was concluded that strategies targeted at better supporting smokers, those with low physical activity levels and men with a higher body mass index (BMI) are required. The second outcome paper (currently under consideration with Public Health Nutrition) aimed to examine how the diet quality of individuals newly diagnosed with T2DM changed over the 12-month 3D study period and to identify factors associated with diet quality changes. To assess changes in DASH, energy, fruit and vegetable intake over time, repeated measure analyses of variance (ANOVA) were used. Multivariate repeated measures models were used to investigate whether these dietary changes were associated with demographic, health or physical characteristics. Participants were categorised into diet quality change profiles based on early (3-month) and long-term (12-months) changes to DASH score. Results showed that diet quality improvements after a diagnosis of T2DM are not maintained to 12-months. The development of cost‐effective, real-world interventions to achieve sustained diet quality change early after diagnosis are warranted. The process evaluation of the 3D study aimed to: (i) evaluate participant perceptions of the processes underpinning the 3D study, (ii) explore participant experiences of the study to give a deeper understanding of its effects, (iii) investigate if involvement in the 3D study may have impacted diet quality and/or physical activity levels over the observation period and (iv) seek reasons for drop out. Results found the design and implementation of the 3D study to be sound. Participants had favourable perceptions towards the processes underpinning the 3D study and positive experiences related to their participation. Participation served as a reminder to some participants to practice healthy diet and exercise behaviours prior to the scheduled interview time, but this did not appear to greatly impact the study results. The research in this thesis contributed important, novel findings relevant to the dietary intake of an at-risk group, providing a solid foundation for future work in this area that was not previously available. The research findings suggest that the majority of people with T2DM do not make significant sustained improvements to their diet quality in the 12-months after diagnosis. In the short term, (3-months after diagnosis) some health factors were associated with diet quality change including having a lower BMI, being a non-smoker and having higher physical activity levels at baseline. These findings will be able to be used to test novel interventions of state and non-government organisations to help reduce the impact of diabetes, improve patients' quality of life and help decrease health care costs attributed to diabetes-related complications.

Diabetes mellitus—in particular, Type 2 diabetes mellitus (T2DM)—is one of the most prevalent chronic illnesses in many countries. Diabetes mellitus is regarded as an independent risk factor for cardiovascular disease (CVD). Cardiovascular disease is one of the main causes of mortality in patients with diabetes, mainly due to macrovascular complications. One of these macrovascular complications in diabetes is atherosclerosis, which involves a complicated pathophysiological process. In addition to hyperglycaemia, oxidative stress (OS) plays a significant role in the pathogenesis of diabetes and its associated risk of CVD. Platelet hyperactivity, in the presence of OS, has a major effect on the progression of atherosclerosis and thrombotic events. Aspirin (AS) is the most-used antiplatelet therapy for the prevention of thrombotic complications in people with T2DM. AS attenuates platelet hyperactivity. Although aspirin is a frequently used therapy for the inhibition of platelet hyperactivity, there is much evidence for AS non-responsiveness. The anthocyanin (AC) antioxidant has been shown to have an inhibitory effect on platelets and consequently may be used as a complement to other antiplatelet therapies to attenuate the negative effect of atherosclerosis and CVD in people with T2DM. Although many dietary intervention studies have shown that intake of AC-rich food may be negatively related to some CVD risk factors, the effect of pure AC on thrombotic markers such as platelet hyperactivity and haemostasis is yet to be explored. The main aim of the studies commenced for this thesis were to examine the effect of AC on thrombotic parameters and reveal the pathways by which AC might affect platelet hyperactivity, thereby providing individuals with T2DM with better protection against CVD. The aim of the first study (see Chapter 4) was to evaluate the in vitro effect of AC on platelet activation and aggregation. Fasting blood samples were collected from 13 screened and healthy volunteers after obtaining ethics clearance and signed informed consent. A full blood examination was conducted, and a dose-response curve was created by incubating platelets with five concentrations of AC (25–200 mg/L). Flow-cytometer assessed platelet activity by recording platelet surface marker expression of activation independent (CD41a) and dependent (P-selectin and PAC-1). Platelet aggregation studies were performed using the turbidimetric method by stimulating platelets using three different agonists: adenosine diphosphate (ADP), collagen and arachidonic acid (AA). The results of this study confirmed that AC at 50 mg/L significantly lowered platelet activation as expressed by the P-selectin surface activation marker and AA-stimulated platelet aggregation. However, a similar effect of AC was not detected when ADP or collagen was applied to induce platelet aggregation. Reduced AA-stimulated platelet aggregation by in vitro–adding of AC suggests that AC may reduce platelet hyperactivity, thus reducing the risk of vascular thrombosis and promoting cardioprotective effects. Following the results of Chapter 4, a subsequent study (see Chapter 5) was conducted to assess if AC had a comparable antithrombotic effect ex vivo. Twenty-six randomly recruited healthy (25–75-year-old) participants contributed to this study and consumed 320 mg of AC a day in the form of Medox® capsules for 28 days. This study was conducted in laboratories of the School of Medical Science at Griffith University. Fasting blood samples were collected pre- and post-intervention to perform platelet activation studies, which were done by measuring platelet surface marker expression of CD41a and P-selectin, and platelet–monocyte aggregates in ADP-stimulated platelets. Platelet aggregation studies were performed by stimulating platelets with various agonists such as ADP, collagen and AA. Full blood examination, coagulation and biochemistry profile analyses were also evaluated pre- and post-intervention. A flow-cytometry analysis showed that AC had a significant effect on the expression of P-selectin as measured by the platelet surface expression of CD62p. A significant decrease in ADP-stimulated platelet aggregation was detected in the blood of healthy individuals. These results endorse the idea that AC might reduce platelet aggregation by affecting a mechanism of platelet activation, specifically the P2Y2–P2Y12 receptor. Similarly, AC significantly reduced platelet activation, as a lesser concentration of fibrinogen and decreased mean platelet volume (MPV) were detected due to AC effects in normal participants. The results from Chapter 5 suggest that AC consumption may enhance protection against platelet hyperactivity–related thrombosis. Based on the results of Chapter 5, the aim of the next study (see Chapter 6) was to identify and elucidate any possible influence of AC on thrombotic risks in people with T2DM. This study involved patients with T2DM. Twenty-four patients with T2DM were recruited for this study, and they consumed 320 mg of AC a day in the form of Medox® capsules for 28 days. Blood pressure and anthropometric measures were taken before and after the intervention period. Fasting blood samples were collected pre- and post-intervention to perform platelet activation studies, which were done by measuring platelet surface marker expression of CD41a and P-selectin in ADP-stimulated platelets. Platelet aggregation, full blood examination, coagulation and biochemistry profile analyses were also evaluated pre- and post-intervention. The data from this study showed that AC had a probable lowering effect on collagen and ADP-induced platelet aggregation in T2DM. This clinical trial also demonstrated the reducing effect of AC on the TC level in the blood. The figures shown in Chapter 6 suggest that the ingestion of AC may mitigate the development of thrombotic risks due to platelet hyperactivity. Following the outcome of Chapter 6, a fourth study (see Chapter 7) was conducted to assess if AC was comparable to AS in lowering different thrombotic biomarkers as well as platelet activation and aggregation. Antiplatelet medications, such as AS, diminish platelet hyperactivity and aggregation and decrease the risk of thrombosis. These antiplatelet drugs inhibit platelet activation through different pathways. Antiplatelet agents are indicated for mitigating thrombosis, which is partly mediated by platelet hyperactivity. However, AS non-responsiveness and side effects have been reported. Antioxidants alleviate the development of atherosclerosis and mitigate the prognosis of CVD. Two groups of healthy participants consumed AC and AS for four weeks. They were tested before and after the intervention period for different parameters including full blood count, platelet activation and aggregation, biochemical tests of lipid profile, uric acid, glucose and C-reactive protein, and coagulation assay. This study (see Chapter 7) showed a significant decrease in platelet hyperactivity—as expressed by CD62p (P-selectin) caused by AC—in the participants, yet the effect of AS was more powerful. AC had a reducing effect on ADP and collagen-stimulated platelet aggregation, but AS applied a greater inhibitory effect on this. Alleviated platelet activation, along with reduced platelet aggregation, were also detected. Lower platelet degranulation correlates with a decrease in thrombus size, as P-selectin (which is expressed by platelets upon activation) is recognised to attract nearby white blood cells (WBCs) dynamically, thus increasing thrombus size. The outcomes from this study (see Chapter 7) suggest that AC could possibly be used to decrease platelet function. However, this study also showed AC to be less useful than AS in lowering the risk of thrombosis. The results achieved from the studies completed for this thesis demonstrate a positive relationship between the consumption of AC and a decrease in platelet activity, which may be instrumental in lowering the risk of thrombosis, thus providing better prevention against CVD. The hypothesised total antioxidant effect of AC may be responsible for reduced platelet activity, which is expected to delay or even prevent macrovascular or microvascular events in patients who suffer from elevated OS as a result of different diseases such as T2DM. Reduced MPV and lowered fibrinogen levels also suggest that ingestion of AC may have an effect in suspending the early stages of atherosclerosis. Thus, AC has the potential to alleviate thrombotic risk and probably reduce the risk of cardiovascular events.

