An unhealthy lifestyle with poor nutrition and lack of exercise, resulting in a person being overweight, is the cause of many common diseases. The German Federal Ministry of Nutrition, Agriculture and Consumer Protection and the German Ministry of Health have initiated the national “IN FORM“ initiative. From 2008 until 2010, 15 million euros a year are to be dedicated to the objective of improving the nutrition and physical fitness in Germany in the long term.

Is a national effort really necessary? Do experts tend to panic-monger? The figures are clear: The metabolic disease known as diabetes has reached the proportions of a worldwide epidemic. It not only endangers human health, but also social structures and national economies. According to the International Diabetes Foundation (IDF), 3.8 million people died in 2007 as a result of diabetes.

The United Nations lists diabetes as the first non-infectious disease on the list of worldwide dangers to human health. The chronic disease no longer only affects first world countries; China and India have also published alarming figures. Estimates predict approximately 300 million diabetes cases worldwide by 2025.

80 percent of the costs of medical treatment occur in the richest countries, the remaining 20 percent are spent in second and third world countries. It is worth noting that in the near future 80 percent of all diabetes patients will live in second and third world countries. Overall, the cost of diabetes treatment is rising faster than the world population.

Up until 2015, three percent of global economic performance will be lost as a result of prosperity diseases if the investment into measures to prevent chronic diseases does not considerably increase (Price Waterhouse Coopers: Working towards wellness. Accelerating the prevention of chronic disease, 2007, p. 10). In the European Union (EU) the number of diabetes sufferers is increasing all the time. The prevalence rate for adults (20 to 79 years) rose from 7.6 to 8.6 percent between 2003 and 2006, accounting for 31 million affected people. Germany has the largest number (11.8) of diabetics. Only now is Europe working on European standards for diabetes prevention (IMAGE: Development and Implementation of a European Guideline and Training Standards for Diabetes Prevention).

In 2006 in Germany, more than seven million people had to undergo diabetes mellitus treatment, most of them type 2 diabetics who are forced to take more and more insulin. Diabetes type 2 is the most expensive chronic disease, costing the German health insurance companies 18 billion euros per year; other sources even talk of up to 60 billion (Prof. Hans Hauner), when the indirect costs are included.

Fifty percent of all cardiac infarctions and strokes are the result of diabetes, along with 30,000 amputations. These diseases are accompanying and secondary diseases, and this is what makes diabetes so dangerous. High blood pressure, elevated blood fat levels and being overweight are what medical experts refer to as "metabolic syndrome", which is known in popular lore as the "deadly quartet". The diseases resulting from diabetes not only damage the vessels of the heart, brain and legs, but also those of the kidneys and eyes.

The situation might become even worse as a growing number of young adults, including children and adolescents are becoming victims of diabetes. In addition, there is a direct correlation between the rising number of overweight people (and here Germany also has the highest number in Europe) and diabetes. 20 percent of all European children are overweight, and it is estimated that this number is increasing by 400,000 every year. 

One detected case equals one that is undetected

But this is only half the truth. Experts believe that one third of all German citizens faces diabetes mellitus. Diabetes type 2 is the major problem and accounts for more than 90 percent of all cases. About five to ten percent of people suffer from diabetes type 1. Diabetes type 2 develops gradually over the years and often remains undetected. Many people are diabetics without knowing it.

Studies have shown that the cost increases linearly with the diagnosis of diabetes. The highest costs arise from resultant vascular diseases such as cardiac infarction and stroke. Experts see the prevention of complications through optimised treatment and diabetes as the best means to prevent the rampant rise in costs.

In order to avoid the cost trap, experts are hoping that there will be a paradigm change – away from the principles of disease-centred treatment towards the principles of health promotion. However, the cost-benefit analysis of the health economists has an “undesired side effect”: successful prevention increases lifespan and hence also the lifelong costs arising from age-related diseases.

