Type 2 diabetes (NIDDM)

Le diabète, la recherche et l'accompagnement.

Diabetes, Research and Support

 

What's new in research

 

The research

The light of the offense

 

https://youtu.be/cDS7YwEh5UI

 

HAS speak of type I diabetes

 

https://youtu.be/PT21wCQtsSw

 

Type 2 diabetes (NIDDM)

 

File prepared in collaboration with Prof. Christian Boitard , Research director at Inserm and diabetologist at Cochin Hospital, Paris - April 2014.

Diabetes corresponds to a sustained elevation of the concentration of glucose in the blood (hyperglycemia). In the case of type 2 diabetes, this phenomenon caused by a disturbance of carbohydrate metabolism appear gradually and insidiously. Researchers are trying to better understand the mechanisms involved in preventing and effectively treating the disease.

 

The incidence of type 2 diabetes is increasing globally, especially with age. The disease usually occurs after 40 years and it is diagnosed at an average age close to 65 years. The incidence is highest between 75 and 79 years with 20% of men and 14% of women treated for this disease. However, type 2 diabetes also affects younger people, including teenagers and even children.

© Inserm / U872

Pancreatic islet of Langerhans, insulin secretory.

 

In France, the overall prevalence of diabetes was estimated at 4.6% of the population in 2011 and type 2 diabetes is 90% of cases. But this figure is largely underestimated because ignores untreated or undiagnosed. But given the silent nature of the disease, about 20% of older people with diabetes aged 18 to 74 years are not diagnosed. This figure decreases sharply with age from 30% among 30-54 years to 13% in 55-74 years.

The prevalence of the disease is also continuously increasing for several years, with an increase of 5.4% per year between 2000 and 2011. The trend is more pronounced in certain populations, especially in the departments overseas and less advantaged departments of a socio-economic perspective. This increase is related to the aging population, the increase in life expectancy of diabetics or a more deleterious lifestyle.

 

A slow and silent evolution

 

Type 2 diabetes develops silently over many years. Hyperglycemia is long asymptomatic and the disease is often discovered incidentally during a blood test, or in case of complications.

The disease is favored by a decrease in insulin sensitivity of cells (known to insulin resistance), especially under the effect of obesity or physical inactivity. To meet the increased demand for insulin resulting in the insulin-secreting pancreatic cells produce more insulin (hyperinsulinemia) until they no longer answer or end up exhausted. Insulin production becomes insufficient leading to accumulation of glucose in the blood (hyperglycemia). In other words, insulin is produced in insufficient quantities meet increased demand.

When cells become resistant to insulin, in particular liver cells, muscle and adipose tissue, hormone no longer able to generate a signal effective to ensure the entry of glucose therein. Glucose is the main "fuel" of the cells, resulting in malfunctions. In addition, the concentration of sugar in the blood increases, this leads to further complications.

 

Risk of complications after 10 to 20 years of evolution

The endothelium of resistance to control his artery arterial diameter by synthesizing chemical and pharmacological smooth muscle. Induced diabetes modification enzymes thereby preventing the artery to adapt to the blood flow. It is composed of AGEs, fruit of the alliance of a sugar and a protein. Image made in neuro vascular biology laboratory and integrated mitochondrial U1083. © Inserm / U1083 BNM The endothelium of resistance to control his artery arterial diameter by synthesizing chemical and pharmacological smooth muscle. Induced diabetes modification enzymes thereby preventing the artery to adapt to the blood flow. It is composed of AGEs, fruit of the alliance of a sugar and a protein. Image made in neuro vascular biology laboratory and integrated mitochondrial U1083. © Inserm / U1083 BNM

© Inserm / U1083 BNM

 

Type 2 diabetes damages the arteries.

 

Prolonged hyperglycemia (high glucose concentration in the blood) leads to serious long-term complications. It is all the more insidious it is usually asymptomatic. These complications can occur after several years of poor glycemic control (usually after 10 to 20 years). They relate mainly to the arteries and micro vessels of the heart, kidney, peripheral nerve and retina, which are affected by the excessive concentration and permanent glucose in the blood. Thus diabetes causes vascular damage that accelerate the atherosclerosis , the cause of myocardial infarction , of stroke or of peripheral arterial disease. Also altering the microphones vessels, diabetes is also the cause of retinopathy, with the risk of visual impairment see blindness, peripheral neuropathy or diabetic nephropathy.

 

The risk of diabetes

 

In practice, diabetes multiplied by three to five the risk of myocardial infarction. In 2006 in France, 12,639 people with diabetes were hospitalized for myocardial infarction and 9% have died. The disease also increases the risk of kidney failure, amputation of a limb or even blindness. In 2006, 2900 people with diabetes began treatment for end stage renal disease (dialysis or transplant) in France 9000 and had to undergo amputation of a lower limb in 2007.

The lifestyle, the main risk factor

 

There is a genetic predisposition to diabetes type 2. The analysis of large cohorts of patients identified genes associated with an increased risk of developing the disease. Most of them are involved in the functioning of pancreatic beta cells. But these genes are very heterogeneous, and none of them can predict the onset of the disease.

 

The genetic component therefore can not alone explain the occurrence of type 2 diabetes, either the dramatic increase in its incidence. The onset of the disease seems to be more correlated with age and to the interaction between the genome and the conditions of life. The incidence of the disease increases with age due to the wear of the cells and organs. Moreover, physical inactivity, high cholesterol, overweight and obesity , or hypertension , increases the risk of developing the disease, although the reasons are clearly identified. Inflammatory mechanisms are nevertheless stigmatized, especially in cases of obesity.

There most likely are other environmental factors that interact with genes, could explain the increased number of cases of type 2 diabetes in the world. Researchers are interested in particular to changes in the intestinal flora, the conditions of fetal development ...

 

© Inserm / Ya k + prod

The crime of light - Françoise Clavel-Chapelon and Guy Fagherazzi were interested in the relationship between consumption of sweetened beverages and sugary drinks

 

The lifestyle, priority treatment

 

The reference treatment of type 2 diabetes is the change in lifestyle: weight loss when necessary, regular physical activity and a balanced diet may be enough to control blood sugar, but these changes are often difficult to implement. implementation and acceptance by the patient.

 

In second-line oral agents to help control blood sugar. There are several therapeutic classes based on different mechanisms of action, administered alone or associated. Biguanides (including metformin) promote the action of insulin. Sulphonylurea and glinides stimulate insulin production in the pancreas. The alpha-glucosidase inhibitors retard carbohydrate absorption after meals. Finally, GLP1 analogues administered by injection, or drugs that block the degradation of GLP-1 (DDP-4 inhibitors) work by slowing gastric emptying, limiting the appetite and stimulating insulin secretion, but only if elevation of blood glucose. They therefore limit the risk of hypoglycemia. Again, the improvement of lifestyle contribute to the efficiency of these treatments.

 

Blood sugar patients are often poorly controlled despite these treatments, especially in the absence of weight loss, if it is impossible to introduce a real physical activity, or when the capacity of the cells of the pancreas to secrete insulin s 'exhausts uncontrollably over the years. They then use insulin therapy. This treatment is to inject insulin several times a day, depending on blood glucose measured in real time, as in type 1 diabetes .

HAS speak of type II diabetes

 

Prevention, research issue number 1

 

Many studies, conducted in particular at Inserm, relate to the identification of risk factors and populations at risk for diabetes type 2. The goal is to try to stem the increase in the incidence of this disease . prevention is the only way to delay the onset of disease. cohort studies in general population ( E3N , NutriNet-health ...) are carried out for example to better understand the links between diet, body weight, lifestyle and diabetes.

 

Researchers are interested also to the biological mechanisms involved in the onset of type 2 diabetes, in order to discover new therapeutic targets.

An Inserm team recently managed to produce lines of human pancreatic beta cell, producer and insulin secretory. This is a valuable tool for studying the mechanisms of the disease and test new drugs in vitro. Researchers have even created a start-up, Endocells to market these lines.

