Diabetes: 50 years of progress, but soaring prevalence

Diabetes management has not ceased to improve over the last 50 years—in most cases, complications can now be avoided with the help of treatment and lifestyle changes. Prof. Christian Boitard, a Professor of Clinical Immunology at Paris Descartes University and Head of the Diabetes Service at the Cochin Hospital in Paris, reviews this progress, and reminds us that prevention is the challenge from now on. The objective: to try to stem this global epidemic.

Could diabetes be the illness of the century? There is not one study that denies the massive increase in the prevalence of this disease in industrialised countries, or its explosion in developing countries. In France alone, the French Institute for Public Health Surveillance (InVS) estimates the proportion of diabetic men at 20% for the 75-79 year age group, and that of diabetic women at 14% for the same age. And since 2000, these rates have been increasing by more than 5% annually.

Marquage en immunofluorescence pour GLUT2 (en vert) et l'insuline (en rouge) sur une coupe de pancréas de rat. GLUT2 est un des transporteurs du glucose : cet isoforme majeur des cellules des îlots de Langerhans du pancréas permet une synthèse et une sécrétion d'insuline adaptée à la glycémie. Les transporteurs du glucose de la famille GLUT sont des protéines présentes dans la membrane des cellules. Leur bon fonctionnement est essentiel à la régulation de la prise alimentaire, qui vise à adapter les besoins et les dépenses énergétiques de notre organisme. Le système nerveux et le système endocrinien jouent un rôle-clé dans ce processus. Image réalisée au Centre de Recherche des Cordeliers, Paris. © Inserm U872

Although these epidemiological indicators are “in the red,” research conducted in this area during the last 50 years gives many reasons for optimism. It allows effective treatment of a large number of patients, and offers appropriate prevention policies to the populations at risk.

Many laboratories are indeed trying to understand and halt this epidemic, especially at Inserm. “Basic research carried out since the 1960s has allowed us to discover the auto-immune origin of type 1 diabetes,” recalls Christian Boitard. In the patients involved, cells from the immune system effectively begin to destroy the pancreatic cells that produce insulin. The source of this dysfunction has still not been fully identified, but the detection of circulating autoantibodies has allowed the development of one of the first diagnostic tests to distinguish this form of diabetes from the others. This diagnosis is very important in choosing treatments,” the researcher reminds us.

Research carried out in recent decades has also enabled a better understanding of the mechanisms of type 2 diabetes: the genes involved, the metabolic pathways controlling the action of insulin on the liver and muscles, the secretion of this hormone, the disruptions involved, etc. “The available data clearly show that the development of the disease can be explained by a combination of genetic factors and disruption of the environment. Diet and sedentary behaviour, two features of the modern world, play an important role,” explains Christian Boitard. By their impact, both direct and indirect, these factors bring about a progressive reduction in insulin production, and a decrease in the sensitivity of the body’s cells to this hormone.

Complications are becoming avoidable

Microanévrysmes sur le versant artériel de la circulation capillaire (rétinite diabétique). © Inserm/Dhermy, Didier

Other research has also enabled a better knowledge of the risks that accompany this metabolic disorder, particularly the potentially fatal cardiovascular complications—myocardial infarction, terminal renal failure, and amputations or problems with vision. The UKPDS study (for United Kingdom Prospective Diabetes Study), published in 1998, is certainly the largest body of work to date, monitoring over 5,000 patients with type 2 diabetes for 20 years.

In 2009, over 34,600 deaths in France were diabetes-related, i.e. 6.3% of all deaths. However, complications of diabetes can be avoided with the help of treatment and good compliance. However, type 2 diabetes, which represents 85-90% of cases, is often silent for years: InVS estimates that in 2006, in the 18-74 year age group, approximately one out of every five people with diabetes was undiagnosed.“The raised blood sugar level is often not detected for several years before diagnosis. However, it has an extremely harmful effect on the tissues and blood vessels,” insists Christian Boitard.

Among the treatments that help to prevent these complications or halt their progress, several drugs were already available in the 1960s, especially two classes of oral diabetes drugs—the sulphonamides and metformin. They are still being used, and their mechanisms of action are better understood. Furthermore, the therapeutic arsenal has expanded to include several other drugs. GLP1 analogues, for example, stimulate insulin production by the pancreas without the risk of hypoglycaemia.

 

Insulin revolution

Recherches sur l'administration orale de systèmes nanoparticulaires d'insuline. Les matériaux utilisés peuvent être des polymères synthétiques comme le poly(alkylcyanoacrylate). © Inserm/Damgé, Christiane

Although insulin was discovered in the 1920s (in Canada), the therapeutic forms of the hormone underwent accelerated development in the 1970s. The first step: so-called “highly purified insulins”, from beef and pork pancreas, much better tolerated by patients. Ten years later, human insulin was being offered to patients, avoiding the risks of potential toxicity associated with the use of an animal hormone. Human insulin was then produced via genetic engineering, by inserting a gene for human insulin into bacteria. Next, in the 1990s, came insulin “analogues,” genetically modified insulins. “They changed the lives of patients. There was no longer a need to wait for half an hour between injecting and eating. Everything can be done at the same time with insulins that provide much better coverage of mealtimes. “Basal” insulins act for a period 24 hours, covering the daily requirement outside of meals, and are absorbed much more steadily after subcutaneous injection than the animal insulins previously available,” explains Christian Boitard. And advances did not stop there—insulin pumps allow delivery of programmed doses of the hormone, close to physiological production, and these doses can be modified according to blood sugar level if necessary. For rare, extremely severe cases, pancreatic transplantation has even been carried out with success.

Les cellules béta sont regroupées sous la forme de petits îlots au sein du pancréas (Îlots de Langerhans). Bien qu'elles n'occupent au total qu'un volume de quelques mm3, ces cellules assurent la totalité de la sécrétion diinsuline. Leur destruction est à l'origine du diabète de type 1. Taille de l'image : 1,1 mm. © Inserm/Université Lille 2/CHRU de Lille/Pattou, François

Thus, where the kidneys are undamaged, the life expectancy of type 1 diabetics is now similar to that of the general population.Similarly, type 2 diabetics can control their blood sugar level by following their treatment plan and agreeing to change their lifestyle habits (healthier diet and regular physical activity). For all, the risk of hypoglycaemic episodes, a source of much anxiety for patients, has become less and less.

Anticipating the risks of diabetes

Understanding the risk factors for diabetes is still a major area of research aimed at stemming the epidemic. With regard to type 1 diabetes, scientists are especially trying to understand what triggers the autoimmune reaction. Infections? Events that occur during foetal development? With respect to type 2 diabetes, the risk factors are better known. However, until now, health information and recommendations from the French National Nutrition and Health Program (PNNS) and advice from physicians have not borne fruit. It is hard to convince people to resume sports and give up food habits of 50-55 years’ standing... Another aspect of research, perhaps more societal, will consist of finding the right arguments!

 

Further information
For further information, visit our information packs on type 1 diabetes and type 2 diabetes

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