Aim To investigate the effects of oral lactate administration on nutrient absorption and substrate utilization in individuals with pre-diabetes.

Hypothesis The addition of lactate to a meal improves postprandial lipemia and reduces lipid storage in ectopic tissues through delayed absorption and faster removal of circulating lipids from circulation.

A recent study showed that oral lactate administration slowed gastric emptying, increased the feeling of being full, induced satiety, and decreased the anticipated future food intake compared with intravenous administration. This shows that lactate has direct effects in the GI tract, which could improve substrate utilization after meals and thereby improve metabolic health. However, it remains unknown whether oral lactate administration has similar effects in other populations (i.e. individuals with obesity) and in relation to a meal.

To address these potential effects, the investigators aim to implement and validate a new tracer method in Denmark to measure meal fat partitioning using an orally ingested fluorine-labeled fatty acid analog (18F-fluoro-6-thiaheptadecanoic acid, 18F-FTHA) combined with positron emission tomography coupled to computed tomography (PET-CT). In a previous study using the aforementioned method, it has been shown that individuals with an impaired glucose tolerance have increased myocardial fatty acid uptake, not explained by potential confounding factors and that this is associated with a reduced systolic ejection fraction. In a recent study, it was found that subjects with insulin resistance have a higher uptake of free fatty acids in visceral adipose tissue compared with subjects without insulin resistance.

This method will enable the investigators to determine how the addition of lactate to a test meal will affect meal fat partitioning. Previous methods for determining fatty acid partitioning and accumulation have either been limited to only determining the accumulation in non-oxidative tissues or very invasive or difficult to perform, making this the first method to non-invasively simultaneously measure the partitioning of meal fatty acids in all human organs.

Work package 1 (WP1):

The investigators will also include 8 healthy individuals (HbA1c mmol/mol< 39, age 50+ years) as a healthy control group, who will be studied twice in a randomized trial following ingestion of a liquid test meal to determine the differences in meal fat partitioning between insulin-sensitive and insulin-resistant individuals and to determine the intraindividual variation in meal fat partitioning. Furthermore, the extra PET scans performed in the healthy individuals will be used for precise quantification of the radiation exposure with the PET method (dosimetry) and validation of the PET method.

Work package 2 (WP2):

In a randomized, double-blinded placebo-controlled crossover trial, the investigators will investigate the effect of 25 g lactate vs. placebo prior to a liquid test meal, with the addition of 18F-FTHA, on two trial days separated by a minimum of seven days and a maximum of one month. The investigators will include 16 individuals with pre-diabetes (HbA1c 39-47 mmol/mol) and from 50+ years of age.

In a WP3 we will include one healthy participant who will receive 18F-FTHA with water instead of a mixed meal, to evaluate if the tracer can be used for diagnostics of lesions of the thoracic duct when given with water.

The investigators will use paired t-tests analyses for comparing CTR and LAC and independent t-test samples for comparing the individuals with pre-diabetes and the healthy individuals.

Based on the results from a previous study using 18F-FTHA-PET, the investigators will need to include 15 individuals to detect a 15% decrease in meal fat uptake in the heart (α=0.05, β=0.80). To account for potential missing values or failed PET-CT scans, the investigators will include a total of 16 individuals.

Inclusion Criteria:

• 50+ years
• Written and oral consent
• HbA1c 39-47 mmol/L

Exclusion Criteria:

• Medicine with an impact on blood glucose and glucose metabolism.
• Newly started medicine (&amp;lt;3 months prior to the inclusion time)
• Medicine changes (&amp;lt;3 months prior to the inclusion time and planned changes during the trial)
• Affected screening blood sample as evaluated by PI
• Hba1c > 47
• Allergy to paracetamol
• Doesn't speak or understand Danish
• Special diets

The eight healthy individuals will be included by the same criteria except for not having pre-diabetes