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Lactate is formed naturally in the body in example during physical activity. However, lactate is also formed during food fermentation where certain bacterial strains form lactate. Lactate can also be produced chemically. An example of this is Ringer-lactate which is used for volume replacement when treating dehydrated patients.
As a source of carbon-molecules, lactate is believed to be an important oxidative fuel source in all major organs and yields adenosine triphosphate (ATP) production through Krebs cycle, the Electron Transport Chain in the mitochondria as well as by being a key precursor for gluconeogenesis.
Metformin is the first drug of choice for type 2 diabetes treatment. Use of metformin often results in a small but significant weight loss in overweight users. It is known that metformin increases the lactate concentration in the gut. It is also known also know that metformin use is associated with an increase in blood concentrations of growth differentiation factor 15 (GDF-15). Receptors for GDF-15 can be found in parts of the brain associated with control of appetite. In rats increases in [GDF-15] results in a decrease in appetite and thus weight loss. GDF-15 is thought to be involved in the normal energy homeostasis.
With this study the investigators want to examine the hormonal, metabolic and mechanical effects of lactate in the gut in healthy volunteers. Our hypothesis is that lactate has beneficial effects which may be though an increase in GDF-15 in the blood.
Volunteers will undergo two study days separated by at least 7 days and a maximum of 1 month.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oral lactate | Active Comparator | Sodium D/L lactate solution, 25g/L in 300mL water |
|
| Iso-lactic intravenous lactate infusion | Placebo Comparator | iv sodium D/L lactate to elevate [lactate] to the same levels as measured on day 1 + oral sodium chloride, 300 mL |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Sodium Lactate | Drug | 25 grams of D/L lactate dissolved in 300mL water. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| GDF-15 | Difference in [GDF-15] between intervention and placebo | 4 hours |
| Measure | Description | Time Frame |
|---|---|---|
| glucagon-like peptide -1 | Difference in [glucagon-like peptide -1] between intervention and placebo | 4 hours |
| Gastric inhibitory peptide (GIP) | Difference in plasma [GIP] between intervention and placebo |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nikolaj Rittig, postdoc | Steno Diabetes Center Aarhus (SDCA), Aarhus universitetshospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital | Aarhus | 8200 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37844838 | Derived | Pedersen MGB, Lauritzen ES, Svart MV, Stoy J, Sondergaard E, Thomsen HH, Kampmann U, Bjerre M, Jessen N, Moller N, Rittig N. Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and beta-hydroxybutyrate in healthy young males. Am J Clin Nutr. 2023 Dec;118(6):1091-1098. doi: 10.1016/j.ajcnut.2023.10.007. Epub 2023 Oct 14. | |
| 35016146 |
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| ID | Term |
|---|---|
| D065906 | Hyperlactatemia |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D019354 | Sodium Lactate |
| ID | Term |
|---|---|
| D007773 | Lactates |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| Intravenous sodium lactate |
| Drug |
intravenous sodium lactate + oral sodium-chlorid solution |
|
| 4 hours |
| free fatty acid | Difference in [free fatty acid ] between intervention and placebo | 4 hours |
| cholecystokinin | Difference in [cholecystokinin] between intervention and placebo | 4 hours |
| Ghrelin | Difference in [Ghrelin] between intervention and placebo | 4 hours |
| Gastrin | Difference in [Gastrin] between intervention and placebo | 4 hours |
| C-peptide | Difference in [C-peptide] between intervention and placebo | 4 hours |
| glucose | Difference in [glucose] between intervention and placebo | 4 hours |
| gastric emptying | [Paracetamol] to asses gastric emptying | 4 hours |
| Evaluation of hunger | Evaluation of hunger, thoughts of future food intake ect using a questionnaire | 4 hours |
| Pedersen MGB, Sondergaard E, Nielsen CB, Johannsen M, Gormsen LC, Moller N, Jessen N, Rittig N. Oral lactate slows gastric emptying and suppresses appetite in young males. Clin Nutr. 2022 Feb;41(2):517-525. doi: 10.1016/j.clnu.2021.12.032. Epub 2021 Dec 24. |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |