The overall objective of INTERCEPT-T2D is to establish whether the Inflammatory-mediated T2D profile contributes to the early onset-complications, thus enabling the identification of patients most at risk of T2D complications and the development of tailored anti-inflammatory interventions to prevent T2D transition to overt T2D-related organ damage.
The context
Type 2 diabetes (T2D) occurs when insulin secretion from pancreatic beta cells fails to compensate for decreasing insulin sensitivity in the whole body. The causes of impaired insulin secretion and insulin resistance are multiple and differ among patients with T2D. Consequently, patients’ individual trajectories of progressive hyperglycemia and subsequent risk of chronic complications are heterogeneous and so far difficult to predict. In this context, onset of diabetic complications appears to be the most important transition phase of T2D evolution towards premature disability and mortality. The challenge is to identify the key triggering factors that could be targeted for efficient interception, before the onset of overt T2Drelated organ disorders.
Among these key triggering factors, chronic systemic inflammation has recently emerged as a major contributor to the onset of T2D complications, including cardiovascular disease, nephropathy, retinopathy, neuropathy and non-alcoholic fatty liver disease (Rohm et al., 2022). Indeed, partners from the INTERCEPT-T2D demonstrated that at the time of diagnosis, a specific subclinical systemic low-grade chronic inflammation already characterises a subgroup of patients with T2D.
Importantly, the inflammatory signature is not only systemic but is also exacerbated in pancreatic islets of some patients with T2D suggesting that the systemic chronic inflammatory status may directly impact on beta cell function.
Based on these pioneer discoveries, we postulate that at early diagnosis, there is already a specific subtype of T2D characterised by an increased inflammatory response leading to various organ damages including beta cell dysfunction that strongly supports the view that inflammatory markers should be used in diabetes medical care to refine T2D associated phenotypes.
The objectives
To unmask the transition towards T2D complications, INTERCEPT-T2D consortium will address the following major questions to achieve a breakthrough in the clinical care of patients with T2D.
INTERCEPT-T2D will fully tackle these issues to elucidate the molecular bases of inflammation-related T2D profiles, opening avenues to precision medicine considering inflammation patterns in the future treatments of citizens suffering from T2D. Our project should lead to potent patients’ stratification, defining a novel classification of patients with T2D at/near diagnosis with an “Inflammatory-mediated T2D” endotype to be specifically targeted.
Methodology
INTERCEPT-T2D methodology is based on 5 major work blocks:
- Define the progression overtime from healthy uncomplicated to advanced complicated T2D
- Identify a subgroup of inflammatory-mediated T2D within the heterogeneity of this disease
- Establish the immune parameters related to the inflammation-mediated T2D (bio-marker identification) and propose a Diabetic Inflammatory Score to predict the disease modification risks.
- Proof-of-concept clinical trial: a novel anti-inflammatory therapy to intercept the disease modifications
INTERCEPT-T2D capitalization
on existing human cohorts
From early diagnosis to advanced T2D
Beyond the state of art
INTERCEPT-T2D excellence and novelty will bring a new and clinically relevant dimension in the T2D classification by taking into consideration at diagnosis inflammatory parameters that are of importance for the transition to T2D-related complications and by proposing a novel anti-inflammatory therapy to patients at risk.