Role of the Liver in Glucose Homeostasis Using Metabolic Imaging

NCT04352738 | Completed

• 1 other identifier: LEMON
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess hepatic glucose uptake using non-invasive metabolic imaging in three different populations that differ in terms of insulin and glucose kinetics. Between-group comparison will address the following two hypotheses: i) Hepatic glucose uptake will be lower in participants with type 1 diabetes compared with matched controls due to lack of portal insulin and delayed pharmacokinetics of subcutaneous bolus insulin. ii) Hepatic glucose uptake will be higher in participants after bariatric surgery compared with matched health controls due to accelerated glucose absorption and earlier and higher peak portal glucose and insulin concentrations.

Conditions

Type 1 Diabetes; Bariatric Surgery Candidate

Keywords

Hepatic glucose metabolism; Deuterium metabolic imaging; Insulin and glucose kinetics; Metabolic imaging

Outcome Measures

Primary Outcomes (1)

• Intrahepatic free glucose concentration

  Over postprandial period (0 to 150 minutes post glucose-ingestion)

Secondary Outcomes (9)

• Postprandial hepatic glycogen increment

  Over postprandial period (0 to 150 minutes post glucose-ingestion)

• Postprandial glucose exposure

  Over postprandial period (0 to 150 minutes post glucose-ingestion)

• Postprandial glucagon exposure

  Over postprandial period (0 to150 minutes post glucose-ingestion)

• Postprandial insulin secretion

  Over postprandial period (0 to 150 minutes post glucose-ingestion)

• Postprandial insulin exposure

  Over postprandial period (0 to 150 minutes post glucose-ingestion)

Other Outcomes (2)

• Quantification of 2H-labelled metabolites other than glucose (i.e. lactate, glutamate/glutamine, water)

  Over postprandial period (0 to 150 minutes post glucose-ingestion)

• Changes in intrahepatocellular lipid (IHCL)

  Over postprandial period (0 to 150 minutes post glucose-ingestion)

Study Arms (3)

Healthy adults (group I)

Diagnostic Test: Multiparametric, multinuclear MR (DMI/ 13C-MRS/ GlycoCEST/GlycoNOE)

Adults with type 1 diabetes (group II)

* T1D for ≥2 years or evidence of undetectable C-peptide (\<100pmol/l with concomitant plasma glucose≥4.0mmol/l). * HbA1c≤8.0mmol/l (64mmol/mol).

Diagnostic Test: Multiparametric, multinuclear MR (DMI/ 13C-MRS/ GlycoCEST/GlycoNOE)

Adults after bariatric surgery (group III)

* Female. * Bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) ≥1 year ago. * Lack of a history of diabetes or pre-diabetes (HbA1c≤5.6% in the absence of anaemia).

Diagnostic Test: Multiparametric, multinuclear MR (DMI/ 13C-MRS/ GlycoCEST/GlycoNOE)

Interventions

Multiparametric, multinuclear MR (DMI/ 13C-MRS/ GlycoCEST/GlycoNOE) DIAGNOSTIC_TEST

Magnetic resonance scanning for 150 minutes involving ingestion of 60g of 6,6, 2H2-glucose diluted in 200ml of tap water. Frequent blood samples will be drawn for measurements of plasma glucose, insulin, C-peptide and glucagon

Adults after bariatric surgery (group III); Adults with type 1 diabetes (group II); Healthy adults (group I)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy participants will be recruited through advertisement on the hospital staff website and website of the Medical faculty according to Swissethics guidelines. Patients with type 1 diabetes and post-bariatric surgery patients will be recruited through referring physicians from the University Hospital Bern or colleagues from local private outpatient clinics.

You may qualify if:

• Age≥18 years
• Capacity to give informed consent
• Willingness to adhere to the study protocol
• In group II (type 1 diabetes), the following criteria must be met in addition:
• T1D for ≥2 years or evidence of undetectable C-peptide (\<100pmol/l with concomitant plasma glucose≥4.0mmol/l)
• HbA1c≤8.0mmol/l (64mmol/mol)
• In group III (bariatric surgery), the following criteria must be met in addition:
• Female
• Bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) ≥1 year ago
• Lack of a history of diabetes or pre-diabetes (HbA1c≤5.6% in the absence of anaemia)

You may not qualify if:

• Pregnancy, planned pregnancy or breastfeeding
• Medication that interfere with glucose metabolism (participation requires discontinuation of these agents at least one week before the study visit) except for individuals with type 1 diabetes
• History of gastrointestinal surgery (other than bariatric surgery for group III)
• Known kidney, liver or heart disease
• Claustrophobia
• Contraindications to magnetic resonance imaging according to designated questionnaire
• Substance abuse
• Physical or psychological condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Inselspital, Bern University Hospital and University Hospital of Bern

Bern, 3010, Switzerland

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Study Officials

• Lia Bally, MD, PhD

  University Hospital Bern & University of Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 20, 2020
• Study Start: April 15, 2021
• Primary Completion: April 21, 2022
• Study Completion: August 30, 2022
• Last Updated: November 15, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)