 

Many works also involve inflammatory processes associated with obesity and which contribute to the onset of diabetes. It has recently been shown that the fat cells of obese patients produce cytokines, inflammatory molecules that promote insulin resistance. Thus, in these individuals, anti-inflammatory drugs constitute a processing track against diabetes. Researchers questioned further about a possible reversibility of these mechanisms: studies have shown that significant weight loss in obese patients improve glycemic control.

© Inserm / U342

Adipocytes in culture.

 

Other teams are interested in changing the intestinal flora, particularly in subjects with type 2 diabetes studies have indeed shown that its composition changes with a fatty diet, and the enteric nervous system (located at the gastrointestinal tract) plays a role in the regulation of metabolism.

 

In parallel, work is conducted to assess the health of patients with diabetes and the effectiveness of treatments. Studies ENTRED provided extensive information on diabetes in France, their medical care, their quality of life , the need for educational process by monitoring national patient cohorts. The new French cohort Gérodiab is in a close context. It will assess the benefit of glycemic control in patients over 70 years.

Early educate the immune system to prevent type 1 diabetes

 

May 26, 2015

 

Inserm researchers have protected mice from type 1 diabetes by making their immune system tolerant to insulin producing cells during embryonic development. In humans, the same approach could be used after birth.

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Desensitize people with type 1 diabetes risk to make their tolerant producing beta cell insulin. Such is the idea of an Inserm team to fight against the disease. A strategy that could be paid to believe their experiments conducted in mice embryonic

Prevent the destruction of insulin-producing cells

 

Type 1 diabetes is an autoimmune disease: The immune system of the individual gradually destroys its own insulin-producing beta cells in the pancreas, often in the first months of life. This destruction takes place in several stages, but the first is a lack of education of T cells during development. "During embryonic and neonatal stage, T cells pass through the thymus. They are faced with some protein structures derived from cells of the self (antigens), and learn to tolerate them. In the case of diabetes, this process works wrong. the antigens of beta cells are not adequately represented and T cells are released from the thymus so that they are not tolerant. they recognize them as if they were foreign agents and will therefore logically s attacking the beta cells, "explains Roberto Mallone * and * Slobodan Culina, who signed the work with colleagues in the team of Sébastien Lacroix-Desmazes **.

 

Re-educate T cells

To prevent the disease from occurring, researchers have attempted to overcome this dysfunction improving the education of T cells during embryonic development. For this, they used the preproinsulin, which is the first beta cell antigen recognized by the immune system. They administered to pregnant rodents, from giving birth to mice that later develop diabetes. "We coupled this protein to an Fc antibody fragment that binds to a receptor of the placenta. This allows the preproinsulin cross the placenta and pass in the embryo as do maternal antibodies. There, thymus protein is transported to the embryo and its presence leads to the elimination of T cells that do not tolerate, "describes Roberto Mallone. A successful experience as nearly 80% of animals born ultimately did not develop diabetes. The experiment conducted by researchers has protected them from disease.

 

Intervening after birth

 

In humans, this therapy would require a track prenatal screening for diabetes, which is impossible hour. So researchers will test this strategy in newborn rodents, by administering the protein by oral route. If this approach is effective, then they will launch the first human trial. For this purpose, they now constitute a cohort of children at high risk of developing type 1 diabetes due to family history. "It will not be possible to test this protein directly from newborns. It will proceed step by assessing its safety first in diabetic patients and in a second step in prevention in young people, by refining the more effective therapeutic window. in theory it should take place before the destruction of beta cells first around the age of one year, but may be a later administration will also be effective. All that remains to be defined, "concludes Roberto Mallone .

 

Note:

 

* 1016 Unit Inserm / CNRS / Université Paris Descartes, Institut Cochin, Paris

** Unit 1138 Inserm / Université Pierre et Marie Curie, Centre des Cordeliers, Paris

 

source:

 

Culina S. et al. Maternal-fetal transfer of preproinsulin through the neonatal Fc receptor Prevents autoimmune diabetes. Diabetes, online edition of April 27, 2015

 

 

 

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