Glucagon-like peptide-1 (GLP-1) is encoded by the preproglucagon gene (Gcg) and expressed in the intestine, pancreas, and central nervous system (CNS). Activation of GLP-1 receptors (GLP-1R) on pancreatic alpha-cells induces insulin secretion in a glucose-dependent manner while activation of CNS GLP-1Rs suppress feeding. Thus, Gcg-derived peptides play an important role in gluco- and body weight regulation, and GLP-1 has been implicated in the success of bariatric surgery. GLP-1 agonists are an effective treatment of type 2 diabetes mellitus (T2DM) and obesity. The predominant source of circulating GLP-1 is the intestine, but the alpha-cell becomes an important source when the islet is metabolically stressed. Further, plasma GLP-1 is increased in T2DM patients in response to inflammation. Nutrient-stimulated GLP-1 functions as an incretin, however, the function of GLP-1 during inflammation is unknown. My dissertation proposes that during inflammation, GLP-1 plays a metabolic role, functioning to regulate glucose levels and food intake, and an immunologic role, functioning to regulate inflammation. I examined the metabolic and immunologic role of Gcg under inflammatory conditions. Using a combination of high-fat diet (HFD)-induced obesity and a mouse model of tissue-specific Gcg expression, I explored the function of GLP-1 in response to inflammation by administering lipopolysaccharide (LPS), a well-established tool for inducing inflammation. LPS is a known anorectic agent that also alters glucose homeostasis; both functions of GLP-1. I hypothesized that HFD would exacerbate physiological responses to LPS including increased plasma GLP-1, decreased blood glucose levels, and increased sickness-induced anorexia, as well as systemic inflammatory responses including increased plasma cytokines. Indeed, HFD did increase plasma pro-inflammatory cytokines, and GLP-1 levels in response to LPS and this was associated with greater anorexia in HFD-fed animals. In the next set of studies, I tested whether GLP-1 secreted from either the pancreas or intestine was directly regulating feeding and glucose responses to LPS. I hypothesized that increases in circulating GLP-1, primarily from the pancreas, were necessary for feeding and glucose responses to LPS. I found that while both pancreatic and intestinal Gcg contribute to circulating levels of GLP-1 after LPS, the availability of either source of GLP-1 had no impact on glucoregulatory or feeding responses. Because pancreatic GLP-1 is the more novel contributor to circulation, I investigated the impact of Gcg on pancreatic inflammation. I found that 24h after LPS, whole-body chow-fed Gcg Null animals had increased macrophage accumulation in the pancreas. I saw a similar trend in HFD-fed Gcg Null mice. Using a GLP-1R reporter mouse, I found that macrophages isolated from the pancreas, but not the bone marrow, express GLP-1R. These data suggest that pancreatic GLP-1 directly regulates local macrophage responses to inflammation. I conclude that under severe inflammatory conditions, GLP-1 plays an immunologic rather than metabolic role in the pancreatic responses to LPS, through direct macrophage regulation. This dissertation indicates a new role for GLP-1 signaling to pancreatic macrophages in response to inflammation. Future studies will explore the impact of this increased macrophage accumulation on long-term pancreatic function. In fact, my preliminary data demonstrate that IP glucose tolerance was impaired 2 weeks following LPS. This lasting impact of inflammation on pancreatic function points to a new use of GLP-1 agonists to protect pancreatic tissue during severe inflammation such as sepsis, or more recently, COVID-19.

Background: Diabetes is a complex, debilitating illness that imposes disease burden on the individual and society. T2DM is more prevalent in the Appalachian region than in any other Region of the United States. If diabetes is poorly controlled, patients are at risk for negative health outcomes. A gap exists in the literature related to understanding of the relationships among person factors, psychosocial factors, and coping patterns. Another gap in the literature is sex differences among these variables. Purpose: The purpose of this study is to examining relationships among person factors, psychosocial factors, and coping patterns in people living with T2DM in north central Appalachia. Method: A convenience sample of 40 men and 40 women who receive chronic management care for T2DM at a small hospital-based rural clinic, Davis Family Care was recruited. Participants were seen between February 2021-August 2021 and met the following inclusion criteria: adults between the age of 18 and 64 years old, able to read and write English, and diagnosed with T2DM. Data was analyzed using the appropriate statistical test based on variable type to seek relationships. Chi-square was conducted on categorical variables. Independent-Sample t tests was conducted on continuous variables. Pearson correlation coefficient, Pearson’s r, was used when variables were normally distributed. Continuous variables that were not normally distributed, Spearman correlation was utilized. For continuous variable of the sum score of coping patterns, a general linear model (GLM) was employed. Linear regression was also employed with coping subscales as the dependent variable and the independent variables were determined by significant relationship to the outcome variable. The enter method was investigated first and then the stepwise method. Results: The largest segment of the sample included those aged 60-64 (31.3%), white (97.5%), who are married or partnered with spouse present (60%), with a high school education (30%), an income level less than $30,000 (61.3%), and unemployed (63.7%). Most common comorbidities were high blood pressure (55%), hyperlipidemia (53.8%), depression (27.5%), lung disease (20%), anxiety (17.5%), coronary artery disease (12.5%), arthritis (12.5%), and stroke (1.3%). Nineteen people had zero comorbidities and one person had all eight comorbidities. Average number of comorbidities in addition to T2DM was 2.11 (SD = 1.916). The average A1C was 8.21 (SD = 2.54), with participants measuring an average BMI of 37.38 (SD = 8.74). Participants reported living with 1.45 people in the home on average and traveling an average of 10.22 (SD = 11.31) miles to Davis Family Care. Participants reported having T2DM for a mean of 8.62 years (SD = 7.97) and being prescribed a mean of 9.4 medications a day (SD = 6.521). Positive correlation was identified among perceived stress of anxiety, depression, diabetes distress, and loneliness. In general, sex differences were identified as female sex in psychosocial factors such as anxiety, depression, and diabetes distress. General linear modeling revealed positive frame of mind to be predictive of four positive coping subscales (active, planning, positive reframing, and acceptance). Diabetes distress was identified as predictive for behavioral disengagement coping and self-blame coping. Female sex was predictive for planning, positive reframing, religion, use of instrumental support, venting, self-distraction, and self-blame coping. Positive frame of mind was predictive for humor and religion coping. Conclusions: People with T2DM in Appalachia are living with a cluster of psychological factors, anxiety, depression, diabetes distress, and loneliness. These factors, along with the known sex differences in coping further complicate the care of persons with T2DM. Findings of this study are foundational to further research that targets diabetes distress and is sex specific.

Type 2 Diabetes Mellitus (T2D) is a major public health issue. Diabetes prevalence is growing and is the 7th leading cause of death in the US. Virginia has a slightly higher prevalence than the national average. Community-based diabetes lifestyle management programs that include a physical activity component are effective at improving glycemic control and influencing lifestyle behavior changes among people with T2D. The Balanced Living with Diabetes (BLD) program uses an active learning approach to improve glycemic control and healthful lifestyles. The Lifelong Improvements through Fitness Together (LIFT) program uses behavioral strategies to improve functional fitness, participant engagement, and program adherence. Participant retention is a challenge for community-based program. Participants may start the program, but then fail to complete the program and/or adhere to program recommendations. Two pilot studies were conducted to evaluate strategies for increasing participant retention and improving outcomes. The first evaluated the implementation and impact of a retention plan implemented in BLD programs conducted from 2015-2017. There were more participants returned to the reunion class session prior the development of the retention plan. There were improvements in some health behavior and self-efficacy indicators in programs that used the retention materials, however, impacts on outcomes were mixed. Preliminary findings showed that the retention plan could be a tool for providing additional support to participants, however strategies for dissemination of the retention plan needs to be reevaluated. The second study evaluated the impact on participant engagement and program outcomes when the LIFT program is incorporated with the BLD program. There was an increase in participant retention, self-efficacy and one health behavior for physical activity and health behaviors related to diet in BLD+LIFT programs. Extension Agents are willing to implement the BLD+LIFT programs, however, clarity of program logistics is needed prior to implementation. Extension Agents indicated that implementation of these programs in locations with older adults that have greater disability may not be the best locations. Having larger studies on the effect of incorporation of LIFT with the BLD with older adult populations that have fewer co-morbidities are needed to determine the impact of addition of the LIFT program with the BLD program on program outcomes.

One in two Australians has a chronic disease, and a quarter has two or more. Despite the widely documented benefits of exercise for the prevention and management of many chronic diseases, the majority of people with a chronic disease remain insufficiently active. The examination of exercise behaviour must be guided by appropriate theoretical frameworks to improve the effectiveness of exercise interventions to support people with a chronic disease to initiate and maintain participation. In this thesis, two studies with complementary methods were used to examine the exercise behaviour change relating to people with Type 2 diabetes mellitus (T2DM) from the perspective of the participant and the practices of exercise practitioners. Study 1, a qualitative study, examined the perspective of participants with a chronic disease in an exercise efficacy trial. Five participants with Type 2 diabetes mellitus (T2DM) completed a semistructured interview 12 to 18 months following the conclusion of a 12-week exercise intervention. Two participants were male, and three participants were female, with an age range of 43 to 83 years. The length of time since diagnosis ranged from four to 26 years. The Theoretical Domains Framework (TDF) was used to code interviews deductively, and a range of strategies was identified as critical for exercise initiation and maintenance. The most commonly reported themes were: (1) reinforcement; (2) beliefs about consequences; (3) behaviour regulation; (4) beliefs about capabilities; (5) social influences; (6) environmental context and resources; (7) emotion; (8) goals, and (9) social/professional role and identity. Behaviour regulation was related to the maintenance of exercise. Study 2, a quantitative study, examined the use of behaviour change techniques (BCTs) by 54 exercise practitioners when working with clients with a chronic disease. Exercise practitioners were mostly female (72.2%) and aged between 25 and 34 years (55.6%). Most of the sample were Accredited Exercise Physiologists (81.5%) and held a postgraduate qualification (65.0%). First, the Behaviour Change Index-Exercise Practitioners (BCI-EP) was developed to measure the use of BCTs in clinical practice. The Index was based on the Coventry, Aberdeen, London-Refined (CALO-RE) taxonomy that describes 40 BCTs relevant to exercise behaviour change. Second, the Index items were grouped according to the dominant TDF domains and administered to examine the use of theory-based BCTs used in practice. BCTs related to the goals and social influences TDF domains were the most frequently reported groups of techniques used by exercise practitioners. Female gender was positively associated with more frequent use of environmental context and resources related techniques compared to male practitioners. Exercise practitioner age was negatively associated with the use of behaviour regulation and beliefs about consequences techniques. Accredited Exercise Physiologists were less likely to use reinforcement BCTs compared to fitness instructors and personal trainers when working with clients with a chronic disease. This research contributes to the body of knowledge by applying the TDF to understand the initiation and maintenance of exercise among people with T2DM. The results provide insights into the strategies that might influence the uptake and maintenance of exercise among people with T2DM. The study also adds to emerging literature about the importance of emotion as a predictor of exercise participation among people with T2DM. Emotion related BCTs could be added to taxonomies such as the CALO-RE to expand existing knowledge of exercise participation to improve T2DM management. The newly developed BCI-EP could be applied for a range of research purposes to assess other practitioner’s use of BCTs and to examine the relationship between the use of BCTs and exercise uptake and adherence in clinical practice, and exercise practitioner education and training. A range of cognitive, affective, social, and environmental theoretical domains were related to exercise behaviour change among people with T2DM. These domains theoretical domains must be integrated into the development of exercise interventions to improve the effectiveness of exercise prescription for people with T2DM.

Type 2 diabetes mellitus (T2DM), driven by overweight and obesity linked to unhealthy diets, is the fastest-growing non-communicable disease in Australia. Considering that food is an important parameter in the regulation of blood glucose response, replacing ‘junk food’ with products that are good regulators of postprandial blood glucose (PPG) may go a long way to reduce the rate of T2DM in Australia. This study was designed to develop new food products that have the potential for use as nutritional preventatives against escalating levels of T2DM within the Australian Indigenous community. Edible portions of eight Australian native plant species namely; Leucopogon parviflorus, Arthropodium strictum, Carpobrotus rossii, Rhagodia candolleana, Typha orientalis, Correa alba, Dianella revoluta and Acacia longifolia were collected from the coast of Warrnambool, Victoria Australia. The plant species were analysed for proximate, minerals, fatty acids and phenolic composition following the methods of the Association of Official Analytical Chemistry (AOAC), Inductively Coupled Plasma Spectometry (ICP), High performance liquid chromatography (HPLC) and gas chromatography/Mass spectrometry analysis (GCMS). Plant species that exhibited significantly high amounts of nutrients, antioxidants and antidiabetic polyphenols were selected for development of potential antidiabetic food preventatives. The developed food products (Acabungi flakes and crackers) were evaluated for acceptability and the cracker was further studied for stability and microbiological load. Its Glycaemic index (GI) was estimated by in-vitro enzymatic starch hydrolysis. All eight plant species were found to be sources of carbohydrates (39.7 - 65.5%), proteins (2.6 - 15.1%), fats (1 - 14.3%), total dietary fibre (1.5 - 17.2%) and contained Ca, Mg, Na and K. The species exhibited consistent antioxidant activity with phyto-components of gallic acid (GA), epigallocatechin (EPC), catechin (CH), epigallocatechingallate (EPG), dihydroquinidine (DHQ), ρ-coumaric acid (PCA) and luteolin (LT). The betacyanin, betanidin 5-O-β-glucoside (BT) was detected in R. candolleana (700 mg/kg) and C. rossi (244 mg/kg) while the alkaloid, Dihydroquinidine (DHQ) was detected in D. revoluta (101 ± 5.7 mg/kg) and T. orientalis (17 ± 7.1 mg/kg). However, not all the compounds were isolated from a single plant species and except for BT, higher quantities of components were extractable in methanol than water (P

Type 2 Diabetes Mellitus (T2DM), a metabolic disorder denoted by elevated blood glucose levels and insufficient insulin action, is growing in prevalence worldwide . Barriers to improving disease outcome resolve primarily around identifying and intervening during the preliminary stages of insulin resistance, a state clinically referred to as pre-diabetes. Emerging evidence suggests that mitochondrial dysfunction may underlie , and potentially precede, progressive insulin resistance, suggesting that biomarkers indicative of mitochondrial dysfunction could predict disease risk and status. In this study, we examined epigenetic modifications, in the form of DNA methylation, in the promoter region of peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α), a known regulator of mitochondrial biogenesis. Following the initiation of a high fat diet, we observed significant genotypic (DNA methylation) and phenotypic (mitochondrial copy number) alterations in C57/BL6 rodent models. These changes preceded overt disease onset, as classified by clinically utilized indices, which included the homeostatic model assessment for insulin resistance (HOMA-IR), the homeostatic model assessment for β-cell dysfunction (HOMA- β), and the quantitative insulin-sensitivity check index (QUICKI). Our data indicate that methylation analysis may serve as an effective clinical parameter to use in conjunction with physiological criterion for the diagnosis of pre-diabetes and the assessment of T2DM disease risk, and adds to the growing body of work seeking to elucidate the role.

Background: Despite the significant inter-individual variability observed in outcomes of aerobic exercise programs among older adults, little is known about the prevalence of nonresponse to exercise in this population. Supervised exercise therapy (SET) is the primary guideline-recommended therapy for the treatment of symptomatic peripheral artery disease (PAD), yet variability in response to outcomes in this population is not well understood. Previous research suggests that individuals with PAD and comorbid diabetes may be less likely to see a benefit in physical function and quality of life outcomes following SET, yet few studies have been designed to directly compare outcomes in these populations, and no studies have examined the potential role of changes in sedentary time during the course of SET in SET outcomes. Additionally, it is unknown if patterns exist in inter- and intra-individual response across a variety of outcomes. Findings of such research could enable informed tailoring of exercise therapy programs to maximize an individual’s potential benefit. Aims: This dissertation aimed to (1) determine the prevalence of nonresponse to aerobic exercise among older adults participating in studies of aerobic exercise programs, and identify factors related to nonresponse that have been examined in the literature; (2) quantify changes in sedentary behavior among older adults with PAD, with and without diabetes, engaging in SET for the management of symptomatic PAD and examine how diabetes and changes in sedentary time are related to SET outcomes; and (3) examine the prevalence of nonresponse to SET among individuals with PAD and explore patterns of nonresponse across of a variety of relevant objective and self-reported outcomes. Methods: Aim 1. A critical review of published studies in which the authors examined variability in response, poor response, or lack of response to aerobic exercise interventions in older adults was conducted. Methods of defining nonresponse, the prevalence of nonresponse, and factors associated with nonresponse are discussed. Aim 2. A pre-test post-test study of older adults (n = 44) initiating a 12-week SET program for symptomatic PAD was conducted in a midwestern hospital system. Participants completed assessments of physical function (six-minute walk test, Short Physical Performance Battery, Walking Impairment Questionnaire), and physical activity and sedentary behavior (assessed objectively via wrist-worn accelerometer) at the time of SET initiation, 6 weeks, and 12 weeks. Changes in sedentary time overall and between participants with and without diabetes were examined. Multiple linear regression was used to examine the influence of diabetes and changes in sedentary time during SET on functional and self-reported outcomes. Aim 3. A secondary analysis of data collected as part of Aim 2 was performed to determine the prevalence of nonresponse to SET in functional and quality of life outcomes using different methods of defining nonresponse reported in the literature. Inter- and intra-individual patterns of response were also examined. Results: Aim 1. A total of 17 articles representing 12 unique studies with 5116 unique participants were eligible for inclusion. Nonresponse to aerobic exercise interventions was prevalent among older adults (1.4-63.4%); age, sex, race, and body mass index were not found to be critical determinants of nonresponse, but there was some evidence to suggest that baseline fitness, health status, and exercise dose were important predictors of nonresponse. Aim 2. On average, sedentary time did not change following the 12-week SET program, although there was substantial inter-individual variability (40% decrease to a 38% increase in average daily minutes of sedentary time). While on average, participants with diabetes reduced their average daily sedentary time, participants without diabetes tended to increase their average sedentary time. In multiple linear regression, neither changes in sedentary time in the first six weeks of SET nor diabetes were significant predictors of changes in total distance attained on the six-minute walk test from baseline to 12 weeks. Aim 3. The prevalence of nonresponse in walking distance when defined as no change or a decline in walking distance was 35.3%, and when defined as the lack of a clinically meaningful improvement (20 meters), the prevalence of nonresponse was 55.9%. Similar patterns of response were observed in both the objective and self-reported measures of physical function. All participants improved in at least one study outcome; however only one participant improved in all measured outcomes. Conclusion: Nonresponse to a single study outcome following participation in aerobic exercise is a common phenomenon among older adults, both with and without PAD. Neither diabetes nor changes in sedentary time were significant predictors of response to SET among individuals with PAD. Exercise studies should include a variety of performance based and patient-reported outcomes, as nonresponse likely represents a failure in just one potential positive adaptation to exercise. Additional research should examine potentially modifiable predictors of response prior to the initiation of or during exercise training (e.g., motivation to exercise, social support), which would foster inquiry and efforts to modify and tailor programming to maximize an individual’s potential benefit from exercise therapy.

