Diabetes mellitus (DM) is a life changing disease which affects a large portion of the population and the economy through high medical costs and loss of productivity. Marrubiin (MAR), a diterpenoid isolated from Leonotis leonurus, a plant indigenous to Southern Africa, is used by traditional healers to alleviate DM symptoms. This study aims to screen the inhibitory potential of MAR and MAR derivatives on PTP1β and glucose uptake properties of Chang liver, C2C12 and 3T3-L1 cells. Marrubiin and 19 of its derivatives were tested to determine the inhibition constants for PTP1β. A Ki of 21 μM and 0.047 μM was detected for oleanolic acid in silico and in vitro, respectively. All other diterpene derivatives did not display substantial levels of inhibition of PTP1β. Treatment of Chang liver cells with the various MAR derivatives (10 μM) did not significantly increase glucose uptake beyond metformin, a known antidiabetic drug. The various treatments showed a protective/proliferative effect on the C2C12 muscle cells with two MAR treatments (DC16 and DC18) significantly increasing glucose uptake as compared to metformin in C2C12 muscle cells. It was noted that DC17, DC18 and MAR significantly increased glucose uptake in 3T3-L1 adipocytes, relative to the control. Contrary to cytotoxicity studies with Chang liver and C2C12 muscle cells, adipocytes displayed no cytotoxicity to treatments while a significant increase in cell viability was seen for DC9 and DC15. To unravel the mechanism of action, Western blotting analysis was completed and an increased expression of PTP1β was observed for treatments with DC17 and DC6 was seen in adipocytes, while DC18 and metformin decreased expression significantly. This correlated with a significant decrease of Ser 612 phosphorylation of insulin receptor substrate (IRS1) for DC17. Real time qPCR of IRS1 and GLUT4 highlighted that DC17 and MAR were able to significantly increase expression of IRS1 and GLUT4, respectively. The results show that MAR and the selected derivatives (DC6, DC17, DC18) have been found to increase glucose uptake in peripheral tissue types with IRS1, GLUT4 and PTP1β being associated with the mechanism of action. However, a complete understanding of the mechanisms is yet to be established.

The need for alternative strategies for the prevention and treatment of diabetes is growing rapidly as type II diabetes is reaching epidemic status in our society. This need was the basis for the creation of this study, as it was necessary to start looking towards medicinal plants as potential antidiabetic treatment and no comprehensive in vitro model existed. In creating a model for determining the effects of alternative traditional medicines as antidiabetic potentiates, it was necessary that two metabolic pathways, namely glucose uptake and insulin secretion, which play a significant role in glucose homeostasis, be at the centre of our investigations. The objective of this project was to optimize the methodology required to screen and ultimately determine the effectiveness of the plant extracts Kankerbos and MRC2003, as antidiabetic potentiates, through observing their effects on glucose utilisation and insulin secretion. If these medicinal plants are going to make a positive contribution to the health of type II diabetic South Africans, then the determination of their efficacy is essential. The cell lines used in this study included 3T3-L1 preadipocytes, Chang liver, C2C12 muscle and INS-1 rat pancreatic cells. Each cell line represents a different in vivo organ that is known to have an influence on glucose homeostasis in our bodies, each with its own unique metabolic pathways and mechanisms of activity, thereby making each one a vital component in the study. The positive controls for the two models were insulin and metformin (glucose utilisation) and glibenclamide (insulin secretion). Insulin was shown to provide a significant increase in the amount of glucose taken up in C2C12 muscle and Chang liver cells for acute conditions. Chronic treatments with metformin provided a significant increase in glucose utilised by Chang liver cells. Glibenclamide was an effective positive control for stimulating insulin secretion by INS-1 cells under acute conditions as there was a significant increase in the amount of insulin secreted. MRC2003 did not show any significant antidiabetic activity. Sutherlandia frutescens (Kankerbos) showed biological activities comparable to some of the more recognized antidiabetic compounds throughout the study. With regards to the glucose utilisation model, Kankerbos was seen to have both acute and chronic effects in different cell lines. In the C2C12 muscle cell line, Kankerbos significantly increased glucose uptake when they were exposed to acute conditions. Kankerbos also had a significant effect on the Chang liver cells as it was observed that under both acute and chronic conditions, this plant extract induced the uptake of glucose into these cells. With respect to the insulin secretion model involving INS-1 cells, no significant effect was seen during acute exposure with Kankerbos treatment. However during chronic exposure, an increase in insulin secretion was initiated by this plant extract. Overall, the results of this study suggest that Kankerbos has a twofold mechanism of action for its glucose-lowering effects. Given that Kankerbos is widely available in South Africa, this study was valuable as it provided an indication that Kankerbos has antidiabetic activities and could possibly be used as an alternative antidiabetic medication.

