41st Annual Meeting of the European Association for the study of Diabetes

The statement of the EASD and American Diabetes Association (ADA) on the metabolic syndrome was discussed during a press briefing. Before the EASD meeting several attempts had been made to formulate a definition of the syndrome, even trying to classify it as a disease. The President of the ADA, Robert Rizza (USA), and the President of EASD, Ele Ferrannini (Italy), believe the scientific basis is not sufficiently compelling to define the syndrome as a disease. Naturally, the treatment of cardiovascular risk factors (hypertension, hyperlipidaemia) is absolutely necessary, as is the treatment of adiposis and physical inactivity. But, they said, the creation of a disease, metabolic syndrome, from the different risk factors was not scientifically justified. Professor Ferrannini has elaborated on this in an editorial in this issue of Practical Diabetes International, but in reply to a question from the journal during the conference, Sir George Alberti (UK) stated the case for the syndrome. He acknowledged that it was a stimulating debate that was taking place. However, the International Diabetes Federation (IDF) had agreed that the metabolic syndrome did indeed exist, and that it was a useful concept, and a relatively easy way of identifying people who were at high risk of both diabetes and cardiovascular disease. This represented a vast population worldwide who could thus be advised and treated as necessary. Some members of the EASD and the ADA had questioned whether the metabolic syndrome was indeed a syndrome because its precise cause was not known. However, the precise cause of type 2 diabetes was not known but it was recognised as something which had to be dealt with. The same applied to type 1 diabetes and, indeed, to many other related conditions. Sir George noted that at a symposium preceding the conference, a show of hands amongst 1500 delegates had revealed that 88% believed the metabolic syndrome did exist. In short, the syndrome did identify people who needed preventative care. He hoped that other studies would be forthcoming to look at long-term consequences, to redefine the syndrome and to help get better measures. Data from endpoint trials comparing the effectiveness of a thiazolidinedione in an intervention group with a group of patients not on thiazolidinedione therapy have to date not been available. Not surprisingly, therefore, the world's first presentation of results from such a trial—the PROactive study—was attended by more than 8000 of the conference delegates. The air of excitement was not dissimilar to that of the famous UK Prospective Diabetes Study presentation in Barcelona some years ago but the results, although encouraging, were not quite so spectacular. In the PROactive trial, 5238 people with diabetes and a high risk of cardiovascular disease were treated with pioglitazone or with a placebo (in addition to existing medication). The results, presented by John Dormandy (UK), showed that HbA1c levels were reduced by 0.5% and less patients in the pioglitazone treated group required insulin treatment (35.9 vs 46.4%). Patients on pioglitazone also had a 16% lower relative risk of myocardial infarction, apoplexy and total mortality rates. The absolute risk in the pioglitazone group was 12.3% compared to 14.4% in the placebo group (absolute risk reduction 2.1%). For further details about the PROactive study see Leader ‘PROactive: early criticism not justified?’ (Jones CJ, Fisher M. Pract Diabetes Int 2005; 22(9): 323–324). In an interesting debate, Geremia Bolli (Italy) and Thomas Pieber (Austria) put the case for and against the insulin analogues. Dr Bolli said that, with SC administration, human insulin was absorbed quite slowly even when given as a bolus injection. This resulted in delayed increase in plasma insulin after meal ingestion in patients with diabetes, in lower plasma peaks and, in a later phase, a slower decrease in plasma insulin. Rapid-acting insulin analogues were the meal-time insulins of choice and had such properties as faster absorption, higher plasma peak, and more rapid waning than human insulin. Thus, with rapid-acting analogues it was possible to limit the post-prandial hyperglycaemia both in types 1 and 2 diabetes, and to reduce the risk for late post-prandial hypoglycaemia. Similarly important benefits were the greater flexibility of lifestyle. The long-acting insulin analogues were the insulin preparations of choice for the nocturnal (fasting) state and, compared to NPH and Lente, they had less pronounced peaks, lower inter- and intra-individual variability, and longer duration of action. As expected from these advantages, the