This thesis investigated the integration of pharmacological and phytochemical data of medicinal plants from the Cree of Eeyou Istchee in Northern Quebec. Data from these 17 plant extracts were assessed for patterns of biological activity and chemical signals that could be explained by taxonomic or plant organ groupings. The Squamish medicinal plant Oplopanax horridus (Sm.) Miq. was also assessed for enzyme inhibition activity across multiple extracts and for bioactive compounds using an untargeted metabolomics approach. A comprehensive data set was assembled documenting the relative activities on the 17 plant extracts in 69 cell-free and cell-based bioassays covering activity on glucohomeostasis, effects of hyperglycemia, and capacity for enzyme inhibition. Multivariate analysis suggests that the leaf part extracts are particularly associated with antioxidant and antiglycation activities, while another discrete group of extracts associate strongly with other sets of glucohomeostasis assays. The activity of extracts on enzyme inhibition appears to be the factor most strongly driving the majority of activity patterns, likely because extracts that interact strongly with more metabolic enzymes will have more effects on other targets in the body. The phytochemical profiles of the Cree medicinal plants were assessed in two ways. First, spectroscopic and chromatographic data for the plant extracts was compared to a database of phytochemical standards using a proprietary Waters software, UNIFI, to match known signals of chemical standards to unidentified peaks in the plant extracts. Second, similarly collected spectroscopic data for the Cree plant extracts was processed using the software MZMine for multivariate analysis in R, revealing the chemical diversity of the bark extracts in relation to the fruit and leaf extracts. Additionally, marker signals were determined for major sample groupings, and the capacity for this analytical approach to be used to tentatively identify unique compounds was demonstrated. Through bioassay guided fractionation of the O. horridus inner bark extract using the CYP 3A4 inhibition assay, the DCM subfraction midway through the non-polar elution on open column chromatography was determined to be the most potent. This fraction contained 10 major peaks on HPLC-DAD analysis. The hot water extract was found to have negligible activity on CYP 3A4 inhibition. Together, this research provides the first integrated look at the pharmacological and phytochemical data from across the Cree anti-diabetic medicinal plants in a statistical way, as well as providing a first look at O. horridus for inclusion in the anti-diabetes project.

Please read the abstract in the section, 00front, of this document / Dissertation (MSc)--University of Pretoria, 2003. / Clinical Epidemiology / MSc / unrestricted

Thesis (MPH.) -- University of Limpopo, 2021 / Background: Diabetes mellitus (DM) is a major public health problem, and it remains one of the global epidemics of non-communicable diseases. Diabetic retinopathy (DR) is a micro-vascular complication of DM due to a prolonged hyperglycaemia, and it is the most common cause of a visual loss in people living with DM. The global increase in the prevalence of DM has led to an increase in prevalence of diabetic complications, such as DR. The primary aim of this study was to investigate the prevalence and determinants of DR among the DM patients receiving treatment from Maruleng public healthcare facilities, Mopani District in the Limpopo Province. Methodology: A quantitative cross-sectional survey was used as a primary source data from the DM patients who were readily available at the selected public healthcare facilities to collect a chronic treatment during the time of the study. Selection of eligible DM patients was done through a convenient sampling technique for those who were readily available or willing to take part of the study after receiving all information about the study for them to consent freely without any form of coercion by researcher or any other person. All selected respondents had undergone face-to-face interviews and basic clinical screening for DR to collect a primary source data using piloted structured researcher-administered questionnaire to record data collected from respondents, and calibrated medical equipment were used to measure a clinical variables during clinical screening. Data analysis was carried out using Statistics and Data Analysis (STATA) version 15 software for windows. The characteristics of DM patients were summarised and analysed using a descriptive statistics. Inferential statistics were performed on dependent variable and independent variables using a logistic regression analysis to determine the strength of association between variables, where a potential predictors of DR among DM patients were identified at significant level of less than 0.05 (p<0.05). Results: Out of the 416 DM patients who participated in the study, the majority were females (n=315; 76%) and all DM patients were above the age of 18 years, with a mean age of 61 years (standard deviation [SD] =11.5). The overall prevalence of DR was 35.4% comprising 32% mild non-proliferative DR (NPDR) and 3.4% moderate NPDR. DR was found to be slightly more prevalent in females, at 35.9%, than in males, at 34.6%; particularly in those females with type 2 DM, at 35.1%, comprising 32.1% mild NPDR and 3% moderate NPDR. DR was more prevalent in older females, at 77.8%, comprising 55.6% mild NPDR and 22.2% moderate NPDR. The DM patients aged 55 years and above were found to be 2.7 times more likely to develop DR, at p<0.001, and DM patients with higher systolic blood pressure of 140 mmHg or more were found to be 1.4 times more likely to develop DR as compared to DM patients with a systolic blood pressure of 139 mmHg or less (≤139 mmHg), at p<0.05. Employed DM patients were 1.4 times more likely to develop DR as compared to unemployed DM patients, at p<0.001. Age of the DM patients, high systolic blood pressure (SBP) or a hypertension of 140 mmHg or more (≥ 140 mmHg), and employment status were significantly associated with higher risk of developing DR among DM patients. Gender, hyperglycaemic state, poor glycaemic control, smoking and high BMI were found to be associated with DR but this association was not statistically significant. Conclusion and recommendations: Slightly more than one third of the DM patients receiving treatment during the study period from the public healthcare facilities in the Maruleng sub-district had some form of DR, which means that nearly four in ten DM patients had some form of DR. Diabetic retinopathy was more prevalent in females, and in older DM patients. Age of the DM patient, employment status, and high systolic blood pressure were significantly associated with an increased risk of developing DR among the DM patients. There is an urgent need to implement a health promotional programmes to educate people about the complications of a diabetes mellitus such as DR, and also to establish a coordinated screening programme for DR among DM patients receiving a chronic treatment, which must be supported by the Department of Health in all public healthcare facilities. Keywords: Diabetes Mellitus, Diabetic Retinopathy, Prevalence, Determinants / Health and Welfare Sector Education and Training Authority (HWSETA)

