Extreme Phenotypes to Identify Susceptibility of Patients Living With Type 2 to Diabetes Related Complications

NCT07250607 | Active Not Recruiting DMC

• 1 other identifier: EXTREME-T2D phase 1
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this observational study is to learn more about the diverse susceptibility to micro and macrovascular complications in individuals living with Type 2 Diabetes (T2D). The main questions of the study are:

• Is the chronic exposure to hyperglycemia the only determinant of diverse susceptibility to diabetes related complications (DRC) across the T2D population?
• Is it possible to develop a reliable tool to identify patients at different susceptibility to DRC?
• Is it possible to predict DRC susceptibility through biomarkers in the field of inflammation, hormonal signaling or non-coding circulating nucleotides. People living with T2D and well screened for complications according to the international recommendations (American Diabetes Association/European Society for the study of Diabetes) will be included in the survey collecting information about chronic exposure to hyperglycemia (diabetes duration + glycemic control) and incidence and severity of each macro and microvascular complication. Based on the survey result, a clinical score will be proposed to distinguish patient at different susceptibility to complications. Then, patients with extreme phenotypes of susceptibility (i.e. those with highest susceptibility for their short exposure to hyperglycemia vs those with lowest susceptibility to complication for their long exposure to hyperglycemia) will be recruited to perform a blood drawn and investigate whether preidentified potential biomarkers could describe the diverse susceptibility to DRC by showing a significant gradient between groups.

Conditions

Diabete Type 2; Diabetes Complications

Keywords

microvascular complications; macrovascular complications; Type 2 Diabetes Mellitus; Cardiovascular diseases

Outcome Measures

Primary Outcomes (1)

• Incidence of Diabetes Related Complications.

  to measure the incidence and intensity of each included micro and macrovascular complication

  through study completion, an average of 12 months

Secondary Outcomes (2)

• DRC score

  Through study completion, an average of 12 months

• Biomarkers

  through study completion, an average of 12 months

Study Arms (3)

Subject with Highest susceptibility to complications (HS-DRC)

Subjects showing a number of diabetes related complication higher than expected compared with other subject with similar disease duration and glycemic control

Subject with lowest susceptibility to complications (LS-DRC)

Subjects showing a number of diabetes related complication lower than expected compared with other subject with similar disease duration and glycemic control

Subject with moderate susceptibility to complications (MS-DRC or control gtoup)

Subjects showing a number of diabetes related complication that is expected for their disease duration and glycemic control according to the DRC distribution in the general T2D population

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Either sex, age between 40 and 80 years old. Diagnosed Type 2 diabetes (proven of exclusion of other forms diabetes if required by the PI) followed up regularly for T2D and with a comprehensive screening for complications including data on coronary, cerevrovascular and peripheral artery disease, and informations about chronic kidney, retinopathy and neuropathy diseases related to diabetes.

You may qualify if:

• Type 2 Diabetes
• Age 40-80 years old

You may not qualify if:

• Diagnosis of forms of diabetes other than T2D
• Any chronic inflammatory diseases or active cancer
• Significant liver disfunction (cirrhosis, AST/ALT \> 3-fold normality range, total bilirubin \> 1,5-fold normal range w/o Gilbert syndrome)
• Any other life expectancy-changing systemic disease.

Sponsors & Collaborators

• Azienda Ospedaliero, Universitaria Pisana: lead

Study Sites (3)

Policlinico Consorziale di Bari

Bari, BA, 70100, Italy

Location

Azienda Rilievo Nazionale Alta Specialità (ARNAS) Garibaldi

Catania, CT, 95100, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, PI, 56120, Italy

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma and serum

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Complications; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Andrea Natali, MD

  University of Pisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 26, 2025
• Study Start: May 1, 2024
• Primary Completion: November 30, 2025
• Study Completion (Estimated): July 31, 2026
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

IT (3)