Quinolinate inhibition of gluconeogenesis is dependent on cytosolic oxalacetate concentration An explanation for the differential inhibition of lactate and pyruvate gluconeogenesis

AbstractIn isolated rat hepatocytes, the phosphoenolpyruvate carboxykinase (PEPCK) inhibitor, quinolinate decreased gluconeogenesis from lactate more than from pyruvate (78 vs 44%). Quinolinate inhibition of PEPCK has been reported to be competitive with oxalacetate (OAA), and therefore higher cytosolic OAA concentrations could be expected to alleviate quinolinate inhibition of PEPCK and hence reduce its effect on gluconeogenesis. With pyruvate as a carbon source, the cytosolic concentration of OAA was higher than with lactate (40 vs 9.7 μM). The levels of OAA were manipulated metabolically by adding asparagine (which provides more cytosolic OAA through the urea cycle) or oleate (which increases malate efflux from the mitochondria). In each of the 8 conditions studied, quinolinate inhibition of gluconeogenesis was inversely related to the levels of OAA in the cytosol. Quinolinate inhibition of asparagine gluconeogenesis was not due to a non-specific effect on urea synthesis

Evidence-based approach for managing hypertension in type 2 diabetes

Blood pressure (BP) control is a critical part of managing patients with type 2 diabetes. Perhaps it is the single most important aspect of diabetes care, which unlike hyperglycemia and dyslipidemia can reduce both micro- and macrovascular complications. Hypertension is more prevalent in individuals with diabetes than general population, and in most cases its treatment requires two or more pharmacological agents (about 30% of individuals with diabetes need 3 or more medications to control BP). In this article we describe the key evidence that has contributed to our understanding that reduced BP translates into positive micro- and macrovascular outcomes. We review the data supporting current recommendation for BP target < 130/80 mmHg. Two studies suggest that a lower BP goal could be even more beneficial. We also present the comparative benefits of various antihypertensive drugs in reducing diabetes-related micro- and macrovascular complications. Finally we propose an evidence-based algorithm of how to initiate and titrate antihypertensive pharmacotherapy in affected individuals. Overall, achieving BP < 130/80 mmHg is more important than searching for the “best” antihypertensive agent in patients with diabetes

Lost in translation: a multi-level case study of the metamorphosis of meanings and action in public sector organisational innovation

This paper explores the early implementation of an organisational innovation in the UK National Health Service (NHS) - Treatment Centres (TCs) - designed to dramatically reduce waiting lists for elective care. The paper draws on case studies of eight TCs (each at varying stages of their development) and aims to explore how meanings about TCs are created and evolve, and how these meanings impact upon the development of the organisational innovation. Research on organisational meanings needs to take greater account of the fact that modern organisations like the NHS are complex multi-level phenomena, comprising layers of interlacing networks. To understand the pace, direction and impact of organisational innovation and change we need to study the interconnections between meanings across different organisational levels. The data presented in this paper show how the apparently simple, relatively unformed, concept of a TC framed by central government, is translated and transmuted by subsequent layers in the health service administration, and by players in local health economies and, ultimately in the TCs themselves, picking up new rationales, meanings, and significance as it goes. The developmental histories of TCs reveal a range of significant re-workings of macro policy with the result that there is considerable diversity and variation between local TC schemes. The picture is of important disconnections between meanings, that in many ways mirror Weick’s (1976) ‘loosely coupled systems’. The emergent meanings and the direction of micro-level development of TCs appear more strongly determined by interactions within the local TC environment, notably between what we identify as groups of ‘idealists’, ‘pragmatists’, ‘opportunists’ and ‘sceptics’ than by the framing (Goffman 1974) provided by macro and meso organisational levels. While this illustrates the limitations of top down and policy-driven attempts at change, and highlights the crucial importance of the front-line local ‘micro-systems’ (Donaldson & Mohr, 2000) in the overall scheme of implementing organisational innovations, the space or headroom provided by frames at the macro and meso levels can enable local change, albeit at variable speed and with uncertain outcomes

