type 2 diabetes

Type 2 diabetes

Health & Household

Diabetes is a lasting excess in the concentration of glucose in the blood (hyperglycemia). In the case of type 2 diabetes, this phenomenon is caused by a disturbance in carbohydrate metabolism.

If it appears gradually and insidiously, the disease has serious, even fatal, long-term consequences. Diabetologists are trying to better understand the mechanisms involved in preventing and treating it effectively, while emphasizing the importance of lifestyle in its occurrence – and therefore in its prevention – as well as its management.

type 2 diabetes


Understanding type 2 diabetes


In France, the overall prevalence of diabetes was estimated at 5% of the population in 2016, type 2 diabetes (T2D) corresponding to 90% of the cases. This figure is, however, largely underestimated since it does not take into account untreated or undiagnosed people. However, given the silent nature of the disease, it is estimated that 20 to 30% of adults with diabetes are undiagnosed. This share decreases with age, falling to 13% among 55-74 year olds.

The incidence of T2D increases with age. The disease usually manifests after 40 years and is diagnosed at an average age close to 65 years. The incidence is maximum between 75 and 79 years with 20% of men and 14% of women treated for this disease. However, type 2 diabetes also affects more and more young people, including adolescents and even children. This is precisely the period during which eating habits and those relating to the practice of physical activity are acquired, two essential levers in the prevention of disease …

Prevalence disease has increased significantly in recent years. The trend remains more marked in certain populations, in particular in the overseas departments and the departments or areas least favored from a socio-economic point of view. Part of the increase is related to the aging population and the longer life expectancy of diabetics, but it is tending to stabilize. On the other hand, nutritional imbalances and a sedentary lifestyle participate more and more in the “propagation” of T2D. This deleterious lifestyle, inducing a general increase in the weight and the number of people suffering from obesity, is of the greatest concern to diabetologists. Another alert: the recent increase in “medicated” diabetes, associated in particular with certain neuroleptics
.

Slow and silent evolution


Type 2 diabetes develops silently for many years. Hyperglycemia remains asymptomatic for a long time and the disease is often discovered by chance during a blood test, or in the event of a complication.

This hyperglycemia comes from a decrease in the sensitivity of cells – especially those of the liver, muscle and adipose tissue – to insulin. This pancreatic hormone has the role of facilitating the penetration of glucose (their main fuel) in the cells, which decreases the blood concentration. To meet the increased insulin demand resulting from this insensitivity, the insulin-secreting cells of the pancreas produce more … until they run out. Insulin production becomes insufficient and glucose builds up irreparably in the blood.

What is “normal” blood sugar?


Normal blood sugar is around 1 g / l on an empty stomach. It varies during the day, increasing in particular for several hours after meals, hence the need to take this measurement on an empty stomach in the morning.

Risk factors: above all lifestyle


Genetic studies show that it is extremely rare for T2D to be caused by a gene mutation. On the other hand, there are undoubtedly genetic profiles (i.e. combinations of genes) which increase the susceptibility to the disease, in other words the risk of becoming diabetic if one adopts an unsuitable lifestyle.

But the main risk factor for DT2 is lifestyle. A diet that is too fatty and too sweet, combined with a sedentary lifestyle (lack of physical exercise), leads to obesity which is in itself a major risk factor for diabetes. Children, via the overconsumption of sodas and other sugary drinks, as well as the disappearance of walking and games in favor of entertainment on the screen, are no longer spared. Certain drugs, in particular neuroleptics, often prescribed in France, can also participate in triggering a T2D.

Other factors come into play, such as the intestinal flora in particular. Not only does this microbiota reflect the lifestyle (nutrition, drugs, sedentary lifestyle) of its host, but it can itself constitute a risk factor and, in certain cases, a direct cause of DT 2. We now know how to identify the ” signature “of a diabetic patient’s microbiota. Therapeutic solutions aimed at treating the microbiota rather than the host could emerge from this knowledge.

Gestational diabetes


There is an increased risk of diabetes in pregnant women: pregnancy can indeed cause so-called “gestational” diabetes. It usually occurs near the end of the 2nd trimester and most often disappears at the end of pregnancy. However, it may be indicative of undiagnosed preexisting diabetes. In this case, the disease continues after childbirth.

