Deciphering the Role of Incretin Hormones in Weight Loss-induced Remission of Type 2 Diabetes (DIABeat) (DiabEATit)

Deciphering the Role of Incretin Hormones in Weight Loss-induced Remission of Type 2 Diabetes

The goal of this mechanistic study is to investigate the role of incretin hormones on weight loss-induced type 2 diabetes remission.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Diabetes Mellitus Type 2 in Obese
• Intervention / Treatment: Behavioral: Weight loss-induced Diabetes Remission

Detailed Description

Participants will undergo an intensive, individualized dietary treatment to achieve a 10% reduction in body weight, during which glucose-lowering therapy will be withdrawn. Before and after the intervention, the patients will undergo:

• measurement of fasting glucose and glycated hemoglobin
• Indirect calorimetry
• oral glucose tolerance test
• intravenous glucose tolerance test
• quality of life and diet-related questionnaires
• 72-hour food records

At the end of the protocol, subjects will be followed up to maintain lifestyle changes and intercept cases of diabetes relapse.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Domenico Tricò, MD, PhD; Phone Number: 050993640; Email: d.trico@unipi.it
• Study Contact Backup: Name: Luca Sacchetta, MD; Phone Number: 050993640; Email: luca.sacchetta@spec-med.unipi.it

Study Locations

• Italy
  • PI
    • Pisa, PI, Italy, 56127
      • Azienda Ospedaliero-Universitaria Pisana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• T2D for less than 6 years;
• age 18-65 years;
• both genders;
• BMI 27-45 kg/m2;
• HbA1c 48-108 mmol/mol (43-108 mmol/mol if on glucose-lowering drugs).

Exclusion Criteria:

• type 1 or secondary/genetic diabetes;
• treatment with insulin, Glucagon-Like Peptide-1 agonists, Gastric Inhibitory Peptide/GLP-1 co-agonists, or pioglitazone;
• weight loss >5% within the previous 6 months;
• eGFR <30 ml/min/1.73m2;
• myocardial infarction within the previous 6 months;
• severe heart failure (NYHA III-IV); eating disorder; substance abuse;
• severe depression;
• known cancer;
• pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Obese subjects with type 2 diabetes mellitus; Individualized weight-loss nutritional intervention	Behavioral: Weight loss-induced Diabetes Remission; Patients will undergo a dietary intervention plus drugs (if needed) with the purpose to obtain a 10% (or at least 10 kg) body weight reduction to achieve diabetes remission

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with incretin effect's restoration after achieving weightloss-induced diabetes remission	The investigators will test whether diabetes remission obtained after 10% weight-loss, induced by an intensive nutritional intervention, is associated with an improvement of the incretin effect from baseline. Diabetes remission will be defined according to the latest international consensus as an HbA1c <48 mmol/mol measured at least 3 months after cessation of glucose-lowering pharmacotherapy. The restoration of the incretin effect will be assessed by measuring both incretin levels and estimated incretin mediated insulin secretion before and after achieving the weight loss during an Oral Glucose Tolerance Test followed by an intravenous Glucose Tolerance Test.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of sustained weightloss-induced diabetes remission assessed by 2 consecutive HbA1c <48mmol/mol within 6 months	Diabetes remission will be defined according to the latest international consensus as an HbA1c <48 mmol/mol measured at least 3 months after cessation of glucose-lowering pharmacotherapy. Thus, diabetes remission will be assessed after the end of the intervention phase (V1). Participants who will achieve diabetes remission at V1 will be monitored by measuring HbA1c for the next 6 months at 3-month intervals (V2 and V3).	36 weeks

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero, Universitaria Pisana
• Investigators: Principal Investigator: Domenico Tricò, MD, PhD, University of Pisa

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Body Weight Changes; Diabetes Mellitus; Diabetes Mellitus, Type 2; Weight Loss
• Other Study ID Numbers: DiabEAT.it

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No