Type 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican-Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM. This was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican-American. Subjects were grouped by T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded what they ate for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via Mothur’s Bayesian classifier and referenced to the Greengenes database. Alpha diversity and taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA. Thirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index (BMI) (diabetes 30 mg/kg2, no diabetes 28 mg/kg2; p=0.4653) and other comorbid conditions. Alpha diversity was not significantly different between those with and without T2DM (3.21 vs. 3.07; p=0.3409). Beta diversity was not significantly associated with T2DM diagnosis (p=0.1249). Sixteen operational taxonomic units (OTUs) were significantly different between groups. There was a significantly lower relative abundance (RA) of Streptococcus in those with T2DM (p=0.04). The Firmicutes to Bacteroidetes ratio was higher in those with T2DM (0.637:1) compared to those without T2DM (0.507:1). In conclusion, although alpha diversity was not different between diabetic and nondiabetic Mexican-Americans, the microbial composition was significantly different

Obesity is associated with a state of chronic inflammation that is thought to be major contributor to disease and atherosclerosis. Many inflammatory pathways that contribute to the development of insulin resistance and atherosclerosis are regulated by IKK- NF-κB signaling. Several studies during the past two decades have highlighted the key role of the IKK/NF-κB pathway in the induction and maintenance of the state of inflammation that underlies metabolic diseases. We addressed the stipulated role of IKKβ to produce proinflammatory cytokines in cultured human adipocytes using small molecule inhibitor. We hypothesized that IKK/NF-kB signaling plays a critical role in inflammatory pathway in human adipocytes which may subsequently contribute to insulin resistance and atherosclerosis. We have developed an effective protocol for deriving adipocytes from in vitro culture of pre-adipocytes and demonstrated upregulation of proinflammatory cytokines in this system. Our results show that IKK inhibition abrogates inflammatory cytokine secretion during adipogenesis and mature adipocytes in dose dependent manner. In conclusion, this study provides the critical role of IKK/NF-kB-mediated inflammatory pathways in human adipocytes; and represents proof of concept for use of appropriate IKK inhibitor as an innovative therapeutic strategy to treat obesity and cardiometabolic diseases. Importance of this work: Obesity is a rapidly growing epidemic representing a serious threat to the health of the population in almost every country around the world. There is an imperative need to understand the mechanisms underlying the obesity and associated cardiometabolic disorders. In this thesis, we have shown that inhibition with specific small molecular inhibitor of IKK abrogated the proinflammatory cytokine release. This study provides a foundation for targeting the IKK NF-kB signaling as therapeutic strategy for metabolic diseases.

Individuals with type 2 diabetes mellitus (T2DM) are at risk for developing life-threatening comorbidities such as cardiovascular disease (CVD). As a consequence, T2DM is associated with increased morbidity and mortality and decreased quality of life, thus highlighting the importance of prevention of T2DM. Further, the prevalence of T2DM is substantially greater in rural populations compared to urban populations, making rural individuals particularly appropriate targets for T2DM prevention. T2DM is a largely preventable disease that is associated with modifiable risk factors such as poor diet, sedentary lifestyle, and obesity. Lifestyle interventions to improve these modifiable risk factors have been used to decrease the risk of developing T2DM. There is little evidence that supports lifestyle interventions as a means to decrease T2DM risk in rural populations with prediabetes, the precursor of T2DM. The purpose of this dissertation was to determine whether rural-living individuals with prediabetes would improve modifiable risk factors, specifically diet quality by following a lifestyle intervention; thereby, decreasing their risk of developing T2DM. Specific aims for this dissertation were to, 1) examine and synthesize data from dietary interventions used to reduce risk of T2DM in rural populations on order to identify gaps and guide future research, 2) critically evaluate validity and reliability of indices used to determine diet quality in research, and 3) determine the effect of a risk reduction program on improving diet quality and glucose control (as a measure of T2DM risk) in rural adults with prediabetes and CVD risk factors. Specific aim one was achieved by a review and synthesis of literature focused on lifestyle and dietary interventions used in rural populations to decrease the risk of developing T2DM. Common goals in these studies were a decrease in weight, decrease in dietary fat and calories, and an increase in physical activity. Decreased weight and increased physical activity were demonstrated in all eight studies, and a decrease in T2DM incidence was also demonstrated in one of the studies. However, diet quality was not adequately assessed in the majority of the studies. Furthermore, none of the studies were randomized controlled trials and only half used a control group. It was concluded that research using a more robust design is needed to determine the effect of lifestyle changes, specifically diet, on T2DM risk in rural populations. Specific aim two was addressed by a critical analysis of six common indices of dietary quality. Validity and reliability of the Healthy Eating Index, the Alternative Healthy Eating Index, the DASH diet score, the Diet Quality Index-Revised, the Healthy Diet Indicator, and the Diet Quality Score were examined. Five of the six indices are valid and reliable tools for measure diet quality but all five rely on an extensive food frequency questionnaire that may be burdensome for participants. The Diet Quality Score does not provide adequate evidence to support its use in research. It was concluded that a short, reliable, and validated diet screener may be useful in research. Specific aim three was addressed by a secondary data analysis of a longitudinal, randomized controlled study of rural residents with CVD risk factors and prediabetes. Diet quality, measured by the Mediterranean Diet Adherence Screener (MEDAS), and glucose control, measured by hemoglobin A1c, were analyzed in a subpopulation of 62 participants with prediabetes. Neither diet quality nor glucose control improved between baseline, four month, and 12 month post intervention. The reliability and validity of the MEDAS in this population is not known and may have been a factor in the lack of intervention effect related to diet quality. Participants were also not informed of their prediabetes status, thus it is not known if this knowledge would have made an impact on the outcomes of the study. In addition, the small sample size limits the statistical power to determine changes between the intervention and control groups. It was concluded that further research is needed to determine if a high quality diet will reduce T2DM risk in this rural population Considering the disproportionate prevalence of T2DM in rural populations compared to their urban counterparts, the results of this dissertation demonstrate a continued need for interventions that decrease modifiable risk factors associated with this disease. Interventions that target obesity, poor diet quality, and sedentary lifestyles in at-risk rural populations that are culturally tailored are needed to decrease risk of developing T2DM and the comorbidities associated with this preventable disease.