Find out more about Pregnancy and Diabetes

Detect and diagnose
“Pre-diabetic” (also known as glucose intolerance) or even diabetic patients usually show no clinical signs for several years. As a result, the average age of care is often too advanced (65 years in France). The hyperglycemia has already been installed for a long time and the damage has started.

The only method of detecting the disease at an early stage is the measurement of fasting blood sugar. It should be routinely performed in people over 50.

Between 1.10 and 1.26 g / l, the patient is considered prediabetic.
If the blood sugar exceeds 1.27 g / l in two successive dosages, diabetes is declared.
Other criteria – post meal glucose, induced glucose, glycated hemoglobin (hemoglobin
 on which glucose is attached) – can confirm or clarify the diagnosis.

Lifestyle, priority treatment
The standard treatment for type 2 diabetes, which must be started before any other, is lifestyle modification, including:

weight loss when necessary
regular physical activity
A balanced diet
These measures may be sufficient to control blood sugar. But these changes are often difficult to implement and accept for the patient.

Next are diabetes medications, which help control blood sugar. There are several therapeutic classes based on different mechanisms of action, administered alone or in combination. As a first drug intention, the practitioner always prescribes metformin. As a second intention, and as part of a personalized medicine approach, he can choose between multiple options:

  • Sulfonylureas and glinides stimulate the production of insulin in the pancreas.
  • Alpha-glucosidase inhibitors delay the absorption of carbohydrates after meals.
  • Agonists
  •  of the glucagon-like peptide-1 receptor (GLP1) slow gastric emptying, limit appetite and stimulate insulin secretion, but only if your blood sugar rises. They therefore limit the risk of hypoglycemia. They can be combined with a so-called “slow” insulin which continually maintains a basal insulin concentration.
  • DDP-4 inhibitors block the breakdown of GLP1,
  • Inhibitors of SGTL2, or iSGTL2, act on the kidney by blocking the reabsorption of glucose.
  • Some of these treatments (GLP1 receptor agonists, iSGLT2) have been shown to have positive cardiovascular, hepatic or renal effects in themselves.

Despite these treatments, some patients’ blood sugar may remain poorly controlled. This is particularly the case in the absence of weight loss, if it is impossible to introduce a “real” physical activity, or when the capacity of the pancreas cells to secrete insulin has been exhausted. over the years. These people then resort to insulin therapy, which consists of injecting insulin, as in type 1 diabetes.

Today there is a variety of “smart” insulins, slow or long acting, which allows to adapt this treatment to all cases. Combined with these insulins, certain anti-diabetic drugs such as GLP1 receptor agonists can also induce significant weight loss.

Microscope pictogram Research challenges
Research on type 2 diabetes continues along two main lines:

  • the mechanisms involved in the onset of the disease (basic research), in order to discover new therapeutic targets
  • the development of therapeutic solutions (preclinical and clinical research).

Regarding the first axis, scientists are currently working to decipher the molecular mechanisms associated with the role of the intestinal microbiota in the occurrence of T2D. Four main phenomena are explored:

  • intestinal inflammatory processes
  • secretion and action of incretins: GLP1 and and GIP (glucose-dependent insulinotropic peptide), two gastrointestinal hormones stimulating insulin secretion after meals
  • intestinal immunity
  • the enteric nervous system (intestine brain axis).

In addition, it has been observed that the fat cells of obese patients produce cytokines, inflammatory molecules promoting insulin resistance. Teams are therefore interested in the mechanisms responsible for the induction of this production of cytokines
.

With regard to the development of new therapeutic solutions, researchers are developing nutritional approaches intended to rebalance the patient’s microbiota. Clinical trials are also underway to assess the value of small synthetic molecules capable of influencing the microbiota / host interaction.

In the shorter term, several new drugs could be put on the market. These are dual agonists, bi (or tri) functional molecules. These injectable peptides indeed act simultaneously on two or even three targets, for example the receptors for GLP1, GIP and glucagon. Among other effects, these molecules induce a very significant weight loss, of the order of 10-15% in a few months.

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