Insulin Sensitivity and Metabolomics During Oral Administration of Glucose and Graded Intravenous Infusion

NCT03223129 | Completed

• 1 other identifier: U911/14
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Bariatric surgery has been proven to be an effective treatment of type 2 diabetes and it has highlighted to role of the small intestine in glucose homeostasis. Improvement of glucose homeostasis occurs just a few days after the bariatric surgery, where parts of the small intestine is bypassed, has been performed. Furthermore, conditioned medium from the duodenum and the jejunum from both diabetic rodents and humans are able to induce insulin resistance in normal mice and in myocytes. Hence the hypothesis is that the small intestine secretes factors that are able to induce insulin resistance. This project aims to study how orally ingested glucose is able to induce insulin resistance and if this response differs in patients with normal glucose tolerance, impaired glucose tolerance and in patients with type 2 diabetes mellitus. To address this question glucose homeostasis will be studied by comparing whole body glucose uptake during a progressively increased oral glucose load with a graded glucose infusion where the blood glucose levels will be kept in the same range as during the oral glucose load in patients with normal glucose tolerance, impaired glucose tolerance and patients with type 2 diabetes mellitus. Previous studied have shown that different metabolites and bile acids could be involved the regulation of glucose homeostasis. Hence, it is possible that the gut regulates metabolites that could be involved in small intestine-induced insulin resistance described above. The aim of this research is to study metabolomics in plasma collected during the oral glucose tolerance test with increasing load of glucose and the graded glucose infusion where plasma glucose level will be held in the same levels as during the oral glucose tolerance test and study the differences in patients with normal glucose tolerance, impaired glucose tolerance and in patients with type 2 diabetes mellitus. The expected results in this study will demonstrate that the gut plays an important role in glucose homeostasis and that this system is dysregulated in type 2 diabetes. More importantly, novel factors derived or regulated from the gut that regulate insulin resistance and glucose tolerance will be identified which could be possible targets for future antidiabetic therapies.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus; Impaired glucose tolerance; Metabolomics

Outcome Measures

Primary Outcomes (1)

• Glucose kinetics

  Whole body glucose uptake will be measured using a double glucose tracer technique during both the oral glucose tolerance test and the graded intravenous glucose infusion.

  1 year

Secondary Outcomes (1)

• Metabolomics

  1 year

Study Arms (3)

Patients with normal glucose tolerance

OTHER

Patients included in this arm will have a plasma glucose below 140 mg/dl after a 2 h oral glucose tolerance test with a glucose load of 75 g. All patients in this arm will undergo oral glucose tolerance test with increasing glucose load and a graded intravenous glucose infusion were plasma glucose levels are held at the same level as during the oral glucose tolerance test.

Other: Oral glucose tolerance test; Other: Graded intravenous glucose infusion

Patients with impaired glucose tolerance

OTHER

Patients included in this arm will have a plasma glucose between 140 mg/dl to 199 mg/dl after a 2 h oral glucose tolerance test with a glucose load of 75 g. All patients in this arm will undergo oral glucose tolerance test with increasing glucose load and a graded intravenous glucose infusion were plasma glucose levels are held at the same level as during the oral glucose tolerance test.

Other: Oral glucose tolerance test; Other: Graded intravenous glucose infusion

Patients with type 2 diabetes mellitus

OTHER

Patients included in this arm will have a plasma glucose above 200 mg/dl after a 2 h oral glucose tolerance test with a glucose load of 75 g. All patients in this arm will undergo oral glucose tolerance test with increasing glucose load and a graded intravenous glucose infusion were plasma glucose levels are held at the same level as during the oral glucose tolerance test.

Other: Oral glucose tolerance test; Other: Graded intravenous glucose infusion

Interventions

Oral glucose tolerance test OTHER

Oral glucose tolerance tests were glucose is administrated orally with an increasing load (25g, 75g, 100 g)

Patients with impaired glucose tolerance; Patients with normal glucose tolerance; Patients with type 2 diabetes mellitus

Graded intravenous glucose infusion OTHER

Graded intravenous glucose infusion where glucose is infused in order to receive an plasma glucose pattern comparable to those received during the oral glucose tolerance tests.

Patients with impaired glucose tolerance; Patients with normal glucose tolerance; Patients with type 2 diabetes mellitus

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 20 and 65
• BMI between 35 and 60 kg/m2
• Ability to understand and comply with the study process.

You may not qualify if:

• History of type 1 diabetes or secondary diabetes;
• Previous bariatric surgery;
• History of medical problems such as mental impairment;
• Major cardiovascular disease;
• Major gastrointestinal disease;
• Major respiratory disease;
• Hormonal disorders;
• Infection;
• History of drug addiction and/or alcohol abuse;
• Internal malignancy;
• Pregnancy;
• Suspected or confirmed poor compliance;

Sponsors & Collaborators

• Catholic University of the Sacred Heart: lead
• Steno Diabetes Center Copenhagen: collaborator

Study Sites (1)

Università Cattolica S. Cuore

Roma, Italy

Location

Related Publications (1)

• Mingrone G, Panunzi S, De Gaetano A, Ahlin S, Spuntarelli V, Bondia-Pons I, Barbieri C, Capristo E, Gastaldelli A, Nolan JJ. Insulin sensitivity depends on the route of glucose administration. Diabetologia. 2020 Jul;63(7):1382-1395. doi: 10.1007/s00125-020-05157-w. Epub 2020 May 8.

  PMID: 32385603 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Intolerance

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Geltrude Mingrone, MD PhD

  The Catholic University of the Sacred Heart

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Patients with either normal glucose tolerance, impaired glucose tolerance or with diagnosed type 2 diabetes mellitus will undergo oral glucose tolerance tests with an increasing load of glucose and thereafter isoglycemic intravenous glucose infusion.

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: July 19, 2017
• Study Start: January 9, 2018
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: July 26, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)