Despite alarming epidemiological figures – there are no national registers, data or clear definitions. According to the IDF, diabetes is underestimated on both the national and the European level. It is estimated that diabetes accounts for about one tenth of all health costs. Precise, comparable data are lacking. In addition, health policy is “frustratingly slow” to react (IDF). Less than 50 percent of all EU member states have a national diabetes plan or any kind of concerted action: It seems very uncertain whether Germany will put such a plan into action in 2010 (see above).

The debate in medical science circles as to whether these diseases originate from one cause, are potentially only of academic importance. If the “deadly quartet” has one single cause, the current state of knowledge holds that it must be related to insulin resistance.

The hopes of finding a single drug for treating diabetes and the diseases associated with it have been dashed – whether it be this glitazone, ACE inhibitors or the “poly pill” (see Scott M. Grundy, Advancing drug therapy of the metabolic syndrome, in: Nature Reviews, Drug Discovery, Vol. 8. May 2009, p. 341). Scientific compliance studies will need to show whether the medical efficiency of a tablet can be increased by combining several substances in one.

Of around 2,500 R&D projects (clinical phases I to III) being undertaken by small and medium-sized biotechnology companies in Europe, 64 projects deal with diabetes (Novumed Life Science Consulting). The big pharmaceutical companies are also working on the development of anti-diabetes drugs. It is estimated that approximately eleven diabetes drugs will be approved by 2012. This estimate is confirmed by the research-based pharmaceuticals producers (VFA Bio), according to whom ten drugs are in phase III, 20 in phase II and 15 in phase I of clinical development.

The family-run company Boehringer Ingelheim is expanding its diabetes activities at its research site in Biberach. The company hopes to launch linagliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, in 2010. This substance, which belongs to a new substance class, inhibits the degradation of the hormone glucagon-like peptide 1 (GLP-1) through the enzyme DPP4. GLP-1 induces the release of insulin in the beta cells.

In addition to linagliptin, Boehringer Ingelheim has two SGLT inhibitors in the pipeline, a licensed one and one from own R&D. In addition, the company is also expanding its activities to indications that have something in common with diabetes – being overweight, dyslipidemia and arteriosclerosis.

It is generally agreed that medical treatment should be only initiated if changing one’s lifestyle does not lead to the expected results. Critics say that most anti-diabetes drugs are based on studies carried out by the manufacturers themselves. Long-term monitoring and data on patient satisfaction with the therapy are rare as are monitoring and data on patient adherence to courses of therapy.

More sport, better nutrition, reduction of the time spent in front of TV and PC – the recipe for diabetes prevention sounds simple but is somewhat more difficult in practice. Although individuals that are at risk of developing diabetes might be able to sustainably change their behaviour and adapt their lifestyle to health-promoting activities and prevention, society has different demands that act in different ways across the board: agriculture, education, sport, nutrition, consumer protection, health, entertainment, market economy, transport and traffic, environment and media. Different objectives have to fit together in a constructive way and this is a clear indication that there must be a strong concerted effort to reverse the current situation in order to be able to override conflicting individual interests.

Diabetes type 2 is ideal for primary prevention. People who are physically fairly active can, even without losing a lot of weight, activate their metabolism and reduce insulin resistance. International studies have shown that six out of ten people affected were able to successfully prevent or postpone the onset of diabetes when they changed their lifestyle in the early stages of the disease. This has been shown in high-risk people (defective glucose tolerance and elevated fasting glucose levels).

For cost reasons, experts consider that closely and continuously monitored lifestyle change is the most appropriate means for population-wide prevention. So far it is difficult to tell who benefits noticeably from lifestyle interventions and who doesn’t. Initial studies, also undertaken in Tübingen (TULIP) show that a prognosis is possible.

Clinical studies have shown that multifactorial therapies and optimal blood glucose level adjustments considerably improve the prognosis of diabetes sufferers. The treatment of diabetes sufferers has improved dramatically over the last few years; but there are still some shortfalls – in particular with regard to old people, migrants, socially disadvantaged persons, pregnant women with gestation diabetes, people with rare diabetes types, small children with diabetes, diabetic adolescents during puberty. The treatment results in Germany are moderate. Germany comes 19th in a European-wide comparison (Euro Consumer Diabetes Index 2008).