Obesity is a leading global health problem contributing to various comorbidities, including cardiovascular disease, type II diabetes mellitus (T2DM) and hypertension. Current conventional medical interventions for the treatment of these diseases are limited with varied efficacy and associated side effects. Thus complementary dietary or alternative therapies have become increasingly popular as alternative treatment methods for obesity and its related comorbidities. There is an immense diversity of plant and animal products, which may be effective agents for attenuating the development of obesity, T2DM and hypertension as they often contain a vast array of bioactive compounds that have been associated with significantly positive health outcomes with minimal side effects. However, the effectiveness of many of these foods and their bioactive molecules in the treatment of human diseases has yet to be fully explored. The overall focus of this thesis was to determine the effectiveness of supplementation with blueberry, yoghurt and their important respective bioactive components, cyanidin-3-O-βglucoside (C3G) and peptides, alone or in combination, on the risk factors of obesity and its related comorbidities. To undertake the overall focus of this thesis, the bioactive peptides were extracted from yoghurt and then these peptides as well as C3G were utilised in a human primary skeletal muscle cell culture experiment. This work was further developed with experimentation with these compounds in addition to supplementation with blueberry and yoghurt in isolation and in combination in a high-fat-high-carbohydrate (HFHC) induced obese mouse model. In order to produce bioactive peptides with angiotensin converting enzyme (ACE) inhibitory activity from yoghurt, the optimal fermentation conditions were determined. The results showed that peptides with ACE inhibitory activity (1.47 ± 0.04 mg/mL of IC50 values) were those obtained from yoghurt fermented by 1% of L. helveticus with Flavourzyme® for 12 h. After further separation, one fraction of peptides showed the highest ACE inhibitory activity with an IC50 of 35.75 ± 5.48 μg/mL. The total content of anthocyanidins and C3G in thirteen brands of blueberry samples were also analysed in order to choose the suitable brand for animal experimentation. Based on these results, Bhatti & Manj blueberries were selected attributed to their higher content of total cyanidin. In order to determine the effects of C3G and peptides on the regulation of glucose metabolism, different concentrations of C3G and peptides, alone or in combination, on glucose uptake and mRNA expression of key genes were investigated in human primary skeletal muscle cells derived from obese and obese diabetic (obese T2DM) individuals. The results showed that both low and high concentration of peptides and the combination of these peptides with high C3G concentration significantly enhanced glucose uptake in the presence or absence of insulin in the human primary skeletal muscle cells derived from obese individuals. However, high peptide concentration only increased glucose uptake in the absence of insulin in the obese T2DM group. In the obese group, high concentration of peptide alone and its combination with low C3G down-regulated the mRNA expression of angiotensin II receptor, type 1 (AGTR-1), and up-regulated the mRNA expression of insulin receptor substrate 1 (IRS-1), and glucose transporter 4 (GLUT4). In the obese T2DM group, the expression of AGTR-1 was decreased at high peptide concentration and its combinations with C3G. To further determine whether C3G and peptides, and their original food sources, blueberries and yoghurt, could attenuate obesity and its related comorbidities, a 16-week animal study using HFHC diet induced obese male C57BL/6 mice was conducted. It was found that blueberry and yoghurt alone, and the combination of peptides and C3G significantly reduced both systolic and diastolic blood pressure. Moreover, yoghurt significantly reduced body weight, percentage body fat and improved intraperitoneal glucose tolerance compared to the HFHC (control) group. Furthermore, peptides and its combination with C3G resulted in a significant reduction in percentage body fat and improvement of intraperitoneal glucose tolerance. However, energy expenditure and locomotor behaviour did not alter in any treatment groups compared to the HFHC group. The mRNA expression of multiple genes related to glucose metabolism in the skeletal muscle (extensor digitorum longus (EDL) and soleus) of mice supplemented as detailed above was determined by quantitative ’real-time’ polymerase chain reaction (PCR). In EDL, yoghurt alone up-regulated the expression of AMPK, IRS-1, PI3K and GLUT4, and down-regulated the expression of AGTR-1. The combination of blueberry and yoghurt down-regulated the mRNA expression of AGTR-1 and FoxO1 in EDL. Furthermore, the combination of C3G and peptides also down-regulated the mRNA expression of AGTR-1 and up-regulated the mRNA expression of GLUT4 in EDL. In soleus, blueberry and yoghurt supplementation alone and their combination down-regulated the mRNA expression of AGTR-1, and upregulated the mRNA expression of GLUT4. Therefore, the outcomes of this thesis highlight that yoghurt and its peptides have the potential to reverse or attenuate metabolic disturbances associated with developing obesity, diabetes and hypertension. Blueberries reduced blood pressure while no inhibition on body weight and body fat gain was observed. Furthermore, C3G may not be effective in eliciting beneficial effects on obesity, diabetes and hypertension possibly due to the low dosage utilised. In conclusion, the results presented within the current thesis support that yoghurt as a fermented dairy product may be a beneficial additive to functional foods or utilized as a dietary component. Blueberry plays a significant role in the treatment of hypertension, which represents a potentially promising dietary intervention worthy of further investigation.

