Diabetes and obesity: our research

Better understanding diabetes

More than 4,5 million people in France have diabetes, but around 1 million of them are unaware of it! The situation is particularly concerning in the Hauts-de-France region, where a combination of genetic and social factors leads to a significantly higher risk of type 2 diabetes and obesity than the national average: 5,5% of the population. Diabetes is characterized by an abnormally high level of glucose (or sugar) in the blood, also known as hyperglycemia. Glucose provides energy to the body's various tissues. If blood glucose levels remain stable even after a meal or physical exertion, it is because a complex regulatory system exists in which insulin plays a crucial role, as it is responsible for the uptake and/or use of glucose by cells.

Diabetes type 1

Type 1 diabetes (approximately 5% of diabetes cases in France) is an autoimmune disease, meaning a chronic inflammatory disease resulting from immune dysfunction that can affect various organs. Insulin is a hormone synthesized in the beta cells of the pancreas, located in the islets of Langerhans; it regulates blood glucose (sugar) levels. Type 1 diabetes originates from insufficient insulin secretion by the pancreas, which gradually destroys the beta cells. This type of diabetes typically manifests in childhood or adolescence. Since the body no longer produces insulin, the only currently available treatment is regular insulin injections combined with a balanced diet and regular exercise.

Diabetes type 2

In type 2 diabetes, blood glucose levels no longer respond to the insulin secreted by the pancreas. It is also called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes and can be diagnosed several years after the onset of the first symptoms. Glucose is then poorly utilized by the cells, explaining the rise in blood glucose levels above normal (hyperglycemia). More common than type 1 diabetes, this type of diabetes generally manifests after the age of 40. Several types of treatment can be offered in addition to a balanced diet.

Hyperglycemia is diagnosed when the fasting blood glucose level is equal to or greater than 1,26 g/L of blood. Blood glucose is measured by self-monitoring using a device, most often from a drop of blood taken from the fingertip.

There are also other rarer forms of diabetes such as gestational diabetes (temporary diabetes which occurs in 6% of pregnant women) or MODY diabetes (Maturity Onset Diabetes Of the Young), a diabetes linked to the mutation of a gene which would represent 2 to 5% of non-insulin-dependent diabetes.

Research on diabetes and obesity at the Pasteur Institute of Lille

The research unit on the genetics of diabetes and obesity was established at the Pasteur Institute of Lille in 1995. It comprises fifty people, including researchers, professors, and engineers. This unit is the origin of the EGID Laboratory of Excellence (Labex) and the LIGAN Personalized Medicine Genomics Equipment of Excellence (Equipex), serving medical research and patients suffering from genetic diseases or cancer.

The goal of EGID is to provide optimal conditions for world-renowned translational diabetes research that truly improves the lives of people with diabetes. The unit operates with two teams. This structure has enabled the identification of new pathways leading to metabolic diseases, the establishment of cellular models allowing for their precise study, and the development of new diagnostic and therapeutic strategies.

In particular, some teams are working on the genetic origins of diabetes. In this respect, the unit was the first team in the world to demonstrate the existence of monogenic forms of diabetes and obesity, and then to explore the genome of diabetics and obese people in search of common genetic variants (genome-wide association studies, or GWAS).

While diabetes is often caused by obesity or being overweight, and blood sugar levels can be improved through dietary adjustments, genetics can also play a role in its development. Professor Froguel explains that “obesity originates in the brain and gut and relates to food regulation, whereas diabetes originates in the pancreas and insulin secretion.”

In parallel, another unit at the Pasteur Institute of Lille is studying the interactions between diabetes and cardiovascular diseases. It is particularly focused on the regulation of genes involved in these pathologies and the consequences of their dysregulation, with a special interest in nuclear receptors, which represent potential therapeutic targets. “We have notably identified the crucial role of a nuclear receptor called PPARα in glucose (sugar) metabolism and we have identified new therapeutic targets, some of which are currently in clinical trials,” explains Professor Bart Staels.

This is notably the case with Elafibranor, a drug developed by the Lille-based company Genfit, which targets this type of receptor in one of the complications of diabetes, NASH (Non-Alcoholic Steatohepatitis), a liver condition that can lead to cirrhosis. The drug, developed by Genfit based on discoveries made at the Pasteur Institute in Lille, has been successfully tested on 800 patients and healthy volunteers in Europe and the United States, and is expected to soon enter phase 3 trials, the final phase before commercialization.

Identify the genes responsible for diabetes

By studying genetics and DNA mutations, the research unit demonstrated that rare mutations certainly cause significant effects in their carriers, and that frequent mutations do not necessarily lead to the most widespread diseases. The teams at this joint research unit at the Pasteur Institute in Lille were the first to identify genes responsible for diabetes. Today, 100 genes have been identified as contributing to diabetes.

In 2017, the unit used its DNA sequencing platform, unique in France, to identify new genes associated with obesity, and also to improve the diagnosis of early-onset type 2 diabetes of genetic origin, finally enabling personalized medicine for certain types of diabetes. The unit also explored the sometimes mysterious function of genes involved in type 2 diabetes, opening up new avenues for treatment. It also launched an ambitious study, awarded a grant by the European Research Council, on the regulatory regions of the genome of pancreatic, liver, adipose, and muscle cells—essential tissues for regulating blood glucose levels. Finally, it conducted studies on the epigenetic effect (modifying gene activity) of the environment on metabolism and its consequences for liver complications in type 2 diabetes.

What are the first signs of diabetes?

The symptoms of diabetes are similar for both types. Patients often experience unusual fatigue, as well as an unusually high level of thirst (polydipsia) and hunger. Frequent and urgent urination are also common. Furthermore, infections and itching in the genital area are frequent.

What is the link between diabetes and obesity?

Obesity and diabetes both present risk factors for comorbidity. Comorbidity is defined as the presence of multiple chronic diseases that require long-term treatment.

The more fat there is in the body, the more insulin the body needs. The pancreas, where insulin is synthesized, is overworked, and if it cannot produce enough insulin (or if there is a complete lack of it), then diabetes can develop in obese individuals. Obesity can therefore be a cause of diabetes.

How is diabetes diagnosed?

Diabetes is most often diagnosed when symptoms appear.

First, a blood test is performed to measure blood glucose levels. Further tests may be prescribed by the attending physician or diabetologist.

Type 1 diabetes

Diagnosis following blood test

fasting blood glucose is greater than or equal to 1,26g/l on two occasions and there are no symptoms
at any time of day, blood glucose is above 2g/l in the presence of symptoms

Confirmation of diagnosis

blood test with HbA1c (glycated hemoglobin) measurement
Urine and renal function tests (creatinine, urea…)
ophthalmological consultation

Additional tests

Electrocardiogram (heart test)
Electromyogram (nerve monitoring test)
Dental follow-up

Type 2 diabetes