Jejunal Ketogenesis and Type 2 Diabetes

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

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?

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?

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