What is the status of medical research to combat type 2 diabetes (T2D)?

An increasingly common chronic disease, type 2 diabetes (T2D) is characterized by elevated blood sugar levels, also known as hyperglycemia. It concerns 92% of diabetic patients, i.e. about 3.6 million French people, and generally affects people over 40 years old.

Thanks to many years of active medical research, scientific advances have made it possible to better understand this disease and to develop treatments for the benefit of patients. What is the status of medical and scientific research on type 2 diabetes?

Discover below the testimony of the Prof. Fabrizio Andreelliwhich contributes to the research work of the Diabetes-Metabolism Department of the Pitié-Salpêtrière Hospital, and of the Nutriomics unit (INSERM / IHU ICAN).

What role does the gut microbiota play in T2D?

The intestinal microbiota is the set of micro-organisms (including bacteria) present in the intestines. Our research teams are interested in the link between microbiota and type 2 diabetes.

They noted that overweight populations show an imbalance in the composition of these intestinal bacteria and an impoverishment of the diversity (variety) of the intestinal flora. This phenomenon is intensified for overweight patients with T2D, who show more alterations in the diversity of their flora.

Can an impoverished gut microbiota promote obesity and type 2 diabetes?

In our laboratory, our research teams therefore contribute to analyze these bacterial species in order to better understand them and to restore a balanced flora in our patients, in order to limit their weight gain and improve their blood sugar levels (blood sugar level), in case of type 2 diabetes.

What impact does bariatric surgery have in T2D?

Research has shown that weight loss improves type 2 diabetes. In fact, physical activity and a balanced diet are part of the hygienic and dietary measures that make it possible to treat T2DM in the first instance, before oral or injectable medication.

In some populations, bariatric surgery to lose weight (gastric banding or more complex surgery that creates an intestinal bypass) helps to normalize blood sugar levels of the patient postoperatively, and even in some cases to make disappear type 2 diabetes. This phenomenon has been observed quickly after the operation (days or weeks)long before the patient begins to lose weight.

What mechanism(s) improve blood glucose after bariatric surgery, before any significant weight loss? Is it the operation itself that induces new signals to wake up the cells that secrete insulin in the pancreas?

In our laboratory, these questions were addressed using a mouse model, recreating the same context as in human patients. In mice and humans, it has been shown that bariatric surgery can awaken the endocrine pancreas, that is, the part of the pancreas that secretes insulin, a hormone that is crucial for controlling blood sugar levels (glucose). Thus, in humans as well as in operated rodents, an increase in insulin secretion is observed, allowing the improvement of blood sugar levels, and even the disappearance of type 2 diabetes.

Analysis of the mechanisms involved in the improvement of diabetes after bariatric surgery revealed involvement of the pancreatic beta cell (endocrine pancreas)which will regain optimal functionality, making it capable of secreting insulin according to the body’s needs in order to regulate blood sugar levels.

Our teams are now working to identify substances that could be released from the operated intestine and that target the endocrine pancreas, thus making it possible to explain how the operated intestine improves the functionality of the pancreas on the basis of the communication between these two organs. The identification of these substances could lead to the creation of new drugs or nutritional solutions to balance the blood sugar levels of patients with type 2 diabetes without bariatric surgery.

What impact does T2D have on the intestinal system?

In patients with type 2 diabetes and who are overweight, the hormonal functioning of the intestinal system is altered. In fact, the intestine has other functions than just absorbing food. Some intestinal cells are specialized in the secretion of hormones that are mainly secreted during meals. These hormones have a double function: to reach the pancreas in order to secrete more insulin to balance blood sugar during meals; and to induce satiety. The production of these hormones called incretin hormones is defective in obesity and type 2 diabetes, which prevents the endocrine pancreas from releasing more insulin and also reduces the satiety message to the brain.

The classic functioning of the intestinal system

  • The microbiota (intestinal bacteria), in contact with food, will interact with the intestine which will release intestinal hormones, or incretin hormones (such as GLP-1), which will circulate in the blood and warn the body that the meal is about to arrive.
  • Upon receiving these hormones, on the one hand the pancreas will secrete more insulin, and on the other hand the brain is informed that satiety must be prepared.

How can we improve the secretion of the missing incretin hormones to increase the secretion of insulin needed to control blood sugar levels?

The identification of one of the incretin hormones, called the GLP-1, has recently allowed research teams to develop a medication to treat type 2 diabetes. This treatment comes in the form of a pre-filled pen of GLP-1, allowing a weekly subcutaneous injection. It will allow to restore this important hormone to the bodywhich is no longer or poorly manufactured by the intestine.

This medication is available for patients with T2DM, and is increasingly recommended when lifestyle modifications are not enough (physical activity, diet…).

A new generation of drugs is expected to be available in 2023-2024, with pens that include 2 or even 3 different gut hormones to enhance the effects on satiety and endocrine pancreas secretion.

“This is a huge hope for all patients. It will prevent diabetes from becoming unbalanced, reduce the risk of complications, and allow for better health,” says Professor. Fabrizio Andreelli, Department of Diabetology, Pitié-Salpêtrière Hospital.