Insulin Sensitivity and Metabolomics During Oral Administration of Glucose and Graded Intravenous Infusion - Full Text View

Purpose

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 our 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, we here hypothesize that the gut regulates metabolites that could be involved in small intestine-induced insulin resistance described above. We therefore aim also 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.

Condition	Intervention
Type 2 Diabetes Mellitus	Other: Oral glucose tolerance test Other: Graded intravenous glucose infusion


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Intervention Model Description: 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. Masking: No masking Primary Purpose: Basic Science
Official Title:	Insulin Sensitivity and Metabolomics During Oral Administration of Glucose and a Graded Intravenous Infusion in Patients With Normal Glucose Tolerance, Impaired Glucose Tolerance and in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:

Drug Information available for: Insulin Insulin human Dextrose

U.S. FDA Resources

Further study details as provided by Geltrude Mingrone, Catholic University of the Sacred Heart:

Primary Outcome Measures:

Glucose kinetics [ Time Frame: 1 year ]
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.

Secondary Outcome Measures:

Metabolomics [ Time Frame: 1 year ]
Plasma levels of small polar metabolites, molecular lipids and conjugated and unconjugated bile acids will be measured during both oral glucose tolerance test and during the graded intravenous glucose infusion.


Enrollment:	23
Actual Study Start Date:	January 9, 2014
Study Completion Date:	January 31, 2017
Primary Completion Date:	January 31, 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Patients with normal glucose tolerance 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 Oral glucose tolerance tests were glucose is administrated orally with an increasing load (25g, 75g, 100 g) Other: Graded intravenous glucose infusion 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 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 Oral glucose tolerance tests were glucose is administrated orally with an increasing load (25g, 75g, 100 g) Other: Graded intravenous glucose infusion 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 type 2 diabetes mellitus 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 Oral glucose tolerance tests were glucose is administrated orally with an increasing load (25g, 75g, 100 g) Other: Graded intravenous glucose infusion 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.

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Eligibility


Ages Eligible for Study:	20 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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;

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03223129

Sponsors and Collaborators

Catholic University of the Sacred Heart

Steno Diabetes Center

Investigators


Principal Investigator:	Geltrude Mingrone, MD PhD	The Catholic University of the Sacred Heart

More Information


Responsible Party:	Geltrude Mingrone, Professor, Catholic University of the Sacred Heart
ClinicalTrials.gov Identifier:	NCT03223129 History of Changes
Other Study ID Numbers:	U911/14
Study First Received:	June 12, 2017
Last Updated:	July 14, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No


Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Geltrude Mingrone, Catholic University of the Sacred Heart:


Type 2 Diabetes Mellitus Impaired glucose tolerance Metabolomics

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Insulin Resistance Glucose Intolerance Glucose Metabolism Disorders Metabolic Diseases	Endocrine System Diseases Hyperinsulinism Hyperglycemia Insulin Hypoglycemic Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 19, 2017