Exocrine-Endocrine Pancreatic Crosstalk: Precision Pathways to Reframe Diabetes Pathophysiology

NCT07670871 | Not Yet Recruiting

• 1 other identifier: 27477
• Study Type: observational
• Target: 440
• Locations: 0 countries
• Sites: N/A

Brief Summary

The EXPAND study is a prospective observational study designed to investigate the biological mechanisms underlying the heterogeneity of type 2 diabetes and related metabolic disorders. The study will enroll adults with and without pancreatic disease, including patients undergoing pancreatic surgery, individuals with chronic pancreatitis, subjects at high risk of type 2 diabetes, and patients with newly diagnosed type 2 diabetes. Clinical, metabolic, imaging, genetic, microbiome, and molecular data will be integrated to identify distinct metabolic endotypes and to investigate the interactions between the exocrine pancreas, endocrine pancreas, and adipose tissue. The ultimate goal is to improve the understanding of diabetes pathophysiology and support the development of precision medicine approaches.

Conditions

Type 2 Diabetes Mellitus (T2DM); Chronic Pancreatitis; Prediabetes; Pancreatic Neoplasms

Keywords

Metabolic Endotypes; Beta Cell Function; Insulin Secretion; Insulin Sensitivity; Exocrine Pancreas; Endocrine Pancreas; Pancreatic Crosstalk; Precision Medicine; Glucose Metabolism; Oral Glucose Tolerance Test; Genetic Risk Score; Fat Adipose Tissue; Hyperglycemic Clamp; Microbiome

Outcome Measures

Primary Outcomes (1)

• Identification and Characterization of Metabolic Endotypes

  Identification and characterization of physiological endotypes of glucose metabolism using unsupervised clustering and archetype analysis integrating metabolic phenotyping, imaging, and biological/multi-omic variables.

  At baseline and during study assessments up to 60 months

Study Arms (5)

Pancreatic Surgery for Non-Endocrine Pancreatic Disease

Adults undergoing partial or total pancreatectomy for non-endocrine pancreatic disease. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination. Pancreatic and adipose tissue specimens obtained during clinically indicated surgery may be analyzed for histopathological, molecular, and multi-omic studies.

Pancreatic Ductal Adenocarcinoma Undergoing Pancreatectomy

Adults with pancreatic ductal adenocarcinoma undergoing partial or total pancreatectomy. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination. Pancreatic and adipose tissue specimens obtained during clinically indicated surgery may be analyzed for histopathological, molecular, and multi-omic studies.

Chronic or Previous Pancreatitis

Adults with chronic pancreatitis or a previous episode of acute pancreatitis. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination.

Individuals at Risk for Type 2 Diabetes

Adults at increased risk of type 2 diabetes, including individuals with impaired fasting glucose and/or impaired glucose tolerance, without exocrine pancreatic disease. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination.

Newly Diagnosed Type 2 Diabetes

Adults with newly diagnosed type 2 diabetes mellitus. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination.

Eligibility Criteria

• Age: 20 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from patients receiving care at Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). The study population includes adults with and without pancreatic disease, including individuals undergoing pancreatic resection, patients with chronic or previous pancreatitis, subjects at increased risk of type 2 diabetes mellitus, and individuals with newly diagnosed type 2 diabetes mellitus. Participants will be consecutively enrolled from the Departments of Endocrinology, Diabetology, Gastroenterology, and Pancreatic Surgery according to the predefined eligibility criteria.

You may qualify if:

• Adults aged 20 to 78 years.
• Ability and willingness to provide written informed consent.
• Eligibility for one of the study cohorts:
• Individuals undergoing pancreatectomy for non-endocrine pancreatic disease.
• Individuals with pancreatic ductal adenocarcinoma undergoing pancreatectomy.
• Individuals with chronic pancreatitis or a previous episode of acute pancreatitis.
• Individuals at increased risk of type 2 diabetes mellitus, including impaired fasting glucose and/or impaired glucose tolerance.
• Individuals with newly diagnosed type 2 diabetes mellitus.
• Ability to undergo study-related metabolic assessments and sample collection procedures.

You may not qualify if:

• Age \<20 years or \>78 years.
• Inability or unwillingness to provide informed consent.
• Pregnancy or breastfeeding.
• Diagnosis of type 1 diabetes mellitus.
• Participation in another interventional clinical trial involving an investigational medicinal product within 30 days before enrollment.
• Clinical conditions that preclude completion of the planned metabolic assessments.
• Inability to comply with study procedures.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples, stool samples, and, for surgical cohorts, pancreatic and adipose tissue specimens obtained from clinically indicated surgical procedures will be retained for biomarker, metabolic, molecular, and multi-omic analyses. Blood samples will also be used for Genetic Risk Score determination.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Pancreatitis, Chronic; Prediabetic State; Pancreatic Neoplasms; Insulin Resistance; Genetic Risk Score

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pancreatitis; Pancreatic Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Hyperinsulinism; Genetic Predisposition to Disease; Disease Susceptibility

Study Officials

• Teresa Mezza

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Teresa Mezza, MD, PhD

CONTACT

+390630156664; teresa.mezza@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: June 26, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): September 1, 2031
• Last Updated: June 26, 2026

Record last verified: 2026-06