The Effects of Glucagon on Hepatic Metabolism in People With Type 2 Diabetes After Caloric Restriction

NCT05499702 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-000233
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Caloric restriction (and RYGB) improves insulin action and lowers fasting glucose, glucagon and EGP, without changes in postprandial EGP and glucagon concentrations. Caloric restriction also improves hepatic steatosis and lowers fasting AA. These changes may represent restoration of glucagon's hepatic actions. This experiment will determine whether caloric restriction improves glucagon's actions on hepatic amino acid, carbohydrate and lipid metabolism in T2DM in comparison to a baseline experiment performed separately in people with T2DM.

Conditions

Type2diabetes

Keywords

glucagon; insulin resistance; caloric restriction; hepatic steatosis; amino acid metabolism

Outcome Measures

Primary Outcomes (1)

• Rate of leucine oxidation in response to rising glucagon concentrations

  tracer-determined amino acid catabolism

  240 minutes of study

Study Arms (1)

Adults with type 2 diabetes

EXPERIMENTAL

20 subjects will be studied on one occasion, following 6 weeks of caloric restriction. They will be instructed to consume a diet of 900 kcal daily using meals derived from "Nutritional Guidelines after Bariatric Surgery". Compliance will be monitored by weekly meetings with the dietician using an electronic record of food intake. After this subjects will undergo a hyperglycemic clamp with 2 doses of glucagon infused.

Behavioral: Caloric Restriction; Drug: Hyperglycemic clamp

Interventions

Caloric Restriction BEHAVIORAL

Subjects will be instructed to consume a diet of 900 kcal daily using meals derived from "Nutritional Guidelines after Bariatric Surgery". Compliance will be monitored by weekly meetings with the dietician using an electronic record of food intake

Adults with type 2 diabetes

Hyperglycemic clamp DRUG

Hyperglycemic clamp to measure the effect of glucagon on hepatic metabolism

Adults with type 2 diabetes

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• We will recruit up to 20 weight-stable, subjects with type 2 diabetes
• BMI ≥ 28 Kg/M2
• Diabetes is managed by diet alone or a combination of oral agents

You may not qualify if:

• History of prior upper abdominal surgery e.g. gastric banding, pyloroplasty, vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.
• Contraindications to MRI (e.g. metal implants, claustrophobia).
• Hematocrit \< 35%
• TSH \< 0.4 or \> 5.5.
• Consumption of \> 2 alcohol drinks per day or \> 14 per week or a positive AUDIT questionnaire.

Sponsors & Collaborators

• Adrian Vella: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

MeSH Terms

Conditions

Insulin Resistance; Fatty Liver

Interventions

Caloric Restriction

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Adrian Vella

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeanette Laugen

CONTACT

5072558110; Laugen.Jeanette@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: caloric restriction for six weeks

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: August 12, 2022
• Study Start: December 15, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)