People with type 2 diabetes mellitus (T2DM) have normal to high bone mineral densities, but counterintuitively have greater fracture risks than people without T2DM, even after accounting for potential confounders like BMI and falls. Therefore, T2DM may alter aspects of the quality of bone, independently of bone mass, through metabolic or biochemical mechanisms as a result of a T2DM disease state. The main objective of this research was to elucidate the material factors that increase fragility in T2DM by characterizing the material properties, microarchitecture, and mechanics of bone from subjects with and without T2DM. The tissue material properties of bone from two clinical populations and from a rodent model of T2DM were evaluated, and the microarchitecture and and mechanics were evaluated for one of the clinical populations. In the rodent model of T2DM, mice with T2DM had more mineralized tissue, more mature collagen, and less heterogenous mineral properties compared to non-DM littermate controls, all of which are consistent with an older tissue that has undergone less remodeling. Tissue properties of the iliac crest from post-menopausal women varied with different stages of glycemic control, from normal glucose tolerance, impaired glucose tolerance, and overt T2DM. Glycemic derangement was associated with increased mineralization, decreased collagen maturity, and atypical mineral maturation, all of which can alter the mechanics of bone. Finally, femoral neck cancellous bone from men with T2DM had increased mineralization, a less mature mineral, more numerous trabeculae, and greater accumulation of non-enzymatically-formed collagen crosslinks compared to men without T2DM. The mechanical properties of the T2DM specimens reflected these alterations: stiffness and strength were greater in the T2DM specimens because of the greater mineral content and improved microarchitecture. Regression modeling of post-yield toughness demonstrated a significant deleterious impact of mineral maturity and non-enzymatic crosslinks once the improvement in microarchitecture was mathematically accounted for. Together, these results indicate a beneficial effect of T2DM on cancellous microarchitecture, but a deleterious effect of T2DM on the collagen matrix and mineral maturation. In conclusion, this work aids in the understanding of how bone becomes more fragile with T2DM, and this work is clinically relevant because it demonstrates that different populations of T2DM patients may have distinctly different bone fragilities as a result of varying tissue composition and microarchitecture.

Metformin is first-line therapy in the treatment of type 2 diabetes mellitus (T2DM). Contraindications due to a perceived increased risk of lactic acidosis include end-stage kidney disease (ESKD) and hepatic insufficiency. These patients are currently excluded from the additional benefits of metformin, including cardiovascular risk reduction. The aim of this thesis, therefore, was to investigate the safety and pharmacokinetics (PK) of metformin in patients with ESKD or chronic liver disease (CLD), patient cohorts that might benefit from using metformin. Predetermined safety targets were plasma metformin and lactate concentrations of less than 5 mg/L and 5 mmol/L, respectively. The first study (Chapter 2) addressed the PK of metformin in patients with T2DM and ESKD (n=4) being managed with haemodiafiltration (HDF). Metformin (500 mg, immediate release, IR) was administered after each HDF session for 6 weeks. Metformin was cleared extensively from plasma, but not erythrocytes, during HDF. Metformin concentrations were largely unchanged between HDF sessions. Plasma metformin and lactate concentrations remained below the specified safety targets. There was no relationship between metformin and lactate concentrations. The second study (Chapter 3) investigated the safety of metformin (250 mg, IR, after HDF) in patients with T2DM and ESKD (n=7) receiving maintenance HDF. Plasma metformin and lactate concentrations remained below targets, with the exception of two occasions in one patient where they were marginally elevated but without evidence of lactic acidosis. The study was ceased following the deaths of two patients. Metformin was not deemed to have contributed to the deaths. The third study (Chapter 4) investigated the safety and PK of metformin (500 mg, IR, twice daily) in patients with all-cause CLD (n=58). Plasma metformin and lactate concentrations were below safety targets. Cirrhosis and T2DM, but not steady-state metformin concentrations, were associated with higher plasma lactate concentrations. The PK in CLD patients were similar to T2DM patients and healthy subjects. These studies provide the first detailed examination of the PK and safety of metformin in patients with ESKD and CLD. Importantly, the data support the proposition that metformin might be used safely in these patient cohorts, thereby allowing its effects additional to glycaemic control, notably cardioprotection, to benefit patients.

Background: Metabolic syndrome (MetS) is characterized by the clustering of hyperglycemia, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol levels and central adiposity. Altitude has been proposed as a protective factor to prevent the development of MetS and its components. Aim: To determine whether living at geographical elevation is associated with MetS and its individual components after adjustment for potential confounders in an Ecuadoran population. Methods: The study included 260 Ecuadoran university graduates over 20 years of age, from the coastal or the Andean Altiplano region. The altitude of residence was imputed with the postal code of each participant residence according to the data of the Ecuadoran Geophysical Institute of the National Polytechnic School. MetS was defined according to the harmonizing definition. Logistic regression models were fitted to assess the relationship between altitude level and the prevalence of MetS and its individual components. To test the internal validity, re-sampling techniques were used (1,000 bootstrap samples).

Matthias B Schulze and colleagues discuss current knowledge on the associations between dietary patterns and cancer, coronary heart disease, stroke, and type 2 diabetes, focusing on areas of uncertainty and future research directions

Type 2 diabetes mellitus (DM) is one of the most common chronic diseases globally, with worldwide prevalence of 8.3%. Due to its long-lasting nature and high risk of complications, the burden of type 2 DM is expected to rise. Patients with type 2 DM have an estimated two-to-six fold higher risk of developing cardiovascular disease (CVD) compared to the general population. Moreover, CVD is considered the leading cause of morbidity and premature mortality in type 2 diabetic patients. CVD risk assessment tools in general are mathematical models or charts used to estimate the risk of a CVD event in an individual. CVD risk estimation is important to plan the initiation of preventive and therapeutic measures for CVD prevention including anti-lipid, anti-hypertensive and anti-platelet therapies, as well as to plan appropriate health education. Various professional guidelines for the management of type 2 DM have advocated the use of CVD risk assessment tools to estimate CVD risk among type 2 diabetic patients using traditional CVD risk factors such as hypertension (HTN), dyslipidemia, high glycosylated hemoglobin (HbA1c), albuminuria, obesity, smoking status, and family history of CVD. However, most of the existing CVD risk assessment tools were derived from Western populations, with very few developed for East Asian populations.

