Reduced postprandial proinsulinaemia and 32-33 split proinsulinaemia after a mixed meal in type 2 diabetic patients following sensitization to insulin with pioglitazone

Objective: Reduced insulin sensitivity associated with fasting hyperproinsulinaemia is common in type 2 diabetes. Proinsulinaemia is an established independent cardiovascular risk factor. The objective was to investigate fasting and postprandial release of insulin, proinsulin (PI) and 32-33 split proinsulin (SPI) before and after sensitization to insulin with pioglitazone compared to a group treated with glibenclamide. Design and patients: A randomized double-blind placebo-controlled trial. Twenty-two type 2 diabetic patients were recruited along with 10 normal subjects. After 4 weeks washout, patients received a mixed meal and were assigned to receive pioglitazone or glibenclamide for 20 weeks, after which patients received another identical test meal. The treatment regimes were designed to maintain glycaemic control (HbA1c) at pretreatment levels so that ß-cells received an equivalent glycaemic stimulus for both test meals. Measurements: Plasma insulin, PI, SPI and glucose concentrations were measured over an 8-h postprandial period. The output of PI and SPI was measured as the integrated postprandial response (area under the curve, AUC). Results: Pioglitazone treatment resulted in a significant reduction in fasting levels of PI and SPI compared to those of the controls. Postprandially, pioglitazone treatment had no effect on the insulin AUC response to the meal but significantly reduced the PI and SPI AUCs. Glibenclamide increased fasting insulin and the postprandial insulin AUC but had no effect on the PI and SPI AUCs. Conclusions: Sensitization to insulin with pioglitazone reduces the amount of insulin precursor species present in fasting and postprandially and may reduce cardiovascular risk. © 2007 The Authors.

Inhaled human insulin (Exubera®):clinical profile and patient considerations

Inhaled human insulin (Exubera®) is a rapid-acting regular human insulin administered by oral inhalation before meals. It provides a non-invasive alternative to multiple subcutaneous injections for the treatment of hyperglycemia in adult patients with type 1 and type 2 diabetes. Compared with subcutaneous rapid-acting insulin analogs, Exubera provides equivalent HbA1c control. As a monotherapy or in combination with oral agents, Exubera also provides greater glycemic control than oral agents alone, at least in patients with high levels of HbA1c. Exubera demonstrates improved patient satisfaction compared with subcutaneous insulin or oral agents alone. When offered as a treatment option together with standard treatments in uncontrolled patients naive to insulin, Exubera increases acceptance of insulin therapy three-fold compared with patients offered standard regimens only. Exubera is well tolerated in comparison to subcutaneous insulin, with a similar incidence of mild to moderate hypoglycemia. Although cough is a common adverse effect early in therapy, this leads to treatment discontinuations in less than 1% of patients. Despite an increased incidence of insulin antibodies compared with subcutaneous administration, and a consistent but minor impact on pulmonary function, long-term safety data of up to 4 years continue to support the safety profile of Exubera.

Nutritional influences on cognitive function:mechanisms of susceptibility

The impact of nutritional variation, within populations not overtly malnourished, on cognitive function and arousal is considered. The emphasis is on susceptibility to acute effects of meals and glucose loads, and chronic effects of dieting, on mental performance, and effects of cholesterol and vitamin levels on cognitive impairment. New developments in understanding dietary influences on neurohormonal systems, and their implications for cognition and affect, allow reinterpretation of both earlier and recent findings. Evidence for a detrimental effect of omitting a meal on cognitive performance remains equivocal: from the outset, idiosyncrasy has prevailed. Yet, for young and nutritionally vulnerable children, breakfast is more likely to benefit than hinder performance. For nutrient composition, despite inconsistencies, some cautious predictions can be made. Acutely, carbohydrate-rich–protein-poor meals can be sedating and anxiolytic; by comparison, protein-rich meals may be arousing, improving reaction time but also increasing unfocused vigilance. Fat-rich meals can lead to a decline in alertness, especially where they differ from habitual fat intake. These acute effects may vary with time of day and nutritional status. Chronically, protein-rich diets have been associated with decreased positive and increased negative affect relative to carbohydrate-rich diets. Probable mechanisms include diet-induced changes in monoamine, especially serotoninergic neurotransmitter activity, and functioning of the hypothalamic pituitary adrenal axis. Effects are interpreted in the context of individual traits and susceptibility to challenging, even stressful, tests of performance. Preoccupation with dieting may impair cognition by interfering with working memory capacity, independently of nutritional status. The change in cognitive performance after administration of glucose, and other foods, may depend on the level of sympathetic activation, glucocorticoid secretion, and pancreatic β-cell function, rather than simple fuelling of neural activity. Thus, outcomes can be predicted by vulnerability in coping with stressful challenges, interacting with nutritional history and neuroendocrine status. Functioning of such systems may be susceptible to dietary influences on neural membrane fluidity, and vitamin-dependent cerebrovascular health, with cognitive vulnerability increasing with age.

Do educators need educating?

Actual text: I was recently at the Spanish College of Optometry biennial conference and attended a meeting of contact lens lecturers from around Spain and Portugal. We discussed various ideas, mainly about how to share good practice and improve standards. What came to my mind was ‘is there a blueprint for training trainers?’ Well probably not but there are many things that we need to acknowledge such as the way students learn for example. Many educators themselves were taught by lecturers who would write on a blackboard or use acetate on an overhead projector, then came the 35 mm slide era followed by the Powerpoint era. More recently there is a move towards a much more integrated approach of various teaching methods. At my university our contact lens and anterior eye lectures generally follow a format where a narrated Powerpoint lecture is uploaded onto our internal virtual learning environment. This narrated version of the slides is designed to give the didactic element of the topic. The students listen to that before attending an interactive seminar on that topic. The seminar is also recorded so that students can listen to that afterwards. The seminar is designed to give additional information, such as case reports, or to clarify key points or for live demonstrations. It is a good way of doubling the contact time with the students without imposing further on an already packed formal timetable as the students can work in their own time. One problem that we noticed with this approach was that attendance can vary. If the students feel that they will gain something from the interactive seminar then they are more likely to attend – exam tips usually win them over! At the Spanish meeting the educators decided that they wanted to have regular meetings. The industry colleagues in attendance said that they were happy to help but could not necessarily give money, but they could offer meeting rooms, pay for lunch and evening meals. They even said that that they were happy to host meetings and invite other companies too (except to manufacturing plants). In the UK the British Committee of Contact Lens Educators (BUCCLE) meets for one day on three occasions in the year. The American Optometric Contact Lens Educators (AOCLE) meets annually at a three day event. Both these organisations get some help from industry. BUCCLE usually has one of its meetings at a university, one at a company training centre/manufacturing plant/national headquarters and one meeting the day before the BCLA annual conference. BUCCLE usually has its pre-BCLA meeting in conjunction with the International Association of Contact Lens Educators (IACLE). So when educators meet what would they discuss; well probably the focus should be on education rather than actual contact lens knowledge. For example sharing ideas on how to teach toric lens fitting would be better than discussing the actual topic of toric lenses itself. Most universities will have an education department with an expert who could share ideas on how to use the internet in teaching or how to structure lectures or assessments etc. In the past I have helped with similar training programmes in other countries and sharing good practice in pedagogy is always a popular topic. Anyone who is involved in education in the field of contact lenses should look at the IACLE web page and look out for the IACLE World Congress in 2015 in the days preceding the BCLA. Finally, IACLE, AOCLE and BUCCLE all exist as a result of generous educational grants from contact lens companies and anyone interested in finding out more about should refer to their respective web pages.