Clinical trial NCT05333718: Characterization of Type 2 Diabetes Subgroups at Diagnosis: a Necessary Step Towards Precision Medicine in Diabetes.
Official title: Caracterización de Subgrupos de Diabetes Tipo 2 al diagnóstico: un Paso Necesario Hacia la Medicina de precisión en Diabetes.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Characteristics Disease
Type 2 Diabetes
Keywords: primary care centers
clusters
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
Collaborators: name: Institut Català de la Salut
First posted: 2022-04-19
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: People with type 2 diabetes mellitus treated in primary care centers in Barcelona and Lleida.

Brief summary: Objectives: The primary objective is to identify and characterize the relevant subgroups ( clusters ) in type 2 diabetes (T2DM) at the time of diagnosis in our region. This objective will be addressed using the six main variables (see Methodology) used so far in previous studies in other populations to develop the clustering of diabetes. Therefore, this is a study in diagnostic precision medicine in diabetes. In addition, as secondary objectives, other phenotypic characteristics of these subgroups (clinical, metabolic, and associated comorbidities) will be evaluated.

Methodology: This project will establish a prospective observational cohort study of 1200 subjects newly diagnosed with T2DM in primary care centers in the healthcare areas of Barcelona city and the territory of Lleida. All newly diagnosed cases of T2DM will be identified and evaluated. Participants will undergo a comprehensive phenotypic evaluation, including the six variables that will allow the characterization of T2DM subgroups: age, antibodies against glutamic acid decarboxylase (GAD), body mass index, glycated hemoglobin, and sensitivity indices ( HOMA-IR) and insulin secretion (HOMA beta), based on the determination of C-peptide. The latest generation cluster analysis (k- means and hierarchical clustering ) will be performed, following the method described in previous studies using the six variables mentioned above. Onset diabetes subgroups and their association with secondary outcome variables will be assessed. The initial prescription of antidiabetic medication will be evaluated. Other procedures of this project include: clinical (including complications) and biochemical evaluation, advanced lipoprotein profile, and validated questionnaires to evaluate diet and physical activity.

Detailed description: A multicenter prospective observational study will be conducted. The study design contemplates a single visit that will coincide with the inclusion of the patient in the study. Prior to the inclusion visit, a pre-selection period is planned in which the possible candidate will be invited, all the study procedures will be explained and clarified, the selection criteria will be checked and the inclusion visit will be scheduled.

The scope of the study is made up of Primary Care Centers (CAP) in 2 large health areas (Barcelona and Lleida). In the Annex 8 section, the characteristics and expected recruitment capacity of each CAP are detailed. We have taken a conservative approach using the lower range of incidence calculated based on our own data from 2019 to 2020. The table provided used an expected acceptance rate for participation of 80%. Additionally, CAPs were selected based on commitment and performance in our previous studies. It is planned to include 1200 participants newly diagnosed with T2DM. Depending on compliance with the recruitment rate, the inclusion of other CAPs is possible to achieve the expected number of participants in the study.

Follow-up of participants and linkage with other databases

For this study, a pragmatic follow-up of the participants will be chosen, which is adapted to the usual clinical practice for the follow-up of diabetes. For this reason, the monitoring will be done from:

* SIDIAP/PADRIS databases, with the link to the electronic medical record of the participants who have accepted this option in the informed consent.
* Electronic medical record, in the event that the link with the SIDIAP/PADRIS databases is not possible for technical reasons (non-ICS centers), the collection of monitoring variables will be done directly from the clinical course (review of clinical history) of participants without scheduling additional study follow-up visits.
* For specific causes of mortality, data linkage with the National Institute of Statistics (INE) will be used.
* If the participants have already participated or are participating in other clinical research studies and want to transfer the data they have provided for other projects to this study, this linking (portability) of the data will be allowed.

All participants will be followed until the end of the study, death or withdrawal of informed consent.

Eligibility criteria: Inclusion Criteria:

* Subjects of both sexes, of legal age (≥18 years)
* Newly diagnosed T2DM according to the criteria of the American Diabetes Association
* With a maximum duration of three months of the disease at the time of inclusion.
* Writen informed consent

Exclusion Criteria:

Subjects with a new diagnosis of other types of diabetes (type 1, MODY, gestational or other causes) will also be evaluated to ensure that the diagnostic criteria for selection are correctly implemented in all potential study participants.

\*For final analysis, subjects with any diagnosis of diabetes other than T2DM will be excluded from the study.

Primary outcomes:
measure: clusters of type 2 diabetes
timeFrame: at inclusion
Secondary outcomes:
measure: gender clinical characteristics
timeFrame: at inclusion
measure: Frequency of various associated comorbidities, including micro and macrovascular complications
timeFrame: 24 month follow-up period
measure: Advanced lipoprotein profile
timeFrame: at inclusion
measure: Lifestyle variables: eating habits and physical activity
timeFrame: at inclusion
measure: Use in real clinical practice of antidiabetics and other treatments at the beginning of the disease
timeFrame: at inclusion
measure: Appearance of different micro- and macro-vascular complications of diabetes
timeFrame: 24 month follow-up period
measure: Metabolomics and genetic profile related to diabetes
timeFrame: at inclusion
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital of Santa Creu i Sant Pau
state: Catalunya
city: Barcelona
country: Spain
facility: Institut Català de la Salut
state: Catalunya
Study officials:
affiliation: Hospital of Santa Creu i Sant Pau
name: Dídac Mauricio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: