Aims: Thiazolidinediones have been advocated as second or third line insulin sensitizing agents in the management of type 2 diabetes (T2DM). Their widespread use has been hampered by concerns about their cardiovascular safety, including fluid retention. Metformin is established as first-line glucose-lowering pharmacotherapy in T2DM. It has also been suggested that it may have benefits in alleviating insulin resistance in type 1 diabetes (T1DM). This thesis examined: (i) cardiovascular, renal and metabolic differences between individuals with T2DM ‘tolerant’ or ‘intolerant’ of TZDs; (ii) risk factors for TZD-associated oedema in T2DM; and (iii) the potential for metformin as adjunct therapy in T1DM. Methods: (i) A small clinical study characterising TZD tolerant and intolerant individuals with T2DM; (ii) A population-based epidemiological study of TZD induced oedema in individuals with T2DM in Tayside, Scotland (using incident loop diuretic prescription as a surrogate); (iii) A systematic review and meta-analysis of published studies of adjunct metformin in T1DM. Results (i) During a five-day high sodium diet, two known TZD-intolerant individuals with T2DM had reductions in haematocrit, aldosterone, and diastolic BP and increases in ANP and central and peripheral augmentation indices which were outwith reference ranges derived from nine TZD-tolerant individuals; (ii) Predictors of time to loop diuretic prescription included age, body mass index, systolic BP, haematocrit, ALT and macrovascular disease but rates of this outcome did not differ by therapy: 4.3% (TZDs) vs 4.7% (other agents) [unadjusted OR 0.909 (95% CI 0.690, 1.196); p = 0.493]; (iii) In meta-analysis of nine small studies in T1DM (192.8 patient-years of follow-up), metformin was associated with a reduction in total daily insulin dose (6.6 units/day; p < 0.001) but no studies examined cardiovascular surrogates or outcomes. Conclusions: Hypotheses were generated for several potential biomarkers predictive of TZD-induced oedema but the clinical importance of TZDs as a risk factor for oedema in individuals with T2DM was questioned. As there is some evidence for the safety of metformin as an adjunct therapy in T1DM but little evidence of efficacy, larger studies are warranted.

Background Over the long term, unhealthy lifestyles can lead to many health problems, especially type 2 diabetes (T2D). The aim of the present study was to determine associations between lifestyle factors (smoking, alcohol consumption, physical activity, and diet) and T2D in American adults (aged ≥20 years) in a nationally representative sample. Methods Data for 12 987 American adults participating in the National Health and Nutrition Examination Survey 2005–2014 were evaluated. Weighted multiple logistic regression models were used to examine associations between the four lifestyle factors and T2D after adjusting for demographics and socioeconomic status (SES). Prevalence trends for T2D were examined using Cochran–Armitage tests. Results There was a significant increasing prevalence trend for T2D among American adults. Smokers and individuals consuming >12 alcoholic drinks in the past year were less likely to report having T2D than non-smokers (odds ratio [OR] 0.41; 95% confidence interval [CI] 0.35–0.48) and those consuming Conclusion All four lifestyle factors were significantly associated with T2D among American adults. The findings of the present study provide useful information for healthcare providers that may help them promote specific lifestyle modifications.

Le diabète de type 2 (DT2) progresse dans le monde entier de manière alarmante. Les complications sont graves et les traitements sont souvent inefficaces et donnent beaucoup d'effets indésirables. Le resvératrol (RSV) et la curcumine (Cur), des polyphénols naturels, sont connus pour leurs différentes activités pharmacologiques, y compris antidiabétiques. Les objectifs de cette étude ont été d'évaluer les effets de la combinaison de ces deux polyphénols sur l'amélioration de la tolérance au glucose. Nos résultats montrent que chez des souris soumises à un régime riche en graisse (HFD), le RSV améliore la tolérance au glucose alors que la Cur n'a pas d'effet significatif. De manière surprenante, lorsque les deux polyphénols sont administrés simultanément, la Cur inhibe l'effet du RSV sur l'amélioration de la tolérance au glucose. Pour expliquer cet antagonisme, nous avons évalué l'effet de ces polyphénols associés ou pas sur le métagénome. Nos résultats indiquent que la Cur et le RSV normalisent la flore intestinale altérée par le HFD. Lors d'une association de ces polyphénols, la Cur inhibe aussi l'effet du RSV sur la croissance de certaines espèces bactériennes. Ainsi, la Cur bloque l'effet inhibiteur du RSV sur Alistipes putredinis. Nos données indiquent que ces polyphénols sont en général anti-inflammatoires mais leur association peut être synergique in vitro ou bien, à l'opposé, antagoniste in vivo pour l'expression de certaines cytokines. Afin d'évaluer l'effet physiologique de la modification de la flore intestinale par les polyphénols, nous avons étudié le métabolome. Parallèlement au métagénome, chacun des polyphénols améliore le profil métabolomique altéré par le HFD. Cependant, la Cur s'oppose à l'effet du RSV. Les données de ce travail indiquent que la Cur n'est pas associable au RSV pour améliorer la tolérance au glucose. / Each year, the worldwide impact of type 2 diabetes (T2D) increases significantly. The complications are serious and treatments are often ineffective and provide a lot of side effects. Resveratrol (RSV) and curcumin (Cur) are natural polyphenols known for their different pharmacological activities, including anti-diabetic. The objectives of this study were to evaluate the effects of the combination of these polyphenols on glucose tolerance improvement. Our results show that in animals fed with a high fat diet (HFD), RSV improved glucose tolerance while Cur displayed no significant effect. Surprisingly, when both polyphenols were administered simultaneously, Cur inhibited the effect of RSV on glucose tolerance improvement. To explain this antagonism between both polyphenols on glucose tolerance, we have evaluated the effect of these compounds on the metagenome associated or not. Our results indicate that RSV and Cur normalized gut flora altered by HFD. When Cur and RSV were administrated simultaneously, Cur inhibited the effect of RSV on the growth of some bacterial species. Thus, Cur blocked the inhibitory effect of RSV on Alistipes putredinis. Our data indicate that these polyphenols displayed generally anti-inflammatory effects, but their combination may be either synergistic in vitro or antagonistic in vivo on the expression of some cytokines. To evaluate the physiological effect of the gut flora changes induced by polyphenols, we have drawn a parallel between metagenome and metabolome data. Each of the polyphenols improved by itself the metabolomic profile altered by HFD. However, Cur hindered the effect of RSV. In a whole, this study indicates that combination of Cur with RSV is not successful to further enhance the RSV-induced improvement of glucose tolerance.

