Objective
The primary objective of SFDT1 is to evaluate the risk factors / determinants of major adverse cardiovascular events (myocardial infarction, stroke, leg arterial obstruction, revascularisation …) in individuals with T1DM.
The secondary objectives are:
(1) to evaluate classical and nonclassical risk factors associated with every component of incident cardiovascular events;
(2) to assess the role of glucose control glucose control (including hypoglycaemia and glucose variability) in health events (complications, quality of livequality of live, mortality);
(3) to assess the relationship between cardiovascular complications and other diabetes-related complications such as yes and kidney complications ;
(4) to identify and characterize novel molecules associated with health events;
(5) to identify psychosocial factors associated with health events;
(6) to identify the impacts of therapeutic and care innovations on metabolic control and diabetic complications;
(7) to identify the impact of medications on metabolic control and diabetic complications; and
(8) to assess the economic burden of T1DM.
Background Rationale
Despite controlling the common cardiovascular disease (CVD) risk factors (i.e. tobacco, hypertension, hypercholesterolemia, hyperglycemia), type 1 diabetes mellitus (T1DM) is still associated with a high risk of CV complications, such as myocardial infarction or stroke or leg artery obstruction. Therefore, determinants of this residual increased CV risk remain to be discovered. They could be related to health in general, physiology/biology, psychology and quality of life and healthcare system.
To improve knowledge of T1DM and its complications, several large-scale initiatives including the Finnish Diabetic Nephropathy Study (FinnDiane), the Swedish National Diabetes Register (NDR), the German Diabetes Study (GDS), and the American T1D Exchange have been developed. All these cohorts or registers have specificities in terms of recruitment, age distribution, logistics, quality and quantity of biobanking, and follow-up. Some, such as the NDR study, which is one of the largest T1DM cohorts worldwide, including 30,000 participants, did not analyse biological specimens; others do not have any continuous glucose monitoring data or detailed information
on socioeconomic, lifestyle or psychological factors. In France, there are few studies including individuals with T1DM, such as the ENTRED study or “Constances”. However, all these French databases present several limitations as they (i) include few individuals with T1DM; (ii) do not use an accurate T1DM phenotyping; (iii) do not systematically include biological analyses; (iv) do not cover a wide range of patient ages; or (v) do not have access to continuous glucose monitoringdata.
To overcome these limits, the SFDT1 cohort was created. Overall, SFDT1 is the first study covering all the key issues on a very large set of people living with T1DM. As many research questions remain unanswered, it was
crucial to design an extensive and detailed hybrid cohort study dedicated to T1DM, combining, for each participant, biological, omics, digital real-world and ePROs data. It is expected that this will aid the identification of important new parameters and validate the results reported in other landmark studies.
Furthermore, the SFDT1 cohort is patient-centered and aims to actively engage participants in all the aspects of the research program and to create a large community of individuals with T1DM. Participants will contribute to research and be partners in the discovery processes
Description of Project
Even after controlling for the traditional risk factors of cardiovascular disease(CVD) (as tobacco, hypertension, hypercholesterolemia, hyperglycemia), type 1 diabetes mellitus (T1DM) is still associated with a high risk of CV complications, such as myocardial infarction or stroke or leg artery obstruction. The determinants of this residual increased CV risk remain to be discovered and this is the primary objective of the prospective cohort of people living with T1DM in France (SFDT1).
The study plans to include 15,000 individuals living with T1DM (13000 adults and 2000 children aged over six years), recruited throughout metropolitan France and overseas French departments and territories. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD).
To answer this question, we will collect the following information:
Usual clinical data during routine visits every three years during 10 years, (According to the French National Health Care System)
Blood, urinary and hair samples collected during the same visits, to be stored in a biobank (specific consent),
Data from connected tools, including continuous glucose monitoring,
psychological and socioeconomic information (Patient-reported outcomes (PRO)) either at visits or through web questionnaires accessible via the internet,
Information on healthcare and consumption from the national health data system (Health Data Hub) with a passive 20-year medico-administrative follow-up (specific consent)
Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area.
Anticipated Outcome
The SFDT1 cohort represents a unique opportunity to increase medical knowledge about T1DM and to improve, on a short term basis, the health of persons living with T1DM. Thanks to our unique set of information (clinical, biological, genetics, medical devices, patients’ reported outcomes), collected from such a large population, we will primarily aim to explain the residual increased risk of cardiovascular events and mortality in individuals with T1DM, even in the absence of the main traditional risk factors. SFDT1 results should lead to key discoveries, interesting biomarkers and should ultimately lead to new treatment strategies.
In addition, our secondary aims are to better understand, especially through patients' reported outcomes, how regular changes involving elements such as environmental, regional or psychosocial factors, can make a difference both in daily T1DM management and in the long-term health status of people living with T1DM. Therefore, our work will also enable us to suggest new intervention strategies to facilitate the life of persons living with T1DM and decrease the burden of the disease. The health data collected will be useful to improve outcomes in clinical practice. Such data will also be used to promote more efficient practices in diabetes centres to manage known risk factors. This should lead to better cardiovascular prevention through changes in risk management.
Relevance to T1D
Type 1 diabetes mellitus (T1DM) accounts for 5−10% of the total cases of diabetes worldwide. The incidence of all diabetes including T1DM is steadily increasing globally. Increased incidence in younger children leads to a longer duration of the disease and consequently prolonged exposure to hyperglycaemia throughout life and higher risk of developing cardiovascular complications. In Sweden from 1998 to 2014, mortality and incidence of cardiovascular outcomes declined substantially amongst persons with diabetes, although fatal outcomes declined less amongst those living with T1DM than amongst
controls. A nationwide, population-based Finnish register of patients diagnosed with T1DM showed an excess of mortality mainly due to myocardial infarction. Age at onset of T1DM is an important determinant of cardiovascular outcomes, with the highest excess risk in females.
The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study showed that intensive treatment of hyperglycaemia in T1DM leads to reduced cardiovascular morbidity and mortality. However, hyperglycaemia per se only partly explains cardiovascular morbidity and mortality in T1DM as two-fold CV mortality has been observed even in the case of good glycaemic control. Other CV risk factors are involved in this over-mortality including the most traditional ones, such as hypertension, dyslipidaemia, smoking, and family history of premature coronary artery disease. The presence of diabetes-related complications, especially nephropathy and subclinical cardiovascular disease, can be used to predict cardiovascular events in this population. It has been shown that patients with T1DM with none of these traditional cardiovascular risk factors had about an 80% higher risk of cardiovascular events compared to non-diabetic individuals. This indicates that other determinants of cardiovascular morbidity and mortality remain to be explored in T1DM.
Before SFDT1, there was a lack of study exploring together the role of new indicators of glucose control (including hypoglycaemia and glucose variability), psychosocial factors and environment, new pathophysiological determinants( i.e. inflammatory pathways) or health care. Recent technological advances have provided new therapeutic options to patients with T1DM, especially insulin pumps, continuous glucose monitoring systems, and hybrid closed loop insulin pumps with continuous glucose monitoring systems.