Skip to main content
OpenTrials
Completed

NCT Number: NCT05767177

Jejunal Ketogenesis and Type 2 Diabetes

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?

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Obesity, Morbid Body Weight Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Incretins Intestines Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Dept of Surgery, Sahlgrenska Universityhospital

Gothenburg, SE41345, Sweden

About this study

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:

  • Does food intake-induced ketogenesis exist in the small intestine of obese individuals?
  • 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?
  • If no to 2: What is the difference?

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Glucemia following Mixed Meal Test

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

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.

Primary outcomes

  1. Glucemia following a Mixed Meal Test:

    Time frame: On day 12 of the respective diet

    The study participant arrives fasted and a venous catheter is placed in one arm for blood sampling. The research subject may eat a brunch for approximately 15 minutes (sandwich, juice, fried egg and sausage; 550-600kcal) and the p-glucose (mM) is checked at 120 min.

    The glucemia after the test meal will be compared in high-carbohydrate diet and high-fad diet (paired samples).

Secondary outcomes

  1. Enteroscopy: ketogenic activity in the small intestine

    Time frame: On day 14 of the respective diet

    The biopsy material is fixed deep-frozen for later analyses.The ketonic activity is represented by the activity the ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) in the tissue.

    Immunofluorescence of antibodies (giving the geography in the duodenal/jejunal mucosa) and western blotting (semi-assessment compared to a steadily-expressed factor in the mucosa, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HMGCS2 will be given as ratio to GAPDH. The western blots in the high-carbohydrate diet will be compared to high-fad diet in each individual (paired samples).

  2. Enteroscopy: mucosal glucose-transport capacity

    Time frame: On day 14 of the respective diet

    A part of the biopsy-material is kept a short time (<2h) in oxygenated preservation medium. The biopsies are then mounted in Ussing chambers for in-vitro functional studies. Activity of the sodium-glucose linked transporter 1 (SGLT1) is measured as the electrogenic response of 10 mM D-glucose, Iep (µA/mm2), given to the luminal compartment of the Ussing chamber. The net change is the % change of Iep from baseline in the glucose-free condition, to Iep after the addition of glucose to a concentration of 10%. The net change after the high-carbohydrate diet will be compared to the one after high-fat diet in each individual (paired samples).

Other outcomes

  1. Glucemia, insulinemia and GLPi-emia following the Mixed Meal Test

    Time frame: On day 12 of the respective diet

    The study participant arrives fasted and a venous catheter is placed in one arm for blood sampling. The research subject may eat a brunch for approximately 15 minutes (Mixed Meal Test (MMT): sandwich, juice, fried egg and sausage; 550-600kcal) and the p-glucose (mM), p-insulin (µUnits/mL) and p-GLP1 (pM) is checked after 15, 30, 45, 60, 90 and120 min.

    The aggregated responses to MMT (linear area under the curve minus the baseline value) over 120 min of the respective agent are compared in high-carbohydrate diet and high-fad diet.

Sponsors and collaborators

Lead sponsor

Göteborg University

Other

Registry information

Official study title

Small Intestinal Ketogenesis - Potential Significance for Type 2 Diabetes in Obesity

Acronym: But2

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Mar 14, 2023
Registry last updated
Apr 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.