INTRODUCTION: Type 2 diabetes mellitus (T2DM), once thought to be an adult disease, now affects large numbers of children. The prevalence of T2DM in children increased 35% between 2001 and 20091 and while it appears to now be leveling off, it is clear that much of the burden of disease falls disproportionately on ethnic minorities. It is well known that there are changes occurring in the microvasculature well before diabetes is diagnosed, and these changes are thought to contribute to micro- and macrovascular complications. Therefore, prediabetes, which is a time of mild hyperglycemia that exists between normal glucose metabolism and overt diabetes, provides a target for behavior modification and potentially the prevention of complications. The mainstay of treatment for diabetes has been lifestyle intervention and treatment with metformin. Research has shown that both intensive lifestyle interventions and metformin are effective for the treatment of T2DM. However, much of this knowledge comes from studies on adults and is simply inferred to youth. Thus, at this time it is still unknown to what extent treatments including lifestyle intervention and metformin should be used, or how they should be utilized, in youth. This is especially true for youth with prediabetes, as this is likely where prevention of the disease needs to occur to have the greatest overall benefit. PROPOSED STUDY: Thus, the proposed study will directly compare two groups treated with standard of care and either metformin daily or intensive lifestyle intervention with a CrossFit™ training modality. The primary outcome is treatment failure and development of diabetes. A secondary outcome is achievement of normoglycemia and its durability. CONCLUSIONS: This study will be the first to examine the longer term outcomes of the use of metformin in youth as well as the effects of high intensity functional training (HIFT) using the CrossFit™ modality. While there is accumulating evidence about the safety of the use of metformin in youth, most studies are of short duration and this study will provide longer term results. Additionally, CrossFit™, a relatively new exercise modality, has not been tested in the literature on youth and as a form of combined aerobic and resistance training, it may provide and effective and interesting means of lifestyle intervention and reversion to normoglycemia in adolescents. In conclusion the results from this study will provide significant clinical relevance.

Cognitive Function, Self-Care, and Glycemic Control in Rural Adults with Type 2 Diabetes Abstract The prevalence of type 2 diabetes mellitus (DM) has increased dramatically over the past two decades, particularly among adults living in rural communities. Related health complications include structural brain changes and decreased cognitive function. Cognitive decline associated with DM may influence one’s ability to perform self-care and affect glycemic control. In turn, poor glycemic control contributes to increased complications associated with DM. Although one’s ability to maintain glycemic control may be highly dependent on cognitive abilities, there is limited understanding about the relationship between cognitive function, self-care, and glycemic control in rural adults with DM. Specific aims of this study were to: 1) examine the relationships between cognitive function, glycemic control, and contributing factors (age, years with DM, education category, cardiovascular (CV) risk, level of depression) in rural adults with DM; 2) examine whether cognitive function predicts glycemic control in rural adults with DM; 3) examine the relationship between cognitive function, self-care, and contributing factors (age, years with DM, education category, everyday problem-solving, and level of depression) in rural adults with DM; and, 4) examine whether cognitive function predicts self-care in rural adults with DM. This descriptive study included a convenience sample of (N=56) rural adults with DM. A face-to-face interview was conducted with each participant, where performance of the cognitive processes of attention, executive function, mental processing speed, and verbal episodic memory was measured with neuropsychological tests. Frequencies of performing DM self-care activities of adherence to diet, exercise, blood glucose monitoring, foot care and medications were queried to determine levels of self-care, and a recent glycohemoglobin was obtained to determine glycemic control. Main results were that cognitive function in domains of attention, executive function, mental processing speed, or verbal episodic memory, after controlling for modifiable and non-modifiable covariates, did not independently explain glycemic control or the frequency of DM self-care activity performance by rural adults with DM. The covariates cardiovascular risk and depression independently explained cognitive function, and depression independently explained self-care performance.

Purpose: To study the occurrence of peripheral arterial disease (PAD) and factors associated with the occurrence of PAD among patients with type 2 diabetes mellitus (T2DM). Design: Descriptive design. Methods: The sample composed of 136 adult patients with T2DM who were treated at Bach Mai hospital, Hanoi, Vietnam. Data were collected using Ankle Brachial Index (ABI) to assess the occurrence of PAD, and 4 questionnaires: patients’ demographic data, clinical information, the self-efficacy for diabetes, and knowledge about PAD. Chi – Square was employed to test association between studied variables. Main findings: The findings revealed that 16.18% had PAD; 36.36% of those with PAD had stage 4-ulceration or gangrene; 63.64% had location of PAD at tibia-peroneal artery and 31.81% at femoro-popliteal artery. Co-morbid diseases, HbA1c, and self-efficacy were significantly associated with the occurrence of PAD (p < .05). There was no association between the occurrence of PAD and knowledge about PAD (p > .05). Conclusion and recommendations: Nurses can empower patients with T2DM to increase self-efficacy as well as providing them with information to control the level of HbA1c and co-morbid diseases.

Fundamento. Un adecuado control de la glucemia y de los factores de riesgo cardiovascular (FRCV) es fundamental en los pacientes con diabetes mellitus tipo 2 (DM2). Sin embargo, diversos estudios han demostrado que el porcentaje de pacientes que alcanzan dichos objetivos es escaso. Hemos evaluado el grado de control de FRCV en pacientes DM2 que acuden con regularidad a una consulta monográfica de diabetes. Pacientes y métodos. Se han estudiado los pacientes con DM2 que acudían a revisión al departamento de Endocrinología de la Clínica Universidad de Navarra con un seguimiento mínimo de un año. Se presentan las características clínicas, complicaciones crónicas y tratamiento médico, así como la clasificación en grupos según el cumplimiento de los objetivos de hemoglobina glicada (HbA1c), perfil lipídico (LDL-colesterol) y presión arterial (PA) individualizados según comorbilidades y años de evolución de la DM2. Resultados. Se han analizado 137 pacientes (75% hombres) con DM2, 67 años de edad media y 12,7 años de evolución. Durante el seguimiento, se encontraron dentro del rango objetivo individualizado de HbA1c el 83,9% de los pacientes, el 67,2% en cuanto a LDL-colesterol y el 76,6% considerando PA. Además, el 68% presentaron las tres variables principales dentro del objetivo. Conclusiones. En nuestra población de DM2 la consecución de objetivos de HbA1c, LDL-colesterol y PA se alcanza en una importante proporción de pacientes (67-91%). Posiblemente la intensa e individualizada atención ofrecida a través de una unidad de diabetes especializada pueda explicar estos resultados.

Diabetes mellitus (DM) has been a major research topic in scientific health studies. Diabetes is a chronic condition in which blood glucose levels are chronically elevated to more than 7.0 mmol/l in fasting plasma glucose test. The most common form of diabetes is Type 2 (TD2M). The International Diabetes Federation (2015) estimated the number of DM cases worldwide to be 415 million people in 2015. This number is predicted to increase by the year 2040, to 642 million people. The purpose of this study was to use the National Health Interview Survey (NHIS) data to identify the risk factors for TD2M and their associations with the obesity as measured by the Body Mass Index (BMI) of diabetic and non-diabetic U.S. adults. The study findings for adults with diabetes included: (a) BMIs decreased as people aged, (b) females tended to have higher BMIs than males, (c) people who are Asian or Hispanic had lower BMIs, (e) smokers had lower BMIs than non-smokers, and (f) people who are more physically active had lower BMIs than less active people. For non-diabetic adults, relationships between BMI and age, gender, ethnicity, geographic region, education, physical activity, and smoking were significant. The relatively low R2 s, however, may indicate that salient variables were absent. Risk factors that might have been included in the IHIS are health history, genetics, diet, and Social relationships.