This study will be focussing on the experiences of Xhosa-speaking patients with DM utilising the NMMM public hospitals complex. In the OPD patients are assessed and treated for all chronic conditions including DM, and patients are seen at monthly intervals or when necessary. The OPD serves the neighbouring black population from the surrounding townships as well as the informal settlements. The effects of urbanisation have resulted in this area having a semi–rural, semi-urban population that is mostly Xhosa speaking. The bulk of the population is unemployed, while others are living on a minimal income. Unemployment in the Eastern Cape ranges from 40% in rural areas, rising to 50 - 60% in the urban areas (Proposed aluminium Pechiney smelter within the Coega IDZ, 2002:4-8). In some homes there is no or little money to buy food, and even less to make use of a health service. Some people live on either a social grant for the elderly, a grant for young children or a disability grant and most people in this area have an income below the level at which payment of taxes for contribution to the economy is possible.

Thesis (M. Pharm) -- University of Limpopo, 2019 / Diabetes mellitus (DM) is a major public health problem, challenging patients, healthcare professionals, health planners and policy makers worldwide. Its prevalence has been on the rise for the past four decades, with this trend expected to continue. With this challenge, the management of DM should be done following evidence-based guidelines to prevent or slow down the development of DM-related complications. According to the Society of Endocrinology Metabolism and Diabetes South Africa (SEMDSA) guidelines, it has been shown that strict glycaemic control and proper clinical monitoring can help with prevention and slowing down development of complications. If left untreated or poorly controlled, DM progresses into an array of complications which may increase morbidity and mortality. The prevalence and management of DM complications was investigated. Objectives: • To determine the prevalence of DM complications at Mankweng Hospital. • To evaluate the management of patients with DM complications at Mankweng Hospital. • To determine the factors contributing to the development of complications. • To determine preventive measures taken on non-complicated patients to prevent them from complicating. Method: A retrospective longitudinal review of 134 randomly selected patient records was conducted for a five-year period spanning from June 2012 to May 2017. A pretested DM complications checklist was used to collect data from the patient records. A cross-sectional study was conducted amongst healthcare professionals caring for patients with DM. A total of 41 healthcare professionals were included in the study where a self-administered questionnaire was used to obtain the data. Both sets of data obtained were analysed using IBM SPSS version 25. xiii Results: Retrospective study The study sample population was entirely consisted of African patients with 70.1% (n=94) females and 29.9% (n=44) males. In the sample, 17.2% were suffering from T1DM while 82.8% were suffering from T2DM. The complications with the highest prevalence were diabetic nephropathy, peripheral neuropathy and diabetic retinopathy with prevalence of 35.8%, 32.1% and 22.4% respectively. Vascular diseases, autonomic neuropathy and diabetic foot ulcer had prevalence of 9.7%, 9% and 6% respectively. The overall prevalence of complications in general was 67.2% which was very high. Cross-sectional study A self-administered questionnaire was distributed amongst 41 healthcare professionals (14 males and 27 females). This sample consisted of 9.8% doctors, 41.5% pharmacists, 17.1% professional nurses, 17.1% physiotherapists, 2.4% podiatrists and 12.2% optometrists. It was discovered that only 92.6% and 84.6% of the participants were compliant with the guidelines in terms of random blood glucose tests and blood pressure (BP) per every visit. Only 50% of the HCPs revealed that HbA1c tests should be done according to the guidelines. Merely 5.6%, 8.3%, 5.3% and 22.7% of the HCPs correctly indicated the frequency of foot examinations, eye examinations, renal function tests and lipogram tests respectively, as per the guidelines. Patient related factors were rated as the most contributory factors (56.4%) to the development of complications. Socio-economic and medication related factors