new long-acting insulin analogues reduced the risk for nocturnal hypoglycaemia. Presenting the contra case, Dr Pieber said that long-term safety remained the key issue in the development of insulin analogues. Despite their apparent advantages, only slight improvements in HbA1c or very modest reductions in the frequency of hypoglycaemia had been seen with the short-acting analogues. And none of the studies performed had investigated long-term outcomes, such as late diabetic complications or mortality. With the long-acting analogues, in most studies there was a reduction of fasting plasma glucose and self-monitored fasting blood glucose but no (or borderline) effect on HbA1c. Although almost all the studies showed a modest reduction in the frequency of hypoglycaemia, in most of them different definitions of severe and nocturnal hypoglycaemia were used. None of the trials had investigated long-term outcome. The structural homology of insulin analogues to IGF-1 had raised concerns regarding the progression of diabetic late complications and potential mitogenic effects, especially in long-term use. A 26-week study from G Rayman (UK) showed that insulin glulisine provided superior post-prandial glucose control with less nocturnal hypoglycaemia compared with regular human insulin in type 2 patients and was associated with a lower rate of nocturnal hypoglycaemia. Nearly 900 patients received SC injections of glulisine 0–15min before meals or regular human insulin 30–45min before meals, plus twice-daily NPH insulin. S Schreiber (Germany) reported that, in daily practice, the introduction of insulin glargine to continued oral antidiabetic therapy could facilitate both the attainment and maintenance of target HbA1c in patients with type 2 diabetes, irrespective of BMI. The results of a nine-month, uncontrolled observation study had demonstrated that the addition of insulin glargine to existing oral therapy was associated with reductions in HbA1c to target levels and the 20-month extension was on nearly 3000 patients. There were reductions in HbA1c and FBG after nine months' treatment with glargine plus oral antidiabetics and these reductions were maintained after 20 months of treatment in all treatment groups, irrespective of BMI. Only three hypoglycaemic episodes were reported in the overall population. Insulin detemir may offer a weight advantage over NPH insulin, especially in overweight or obese people with type 2 diabetes initiating insulin therapy, according to Kkjeld Hermansen (Denmark). A total of 476 insulin-naïve patients inadequately controlled by oral agents received additional detemir or NPH twice daily (morning and evening). The insulin dose was aggressively titrated over a 24-week active treatment period. Mean HbA1c decreased similarly with both insulins but, regardless of baseline BMI, patients gained less weight with detemir than with NPH insulin. Results presented by Katarina Raslova (Slovak Republic) as an analysis of data from 900 patients showed greater weight gain with NPH and a slight weight loss in the most obese patients on detemir (Figure 1). Analysis of data from 900 patients: change in weight by BMI categories. (K Raslova, Slovak Republic) The era of the inhaled insulins is now almost upon us and E Stridde (Germany) reported on insulin preferences in 239 type 2 patients poorly controlled on oral antidiabetic drugs. The patients discussed treatment optimisation options with a physician. In Step One, patients had the choice of optimising treatment by using an additional oral drug or of switching to SC insulin. Patients who opted for oral optimisation were included in Step Two. After another discussion regarding treatment optimisation the patients had the choice between oral drugs, injected insulin, or inhaled insulin. In Step One, 80% of the patients decided to continue on oral drugs and 20% chose injected insulin. A total of 191 patients entered Step Two. Only 4% opted for injected insulin, 41% opted for inhaled insulin and 55% decided to stay on oral drugs. Based on an analysis of laboratory results (HbA1c, LDL-C, CRP etc) it was concluded that the entire study population required treatment optimisation. Whilst the acceptance of insulin was low when the only option was injected insulin the willingness to switch to insulin could be increased dramatically if inhaled insulin were added as a treatment option and thus, observed Dr Stridde, may help overcome the barriers to insulin treatment in this subset of type 2 patients. RP Hayes (USA) presented a study assessing the impact of the Lilly/Alkermes Inhaled Insulin System. This system uses a small, breath-actuated device to deliver inhaled insulin to patients as an alternative to mealtime