Perception of risk, feelings of vulnerability and effects on driving behaviour in women drivers across the lifespan.

Sustained driving in older age has implications for quality of life and mental health. Studies have shown that despite the recognised importance of driving in maintaining health and social engagement, many women give up driving prematurely or adopt self-imposed restrictive driving practices. Emotional responses to driving have been implicated in these decisions. This research examined the effect of risk perception and feelings of vulnerability on women’s driving behaviour across the lifespan. It also developed and tested a modified theory of planned behaviour intervention to positively affect driving habits. The first two studies (N=395) used quantitative analysis to model driving behaviours affected by risk perception and feelings of vulnerability, and established that feelings of vulnerability do indeed affect women’s driving behaviour, specifically resulting in increases in driving avoidance and the adoption of maladaptive driving styles. Further, that self-regulation, conceptualised as avoidance, is used by drivers across the lifespan. Qualitative analysis of focus group data (N=48) in the third study provided a deeper understanding of the variations in coping behaviours adopted by sub-groups of drivers and extended the definition of self-regulation to incorporate adaptive coping strategies. The next study (N=64) reported the construction and preliminary validation of the novel self-regulation index (SRI) to measure wider self-regulation behaviours using an objective measure of driving behaviour, a simulated driving task. The understanding gained from the formative research was used in the final study, an extended theory of planned behaviour intervention to promote wider self-regulation behaviour, measured using the previously validated self-regulation index. The intervention achieved moderate success with changes in affective attitude and normative beliefs as well as self-reported behaviour. The results offer promise for self-regulation, incorporating a spectrum of planning and coping behaviours, to be used as a mechanism to assist drivers in achieving their personal mobility goals whilst promoting safe driving.

Obesity in the pathogenesis of type 2 diabetes

Obesity, and especially visceral adiposity, escalates the development of insulin resistance and type 2 diabetes. Excess adipose tissue contributes to a chronic increase in circulating fatty acids reducing the usage of glucose as a source of cellular energy. Excess fatty acids also result in increased deposition of fat in muscle and liver, and increased metabolites such as diacylglycerol and ceramide which activate isoforms of protein kinase C that impede cellular insulin signalling. Chronically raised lipid levels also impair islet beta cell function, acting in conjuction with insulin resistance to aggravate hyperglycaemia. The detrimental effects of several adipokines such as TNF, IL6 and RBP4, which are produced in excess by an increased adipose mass, and reduced production of adiponectin are further mechanisms through which obesity potentiates the development of type 2 diabetes. © 2011 The Author(s).

Interventions against obesity through increased lipolysis in adipose tissue

Obesity is a disease of excess adiposity affecting> 17% of men and >20% of women in Britain. Clinically, it is defined by a Body Mass Index (BMI, kg/m2) of 2:30. Obesity is a confounding factor that promotes insulin resistance, hyperinsulinaemia and type 2 diabetes. Type 2 diabetes accounts for >90% of all cases of diabetes, with a prevalence of 2-6% of adults in most western societies, a majority of which are overweight or obese. Weight loss in obese patients reduces the risk of developing diabetes by >50%. This thesis has investigated the first part of a two-stage therapeutic intervention against obesity in which adipose tissue lipolysis will be combined with increased energy expenditure: the approach is also designed to consider agents that will benefit glycaemic control in coexistent obesity and diabetes by improving insulin sensitivity. Rodent and human in vitro models of adipocyte biology and skeletal muscle have been developed, characterised and evaluated. They include isolated epididymal and parametrial adipocytes of lean and obese diabetic ob/ob mice, cultured 3T3-Ll preadipocytes, isolated human omental and subcutaneous adipocytes and rat L6 cultured muscle cells. Compounds investigated for anti-obesity and anti-diabetic properties include M2 (sibutramine metabolite), 3-guanidinopropionic acid and mazindol. In vivo studies were undertaken to investigate these compounds further in lean and ob/ob mice. In vivo studies indicated that M2 and 3-guanidinopropionic acid reduced body weight gain in ob/ob mice. The three compounds increased lipolysis in adipocytes isolated from lean and ob/ob mice and human adipose depots. The direct action of these compounds was mediated via a pathway involving the f3 adrenoceptors and components of the lipolytic signalling pathway, including protein kinase A and p38 MAP kinase. In addition, M2 and mazindol were capable of increasing glucose uptake into insulin sensitive tissues. M2 and mazindol can act directly on adipose tissue and skeletal muscle to increase glucose uptake via a pathway involving new protein synthesis and activation of the glucose transporters. The M2-stimulated pathway is activated by the conversion of phosphatidylinositol bisphosphate to phosphatidylinositol trisphosphate by phosphatidylinositol 3-kinase. Thus, M2, mazindol and 3-GPA showed pharmacodynamic properties which suggested they might be potential therapeutic treatments for obesity and diabetes.