Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy

NCT ID: NCT02175459

Last Updated: 2024-05-23

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2024-12-31

Brief Summary

Regeneration of mature cells that produce functional insulin represents a major focus of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes. The capacity to adapt in response to diverse physiological conditions during life and the consequent ability to cope for increased metabolic demands is a distinctive feature of the endocrine pancreas in the regulation of glucose homeostasis. Both beta and alpha cells are dynamically regulated to continually maintain a balance between proliferation, neogenesis, and apoptosis. In this proposal, the investigators will focus on exploring key mechanism(s) that potentially regulate islet cell plasticity in altered glucose metabolic states.

Investigators will explore in a unique cohort of individuals who undergo duodenal pancretectomy. Prior to their surgery will be performed in vivo studies (Hyperglycemic clamp, Euglycemic Hyperinsulinemic clamp and Mixed Meal Tests) to accurately assess glucose homeostasis parameters to classify each individual into metabolic phenotypes. Then exploit the opportunity to collect pancreas samples from these patients who will be evaluated again after surgery, the investigators will determine the ability of the remnant pancreas to compensate for the acute reduction in islet mass and perform correlations between ex vivo and in vivo parameters.

Specifically, the patients will be subjected to incretin secretion (mixed meal), metabolic status (OGTT), insulin secretion characteristics (first and second phase responses), β-cell insulin content evaluation (arginine bolus). Subsequently, pancreas samples will be evaluated for morphometry, and proteomics and gene expression analyses of islet cell samples obtain by laser capture will allow a detailed investigation of mechanisms that contribute to islet plasticity. The overall goal of this project is to investigate key mechanisms driving the ability of islet mass to adapt to diverse metabolic states. We aim to explore modifications in gene expression and proteomics and correlate them with specific metabolic phenotypes, in order to determine key regulators of islet morphology.

Conditions

GLUCOSE METABOLISM; DIABETES; PANCREATIC ISLETS; Exocrine Pancreatic Dysfunction; Exocrine Pancreas Conditions; Exocrine Pancreatic Insufficiency; Endocrine Pancreas Disorder

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Eligibility Criteria

Inclusion Criteria

• SCHEDULED FOR PANCREATECTOMY
• NO DIABETIC and DIABETIC

Exclusion Criteria

• CHRONIC DESEASES
• STEROID THERAPY

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Joslin Diabetes Center

OTHER

Sponsor Role: collaborator

University of Siena

OTHER

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: collaborator

Istituto di Neuroscienze Consiglio Nazionale delle Ricerche

NETWORK

Sponsor Role: collaborator

University of Pisa

OTHER

Sponsor Role: collaborator

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Giaccari Andrea

associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Endocrinology - Catholic University

Rome, RM, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

TERESA MEZZA, MD, PHD

Role: CONTACT

TERESA.MEZZA@UNICATT.IT

+39063015 ext. 6664

References

Quero G, Laterza V, Di Giuseppe G, Lucinato C, Massimiani G, Nista EC, Sionne F, Biffoni B, Brunetti M, Rosa F, De Sio D, Ciccarelli G, Fiorillo C, Menghi R, Langellotti L, Soldovieri L, Gasbarrini A, Pontecorvi A, Giaccari A, Alfieri S, Tondolo V, Mezza T. A single-center prospective analysis of the impact of glucose metabolism on pancreatic fistula onset after pancreaticoduodenectomy for periampullary tumors. Am J Surg. 2024 Dec;238:115987. doi: 10.1016/j.amjsurg.2024.115987. Epub 2024 Sep 24.

Reference Type: DERIVED

PMID: 39342881 (View on PubMed)

Mezza T, Ferraro PM, Di Giuseppe G, Moffa S, Cefalo CM, Cinti F, Impronta F, Capece U, Quero G, Pontecorvi A, Mari A, Alfieri S, Giaccari A. Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional beta cells in predicting diabetes. J Clin Invest. 2021 Jun 15;131(12):e146788. doi: 10.1172/JCI146788.

Reference Type: DERIVED

PMID: 33905373 (View on PubMed)

Mezza T, Ferraro PM, Sun VA, Moffa S, Cefalo CMA, Quero G, Cinti F, Sorice GP, Pontecorvi A, Folli F, Mari A, Alfieri S, Giaccari A. Increased beta-Cell Workload Modulates Proinsulin-to-Insulin Ratio in Humans. Diabetes. 2018 Nov;67(11):2389-2396. doi: 10.2337/db18-0279. Epub 2018 Aug 21.

Reference Type: DERIVED

PMID: 30131390 (View on PubMed)

Other Identifiers

14081985

Identifier Type: -

Identifier Source: org_study_id