Review of biphasic insulin aspart in the treatment of type 1 and 2 diabetes

Nazia Raja-Khan, Sarah S Warehime, Robert A GabbayDivision of Endocrinology, Diabetes, and Metabolism, Penn State Institute for Diabetes and Obesity, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USABackground: Insulin is an effective treatment for achieving glycemic control and preventing complications in patients with diabetes. In order to make insulin therapy more acceptable to patients, newer formulations of insulin have been developed, such as biphasic insulins. Biphasic insulins conveniently provide both prandial and basal insulin in a single injection. One of the most well-studied biphasic insulins is biphasic insulin aspart 70/30.Objective: Our goal was to review the current literature on the safety and efficacy of biphasic insulin aspart in type 1 and type 2 diabetes.Methods: A MEDLINE search was conducted using the terms &ldquo;biphasic insulin aspart&rdquo; to identify clinical studies and reviews.Results: Biphasic insulin aspart more effectively reduces post-prandial glucose compared to other biphasic insulins and basal insulins. Compared to biphasic insulin aspart, fasting glucose levels are lower with NPH, similar with glargine, and similar or lower with biphasic human insulin. Treat-to-target trials have shown that a goal HbA1c below 6.5 or 7% can be achieved with biphasic insulin aspart. The risk of hypoglycemia is similar to or less than that seen with other biphasic insulins or NPH insulin.Conclusion: Biphasic insulin aspart 70/30 is a safe and effective treatment option for patients with diabetes.Keywords: biphasic insulin aspart, insulin, diabete

Addressing diabetes at the crossroads of global pandemic and regional culture Comment on “The curse of wealth – Middle Eastern countries need to address the rapidly rising burden of diabetes”

As diabetes and obesity rates continue to climb at astronomical rates in the Middle East, future generations are at an even greater risk for diabetes and the associated complications. Many factors are at play and it is clear that creative solutions are needed to retool provider resources in the Middle East towards prevention of diabetes and its complications while leveraging technology to maximize outreach within the accepted cultural norms. Only by building the capacity to address the current diabetes burden as well focusing on prevention for the future, can Middle East countries create a strong infrastructure for a successful future

Comparison of retinal vasodilator and constrictor responses in type 2 diabetes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93551/1/j.1755-3768.2012.02445.x.pd

Impaired retinal vasodilator responses in prediabetes and type 2 diabetes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99677/1/aos12129.pd

“Even if You Know Everything You Can Forget”: Health Worker Perceptions of Mobile Phone Text-Messaging to Improve Malaria Case-Management in Kenya

This paper presents the results of a qualitative study to investigate the perceptions and experiences of health workers involved in a a cluster-randomized controlled trial of a novel intervention to improve health worker malaria case-management in 107 government health facilities in Kenya. The intervention involved sending text-messages about paediatric outpatient malaria case-management accompanied by “motivating” quotes to health workers’ mobile phones. Ten malaria messages were developed reflecting recommendations from the Kenyan national guidelines. Two messages were delivered per day for 5 working days and the process was repeated for 26 weeks (May to October 2009). The accompanying quotes were unique to each message. The intervention was delivered to 119 health workers and there were significant improvements in correct artemether-lumefantrine (AL) management both immediately after the intervention (November 2009) and 6 months later (May 2010). In-depth interviews with 24 health workers were undertaken to investigate the possible drivers of this change. The results suggest high acceptance of all components of the intervention, with the active delivery of information in an on the job setting, the ready availability of new and stored text messages and the perception of being kept ‘up to date’ as important factors influencing practice. Applying the construct of stages of change we infer that in this intervention the SMS messages were operating primarily at the action and maintenance stages of behaviour change achieving their effect by creating an enabling environment and providing a prompt to action for the implementation of case management practices that had already been accepted as the clinical norm by the health workers. Future trials testing the effectiveness of SMS reminders in creating an enabling environment for the establishment of new norms in clinical practice as well as in providing a prompt to action for the implementation of the new case-management guidelines are justified