BACKGROUND: While not definitive, many studies demonstrate a link between type 2 diabetes mellitus (DM) and a higher risk of all-cause dementia and Alzheimer’s disease (AD). This study aims to compare the risk of developing all-cause dementia or AD in subjects with a history of controlled versus uncontrolled DM. METHODS: Framingham Heart Study (FHS) Offspring Cohort participants that were without dementia and at least 45 years old when they attended the 7th biennial examination (n = 2978 persons) were included in this prospective community-based cohort study. Subjects were designated a history of controlled DM if they had a positive history of DM and fasting blood glucose (FBG) less than 140 mg/dL. Subjects were designated a history of uncontrolled DM if they had a positive history of DM and FBG greater than or equal to 140 mg/dL. All-cause dementia was determined through criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). AD was determined through criteria from the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA). Models were adjusted for age, self-reported sex, education and cardiovascular risk factors. RESULTS: At baseline, 333 participants (11.2%) were positive for ‘current diabetes.’ In the 20-year follow-up period, 12.2% of uncontrolled DM subjects, 11.2% of controlled DM subjects, and 6.4% of normal control (NC) subjects developed all-cause dementia. Relative risk for all-cause dementia with controlled DM was 1.62 (95% confidence interval, 0.900 - 2.93). Relative risk for all-cause dementia with uncontrolled DM was 1.72 (95% confidence interval, 1.02 - 2.89). 11% of uncontrolled DM subjects, 7.9% of controlled DM subjects, and 4.7% of NC subjects eventually acquired AD. The relative risk for AD with controlled DM was 1.76 (95% confidence interval, 0.890 – 3.47). Relative risk for AD with uncontrolled DM was 2.15 (95% confidence interval, 1.22 - 3.80). CONCLUSION: In the FHS Offspring Cohort, subjects with uncontrolled DM were at higher risk of developing all-cause dementia and AD compared to controlled DM and NC participants. The controlled DM status was not found to be a risk factor for all-cause dementia or AD.

Bullosis diabeticorum, or diabetic bullae, is a non-inflammatory blistering condition that is virtually diagnostic of diabetes. Diabetic bullae most often present as painless, tense, superficial bullae that occur in an acral distribution and commonly heal in 2-6 weeks without scarring, but complications such as secondary bacterial infection or hemorrhage may occur. The diagnosis of bullosis diabeticorum in a nondiabetic patient should prompt screening for diabetes. A case of recurrent bullae in a prediabetic patient is presented, with a review of the clinical features and significance of bullosis diabeticorum.

BACKGROUND: Alveolar bone resorption is more severe in type 2 diabetes-potentiated periodontitis. The key cells responsible for bone resorption are the osteoclast and their quantity and activity are regulated by the RANK/RANKL/OPG system. One of the major RANKL-expressing sources in diseased periodontal tissue are activated B and T lymphocytes, therefore it was hypothesized that type 2 diabetes up-regulates B cell RANKL function. OBJECTIVE: The aim of this study was to compare the effect of diabetes on the ability of B and T lymphocytes to stimulate osteoclast activity. MATERIALS AND METHODS: Metabolic status (diabetic vs normal) of mice were established using either a low-fat diet (LFD) or high-fat diet (HFD). Spleen lymphocytes were harvested and purified, then cultured in different combinations with adherent mouse leukemic monocyte/macrophage cell line cells over dentin-coated wells and observed for osteoclastic activity that breaks down the dentin-coating. The area of clearance was used to represent the level of activity. RESULTS: No difference in osteoclastic activity were noted between the two metabolic statuses, between B or T cells, between lymphocyte stimulated or not. CONCLUSION: The findings counters our hypothesis, and are inconsistent with the currently available evidence. Repeat of the experiment is warranted before valid conclusion can be drawn from the data.

The prevalence of diabetes is increasing among persons of Caribbean ancestry in the United States, yet there is little research on the differences in the health and nutrition patterns of diabetics from this population. This study created a culturally-sensitive diabetes education program for the staff of an internal medicine practice that treated patients from the English-speaking Caribbean. The project was guided by the health belief model, as well as Leininger's theory of transcultural nursing. Methodology of project had a quality improvement focus. The comprehensive curriculum included diabetes medications, physical activity, culturally-tailored medical nutrition therapy, complications, self-care behavior, problem solving, and goals. Tools incorporated into the program included DVD, self-learning power point modules, and staff and patient education materials. The diabetes education program was introduced to 16 members of the internal medicine staff, chosen by the physician. A question and answer session was included, during which medical personnel articulated satisfaction with the program. Also verbalized was their increased understanding of diabetes education, and medical nutrition therapy tailored towards English-speaking Caribbean diabetics. The implication for social change indicates that in order for patients of the target population to receive quality, culturally-specific diabetes education, medical personnel must receive structured culturally-tailored diabetes education. Education translated into evidence-based patient education and practices. Program evaluation can be undertaken by monitoring staff and patient satisfaction, and improved patients' hemoglobin A1C.

Diabetes has quickly become an epidemic in the United States and affects all genders and races. Some ethnic groups are at greater risk for being diagnosed and face devastating health consequences due to poor diabetes self-management. Diabetes self-management education (DSME) is considered to be a positive step toward patient self-efficacy and diabetes management. The benefits of diabetes self-management education can only be realized if patients diagnosed with diabetes not only enroll, but complete the program. The purpose of this research study was to investigate the association between race and gender and dropout rates among participants enrolled in a DSME program. Archival data from a DSME were collected for 352 participants enrolled in the program. A multiple logistic regression was used to analyze whether independent variables of race and gender were predictors of dropout rates. Chi-square was used to explore if there was an association between race and gender and drop-out rates. Results revealed that there was no statistically significant association between race and gender and dropout rates from participants in a DSME program. Positive implications for social change include exploring the reasons participants choose to drop-out of a DSME program and potentially identify those at risk for droppoing out due to challenges and barriers.

Indiana University-Purdue University Indianapolis (IUPUI) / In this exploratory, qualitative study, the author examined the lived experiences of low-income type 2 diabetics around managing their diabetes. Semi-structured, individual interviews were conducted with volunteer participants from a Midwest student outreach clinic (N=14; 8 men, 6 women). Interviews were first analyzed using LUUUUTT model from the Coordinated Management of Meaning (CMM) theory for gaps between stories lived and stories told. Findings suggest that the lived experience of the majority of the participants had low social support and heightened stress around managing their diabetes. Using the Communication Complex framework, the patterns of interactions around these two tensions were analyzed to make suggestions for change.

Indiana University-Purdue University Indianapolis (IUPUI) / The role of beta cell miR-21 in Type 1 Diabetes (T1D) pathophysiology has been controversial. Here, we sought to define the context of beta cell miR-21 upregulation in T1D and the phenotype of beta cell miR-21 overexpression through target identification. Furthermore, we sought to identify whether circulating extracellular vesicle (EV) beta cell-derived miR-21 may reflect inflammatory stress within the islet during T1D development.. Results suggest that beta cell miR-21 is increased in in-vivo models of T1D and cytokine-treated cells/islets. miR-21 overexpression decreased cell count and viability, and increased cleaved caspase-3 levels, suggesting increased cell death. In silico prediction tools identified the anti-apoptotic mRNA B Cell Lymphoma 2 (BCL2) as a conserved miR-21 target. Consistent with this, miR-21 overexpression decreased BCL2 transcript and protein expression, while miR-21 inhibition increased BCL2 protein levels and reduced cleaved caspase-3 levels following cytokine-treatment. miR-21-mediated cell death was abrogated in 828/33 cells, which constitutively overexpress BCL-2. Luciferase assays suggested a direct interaction between miR-21 and the BCL2 3’untranslated region. With miR-21 overexpression, PRP revealed a shift of BCL-2 message toward monosome-associated fractions, indicating inhibition of BCL2 translation. Finally, overexpression in dispersed human islets confirmed a reduction in BCL2 transcripts and increased cleaved caspase 3 production. Analysis of EVs from human beta cells and islets exposed to cytokines revealed a 3-5-fold increase in miR-21. Nanoparticle tracking analysis showed no changes in EV quantity in response to cytokines, implicating specific changes within EV cargo as responsible for the miR-21 increase. Circulating EVs from diabetic non-obese diabetic (NOD) mice displayed progressive increases in miR-21 that preceded diabetes onset. To validate relevance to human T1D, we assayed serum samples collected from 19 pediatric T1D subjects at the time of diagnosis and 16 healthy controls. Consistent with our NOD data, EV miR-21 was increased 5-fold in T1D samples. In conclusion, in contrast to the pro-survival role reported in other systems, our results demonstrate that miR-21 increases beta cell death via BCL2 transcript degradation and inhibition of BCL2 translation. Furthermore, we propose that EV miR-21 may be a promising marker of developing T1D.