The number of chronic wounds is increasing on a global scale due to the diabetes epidemic. Diabetes wounds cause great human suffering and place a heavy burden on health care systems. Specialist in internal medicine and diabetologist Dr Dieter Scholz expects new therapies to be developed for practical wound management, and believes these will come from biotechnology.
Diabetes mellitus is a rapidly growing lifestyle disease that is caused by a combination of genetic predisposition, a lack of exercise and particularly overeating. The start of the third millennium is the first time in the history of mankind that more people are dying from overeating than from famine. In 2017, the International Diabetes Federation (IDF) found that some 425 million people worldwide were suffering from diabetes, over half of whom in Central and East Asia. This figure had grown by 10 million since 2015, and can be expected to rise further if no countermeasures are taken. The IDF estimates there may be as many as 693 million people with diabetes in the world by 2045.
In Central and East Asia, the regions that are hardest hit, factors include the high population level combined with an unfavourable genetic disposition, a lack of health education and a poor diet among the rapidly growing middle classes. China and India alone are now home to about 40% of the world’s diabetics.
Diabetes is also on the rise in Germany and other European countries, where it is encouraged by the increase in obesity due to a mainly sedentary lifestyle and high-calorie nutrition. About 58 million diabetics live in Europe. In Germany, IDF says around 7 million people are affected by the disease, though there are certainly a large number of unregistered cases. On the whole, Germany ranks only just below the ten countries with the highest prevalence. Owing to Germany’s ageing population, slightly over 5 million people older than 65 years of age suffer from diabetes, which explains why Germany actually ranks fourth in this age group by global comparison after China, the USA and India.
Obesity is the driving factor
In line with these figures, the number of overweight people has also risen steadily in past years, especially in industrialised countries. According to Statista, the number of obese adults in many OECD countries rose by more than 20% between 1990 and 2015. The USA topped the list in 2015, with an obesity rate of around 34%. The high number of overweight adults in Germany has been constant for a number of years. According to the Robert Koch Institute, some 53% of women and 67% of men in Germany were overweight in 2012. The proportion of obese individuals has risen among men in particular, but the number of obese adolescents is also a cause for concern.
Suffering and costs caused by diabetes wounds
Fifteen per cent of Germany’s diabetics suffer from a chronic wound at some point in their lives. These wounds are most often found on the feet; in fact, one speaks of the diabetic foot syndrome (DFS). About 12per cent of these wounds lead to amputations, about half of them below and half above the ankle.
Over half of these people can no longer walk after being amputated above the ankle, which is a source of great suffering. In Germany, some 44,000 amputations are carried out on the lower extremities each year. Roughly 70% of them (30,000 cases) are connected to diabetes, according to a study carried out by the scientific service (WIdO) of the AOK health insurance scheme relating to 2001. About 13,000 of these amputations are carried out above the ankle.
This engenders enormous costs for society as a whole. The US government estimated the cost of a leg amputation to be USD 60,000 in connection with the introduction of countermeasures under the Diabetic Foot Complication and Lower Extremity Amputation Reduction Act of 2003. A Swedish study came to similar results. Depending on the extent of the amputation, it determined costs of between USD 43,000 and 65,000 (Larsson J., Apelqvist J. et al., 1995).
Even without amputation, diabetic foot syndrome is very expensive to treat. According to a study, roughly EUR 2.5 billion are spent in Germany each year for the treatment of chronic DFS wounds (Hauner H., 2006). This explains the high interest in new wound therapy approaches in order to reduce human suffering and costs to the economy.
Causes of diabetic foot syndrome
None of our other organs has to bear such a heavy load as our feet, which have to carry our body weight with every step we take. An average German takes about 5,000 steps every day. Even a lazy car driver who always takes the lift and works at the computer achieves an average of 2,000 steps. People who take between 10,000 and 15,000 steps have a sporty lifestyle. If we multiply the average 5,000 steps by a body weight of, say, 75 kilos, the feet have to bear a load of about 400 metric tons a day.
Such extreme mechanical stress can only be borne if the feet are provided with an efficient supply of blood and nervous energy. But because the foot is naturally the furthest away from our heart and brain, it is at a disadvantage compared with other organs. The distance to be travelled from the heart vessels to the foot makes it especially susceptible to arteriosclerosis. Typically, diabetics have a high risk of premature calcified arterial plaque buildup and narrowing of the arteries especially in the lower leg. Poor circulation in the feet makes them even more vulnerable and at risk of mechanical damage. If such damage is not repaired, bacterial invasion often follows.
