MMed, Internal Medicine, Faculty of Health Sciences,University of the Witwatersrand / Aims: To determine whether impairment of the executive functioning domain of cognition could be detected by a battery of simple bedside cognitive tests of executive function associated with inadequate glycaemic control. Methods: People with type 2 diabetes attending a tertiary referral diabetic clinic who consented to participate in the study underwent a brief battery of cognitive testing (the Bedside Executive Screening Test) designed to detect executive function impairment. Glycaemic control was determined using glycated haemoglobin levels (HbA1c). Inadequate glycaemic control was defined as HbA1c ≥ 7.0%. Results: Executive function impairment was detected in 51 (52%) of the 98 study participants. The presence of executive function impairment was significantly associated with poor glycaemic control (HbA1c ≥ 7.0%) (odds ratio 4.9, 95% confidence interval 1.3 – 18.8, p=0.019). There were no significant differences between patients with and without executive function impairment with regard to age, target organ damage, patient reported adherence, and hypoglycaemic therapy. Patients with a lower level of education were more likely to demonstrate executive impairment when glycaemic control was poor (p=0.013). Conclusion: Executive function impairment is common in a population of people with difficult-to-manage type 2 diabetes. The presence of executive impairment is significantly associated with poor glycaemic control.

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

Thesis (M Med (Family Medicine) -- University of Limpopo, 2011. / Introduction The burden of type 2 diabetes mellitus continues to rise and constitutes a real threat especially in the developing world. As for most non-communicable diseases, change of behavior and adoption of healthy lifestyle habits help to prevent and slow down the increase of type 2 diabetes mellitus. Aim of the Study To establish the knowledge, attitudes and practices regarding lifestyle modifications among type 2 diabetic patients attending the diabetic clinic at Mamelodi hospital. Methods: This cross sectional study describes the knowledge, attitudes and practices regarding lifestyle modifications (KAP) among 217 type 2 diabetes mellitus patients attending Mamelodi Hospital, Pretoria, Republic of South Africa. A face-to-face interview using a structured questionnaire was carried out for data collection. Socio-demographic characteristics of the participants and anthropometric measurements were obtained and the body mass index (8MI) of participants were determined. The Knowledge, attitude and practice of participants were assessed. 2 Results: Majority of participants were female 176(81.1 %), while male were 41 (18.9%). This amounted to a female to male ratio of 4:1. Most participants were in the age group 51-60 years 93(42.9%). Majority of them had low level of education 108(49.5%) and low income 206(94.9%). Majority of participants were obese 153(71 %) with more female diabetic patients being obese 120 (78.4%) than male 33 (21.6%). 15 participants (14 females and 1 male) were morbidly obese (BMI~40kg/m2). 108 participants (49.5%) did not have a formal education. No respondent had good knowledge and 92.6% of respondents had poor knowledge of the benefits of exercise, weight loss and healthy diet. Majority of respondents (97.7%) had bad practices in relation to lifestyle modifications. Nevertheless, majority of them (84.3%) had positive attitudes toward lifestyle modifications. Significant positive correlation (r= 0.170, p=0.012) was found between the global knowledge level and attitude level alone, whereas there was no significant correlation found between the global knowledge level and practice level as well as the attitude level and practice level. Conclusion: In conclusion, despite positive attitudes of participants toward healthy lifestyle habits, the knowledge and practices regarding lifestyle modifications among type 2 diabetes mellitus patients attending Mamelodi Hospital were generally low. Nevertheless the positive attitudes of participants should be encouraged and the implementation of a lifestyle intervention program will help improve the knowledge and practices of type 2 diabetes mellitus patients attending Mamelodi Hospital for the better management and control of this current pandemic of type 2 diabetes mellitus.

Background: Exercise is widely recognized as the cornerstone of management of type II diabetes (T2D). However, it is also known that people with T2D have poor adherence to exercise regimens, which is largely thought to be because of poor exercise tolerance. Recent studies have suggested that this exercise intolerance may be caused by a reduction in exercising muscle blood flow. One physiological mechanism which could potentially contribute is the muscle metaboreflex (MMR). This mechanism is thought to be a pressure-based flow-improving mechanism, but as a result of reduced efficacy of vasodilators and sympatholytic agents, might in fact be restraining the flow-improvement in persons with T2D. Hypothesis: Persons with T2D would not improve exercising muscle blood flow upon MMR activation. This absence of flow-improvement will be due to an augmented vasoconstriction in the exercising muscle. Methods: T2D (n=7) and CTL (n=6) participants performed rhythmic forearm handgrip exercise at an intensity equivalent to 20% MVC for 9 minutes with and without the application of ischemic plantar flexion (IPF). Forearm blood flow (FBF), mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), total peripheral resistance (TPR) and forearm vascular conductance (FVK) were quantified for the last thirty seconds of each of four time points during the protocol. Plasma norepinephrine was measured via deep venous and arterialized venous blood sampling. Results: Steady state exercising FBF was increased in CTL but not in T2D during MMR activation (mean ± SE mL/min: CTLControl 161.16 ± 5.95, CTLMMR 212.72 ± 9.49, T2DControl 156.71 ± 13.08, T2DMMR 144.22 ± 10.55). This occurred despite similar increases in MAP, CO, HR, and TPR (across groups and treatment conditions, NS). FVK increased in CTL during the MMR protocol compared to the Control protocol, but decreased in the T2D group using the same comparison (mean ± SE mL/min/100 mm Hg: CTLControl 144.74 ± 5.63, CTLMMR 176.76 ± 11.99, T2DControl 143.29 ± 13.44, T2DMMR 103.53 ± 8.44). Conclusions: In the exercise model utilized, persons with T2D do not demonstrate the MMR-induced flow improvement seen in CTL. This impaired muscle blood flow in T2D is the result of MMR induced exercising limb vasoconstriction. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2012-01-31 09:30:42.604

No description available.

Alzheimer’s disease (AD) is the most reoccurring type of dementia, and remains incurable. Much work has been done to investigate the connections between AD development, type 2 diabetes and insulin receptor signaling abnormalities. Full length amyloid precursor protein (flAPP) is a large transmembrane protein that has significant physiological activities including in utero fetal development. Alpha secretase enzymes cleave flAPP, producing secreted amyloid precursor protein alpha (sAPPα), which has neuroprotective properties, including protection against neuronal apoptosis as well as the induction of neuronal outgrowth. There is no known dedicated receptor for the physiological action of sAPPα. Our data suggest that the physiological actions of sAPPα are a result of the physical interaction between sAPPα and the neuronal insulin receptor. We have shown that sAPPα phosphorylates, and thus activates, the neuronal insulin receptor as well as specific downstream proteins, including insulin receptor substrate (IRS), and protein kinase B (Akt). We have also shown that the observed interaction between sAPPα and neuronal insulin receptors is physical and that sAPPα competes with insulin for the insulin binding site. These findings may have implications for therapies aimed at slowing down the progression of AD through the activation of the insulin receptor pathway, since in neurons, insulin and the insulin receptor pathway are critical to the neuronal health and plasticity.

Proefschrift Universiteit van Amsterdam. / Met lit. opg. - Met samenvatting in het Nederlands.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.