insulin injection. The results in this randomised, open-label, crossover trial on 119 type 1 patients found that those receiving inhaled insulin had significantly greater treatment satisfaction and greater insulin delivery system satisfaction compared with injected insulin. In addition, they agreed more strongly that inhaled insulin could be incorporated into their lives (e.g. facilitates travel, reduces embarrassment, and reduces reluctance to use pre-meal insulin) as compared to injected insulin. A multicentre 26-week study, conducted in 13 countries and presented by Robert Heine (The Netherlands), supported the potential use of the inhaled insulin, exenatide, prior to the addition of starter basal insulin for long-standing type 2 diabetes patients sub-optimally controlled with oral combination therapy. Over 550 patients were randomised to exenatide or insulin glargine QD, adjunctive to pre-existing metformin plus a sulphonylurea. Exenatide achieved similar improvements in overall glycaemic control to glargine titration. Glargine predominantly reduced fasting plasma glucose, while exenatide was associated with a lower incidence of nocturnal hypoglycaemia, better postprandial glucose control, and progressive weight reduction. A joint EASD/ADA symposium considered the treatment of type 2 diabetes in children and adolescents. Jonathan Shaw (Australia) said that although great uncertainty remained over the precise prevalence and incidence of type 2 diabetes in children and adolescents, it was clear that type 2 diabetes existed in all ethnic groups, was almost certainly increasing, and was associated with at least as much microvascular disease as is seen in type 1 diabetes, with the addition of macrovascular risk factors from an early age. Dorothy Becker (USA) told delegates that there was now evidence of a mixed type 1 and type 2 pathogenesis in the young. Improvements in screening (resulting in earlier diagnosis) together with the rampant increase of obesity had blurred the distinction between types 1 and 2 on clinical grounds. Thus, early type 1 diabetic people may present without any evidence of ketosis and at a time when random levels of C-peptide may be fairly normal for age. Studies had shown that a large proportion of children and adolescents with by definition type 1A diabetes had at least some features of type 2 diabetes. A US study demonstrated that nearly 80% of children and adolescents diagnosed clinically as having type 2 diabetes had evidence of islet cell auto-immunity. And youths with clinical type 2 diabetes with minimal or no evidence of auto-immunity had markedly decreased insulin secretion compared to weight- and age-matched non-diabetic subjects. This evidence of mixed pathogenesis of diabetes in youth suggested a possible need for new definitions and classifications. The terms type 11/2 diabetes, hybrid diabetes or double diabetes had been used. A new classification of diabetes in youth was now proposed: (1) insulin deficient diabetes; (2) insulin resistant diabetes; (3) insulin deficient plus insulin resistant diabetes. Discussing treatment in type 2 children, Arian Rosenbloom (USA)said the goals were weight loss, normalisation of glycaemia and HbA1c, control of hypertension and hyperlipidaemia, reduction of acanthosis, and the correction of hyperandrogenism. The spectrum of disease at diagnosis ranged from asymptomatic hyperglycaemia to diabetic ketoacidosis and hyperglycaemic hyperosmolar states which were associated with a high morbidity and mortality in type 2 children. Patients with symptoms and ketosis or with random glucose >14mmol/L required insulin with metformin but could be weaned off the insulin when pre- and post-meal glucose was 5–7 and 10mmol/L. Children not acutely ill at diagnosis could attain glycaemic control with diet and exercise, but most required drug therapy eventually. Metformin was the only oral hypoglycaemic currently approved for use in children but studies were underway with rosiglitazone, meglitinide, and metformin/glyburide. Dr Rosenbloom advised health care workers always to consider non-compliance as the reason for treatment inadequacy. Behaviour modification to increase physical activity and decrease unhealthy food intake was difficult but must be a part of any regimen and required a team effort and family commitment. Figures released by the IDF during the EASD meeting estimated that in 2003 approximately 194 million people around the world had diabetes (Figure 2). By 2025 this figure is expected to rise to 333 million, amounting to 6.3% of the world's population. India has the largest diabetes population in the world with an estimated 35 million people, amounting to 8% of the adult population. In