had most of the HCPs (36.1% and 29% respectively) rating them as moderate in terms of how much they contribute to the development of complications. The factors rated the least were healthcare team (32.4%) and health system (33.3%) related factors. Conclusion: There was a high prevalence of overall complications in general, with diabetic nephropathy, peripheral neuropathy and diabetic retinopathy being the three highest individual complications. There was poor monitoring of patients with complications as the compliance with the SEMDSA guidelines was very low. Patient related factors xiv were rated the most contributory factors to the development of complications in patients with DM. Recommendations: There is need to implement patient-centred DM care which makes sure that the patient is involved in decision making so that they take responsibility of their own health. There is need for the development and implementation of institutional quality improvement programs where regular audits of the processes of DM care and outcomes are monitored. Limitations: • The limitations of the study are that the researcher completely relied on patient records. • The sample size for HCPs was very small and therefore the study results cannot be generalised. / HWSETA

Type 2 diabetes mellitus is a chronic disease of pandemic magnitude, increasingly contributing to the disease burden of countries in the developing world, largely because of the effects of unhealthy lifestyles fuelled by unbridled urbanisation. In certain settings, patients with diabetes are more likely to have a healthcare encounter with a pharmacist than with any other healthcare provider. The overall aim of the study was to investigate the potential of South African community pharmacists to positively influence patient adherence and metabolic control in Type 2 diabetes. The designated primary endpoint was glycated haemoglobin, with the intermediate health outcomes of blood lipids, serum creatinine, blood pressure and body mass index serving as secondary endpoints. Community pharmacists and their associated Type 2 diabetes patients were recruited from areas throughout South Africa using the communication media of various nonstatutory pharmacy organisations. Although 156 pharmacists initially indicated interest in participating in the study, only 28 pharmacists and 153 patients were enrolled prior to baseline data collection. Of these, 16 pharmacists and 57 patients participated in the study for the full twelve months. Baseline clinical and psychosocial data were collected, after which pharmacists and their patients were randomised, nine pharmacists and 34 patients to the intervention group and 8 pharmacists and 27 patients to the control group. The sample size calculation revealed that each group required the participation of a minimum of 35 patients. Control pharmacists were requested to offer standard pharmaceutical care, while the intervention pharmacists were provided with a scope of practice diabetes care plan to guide the diabetes care they were to provide. Data were again collected 12-months postbaseline. At baseline, proportionally more intervention patients (82.4%) than control patients (59.3%) were using only oral anti-diabetes agents (i.e. not in combination with insulin), while insulin usage, either alone or in combination with oral agents was conversely greater in the control group (40.7%) than in the intervention group (17.6%) (Chi-squared test, p=0.013). Approximately half of the patients (53.8% control and 47.1% intervention) reported having their HbA1c levels measured in terms of accepted guidelines. There was no significant difference in HbA1c between the groups at the end of the study (Independent t-test, p=0.514). In the control group, the mean HbA1c increased from 7.3±1.2% to 7.6±1.5%, while for the intervention patients the variable remained almost constant (8.2±2.0% at baseline and 8.2±1.8% at post-baseline). Similarly, there were no significant differences between the groups with regard to any of the designated secondary clinical endpoints. Adherence to medication and self-management recommendations was similarly good for both groups. There were no significant differences between the two groups for any of the other psychosocial variables measured. In conclusion, intervention pharmacists were not able to significantly influence glycaemic control or therapeutic adherence compared to the control pharmacists.