Diabetic cardiomyopathy characterized by left ventricular hypertrophy predisposes diabetic and obese individuals to development of cardiac dysfunction and subsequently to heart failure. Whether hyperinsulinemia has an underlying role in development and or progression of diabetic heart disease is not well understood. We therefore studied the effects of acute hyperinsulinemia on cardiac function in euglycemic states. Acute hyperinsulinemia neither affected baseline nor inotropic response to β-adrenergic stimulation. Previous studies from our laboratory have indicated a potential role for GRK2, a serine threonine kinase in development of cardiac dysfunction in diabetic states in humans as well as in mice. To assess whether GRK2 mediates the detrimental effects of chronic hyperinsulinemia on cardiac dysfunction in mouse model of diet induced obesity, we utilized cardiomyocyte knockout of GRK2. Our results suggested lack of cardiac functional impairments in high fat fed wildtype mice, which hindered our attempts to ascertain the role of GRK2 in diabetic cardiomyopathy. Mouse models of diet induced obesity have been routinely used to study the effects of obesity and diabetes on cardiac dysfunction but recent evidence from multiple research groups has emphasized the need for evaluation of the utility and relevance of the murine diet induced obesity model for studying cardiovascular abnormalities associated with hyperinsulinemic states, including T2DM and obesity. We therefore studied the effect of chronic fat feeding (>20 weeks) alone or in combination with concomitant hypertension on cardiac function in C57BL/6J mice. Different diets were formulated with either lard (32% saturated fat, 68% unsaturated fat) or hydrogenated coconut oil (95% saturated fat) as the source of fat and fatty acids, which contributed 60% of total calories. Insulin resistance and glucose intolerance were readily observed in mice fed a high fat diet in each of the studies. HFD resulted in the development of cardiac hypertrophy; however cardiac function as measured by B-mode echocardiography and LV catheterization was unaffected in high fat diet groups compared to their respective control diet groups. Further, dietary fat feeding regardless of the source of fat modestly altered the gene expression of a few pathological hypertrophic markers or of fibrosis related genes. However, there was an increase in expression of PPARa target genes such as Pdk4 and fatty acid metabolism genes including CD36, AcadL and Cpt1b. Cardiac mitochondrial function as assessed by oxygen consumption rates, ATP synthesis rates and reactive oxygen species production rates were unaltered in high fat diet fed mice. These results suggest that while chronic fat feeding in mice causes cardiac hypertrophy and potentially cardiometabolic remodeling, it might not be sufficient to activate pathological hypertrophic mechanisms that impair cardiac function and cause cardiac fibrosis.

Obesity-related diseases have been increasing in African immigrants throughout the United States. Although research has been done to identify risk factors associated with many ethnic groups in the United States, only a few studies exist that explore obesity and type 2 diabetes diseases among Central African immigrants. The conceptual framework for this qualitative case study was social constructivism and the health belief model. The primary research question addressed the potential underlying causes for an increase in obesity and type 2 diabetes among Central African Immigrants. The secondary research questions explored how culture, illiteracy, and religion contribute to the problem of obesity in Central African immigrants, and what strategies could be effective in preventing and reducing the increase of obesity and type 2 diabetes in this population. Interviews with 17 Central African immigrants living in the northeastern U.S. were conducted to explore their social, cultural, and behavioral factors that influence the prevalence of obesity. Interview responses were transcribed and entered into NVivo software for data analysis. The results revealed that socioeconomic issues, cultural differences, and language gaps were the primary risk factors. Feeling stressed and overwhelmed and a lack of communication were also found to be significant. The results could provide health administrators and health educators with a platform for advancing policies and programs to foster greater health and well-being among Central African immigrants and thus contribute to the overall social welfare of Central African immigrants.