China, where 2.7% of the adult population is affected by type 2 diabetes, the number of people with the condition is likely to exceed 50 million within the next 25 years. And the African continent has approximately 14 million people with diabetes. These figures were revealed as the IDF launched the preliminary programme of its 19th World Diabetes Congress which will take place in Cape Town, South Africa, 3–7 December 2006. ‘The opportunity to share at an international level the latest scientific advances and knowledge on more practical aspects such as education, advocacy and raising awareness in the field of diabetes will make the programme truly diverse and unique,’ said Professor Sir George Alberti, Chair of the Congress Organising Committee. The Congress will address a broad spectrum of diabetes-related issues grouped into seven official programme streams: Basic Science; Clinical Advances; Education and Care; Healthcare Organisation; Epidemiology and Public Health; Living with Diabetes; and Diabetes in Africa. Professor Francois Bonnici (South Africa) said that by bringing together so many professionals, the Congress had the potential to influence local health authorities and to make the global fight against diabetes a higher priority. An essential goal of the Congress was to help IDF's 191 member associations to develop strategies that will serve to prevent diabetes in the 151 countries that they represent and to offer optimum health care and education for people with the condition. Prevalence of diabetes 2003: IDF Atlas map 1.1. (Source: Diabetes Atlas, 2nd edn. © IDF, 2003) Speaking during a session on the global epidemic, Stig Pramming (Denmark) said that regional plans to improve diabetes care had seen an increased use of evidence-based and systematic approaches. Gradually, these regional or national plans had become more and more comprehensive and sophisticated — but very few had attempted to give economic guidance on how to implement them in practice. In a WHO survey in 2001, 69% of 167 countries claimed to have a national plan for diabetes prevention and 62% had a unit for the prevention and control of chronic disease—but only had a budget line specifically to fund the programme. Moreover, only 45% had systems to monitor implementation and follow up of the initiatives, and only 28% produced an annual progress report. National programmes for the management of chronic diseases all had one inherent problem: they dealt primarily with secondary and tertiary prevention of disease, and seldom addressed primary prevention of the condition. They were often disease specific and rarely took underlying environmental causes into account. Dr Pramming suggested courses of action that went beyond the medical. One such programme, the Oxford Health Alliance, spearheaded a new approach that facilitates the redesign of the environment so as to help people to make healthy lifestyle choices. It took a multi-stakeholder approach to health care, dealing with the accessibility of consumer products, the social and physical structure of society, and the impact of the mass media and corporations. At a separate EASD briefing, the IDF launched the first ever evidence- based Global Guideline for Type 2 Diabetes. The Guideline calls for a more aggressive approach to the management of type 2 diabetes across the globe. It was developed by leading diabetes experts from all IDF regions, including representatives from countries in very different states of economic development. The Guideline suggests three levels of care: standard care is evidence-based care which is cost-effective in most nations with a well developed service base and national health care funding systems; minimal care seeks to achieve the major objectives of diabetes management, but is provided in health care settings with very limited resources; and comprehensive care includes the most up-to-date and complete range of health technologies that can be offered to people with diabetes, with the aim of achieving best possible outcome. The Guideline recommends maintaining HbAlc 6.5% to minimise the risk of complications developing, and supports this with clear recommendations over patient education, self-monitoring of glucose levels, and active use of tablets and insulin to attain target levels. As well as blood glucose, the evidence that BP and blood fat lowering is beneficial in people with diabetes is found to be overwhelming, and appropriate recommendations for monitoring and treating those modalities are also included. The Guideline also identifies cost-effective methods for identifying problems with eyes, kidneys and feet when preventative measures fail; early and proven treatments can then be started.