Jejunal Ketogenesis and Type 2 Diabetes

NCT ID: NCT05767177

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2025-04-22

Brief Summary

The goal of this cross-over study in obese subjects is to learn about the common co-morbidity type 2 diabetes and the local formation of ketone bodies. The type of study is an exploratory trial with the participants as own controls. The main questions it aims to answer are: 1. Does food intake-induced ketogenesis exist in the small intestine of obese individuals? 2. Are insulin resistance, the incretin GLP-1 release and the glucose transporter SGLT1 affected in obese individuals without type 2 diabetes in the same way as those with type 2 diabetes?

Detailed Description

The investigators have recently shown that the mucosa in the middle small intestine, the jejunum, in human volunteers produce ketones bodies.This situation is thus contrary to the common view that ketone bodies are formed by the liver during fasting/starvation. Obesity is commonly associated with hyperglycaemic conditions and diabetes mellitus type 2.This has given rise to the question of whether obesity results in disturbances in the intestinal food-induced ketogenesis and whether this influence contributes to the development of type 2 diabetes mellitus?

The project's questions are therefore:

1. Does food intake-induced ketogenesis exist in the small intestine of obese individuals?

2. Are insulin resistance, the incretin GLP-1 release and the glucose transporter SGLT1 affected in obese individuals without type 2 diabetes in the same way as those with type 2 diabetes?

3. If no to 2: What is the difference?

Conditions

Obesity, Morbid; Diabetes Mellitus, Type 2; Intestines; Incretins

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

High Carbohydrate Diet vs High Fat Diet

In the current project, the situation applies to individuals with obesity (body mass index (BMI) 35 to 45 kg/m2). In one case the diet is of the type "high-carbohydrate diet" and in the other case "high-fat diet". The idea is that the research subjects should subsist on these diets for the respective 14 days. The energy content of the diet periods must be the same and correspond to the participants' daily needs. Each participant is drawn to one diet for 2 weeks. After a break of at least 3 weeks, the second diet is taken for 2 weeks.

Group Type: EXPERIMENTAL

Glucemia following Mixed Meal Test

Intervention Type: OTHER

On day 12 of each diet, a venous catheter is placed in one arm for blood sampling and the research person must answer questions about any gastrointestinal complaints in connection with the current diet. At approximately 09:00, the research subject may eat a brunch for approximately 15 minutes (sandwich, juice, fried egg and sausage; 550-600kcal). Venous blood samples are taken before and 15, 30, 45, 60, 90 and 120 minutes after the meal.

Enteroscopy - mucosal ketogenic activity as well as glucose transport

Intervention Type: OTHER

On day 14 of each diet period, an enteroscopy is performed. This step is performed to obtain samples (biopsy) of the mucosa of the small intestine (duodenum and jejunum) and is performed at the Gastro-endoscopic departments SU-Sahlgrenska, or SU-Eastern hospital. Endoscopy is experienced by some individuals as unpleasant, which is why local anesthesia and sometimes sedation (midazolam + pethidine or rapifen) can be offered according to standard routine in the endoscopy department.

Interventions

Glucemia following Mixed Meal Test

On day 12 of each diet, a venous catheter is placed in one arm for blood sampling and the research person must answer questions about any gastrointestinal complaints in connection with the current diet. At approximately 09:00, the research subject may eat a brunch for approximately 15 minutes (sandwich, juice, fried egg and sausage; 550-600kcal). Venous blood samples are taken before and 15, 30, 45, 60, 90 and 120 minutes after the meal.

Intervention Type: OTHER

Enteroscopy - mucosal ketogenic activity as well as glucose transport

On day 14 of each diet period, an enteroscopy is performed. This step is performed to obtain samples (biopsy) of the mucosa of the small intestine (duodenum and jejunum) and is performed at the Gastro-endoscopic departments SU-Sahlgrenska, or SU-Eastern hospital. Endoscopy is experienced by some individuals as unpleasant, which is why local anesthesia and sometimes sedation (midazolam + pethidine or rapifen) can be offered according to standard routine in the endoscopy department.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• BMI 35 to 45 kg/m2

Exclusion Criteria

• Insulin-treated diabetes
• Sequelae of previous diabetes-associated disease (foot, eyes and kidneys, or cardiovascular incident, etc.)
• Diabetes, hypertension, lipid disorder that has not been stabilized for at least 1 month by adequate pharmacological treatment
• Continuous NSAID use
• Preferably otherwise medication-free (exceptions can be made)
• Not operated on in the abdomen (appendectomy excluded)
• Previously known organic gastrointestinal disease, except for gastroesophageal reflux disease (GERD)
• Smokers
• Pregnancy and breastfeeding
• History of drug abuse or other circumstances deemed to jeopardize the patient's ability to participate in the research project

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Göteborg University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lars Fändriks, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Göteborg University

Locations

Dept of Surgery, Sahlgrenska Universityhospital

Gothenburg, , Sweden

Countries

Sweden

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Ketogen05

Identifier Type: -

Identifier Source: org_study_id