NCT03223129

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

Completed NA Last updated 26 July 2019

What this trial tests

NA trial testing Oral glucose tolerance test in Type 2 Diabetes Mellitus in 23 participants. Completed in 31 January 2019.

Timeline

9 January 2018

Primary endpoint
31 January 2019

31 January 2019

Quick facts

Lead sponsor	Catholic University of the Sacred Heart
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	23
Start date	9 January 2018
Primary completion	31 January 2019
Estimated completion	31 January 2019
Sites	1 location across Italy

Drugs / interventions tested

• Oral glucose tolerance test — full drug profile →
• Graded intravenous glucose infusion

Conditions studied

• Type 2 Diabetes Mellitus — all drugs for Type 2 Diabetes Mellitus →

Sponsor

Catholic University of the Sacred Heart

Who can join

Adults 20 to 65, any sex, with Type 2 Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Insulin sensitivity depends on the route of glucose administration.
   Mingrone G, Panunzi S, De Gaetano A, Ahlin S, et al · · 2020 · cited 27× · PMID 32385603 · DOI 10.1007/s00125-020-05157-w
2. A modelling approach to hepatic glucose production estimation.
   Panunzi S, De Gaetano A. · · 2022 · cited 2× · PMID 36542610 · DOI 10.1371/journal.pone.0278837