In Africa, use of medicinal plants for the treatment of diabetes is very common. However, efficacy on co-administering of medicinal plants with therapeutic drugs hasn't been fully determined, especially for African medicinal plants. The current study focused on assessing the in vitro modulation effects of three popular African medicinal plants, namely: Aloe ferox, Sutherlandia frutescens and Prunus africana (including five commercial preparations containing these medicinal plants) on two of the most important anti-diabetic drug metabolising enzymes, Cytochrome P450 (CYP450) 2C9 and CYP3A4 and a key drug efflux transporter, P-glycoprotein (P-gp). Vivid® microsome-based screening kits were used to assess inhibitory potency of plants preparations on CYP2C9 and CYP3A4 enzymes activities. The study showed that P. africana was a more potent inhibitor of CYP2C9 and CYP3A4 activity than the corresponding positive controls Ginkgo biloba and St. John's wort, which are known to cause clinically significant drug-herb interactions. S. frutescens leaf extract demonstrated potent to moderate inhibition on both the tested CYP activities, while its commercial products (Promune® and Probetix®) possessed moderate to mild inhibitory effects on the activities of both CYPs. Potent inhibitory effect on CYP2C9 and CYP3A4 was seen with Aloe Ferox®. Prosit® and Aloes powder® showed potent to moderate inhibition on CYP2C9 activity and moderate to mild inhibition on CYP3A4 activity. In addition to CYP450 activity, the present study also investigated the effects of the selected medicinal plant products on the activity of the main drug efflux protein, P-gp. A screening assay was specifically developed to assess the potential for herbal remedies to interact with P-gp mediated drug absorption. The assay is based on the principle of the reversal of drug resistance in modified Caco-2 cells specifically altered to express high iv efflux protein activity. These cells display a multidrug resistance phenotype and the addition of a plant extract containing a P-gp inhibitor or substrate will inhibit or compete with any cytotoxic drug and consequently reverse the drug resistance. The suitability of the assay was confirmed using a known P-gp inhibitor. The study observed that the anti-proliferation effect of vinblastine was significantly enhanced in vinblastine-resistant Caco-2 cells, which have high P-gp expression, when they were exposed to the selected African herbal preparations. This observation indicates that the studied plant preparations may alter P-gp functionality and therefore lead to interference with the absorption of co-administered drugs. The outcomes of this study provide useful information on whether there are any potential drug-herb interactions between the commonly used African medicinal plants and oral anti-diabetic drugs, at the level of CYP and P-gp drug metabolism and could contribute to better therapeutic management of Type II diabetics. However these predicted interactions will need to be verified in a clinical setting.

Thesis (M. A. (Nursing Science)) -- University of Limpopo, 2019 / Background: Non-attendance of diabetic patients at primary health care facilities for scheduled appointments has been identified as one of the most pressing issues in chronic illness, including diabetes mellitus, management and results into uncontrolled illnesses. Diabetes mellitus has an increased mortality and morbidity rate, thus has been identified as the second most frequent killer disease in South Africa. Aim of the study: The purpose of the study is to determine self-management strategies to maintain a healthy life for diabetic patients under treatment in primary health care facilities in the Sekhukhune District. Methods: A qualitative, phenomenological, explorative and descriptive study design was conducted in 5 clinics of the Sekhukhune District in the Elias Motswaledi Municipality in Limpopo Province. Data were collected through one-to-one interviews using semi-structured guide. An non-probability purposive sampling method was used to select participants until data saturation was reached. Data were analysed using Tech’s coding qualitative data analysis approach. Results: The findings of this research reveal that diabetic patients know the importance of adherence to diet. However, they also elaborated on the challenges they face, like inability to afford proper diet and their stress levels. They are aware of predisposing factors and recommend support structures like food parcels as well as adhering to the prescribed treatment. Conclusion and recommendations: Diabetic patients lack self-management strategies to maintain their quality of life when diagnosed with diabetes. Furthermore, the study concludes that diabetics lack encouragement and empowerment from health care workers and their families. The study recommends that diabetic patients adhere to a prescribed diet and treatment and that they could be offered food parcels and taught how to avoid factors that could trigger stress. Additionally, it is recommended that support structures be developed to assist diabetic patients about self-management strategies that they could use in order to maintain a good quality of v life. It is also recommended that the Department of Health employ Home-Based Carers in the facilities to assist diabetic patients with their day-to-day care.