Type 2 diabetes mellitus self-management is a challenging process that brings forward a variety of emotional responses. The purpose of this work was to explore relationships between diabetes distress, self-efficacy and resilience and outcomes of glycosylated hemoglobin, quality of life and health status. A cross sectional descriptive design was used for this pilot study of 78 individuals enrolled from an Endocrine clinic in the Midwest United States and a Primary Care clinic in the southeast United States. Data were analyzed using descriptive statistics to characterize the sample and model variables. Spearman’s correlation was completed to identify relationships among variables. A stepwise building approach was used to identify significant interactions and determine predictors of the study outcomes. The results of this study confirm the presence of facilitators and barriers in type 2 diabetes mellitus self-management and their relationships with distal outcomes. The findings demonstrate that diabetes distress is a predictor of health status and quality of life. The findings of this study provide a link to other facilitator and barrier variables such as provider collaboration, diabetes self-management education, treatment regimen, ethnicity and years since diagnosis which can be incorporated into the comprehensive theoretical model. This study contributes to the understanding of the emotional aspect of diabetes as it relates to self-management of T2DM. Continuing this work will allow researchers to examine and better understand important factors of self-management. This ongoing work will hopefully lead to improved support in self-management efforts and better outcomes.

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

Type 2 diabetes (T2DM) is a health epidemic that continues to worsen. A major concern is that treatment adherence rates hover around 50%, despite the introduction of new medications, treatments, and technology. Lack of adherence by patients can lead to complications like blindness, kidney disease, and amputations. While there have been many studies conducted to evaluate patient factors related to adherence, fewer studies have been conducted to evaluate the role of the physician-patient relationship. The purpose of this study was to examine the correlation between the physician-patient relationship and patient treatment adherence, and examine the moderators of age, education, ethnicity, and income. Gender was included as a moderator in a secondary analysis. Two theories formed the theoretical framework of this study: biopsychosocial model and self-efficacy theory. This quantitative nonexperimental study was completed with survey data collected from 92 participants in the United States ages 18 or older who were under treatment for T2DM for at least a year, and who had seen their physician at least once in the previous year. Correlational and regression analyses were conducted using data from the modified Clinician and Group Survey and the Diabetes Management Self-Questionnaire. The physician-patient relationship predicted treatment adherence, and gender moderated the relationship. These findings suggest the importance of the physician-patient relationship as a factor in patient treatment adherence. This has important implications for social change because an understanding of which physician factors lead to treatment adherence may help improve patient outcomes, reduce T2DM complications, improve patient quality of life, and reduce healthcare costs.

Type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) are 2 chronic diseases with common risk factors related to physical inactivity, obesity, and diet. Literature on T2DM as a risk factor for CRC development and survival in Oman is scarce. Using de-identified archival data provided by Sultan Qaboos University Hospital (SQUH) Oman, a retrospective, case-control, and time-to-event study designs were used to compare odds of developing CRC, and survival rates among adults with and without T2DM. The ecosocial theory provided the theoretical base for this research. Logistic regression was used to examine the odds of developing CRC among 114 cases versus 170 hospital controls. The Cox proportional hazards regression was used to compare survival rates among 228 CRC cases by T2DM status and survival rates by T2DM status across strata of gender, age group, and tumor location and cancer stage. According to the study findings, after having adjusted for potential confounding variables, there was no association between T2DM and odds of developing CRC (OR = 1.49, 95% CI: 0.29-7.68, p = 0.64) or between T2DM and CRC survival rates (HR = 1.07, 95% CI: 0.65 -1.75, p = 0.80). There was also no association between T2DM and CRC survival rates across the strata of potential effect modifiers examined. This research could contribute to positive social change by creating awareness among policy makers that will provide them with information on CRC risk-reduction strategies in the Omani population.

The goal of diabetes education programs (DEPs) is to improve patients' pattern-management habits for those with type 2 diabetes (T2D), though participation in DEPs is lower than expected due to low physician referral rates. This retrospective study examined secondary data of 162 T2D patients who had been referred to a DEP in a community center in RI to determine whether the source of referral affected patient attendance, participation persistence, and outcomes. Self-referred (n = 62) and physician-referred (n = 100) groups were analyzed for possible associations among the aforementioned variables. Chi-square (p = .04) and logistic regression (p = .04) indicated that the referral source for a DEP does have an effect on participation rates, while logistic regression showed that odds for self-referred patients to participate were 1.97 times higher. Multiple linear regression found no difference between the referral source and the number of sessions patients completed, though covariate analysis showed that age (p = .02) contributes to the model. Multiple linear regression showed no difference between the number of sessions attended and changes in hemoglobin A1c (HbA1c) levels. It is important to note that those who completed the program and reported pre- and post-program HbA1c levels (n = 7) all reported improved outcomes. This highlights the limitation of the small sample size (n = 7), which increased the possibility of a Type II error. This community center DEP model can serve as a blueprint, highlighting the importance of diabetes education and leading to positive social change by improving referral and participation rates and resulting in fewer complications, a decreased disease burden, and an improved quality of life.