<i>RD Lawrence Lecture 2015</i>. Old habits are hard to break:lessons from the study of hypoglycaemia

Despite the introduction of newer technologies and improved insulin formulations, recurrent hypoglycaemia continues to affect the lives of many people with Type 1 and Type 2 diabetes. Developing strategies or therapies designed to prevent or minimize hypoglycaemia risk is of utmost importance to help individuals safely achieve glycaemic targets. Novel, educational or behavioural approaches need to be based on a clear understanding of the mechanisms underpinning both the detection of hypoglycaemia and why repeated exposure to hypoglycaemia leads to the development of a clinical syndrome referred to as impaired awareness of hypoglycaemia. In the present review, I propose that impaired awareness of hypoglycaemia may represent a form of learning called habituation, a response that, at a cellular level, represents a biological adaptation designed to protect the organism from future exposure to that stressor. In diabetes, this survival response to low glucose is, however, overwhelmed by high systemic insulin levels resulting from exogenous insulin therapy, leading to progressively more severe hypoglycaemia. A recognition of the underlying mechanism means that the development of impaired awareness of hypoglycaemia can perhaps be better understood and explained to individuals with diabetes, and novel therapeutic approaches such as dishabituation or cognitive behavioural therapies can be considered. This article is protected by copyright. All rights reserved.</p

Temporal changes in frequency of severe hypoglycemia treated by emergency medical services in types 1 and 2 diabetes:a population-based data-linkage cohort study

Background&nbsp; Almost 20 years ago, the frequencies of severe hypoglycemia requiring emergency medical treatment were reported in people with types 1 and 2 diabetes in the Tayside region of Scotland. With subsequent improvements in the treatment of diabetes, concurrent with changes in the provision of emergency medical care, a decline in the frequency of severe hypoglycemia could be anticipated. The present population-based data-linkage cohort study aimed to ascertain whether a temporal change has occurred in the incidence rates of hypoglycemia requiring emergency medical services in people with types 1 and 2 diabetes.&nbsp; Methods&nbsp; The study population comprised all people with diabetes in Tayside, Scotland over the period 1 January 2011 to 31 December 2012. Patients&rsquo; data from different healthcare sources were linked anonymously to measure the incidence rates of hypoglycemia requiring emergency medical services that include treatment by ambulance staff and in hospital emergency departments, and necessitated hospital admission. These were compared with data recorded in 1997&ndash;1998 in the same region.&nbsp; Results&nbsp; In January 2011 to December 2012, 2029 people in Tayside had type 1 diabetes and 21,734 had type 2 diabetes, compared to 977 and 7678, respectively, in June 1997 to May 1998. In people with type 2 diabetes, the proportion treated with sulfonylureas had declined from 36.8 to 22.4% (p&lt;0.001), while insulin-treatment had increased from 11.7 to 18.7% (p&lt;0.001). The incidence rate of hypoglycemia requiring emergency medical treatment had significantly fallen from 0.115 (95% CI: 0.094&ndash;0.136) to 0.082 (0.073&ndash;0.092) events per person per year in type 1 diabetes (p&lt;0.001), and from 0.118 (0.095&ndash;0.141) to 0.037 (0.003&ndash;0.041) in insulin-treated type 2 diabetes (p=0.008). However, the absolute annual number of hypoglycemia events requiring emergency treatment was 1.4-fold higher.&nbsp; Conclusions&nbsp; Although from 1998 to 2012 the incidences of hypoglycemia requiring emergency medical services appeared to have declined by a third in type 1 diabetes and by two thirds in insulin-treated type 2 diabetes, because the prevalence of diabetes was higher (2.7 fold), the number of severe hypoglycemia events requiring emergency medical treatment was greater

Defective Awakening Response to Nocturnal Hypoglycemia in Patients with Type 1 Diabetes Mellitus