The nerve channels are even longer than the blood vessels. They are almost two metres long from the brain to the foot. These nerve channels are at risk due to increased sugar levels, because chronic high blood sugar damages the insulating layer that surrounds the nerve cell. As with an electrical cable, this insulation damage leads to a malfunction or complete breakdown of the nerve channel.
Since nerve length plays a key role with regard to the nerves’ sensitivity to noxae, it is feeling in the toes that is almost always affected first in diabetic patients. In people who have been suffering from poorly controlled diabetes for a long time, the fingers may also become numb. Tall people are more often affected than short people, for the given reasons.
Almost all amputations begin with often minimal damage to the feet, such as little sores on the small toe caused by pressure from shoes. But since minor injuries to the nerves often go unnoticed and untreated, bacteria may enter the lymph vessels. Because the immune system is impaired by sugar, it cannot adequately fight against bacteria, which invade the skin, tendons and later also the bones, and multiply there. The point of no return is rapidly reached. If wound dressings and antibiotics have no effect, the only option left is often a complex operation.
Conditions for wound healing
Even today, we do not yet understand all of the factors that decide whether a wound will heal or worsen. A complex series of cleaning and repair processes have to take place in the wound before it can close up. These are regulated by precisely coordinated gene expression and suppression in the affected body cells. The mediators required for wound healing have to be available at precisely the right moment.
However, little research has yet been done into these processes, which remain a key topic for genetic analysis. The fact that has been clearly confirmed by scientific clinical studies is the need for sufficient circulation, removal of pressure, the need to fight infection and, if necessary, to clean the wound by mechanical means.
Next to these four recognised cornerstones of therapy, improvements in wound dressing would be highly desirable. Although the market for dressing materials continues to grow, and both doctors and patients are promised rapid healing, until today none of the newly offered dressings have been proven to be superior. There is a huge potential for improvement.
Paradigm shift in medicine
Recent developments in medicine show that a paradigm shift in the treatment of human diseases is imminent. Advances in biotechnology have already led to initial applications in human medicine. The first success stories have been reported especially in therapies for fat metabolism disorders using antisense oligonucleotides (ASOs) or gene transfers. The range of applications meanwhile extends to the first successful cloning of primates in China in early 2018, a practice that remains ethically controversial.
These developments in biotechnology can also be expected to lead to new applications in the therapy of chronic wounds in the foreseeable future. Such applications make it possible to resynchronise the faulty sequence of cellular processes in the chronic wound by intervening in the cellular steering of wound healing, enabling the wound to close up in an ordered process. Pharmaceutical products and wound dressings based on biotechnology are another worthwhile target of such developments. They too will become established elements in the treatment of chronic wounds.
The large and profitable market this opens up to research companies will accelerate the development of new measures for closing wounds. Doctor and nursing staff at hospitals are eagerly awaiting practical developments by innovative research laboratories.
- International Diabetes Federation (2017): IDF Diabetes Atlas, 8th ed., Brussels, Belgium www.diabetesatlas.org
- Statista | Das Statistik-Portal: Anteil der Erwachsenen mit Fettleibigkeit in ausgewählten OECD-Ländern im Zeitraum der Jahre 1990 bis 2015 https://de.statista.com/statis...
- Wissenschaftlicher Dienst der AOK: www.wido.de
- Diabetic Foot Complication and Lower Extremity Amputation Reduction Act of 2003: www.congress.gov/bill/108th-co...
- Larsson, J., Apelqvist, J. et al. (1995): Decreasing incidence of major amputation in diabetic patients: a consequence of a multidisciplinary foot care team approach?, Diabetic Medicine, Jg. 12, Nr. 9, S. 770–776 www.ncbi.nlm.nih.gov/pubmed/85...
- Hauner, H. (2006): Die Kosten des Diabetes mellitus und seiner Komplikationen in Deutschland. Deutsche Medizinische Wochenschrift, Jg. 131, Suppl. 8, S. 240–242; s. a. Robert-Koch-Institut (2011): Diabetes mellitus in Deutschland. GBE Kompakt 3/2011 www.rki.de/DE/Content/Gesundhe...