Clinical trial NCT05767177: Jejunal Ketogenesis and Type 2 Diabetes
Official title: Small Intestinal Ketogenesis - Potential Significance for Type 2 Diabetes in Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity, Morbid
Diabetes Mellitus, Type 2
Intestines
Incretins
Lead sponsor: Göteborg University
Sponsor class: OTHER
First posted: 2023-03-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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?

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

Primary outcomes:
measure: Glucemia following a Mixed Meal Test:
timeFrame: On day 12 of the respective diet
Secondary outcomes:
measure: Enteroscopy: ketogenic activity in the small intestine
timeFrame: On day 14 of the respective diet
measure: Enteroscopy: mucosal glucose-transport capacity
timeFrame: On day 14 of the respective diet
Other outcomes:
measure: Glucemia, insulinemia and GLPi-emia following the Mixed Meal Test
timeFrame: On day 12 of the respective diet
Locations:
city: Gothenburg
country: Sweden
facility: Dept of Surgery, Sahlgrenska Universityhospital
Study officials:
affiliation: Göteborg University
name: Lars Fändriks, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: