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

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

Interventions

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.

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen

  collaborator OTHER

• Catholic University of the Sacred Heart

  lead OTHER

Principal Investigators

• Geltrude Mingrone, MD PhD · The Catholic University of the Sacred Heart

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-01-09

Primary Completion

2019-01-31

Completion

2019-01-31

Countries

• Italy

Study Locations