Thesis (Ph.D.(Nursing Science)) -- University of Limpopo, 2021 / Health literacy related to medication use or instructions is crucial to diabetes mellitus patients. The verbal or written instructions are given to diabetes mellitus patients regarding medication use is important to improve patient care, safety, and compliance to treatment. However, the information provided to diabetes mellitus patients regarding medication use is not known as they continue to experience complications. The study aimed to develop and implement an educational programme, to enhance health literacy on prescribed medication instructions among diabetes mellitus patients on treatment at Ga-Dikgale village clinics in Capricorn District, Limpopo Province. The objectives of the study were to explore the knowledge, and practices of diabetes mellitus patients on treatment. Thus, to describe the provided information regarding prescribed medication usage contained in the diabetes mellitus medication packaging, medicine leaflets, and prescriptions. Therefore, to also describe the effects of poor health literacy on prescribed medication instructions among diabetes mellitus patients on treatment at Ga- Dikgale village clinics in Capricorn District, Limpopo Province. Data were collected using a mixed-method approach and a mixed-method sampling technique was used to select 18 participants for the qualitative strand. Whereas, there were 137 respondents for the quantitative strand. Tesch’s proposed eight steps to analyse the data were adopted to analyse the qualitative data and SSPS version 25 was used for analysing quantitative data. The results showed the following findings: patients lack knowledge about diabetes as a disease, misinterpret medication instructions, and are noncompliant to the treatment. This non-compliance is intensified by negligence and poor comprehension of medication instructions. As a result, to help diabetes mellitus patients with compliance with diabetes treatment, ongoing implementation of the educational programme should be instituted. The Limpopo’s Department of Health has to offer in-service vii education to the health professionals, who dispense medications on the interpretation of medication instructions. The high school curriculum is ought to incorporate health literacy to prescribe medication instructions. / National Institute for the Humanities and Social Sciences (NIHSS) and South African Humanities Deans Association (SAHUDA)

Thesis (MFamMed)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Background Diabetes is a significant contributor to the burden of disease in South Africa and to the reasons for encounter in primary care. There is little structured and systematic education of patients that supports self-care. This study was a qualitative assessment of a diabetes group education programme in Community Health Centres of the Cape Town Metropolitan District. The programme offered four sessions of group education and was delivered by trained health promoters using motivational interviewing as a communication style. The aim of the study was to evaluate the programme by exploring the experiences of the patients who attended. Methods Thirteen individual in depth interviews were conducted. Each patient had attended the educational programme and came from a different health centre in the intervention arm of a larger randomised controlled trial. The interviews were audiotaped, transcribed and then analyzed using the framework approach. Results Patients expressed that they gained useful new knowledge about diabetes. The use of educational material was experienced positively and enhanced recall and understanding of information. The general experience was that the health promoters were competent, utilised useful communication skills and the structure of sessions was suitable. Patients reported a change in behaviour especially with diet, physical activity, medication and foot care. There were organizational and infrastructural problems experienced specifically with regards to the suitability of the venue and communication of information regarding the timing and location of the sessions. Conclusion This study supports the wider implementation of this programme following consideration of recommendations resulting from patient feedback. However, only patients who attended the educational sessions were interviewed and the results of the larger controlled trial must still be obtained.