BACKGROUND: Nocturnal hypoglycemia frequently occurs in patients with type 1 diabetes mellitus (T1DM). It can be fatal and is believed to promote the development of the hypoglycemia-unawareness syndrome. Whether hypoglycemia normally provokes awakening from sleep in individuals who do not have diabetes, and whether this awakening response is impaired in T1DM patients, is unknown. METHODS AND FINDINGS: We tested two groups of 16 T1DM patients and 16 healthy control participants, respectively, with comparable distributions of gender, age, and body mass index. In one night, a linear fall in plasma glucose to nadir levels of 2.2 mmol/l was induced by infusing insulin over a 1-h period starting as soon as polysomnographic recordings indicated that stage 2 sleep had been reached. In another night (control), euglycemia was maintained. Only one of the 16 T1DM patients, as compared to ten healthy control participants, awakened upon hypoglycemia (p = 0.001). In the control nights, none of the study participants in either of the two groups awakened during the corresponding time. Awakening during hypoglycemia was associated with increased hormonal counterregulation. In all the study participants (from both groups) who woke up, and in five of the study participants who did not awaken (three T1DM patients and two healthy control participants), plasma epinephrine concentration increased with hypoglycemia by at least 100% (p < 0.001). A temporal pattern was revealed such that increases in epinephrine in all participants who awakened started always before polysomnographic signs of wakefulness (mean ± standard error of the mean: 7.5 ± 1.6 min). CONCLUSIONS: A fall in plasma glucose to 2.2 mmol/l provokes an awakening response in most healthy control participants, but this response is impaired in T1DM patients. The counterregulatory increase in plasma epinephrine that we observed to precede awakening suggests that awakening forms part of a central nervous system response launched in parallel with hormonal counterregulation. Failure to awaken increases the risk for T1DM patients to suffer prolonged and potentially fatal hypoglycemia

Experimental Models of Impaired Hypoglycaemia-Associated Counter-Regulation

Impaired awareness of hypoglycaemia (IAH) affects around a quarter of patients with diabetes who receive insulin treatment. This condition is characterised by a progressive reduction in symptomatic and behavioural responses to hypoglycaemia, increasing risk of deeper drops in blood glucose, unconsciousness, and collapse. Thus, patients with IAH experience severe hypoglycaemic episodes more frequently, resulting in significant morbidity and mortality. IAH is thought to develop as a consequence of whole-body adaptations to repeated insulin-induced hypoglycaemia (RH), with widespread deficits in the hypoglycaemia counter-regulatory response (CRR). Despite this important insight, the precise pathophysiology by which RH leads to an attenuated CRR is unknown. Studies into the underlying mechanisms of IAH have employed a variety of protocols in humans and experimental species. The use of animal models has many investigational benefits, including the unprecedented increase in the availability of transgenic strains. However, modelling impaired hypoglycaemia-associated counter-regulation remains challenging and appropriate interpretation of findings across species and protocols even more so. Here, we review the experimental modelling of IAH and impaired hypoglycaemia-associated counter-regulation, with a focus on understanding species-specific variation in glucose homeostasis. This review will aid investigators in interpreting outputs from different studies in IAH and aid progress in the field.</p

Megatrendien vaikutus kuluttajiin Euroopan viinimarkkinoilla

Global megatrends, such as sustainability, health consciousness, and digitalisation affect consumer behaviour in different ways in different areas of the European wine market. This thesis explores the ways the wine industry has gone through major changes in the last years, and what roles these megatrends have played in this change, while outlining strategic implications for stakeholders in adapting to these evolving market dynamics.Globaalit megatrendit, kuten vastuullisuus, kehittynyt terveysajattelu ja digitalisaatio vaikuttavat kuluttajien ostokäyttäytymiseen eri tavoin eri Euroopan viinimarkkinoiden alueilla. Tämä opinnäytetyö tarkastelee merkittäviä tapoja, joilla viiniteollisuus on muuttunut viime vuosina sekä sitä, mikä rooli näillä megatrendeillä on muutoksessa ollut. Lisäksi työ kuvaa strategisia linjauksia, joita alan toimijoiden on tehtävä sopeutuakseen muuttuviin markkinaolosuhteisiin