Diabetes type 1 is often genetic, and has a long preclinical phase. Therefore the progression and outcome of diabetes type 1 can easily be predicted. The autoantibodies of ß-cell antigens and genetic markers (HLA) of this organ-specific autoimmune disease can be measured. Experts hope that the destruction of beta cells can be modulated in the medium to long term and will enable the primary prevention of diabetes.

Diagnostics is sometimes made difficult through inadequate measurement methods, blood samples or by only measuring the fasting plasma glucose level. The oral glucose tolerance test (OGTT) is regarded as the gold standard, in particular in the early phase of the disease. But this test is only reimbursed by the insurance companies when patients have elevated fasting plasma glucose values. There are many treatment gaps, including the lack of regular check-ups or high-risk patient screening.

The differential diagnosis of diabetes can also be improved. Diabetes is very heterogenic and many mixed types are known. Experts are hopeful about molecular biology tests that are able to determine the type of diabetes and the degree of insulin secretion disturbance and insulin resistance with greater accuracy.

Experts believe that a better understanding of the causes and pathogenesis of diabetes types and their complications depends on the further development of individualised prevention, diagnostics and therapy. Since 2008, the EU commission has been supporting coordinated research funding with DIAMAP – Roadmap for Diabetes Research in Europe, which has enabled medical associations and drug manufacturers to develop a European-wide research strategy within the next two years.

In Germany, there is huge demand for insights from basic research, epidemiological research and bedside research. The situation in Germany is characterised by the fact that research funding is not given jointly by the Ministry of Health and the Ministry of Research. But nevertheless, the TU Dresden is the first university with a European chair for diabetes prevention and treatment, sponsored by the insulin manufacturer Sanofi-Aventis.

Approaches that take into account the complex interaction between sensitivity genes and the environment, the psychosocial context, food and physical activity are, according to the current state of knowledge, of key importance. A lot of hope is placed on progress made in imaging, measurement sensor technology, the use of adult stem cells and the regeneration of insulin-producing cells.

Walter Pytlik

Sources/Literature:

Helmholtz Centre Munich, FLUGS - Information Service Life Sciences, Diabetes mellitus Typ 2 – Lebensstil und Gene entscheiden, Munich, 28.05.2008
International Diabetes Foundation (IDF): www.idf.org
Gesundheitsziele.de, Forum Health Targets Germany, Diabetes mellitus type 2 workgroup: www.gesundheitsziele.de
Robert Koch Institute/Federal Statistical Office: Diabetes mellitus. Federal Health Monitoring System, issue 24, 2005
Robert Koch Institute/Federal Statistical Office: Health in Germany, July 2006.
National Action Forum Diabetes mellitus (NAFDM): 2. draft - National Action Plan Metabolic Syndrome, Adipositas, Diabetes mellitus: Prevention-Treatment-Research, May 2008
Fraunhofer Institute for Systems- and Innovation Research: Health Technology Assessment, www.inno-hta.eu, www.metaforum-innovation.de
Forster, Thomas: Krankheitskostenrechnung für Deutschland, Federal Statistical Office, Wirtschaft und Statistik 12/2004;
VFA Bio: Medizinische Biotechnologie in Deutschland 2009
Federation of European Nurses in Diabetes/International Diabetes Foundation Europe: Diabetes. The Policy Puzzle: Is Europe Making Progress? 2nd edition,
Euradia (Alliance for European Diabetes Research) www.euradia.org
German Diabetes Union/National Action Forum Diabetes Mellitus, Diabetes 2009. Federal Health Monitoring, Mainz 2008 (November)
Boehringer Ingelheim, R & D Press Conference, 17.10.2008.
About R&D projects for diabetic complications: Calcutt, Nigel/Cooper, Mark et. al, in: Nature Reviews Drug Discovery, Vol. 8, May 2009, p. 417ff.
German Health Report. Diabetes 2009, presented by: German Diabetes Union and NAFDM, November 2008.